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Most of my Anki-based reading is much shallower than my read of the AlphaGo paper. Rather than spending days on a paper, I'll typically spend 10 to 60 minutes, sometimes longer for very good papers. Here's a few notes on some patterns I've found useful in shallow reading.
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Augmenting Long-term Memory
Anki cards to study in preparation for some (possibly hypothetical) future use, it's better to find a way to use Anki as part of some creative project. Using Anki to do shallow reads of papers <span>Most of my Anki-based reading is much shallower than my read of the AlphaGo paper. Rather than spending days on a paper, I'll typically spend 10 to 60 minutes, sometimes longer for very good papers. Here's a few notes on some patterns I've found useful in shallow reading. As mentioned above, I'm usually doing such reading as part of the background research for some project. I will find a new article (or set of articles), and typically spend a few minutes




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This doesn't mean reading every word in the paper. Rather, I'll add to Anki questions about the core claims, core questions, and core ideas of the paper. It's particularly helpful to extract Anki questions from the abstract, introduction, conclusion, figures, and figure captions. Typically I will extract anywhere from 5 to 20 Anki questions from the paper. It's usually a bad idea to extract fewer than 5 questions – doing so tends to leave the paper as a kind of isolated orphan in my memory.
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es assessing it. Does the article seem likely to contain substantial insight or provocation relevant to my project – new questions, new ideas, new methods, new results? If so, I'll have a read. <span>This doesn't mean reading every word in the paper. Rather, I'll add to Anki questions about the core claims, core questions, and core ideas of the paper. It's particularly helpful to extract Anki questions from the abstract, introduction, conclusion, figures, and figure captions. Typically I will extract anywhere from 5 to 20 Anki questions from the paper. It's usually a bad idea to extract fewer than 5 questions – doing so tends to leave the paper as a kind of isolated orphan in my memory. Later I find it difficult to feel much connection to those questions. Put another way: if a paper is so uninteresting that it's not possible to add 5 good questions about it, it's usual




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How to avoid Ankifying misleading work?

As an example, let me describe how I Ankified a paper I recently read, by the economists Benjamin Jones and Bruce Weinberg* * Benjamin F. Jones and Bruce A. Weinberg, Age Dynamics in Scientific Creativity, Proceedings of the National Academy of Sciences (2011). . The paper studies the ages at which scientists make their greatest discoveries.

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Augmenting Long-term Memory
useful are forms such as Ankification etc. misleading work. Many papers contain wrong or misleading statements, and if you commit such items to memory, you're actively making yourself stupider. <span>How to avoid Ankifying misleading work? As an example, let me describe how I Ankified a paper I recently read, by the economists Benjamin Jones and Bruce Weinberg** Benjamin F. Jones and Bruce A. Weinberg, Age Dynamics in Scientific Creativity, Proceedings of the National Academy of Sciences (2011).. The paper studies the ages at which scientists make their greatest discoveries. I should say at the outset: I have no reason to think this paper is misleading! But it's also worth being cautious. As an example of that caution, one of the questions I added to Anki w




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As an example of that caution, one of the questions I added to Anki was: “What does Jones 2011 claim is the average age at which physics Nobelists made their prizewinning discovery, over 1980-2011?” (Answer: 48). Another variant question was: “Which paper claimed that physics Nobelists made their prizewinning discovery at average age 48, over the period 1980-2011?” (Answer: Jones 2011). And so on.

Such questions qualify the underlying claim: we now know it was a claim made in Jones 2011, and that we're relying on the quality of Jones and Weinberg's data analysis. In fact, I haven't examined that analysis carefully enough to regard it as a fact that the average age of those Nobelists is 48. But it is certainly a fact that their paper claimed it was 48. Those are different things, and the latter is better to Ankify.

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Augmenting Long-term Memory
e paper studies the ages at which scientists make their greatest discoveries. I should say at the outset: I have no reason to think this paper is misleading! But it's also worth being cautious. <span>As an example of that caution, one of the questions I added to Anki was: “What does Jones 2011 claim is the average age at which physics Nobelists made their prizewinning discovery, over 1980-2011?” (Answer: 48). Another variant question was: “Which paper claimed that physics Nobelists made their prizewinning discovery at average age 48, over the period 1980-2011?” (Answer: Jones 2011). And so on. Such questions qualify the underlying claim: we now know it was a claim made in Jones 2011, and that we're relying on the quality of Jones and Weinberg's data analysis. In fact, I haven't examined that analysis carefully enough to regard it as a fact that the average age of those Nobelists is 48. But it is certainly a fact that their paper claimed it was 48. Those are different things, and the latter is better to Ankify. If I'm particularly concerned about the quality of the analysis, I may add one or more questions about what makes such work difficult, e.g.: “What's one challenge in determining the age




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If I'm particularly concerned about the quality of the analysis, I may add one or more questions about what makes such work difficult, e.g.: “What's one challenge in determining the age of Nobel winners at the time of their discovery, as discussed in Jones 2011?” Good answers include: the difficulty of figuring out which paper contained the Nobel-winning work; the fact that publication of papers is sometimes delayed by years; that sometimes work is spread over multiple papers; and so on.
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Augmenting Long-term Memory
regard it as a fact that the average age of those Nobelists is 48. But it is certainly a fact that their paper claimed it was 48. Those are different things, and the latter is better to Ankify. <span>If I'm particularly concerned about the quality of the analysis, I may add one or more questions about what makes such work difficult, e.g.: “What's one challenge in determining the age of Nobel winners at the time of their discovery, as discussed in Jones 2011?” Good answers include: the difficulty of figuring out which paper contained the Nobel-winning work; the fact that publication of papers is sometimes delayed by years; that sometimes work is spread over multiple papers; and so on. Thinking about such challenges reminds me that if Jones and Weinberg were sloppy, or simply made an understandable mistake, their numbers might be off. Now, it so happens that for this




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It's worth deliberately practicing such switches, to avoid building a counter-productive habit of completionism in your reading. It's nearly always possible to read deeper into a paper, but that doesn't mean you can't easily be getting more value elsewhere. It's a failure mode to spend too long reading unimportant papers.
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ly good resources are worth investing time in. But most papers don't fit this pattern, and you quickly saturate. If you feel you could easily find something more rewarding to read, switch over. <span>It's worth deliberately practicing such switches, to avoid building a counter-productive habit of completionism in your reading. It's nearly always possible to read deeper into a paper, but that doesn't mean you can't easily be getting more value elsewhere. It's a failure mode to spend too long reading unimportant papers. Syntopic reading using Anki I've talked about how to use Anki to do shallow reads of papers, and rather deeper reads of papers. There's also a sense in which it's possible to use Anki n




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There's also a sense in which it's possible to use Anki not just to read papers, but to “read” the entire research literature of some field or subfield. Here's how to do it.
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It's a failure mode to spend too long reading unimportant papers. Syntopic reading using Anki I've talked about how to use Anki to do shallow reads of papers, and rather deeper reads of papers. <span>There's also a sense in which it's possible to use Anki not just to read papers, but to “read” the entire research literature of some field or subfield. Here's how to do it. You might suppose the foundation would be a shallow read of a large number of papers. In fact, to really grok an unfamiliar field, you need to engage deeply with key papers – papers lik




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In fact, to really grok an unfamiliar field, you need to engage deeply with key papers – papers like the AlphaGo paper. What you get from deep engagement with important papers is more significant than any single fact or technique: you get a sense for what a powerful result in the field looks like. It helps you imbibe the healthiest norms and standards of the field. It helps you internalize how to ask good questions in the field, and how to put techniques together. You begin to understand what made something like AlphaGo a breakthrough – and also its limitations, and the sense in which it was really a natural evolution of the field. Such things aren't captured individually by any single Anki question. But they begin to be captured collectively by the questions one asks when engaged deeply enough with key papers
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o read papers, but to “read” the entire research literature of some field or subfield. Here's how to do it. You might suppose the foundation would be a shallow read of a large number of papers. <span>In fact, to really grok an unfamiliar field, you need to engage deeply with key papers – papers like the AlphaGo paper. What you get from deep engagement with important papers is more significant than any single fact or technique: you get a sense for what a powerful result in the field looks like. It helps you imbibe the healthiest norms and standards of the field. It helps you internalize how to ask good questions in the field, and how to put techniques together. You begin to understand what made something like AlphaGo a breakthrough – and also its limitations, and the sense in which it was really a natural evolution of the field. Such things aren't captured individually by any single Anki question. But they begin to be captured collectively by the questions one asks when engaged deeply enough with key papers. So, to get a picture of an entire field, I usually begin with a truly important paper, ideally a paper establishing a result that got me interested in the field in the first place. I d




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So, to get a picture of an entire field, I usually begin with a truly important paper, ideally a paper establishing a result that got me interested in the field in the first place. I do a thorough read of that paper, along the lines of what I described for AlphaGo. Later, I do thorough reads of other key papers in the field – ideally, I read the best 5-10 papers in the field. But, interspersed, I also do shallower reads of a much larger number of less important (though still good) papers.
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the field. Such things aren't captured individually by any single Anki question. But they begin to be captured collectively by the questions one asks when engaged deeply enough with key papers. <span>So, to get a picture of an entire field, I usually begin with a truly important paper, ideally a paper establishing a result that got me interested in the field in the first place. I do a thorough read of that paper, along the lines of what I described for AlphaGo. Later, I do thorough reads of other key papers in the field – ideally, I read the best 5-10 papers in the field. But, interspersed, I also do shallower reads of a much larger number of less important (though still good) papers. In my experimentation so far that means tens of papers, though I expect in some fields I will eventually read hundreds or even thousands of papers in this way. You may wonder why I don'




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You may wonder why I don't just focus on only the most important papers. Part of the reason is mundane: it can be hard to tell what the most important papers are.
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rtant (though still good) papers. In my experimentation so far that means tens of papers, though I expect in some fields I will eventually read hundreds or even thousands of papers in this way. <span>You may wonder why I don't just focus on only the most important papers. Part of the reason is mundane: it can be hard to tell what the most important papers are. Shallow reads of many papers can help you figure out what the key papers are, without spending too much time doing deeper reads of papers that turn out not to be so important. But there




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But there's also a culture that one imbibes reading the bread-and-butter papers of a field: a sense for what routine progress looks like, for the praxis of the field.
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rtant papers are. Shallow reads of many papers can help you figure out what the key papers are, without spending too much time doing deeper reads of papers that turn out not to be so important. <span>But there's also a culture that one imbibes reading the bread-and-butter papers of a field: a sense for what routine progress looks like, for the praxis of the field. That's valuable too, especially for building up an overall picture of where the field is at, and to stimulate questions on my own part. Indeed, while I don't recommend spending a large




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Indeed, while I don't recommend spending a large fraction of your time reading bad papers, it's certainly possible to have a good conversation with a bad paper. Stimulus is found in unexpected places.
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routine progress looks like, for the praxis of the field. That's valuable too, especially for building up an overall picture of where the field is at, and to stimulate questions on my own part. <span>Indeed, while I don't recommend spending a large fraction of your time reading bad papers, it's certainly possible to have a good conversation with a bad paper. Stimulus is found in unexpected places. Over time, this is a form of what Mortimer Adler and Charles van Doren dubbed syntopic reading** In their marvelous “How to Read a Book”: Mortimer J. Adler and Charles van Doren, “How t




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Over time, this is a form of what Mortimer Adler and Charles van Doren dubbed syntopic reading
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while I don't recommend spending a large fraction of your time reading bad papers, it's certainly possible to have a good conversation with a bad paper. Stimulus is found in unexpected places. <span>Over time, this is a form of what Mortimer Adler and Charles van Doren dubbed syntopic reading** In their marvelous “How to Read a Book”: Mortimer J. Adler and Charles van Doren, “How to Read a Book: The Classic Guide to Intelligent Reading” (1972). I build up an understanding of




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I start to identify open problems, questions that I'd personally like answered, but which don't yet seem to have been answered. I identify tricks, observations that seem pregnant with possibility, but whose import I don't yet know. And, sometimes, I identify what seem to me to be field-wide blind spots. I add questions about all these to Anki as well. In this way, Anki is a medium supporting my creative research.
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(1972). I build up an understanding of an entire literature: what's been done, what's not yet been done. Of course, it's not literally reading an entire literature. But functionally it's close. <span>I start to identify open problems, questions that I'd personally like answered, but which don't yet seem to have been answered. I identify tricks, observations that seem pregnant with possibility, but whose import I don't yet know. And, sometimes, I identify what seem to me to be field-wide blind spots. I add questions about all these to Anki as well. In this way, Anki is a medium supporting my creative research. It has some shortcomings as such a medium, since it's not designed with supporting creative work in mind – it's not, for instance, equipped for lengthy, free-form exploration inside a s




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This captures something of the immense emotional effort I used to find required to learn a new field. Without a lot of drive, it was extremely difficult to make a lot of material in a new field stick. Anki does much to solve that problem.
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tlewood wrote** In “Littlewood's miscellany”, edited by Béla Bollobás (1986).: I have tried to learn mathematics outside my fields of interest; after any interval I had to begin all over again. <span>This captures something of the immense emotional effort I used to find required to learn a new field. Without a lot of drive, it was extremely difficult to make a lot of material in a new field stick. Anki does much to solve that problem. In a sense, it's an emotional prosthetic, actually helping create the drive I need to achieve understanding. It doesn't do the entire job – as mentioned earlier, it's very helpful to ha




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In a sense, it's an emotional prosthetic, actually helping create the drive I need to achieve understanding. It doesn't do the entire job – as mentioned earlier, it's very helpful to have other commitments (like a creative project, or people depending on me) to help create that drive.
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nal effort I used to find required to learn a new field. Without a lot of drive, it was extremely difficult to make a lot of material in a new field stick. Anki does much to solve that problem. <span>In a sense, it's an emotional prosthetic, actually helping create the drive I need to achieve understanding. It doesn't do the entire job – as mentioned earlier, it's very helpful to have other commitments (like a creative project, or people depending on me) to help create that drive. Nonetheless, Anki helps give me confidence that I can simply decide I'm going to read deeply into a new field, and retain and make sense of much of what I learn. This has worked for all




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Make most Anki questions and answers as atomic as possible: That is, both the question and answer express just one idea.
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ive learning: Twenty rules of formulating knowledge.. There's a lot in this section, and upon a first read you may wish to skim through and concentrate on those items which most catch your eye. <span>Make most Anki questions and answers as atomic as possible: That is, both the question and answer express just one idea. As an example, when I was learning the Unix command line, I entered the question: “How to create a soft link from linkname to filename?” The answer was: “ln -s filename linkname”. Unfor




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As an example, when I was learning the Unix command line, I entered the question: “How to create a soft link from linkname to filename?” The answer was: “ln -s filename linkname”. Unfortunately, I routinely got this question wrong.

The solution was to refactor the question by breaking it into two pieces. One piece was: “What's the basic command and option to create a Unix soft link?” Answer: “ln -s …”. And the second piece was: “When creating a Unix soft link, in what order do linkname and filename go?” Answer: “filename linkname”.

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o skim through and concentrate on those items which most catch your eye. Make most Anki questions and answers as atomic as possible: That is, both the question and answer express just one idea. <span>As an example, when I was learning the Unix command line, I entered the question: “How to create a soft link from linkname to filename?” The answer was: “ln -s filename linkname”. Unfortunately, I routinely got this question wrong. The solution was to refactor the question by breaking it into two pieces. One piece was: “What's the basic command and option to create a Unix soft link?” Answer: “ln -s …”. And the second piece was: “When creating a Unix soft link, in what order do linkname and filename go?” Answer: “filename linkname”. Breaking this question into more atomic pieces turned a question I routinely got wrong into two questions I routinely got right** An even more atomic version would be to break the first




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Note that this doesn't mean you shouldn't also retain some version of the original question. I still want to know how to create a soft link in Unix, and so it's worth keeping the original question in Anki. But it becomes an integrative question, part of a hierarchy of questions building up from simple atomic facts to more complex ideas.
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nd knows exactly where to focus. In general, I find that you often get substantial benefit from breaking Anki questions down to be more atomic. It's a powerful pattern for question refactoring. <span>Note that this doesn't mean you shouldn't also retain some version of the original question. I still want to know how to create a soft link in Unix, and so it's worth keeping the original question in Anki. But it becomes an integrative question, part of a hierarchy of questions building up from simple atomic facts to more complex ideas. Incidentally, just because a question is atomic doesn't mean it can't involve quite complex, high-level concepts. Consider the following question, from the field of general relativity:




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One benefit of using Anki in this way is that you begin to habitually break things down into atomic questions. This sharply crystallizes the distinct things you've learned. Personally, I find that crystallization satisfying, for reasons I (ironically) find difficult to articulate. But one real benefit is that later I often find those atomic ideas can be put together in ways I didn't initially anticipate. And that's well worth the trouble.
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question, assuming you know what the Robertson-Walker metric is, what dr2 means, what k means, and so on. But conditional on that background knowledge, it's quite an atomic question and answer. <span>One benefit of using Anki in this way is that you begin to habitually break things down into atomic questions. This sharply crystallizes the distinct things you've learned. Personally, I find that crystallization satisfying, for reasons I (ironically) find difficult to articulate. But one real benefit is that later I often find those atomic ideas can be put together in ways I didn't initially anticipate. And that's well worth the trouble. Anki use is best thought of as a virtuoso skill, to be developed: Anki is an extremely simple program: it lets you enter text or other media, and then shows you that media on a schedule




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Part of developing Anki as a virtuoso skill is cultivating the ability to use it for types of understanding beyond basic facts. Indeed, many of the observations I've made (and will make, below) about how to use Anki are really about what it means to understand something. Break things up into atomic facts. Build rich hierarchies of interconnections and integrative questions. Don't put in orphan questions. Patterns for how to engage with reading material. Patterns (and anti-patterns) for question types. Patterns for the kinds of things you'd like to memorize. Anki skills concretely instantiate your theory of how you understand; developing those skills will help you understand better. It's too strong to say that to be a virtuoso Anki user is to be a virtuoso in understanding. But there's some truth to it.
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al questions about the design of the AlphaGo systems – on subjects such as how AlphaGo avoided over-generalizing from training data, the limitations of convolutional neural networks, and so on. <span>Part of developing Anki as a virtuoso skill is cultivating the ability to use it for types of understanding beyond basic facts. Indeed, many of the observations I've made (and will make, below) about how to use Anki are really about what it means to understand something. Break things up into atomic facts. Build rich hierarchies of interconnections and integrative questions. Don't put in orphan questions. Patterns for how to engage with reading material. Patterns (and anti-patterns) for question types. Patterns for the kinds of things you'd like to memorize. Anki skills concretely instantiate your theory of how you understand; developing those skills will help you understand better. It's too strong to say that to be a virtuoso Anki user is to be a virtuoso in understanding. But there's some truth to it. Use one big deck: Anki allows you to organize cards into decks and subdecks. Some people use this to create a complicated organizational structure. I used to do this, but I've gradually




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Anki isn't just a tool for memorizing simple facts. It's a tool for understanding almost anything. It's a common misconception that Anki is just for memorizing simple raw facts, things like vocabulary items and basic definitions. But as we've seen, it's possible to use Anki for much more advanced types of understanding
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, like many tools, it requires skill to use well. It's worth thinking of Anki as a skill that can be developed to virtuoso levels, and attempting to continue to level up toward such virtuosity. <span>Anki isn't just a tool for memorizing simple facts. It's a tool for understanding almost anything. It's a common misconception that Anki is just for memorizing simple raw facts, things like vocabulary items and basic definitions. But as we've seen, it's possible to use Anki for much more advanced types of understanding. My questions about AlphaGo began with simple questions such as “How large is a Go board?”, and ended with high-level conceptual questions about the design of the AlphaGo systems – on s




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Use one big deck: Anki allows you to organize cards into decks and subdecks. Some people use this to create a complicated organizational structure. I used to do this, but I've gradually* * It's gradual because questions sometimes need to be rewritten due to the changed context. For instance, both my Emacs and Unix command line decks had very similar questions, along the lines of: “How to delete a word?” Those questions need to be rewritten, e.g. as: “In Emacs, how to delete a word?” (This, by the way, may seem a strange question for a long-time Emacs user such as myself. In fact, I've used Anki to help me change the way I delete words in Emacs, which is why I have an Anki question on the subject. I have made many improvements to my Emacs workflow this way.) merged my decks and subdecks into one big deck. The world isn't divided up into neatly separated components, and I believe it's good to collide very different types of questions.
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u understand; developing those skills will help you understand better. It's too strong to say that to be a virtuoso Anki user is to be a virtuoso in understanding. But there's some truth to it. <span>Use one big deck: Anki allows you to organize cards into decks and subdecks. Some people use this to create a complicated organizational structure. I used to do this, but I've gradually** It's gradual because questions sometimes need to be rewritten due to the changed context. For instance, both my Emacs and Unix command line decks had very similar questions, along the lines of: “How to delete a word?” Those questions need to be rewritten, e.g. as: “In Emacs, how to delete a word?” (This, by the way, may seem a strange question for a long-time Emacs user such as myself. In fact, I've used Anki to help me change the way I delete words in Emacs, which is why I have an Anki question on the subject. I have made many improvements to my Emacs workflow this way.) merged my decks and subdecks into one big deck. The world isn't divided up into neatly separated components, and I believe it's good to collide very different types of questions. One moment Anki is asking me a question about the temperature chicken should be cooked to. The next: a question about the JavaScript API. Is this mixing doing me any real good? I'm not




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Avoid orphan questions: Suppose I'm reading online and stumble across a great article about the grooming habits of the Albanian giant mongoose, a subject I never previously knew I was interested in, but which turns out to be fascinating. Pretty soon I've Ankified 5 to 10 questions. That's great, but my experience suggests that in a few months I'll likely find those questions rather stale, and frequently get them wrong. I believe the reason is that those questions are too disconnected from my other interests, and I will have lost the context that made me interested.

I call these orphan questions, because they're not closely related to anything else in my memory.

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n to use JavaScript to control the cooking of a chicken. But I don't think this mixing does any harm, and hope it is creatively stimulating, and helps me apply my knowledge in unusual contexts. <span>Avoid orphan questions: Suppose I'm reading online and stumble across a great article about the grooming habits of the Albanian giant mongoose, a subject I never previously knew I was interested in, but which turns out to be fascinating. Pretty soon I've Ankified 5 to 10 questions. That's great, but my experience suggests that in a few months I'll likely find those questions rather stale, and frequently get them wrong. I believe the reason is that those questions are too disconnected from my other interests, and I will have lost the context that made me interested. I call these orphan questions, because they're not closely related to anything else in my memory. It's not bad to have a few orphan questions in Anki – it can be difficult to know what will turn out to be of only passing interest, and what will grow into a substantial interest, conn




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It's particularly worth avoiding lonely orphans: single questions that are largely disconnected from everything else. Suppose, for instance, I'm reading an article on a new subject, and I learn an idea that seems particularly useful. I make it a rule to never put in one question. Rather, I try to put at least two questions in, preferably three or more. That's usually enough that it's at least the nucleus of a bit of useful knowledge. If it's a lonely orphan, inevitably I get the question wrong all the time, and it's a waste to have entered it at all.
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l minority of your questions are orphans, that's a sign you should concentrate more on Ankifying questions related to your main creative projects, and cut down on Ankifying tangential material. <span>It's particularly worth avoiding lonely orphans: single questions that are largely disconnected from everything else. Suppose, for instance, I'm reading an article on a new subject, and I learn an idea that seems particularly useful. I make it a rule to never put in one question. Rather, I try to put at least two questions in, preferably three or more. That's usually enough that it's at least the nucleus of a bit of useful knowledge. If it's a lonely orphan, inevitably I get the question wrong all the time, and it's a waste to have entered it at all. Don't share decks: I'm often asked whether I'd be willing to share my Anki decks. I'm not. Very early on I realized it would be very useful to put personal information in Anki. I don't




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Don't share decks: I'm often asked whether I'd be willing to share my Anki decks. I'm not. Very early on I realized it would be very useful to put personal information in Anki. I don't mean anything terribly personal – I'd never put deep, dark secrets in there. Nor do I put anything requiring security, like passwords. But I do put some things I wouldn't sling about casually.
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sually enough that it's at least the nucleus of a bit of useful knowledge. If it's a lonely orphan, inevitably I get the question wrong all the time, and it's a waste to have entered it at all. <span>Don't share decks: I'm often asked whether I'd be willing to share my Anki decks. I'm not. Very early on I realized it would be very useful to put personal information in Anki. I don't mean anything terribly personal – I'd never put deep, dark secrets in there. Nor do I put anything requiring security, like passwords. But I do put some things I wouldn't sling about casually. As an example, I've a (very short!) list of superficially charming and impressive colleagues who I would never work with, because I've consistently seen them treat other people badly. I




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Construct your own decks: The Anki site has many shared decks, but I've found only a little use for them. The most important reason is that making Anki cards is an act of understanding in itself. That is, figuring out good questions to ask, and good answers, is part of what it means to understand a new subject well. To use someone else's cards is to forgo much of that understanding.
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t is right to spread casually: I may have misinterpreted the other person's actions, or have misunderstood the context they were operating in. But it's personally useful for me to have in Anki. <span>Construct your own decks: The Anki site has many shared decks, but I've found only a little use for them. The most important reason is that making Anki cards is an act of understanding in itself. That is, figuring out good questions to ask, and good answers, is part of what it means to understand a new subject well. To use someone else's cards is to forgo much of that understanding. Indeed, I believe the act of constructing the cards actually helps with memory. Memory researchers have repeatedly found that the more elaborately you encode a memory, the stronger the




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Indeed, I believe the act of constructing the cards actually helps with memory. Memory researchers have repeatedly found that the more elaborately you encode a memory, the stronger the memory will be. By elaborative encoding, they mean essentially the richness of the associations you form.

For instance, it's possible to try to remember as an isolated fact that 1962 was the year the first telecommunications satellite, Telstar, was put into orbit. But a better way of remembering it is to relate that fact to others. Relatively prosaically, you might observe that Telstar was launched just 5 years after the first Soviet satellite, Sputnik. It didn't take long to put space to use for telecommunications. Less prosaically – a richer elaboration – I personally find it fascinating that Telstar was put into orbit the year before the introduction of ASCII, arguably the first modern digital standard for communicating text. Humanity had a telecommunications satellite before we had a digital standard for communicating text! Finding that kind of connection is an example of an elaborative encoding.

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lf. That is, figuring out good questions to ask, and good answers, is part of what it means to understand a new subject well. To use someone else's cards is to forgo much of that understanding. <span>Indeed, I believe the act of constructing the cards actually helps with memory. Memory researchers have repeatedly found that the more elaborately you encode a memory, the stronger the memory will be. By elaborative encoding, they mean essentially the richness of the associations you form. For instance, it's possible to try to remember as an isolated fact that 1962 was the year the first telecommunications satellite, Telstar, was put into orbit. But a better way of remembering it is to relate that fact to others. Relatively prosaically, you might observe that Telstar was launched just 5 years after the first Soviet satellite, Sputnik. It didn't take long to put space to use for telecommunications. Less prosaically – a richer elaboration – I personally find it fascinating that Telstar was put into orbit the year before the introduction of ASCII, arguably the first modern digital standard for communicating text. Humanity had a telecommunications satellite before we had a digital standard for communicating text! Finding that kind of connection is an example of an elaborative encoding. The act of constructing an Anki card is itself nearly always a form of elaborative encoding. It forces you to think through alternate forms of the question, to consider the best possibl




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The act of constructing an Anki card is itself nearly always a form of elaborative encoding. It forces you to think through alternate forms of the question, to consider the best possible answers, and so on. I believe this is true for even the most elementary cards
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ommunicating text. Humanity had a telecommunications satellite before we had a digital standard for communicating text! Finding that kind of connection is an example of an elaborative encoding. <span>The act of constructing an Anki card is itself nearly always a form of elaborative encoding. It forces you to think through alternate forms of the question, to consider the best possible answers, and so on. I believe this is true for even the most elementary cards. And it certainly becomes true if you construct more complex cards, cards relating the basic fact to be remembered to other ideas (like the Telstar-ASCII link), gradually building up a




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Cultivate strategies for elaborative encoding / forming rich associations: This is really a meta-strategy, i.e., a strategy for forming strategies. One simple example strategy is to use multiple variants of the “same” question. For instance, I mentioned earlier my two questions: “What does Jones 2011 claim is the average age at which physics Nobelists made their prizewinning discovery, over 1980-2011?” And: “Which paper claimed that physics Nobelists made their prizewinning discovery at average age 48, over the period 1980-2011?” Logically, these two questions are obviously closely related. But in terms of how memory works, they are different, causing associations on very different triggers.
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elementary questions, such as art decks which ask questions such as who painted a particular painting. But for deeper kinds of understanding, I've not yet found good ways of using shared decks. <span>Cultivate strategies for elaborative encoding / forming rich associations: This is really a meta-strategy, i.e., a strategy for forming strategies. One simple example strategy is to use multiple variants of the “same” question. For instance, I mentioned earlier my two questions: “What does Jones 2011 claim is the average age at which physics Nobelists made their prizewinning discovery, over 1980-2011?” And: “Which paper claimed that physics Nobelists made their prizewinning discovery at average age 48, over the period 1980-2011?” Logically, these two questions are obviously closely related. But in terms of how memory works, they are different, causing associations on very different triggers. What about memory palaces and similar techniques? There is a well-known set of memory techniques based around ideas such as memory palaces, the method of loci, and others** An entertain




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Here's Joshua Foer recounting a conversation where mnemonist Ed Cooke describes one basic technique:

Ed then explained to me his procedure for making a name memorable, which he had used in the competition to memorize the first and last names associated with ninety-nine different photographic head shots in the names-and-faces event. It was a technique he promised I could use to remember people's names at parties and meetings. “The trick is actually deceptively simple,” he said. “It is always to associate the sound of a person's name with something you can clearly imagine. It's all about creating a vivid image in your mind that anchors your visual memory of the person's face to a visual memory connected to the person's name. When you need to reach back and remember the person's name at some later date, the image you created will simply pop back into your mind… So, hmm, you said your name was Josh Foer, eh?” He raised an eyebrow and gave his chin a melodramatic stroke. “Well, I'd imagine you joshing me where we first met, outside the competition hall, and I'd imagine myself breaking into four pieces in response. Four/Foer, get it? That little image is more entertaining—to me, at least—than your mere name, and should stick nicely in the mind.”
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overview is: Joshua Foer, “Moonwalking with Einstein” (2011).. This is an extreme form of elaborative encoding, making rich visual and spatial associations to the material you want to remember. <span>Here's Joshua Foer recounting a conversation where mnemonist Ed Cooke describes one basic technique: Ed then explained to me his procedure for making a name memorable, which he had used in the competition to memorize the first and last names associated with ninety-nine different photographic head shots in the names-and-faces event. It was a technique he promised I could use to remember people's names at parties and meetings. “The trick is actually deceptively simple,” he said. “It is always to associate the sound of a person's name with something you can clearly imagine. It's all about creating a vivid image in your mind that anchors your visual memory of the person's face to a visual memory connected to the person's name. When you need to reach back and remember the person's name at some later date, the image you created will simply pop back into your mind… So, hmm, you said your name was Josh Foer, eh?” He raised an eyebrow and gave his chin a melodramatic stroke. “Well, I'd imagine you joshing me where we first met, outside the competition hall, and I'd imagine myself breaking into four pieces in response. Four/Foer, get it? That little image is more entertaining—to me, at least—than your mere name, and should stick nicely in the mind.” I've experimented with these techniques, and while they're fun, they seem most useful for memorizing trivia – sequences of playing cards, strings of digits, and so on. They seem less we




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I've experimented with these techniques, and while they're fun, they seem most useful for memorizing trivia – sequences of playing cards, strings of digits, and so on. They seem less well developed for more abstract concepts, and such abstractions are often where the deepest understanding lies.
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nd I'd imagine myself breaking into four pieces in response. Four/Foer, get it? That little image is more entertaining—to me, at least—than your mere name, and should stick nicely in the mind.” <span>I've experimented with these techniques, and while they're fun, they seem most useful for memorizing trivia – sequences of playing cards, strings of digits, and so on. They seem less well developed for more abstract concepts, and such abstractions are often where the deepest understanding lies. In that sense, they may even distract from understanding. That said, it's possible I simply need to figure out better ways of using these ideas, much as I needed to figure out Anki. In




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95% of Anki's value comes from 5% of the features: Anki has ways of auto-generating cards, of tagging cards, a plugin ecosystem, and much else. In practice, I rarely use any of these features. My cards are always one of two types: the majority are simple question and answer; a substantial minority are what's called a cloze: a kind of fill-in-the-blanks test. For instance, I'll use clozes to test myself on favorite quotes
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investigating some of the techniques used by practitioners to form rich associations. As Foer says, quoting a memory expert, there is great value in learning to “think in more memorable ways”. <span>95% of Anki's value comes from 5% of the features: Anki has ways of auto-generating cards, of tagging cards, a plugin ecosystem, and much else. In practice, I rarely use any of these features. My cards are always one of two types: the majority are simple question and answer; a substantial minority are what's called a cloze: a kind of fill-in-the-blanks test. For instance, I'll use clozes to test myself on favorite quotes: “if the personal computer is truly a __ then the use of it would actually change the __ of an __", __, __” (Answer: new medium, thought patterns, entire civilization, Alan Kay, 1989).




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I know many people who try Anki out, and then go down a rabbit hole learning as many features as possible so they can use it “efficiently”. Usually, they're chasing 1% improvements. Often, those people ultimately give up Anki as “too difficult”, which is often a synonym for “I got nervous I wasn't using it perfectly”. This is a pity. As discussed earlier, Anki offers something like a 20-fold improvement over (say) ordinary flashcards.
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pment, but you can spend a lifetime learning to use them well. Similarly, basic Anki practice can be developed enormously. And so I've concentrated on learning to use those basic features well. <span>I know many people who try Anki out, and then go down a rabbit hole learning as many features as possible so they can use it “efficiently”. Usually, they're chasing 1% improvements. Often, those people ultimately give up Anki as “too difficult”, which is often a synonym for “I got nervous I wasn't using it perfectly”. This is a pity. As discussed earlier, Anki offers something like a 20-fold improvement over (say) ordinary flashcards. And so they're giving up a 2,000% improvement because they were worried they were missing a few final 5%, 1% and (in many cases) 0.1% improvements. This kind of rabbit hole seems to be




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Procedural versus declarative memory: There's a big difference between remembering a fact and mastering a process. For instance, while you might remember a Unix command when cued by an Anki question, that doesn't mean you'll recognize an opportunity to use the command in the context of the command line, and be comfortable typing it out. And it's still another thing to find novel, creative ways of combining the commands you know, in order to solve challenging problems.

Put another way: to really internalize a process, it's not enough just to review Anki cards. You need to carry out the process, in context. And you need to solve real problems with it.

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le with it. I have adopted Anki for less personal stuff – things like people's food preferences. And maybe over time I'll use it for storing more personal facts. But for now I'm taking it slow. <span>Procedural versus declarative memory: There's a big difference between remembering a fact and mastering a process. For instance, while you might remember a Unix command when cued by an Anki question, that doesn't mean you'll recognize an opportunity to use the command in the context of the command line, and be comfortable typing it out. And it's still another thing to find novel, creative ways of combining the commands you know, in order to solve challenging problems. Put another way: to really internalize a process, it's not enough just to review Anki cards. You need to carry out the process, in context. And you need to solve real problems with it. With that said, I've found the transfer process relatively easy. In the case of the command line, I use it often enough that I have plenty of opportunities to make real use of my Ankifi




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Getting past “names don't matter”: I'm a theoretical physicist by training. There is a famous story in physics, told by Richard Feynman, dismissing the value of knowing the names of things. As a child, Feynman was out playing in a field with a know-it-all kid. Here's what happened, in Feynman's telling* * Richard P. Feynman, “What Do You Care What Other People Think? Further Adventures of a Curious Character” (1989). :

One kid says to me, “See that bird? What kind of bird is that?”

I said, “I haven't the slightest idea what kind of a bird it is.”

He says, “It'a brown-throated thrush. Your father doesn't teach you anything!”

But it was the opposite. He [Feynman's father] had already taught me: “See that bird?” he says. “It's a Spencer's warbler.” (I knew he didn't know the real name.) “Well, in Italian, it's a Chutto Lapittida. In Portuguese, it's a Bom da Peida… You can know the name of that bird in all the languages of the world, but when you're finished, you'll know absolutely nothing whatever about the bird! You'll only know about humans in different places, and what they call the bird. So let's look at the bird and see what it's doing — that's what counts.” (I learned very early the difference between knowing the name of something and knowing something.)
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this vein: miming the action of typing commands while I review my Anki cards. But my subjective impression was that it doesn't work so well, and it was also quite annoying to do. So I stopped. <span>Getting past “names don't matter”: I'm a theoretical physicist by training. There is a famous story in physics, told by Richard Feynman, dismissing the value of knowing the names of things. As a child, Feynman was out playing in a field with a know-it-all kid. Here's what happened, in Feynman's telling** Richard P. Feynman, “What Do You Care What Other People Think? Further Adventures of a Curious Character” (1989).: One kid says to me, “See that bird? What kind of bird is that?” I said, “I haven't the slightest idea what kind of a bird it is.” He says, “It'a brown-throated thrush. Your father doesn't teach you anything!” But it was the opposite. He [Feynman's father] had already taught me: “See that bird?” he says. “It's a Spencer's warbler.” (I knew he didn't know the real name.) “Well, in Italian, it's a Chutto Lapittida. In Portuguese, it's a Bom da Peida… You can know the name of that bird in all the languages of the world, but when you're finished, you'll know absolutely nothing whatever about the bird! You'll only know about humans in different places, and what they call the bird. So let's look at the bird and see what it's doing — that's what counts.” (I learned very early the difference between knowing the name of something and knowing something.) Feynman (or his father) goes on to a thoughtful discussion of real knowledge: observing behavior, understanding the reasons for it, and so on. It's a good story. But it goes too far: na




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Feynman (or his father) goes on to a thoughtful discussion of real knowledge: observing behavior, understanding the reasons for it, and so on.

It's a good story. But it goes too far: names do matter. Maybe not as much as the know-it-all kid thought, and they're not usually a deep kind of knowledge. But they're the foundation that allows you to build up a network of knowledge.

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t they call the bird. So let's look at the bird and see what it's doing — that's what counts.” (I learned very early the difference between knowing the name of something and knowing something.) <span>Feynman (or his father) goes on to a thoughtful discussion of real knowledge: observing behavior, understanding the reasons for it, and so on. It's a good story. But it goes too far: names do matter. Maybe not as much as the know-it-all kid thought, and they're not usually a deep kind of knowledge. But they're the foundation that allows you to build up a network of knowledge. This trope that names don't matter was repeatedly drilled into me during my scientific training. When I began using Anki, at first I felt somewhat silly putting questions about names fo




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What do you do when you get behind? Anki becomes challenging when you get behind with cards. If you skip a day or two – or fifty – the cards begin to back up. It's intimidating to come back to find you have 500 cards to review in a day. Even worse, if you fall out of the Anki habit, you can get a very long way behind. I largely stopped using Anki for a 7-month period, and came back to thousands of backlogged cards.

Fortunately, it wasn't that hard to catch up. I set myself gradually increasing quotas (100, 150, 200, 250, and eventually 300) of cards per day, and worked through those quotas each day for several weeks until I'd caught up.

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analytically about the painting – say, about the clever use of color gradients – I could add more detailed questions. But I'm pretty happy just committing the experience of the image to memory. <span>What do you do when you get behind? Anki becomes challenging when you get behind with cards. If you skip a day or two – or fifty – the cards begin to back up. It's intimidating to come back to find you have 500 cards to review in a day. Even worse, if you fall out of the Anki habit, you can get a very long way behind. I largely stopped using Anki for a 7-month period, and came back to thousands of backlogged cards. Fortunately, it wasn't that hard to catch up. I set myself gradually increasing quotas (100, 150, 200, 250, and eventually 300) of cards per day, and worked through those quotas each day for several weeks until I'd caught up. While this wasn't too difficult, it was somewhat demoralizing and discouraging. It'd be better if Anki had a “catch up” feature that would spread the excess cards over the next few week




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One caution is with books: reading an entire book is a big commitment, and adding Anki questions regularly can slow you down a lot. It's worth keeping this in mind when deciding how much to Ankify. Sometimes a book is so dense with great material that it's worth taking the time to add lots of questions. But unmindfully Ankifying everything in sight is a bad habit, one I've occasionally fallen into.
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Ankify. I then enter it into Anki later. This requires some discipline; it's one reason I prefer to set a small quota, so that I merely have to enter a few questions later, rather than dozens. <span>One caution is with books: reading an entire book is a big commitment, and adding Anki questions regularly can slow you down a lot. It's worth keeping this in mind when deciding how much to Ankify. Sometimes a book is so dense with great material that it's worth taking the time to add lots of questions. But unmindfully Ankifying everything in sight is a bad habit, one I've occasionally fallen into. What you Ankify is not a trivial choice: Ankify things that serve your long-term goals. In some measure we become what we remember, so we must be careful what we remember** With apologi




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Avoid the yes/no pattern: One bad habit I sometimes slide into is having lots of Anki questions with yes/no answers. For instance, here's a not-very-good question I added when learning about graphical models in machine learning:

Is computing the partition function intractable for most graphical models?

The answer is “yes”. That's fine, as far as it goes. But it'd help my understanding to elaborate the ideas in the question. Can I add a question about for which graphical models the partition function is tractable? Can I give an example of a graphical model for which the partition function is intractable? What does it mean for computing the partition function to be intractable anyway? Yes/no questions should, at the least, be considered as good candidates for question refactoring*

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mentation. Part of the problem is that I don't have a very good system for note taking, period! If I worked more on that, I suspect the whole thing would get a lot better. Still, it works okay. <span>Avoid the yes/no pattern: One bad habit I sometimes slide into is having lots of Anki questions with yes/no answers. For instance, here's a not-very-good question I added when learning about graphical models in machine learning: Is computing the partition function intractable for most graphical models? The answer is “yes”. That's fine, as far as it goes. But it'd help my understanding to elaborate the ideas in the question. Can I add a question about for which graphical models the partition function is tractable? Can I give an example of a graphical model for which the partition function is intractable? What does it mean for computing the partition function to be intractable anyway? Yes/no questions should, at the least, be considered as good candidates for question refactoring** By analogy with code smells, we can speak of “question smells”, as suggesting a possible need for refactoring. A yes/no construction is an example of a question smell. Aren't external




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Fluency matters in thinking. Alan Kay and Adele Goldberg have proposed* * Alan Kay and Adele Goldberg, Personal Dynamic Media (1977). the thought experiment of a flute in which there is “a one-second delay between blowing a note and hearing it!” As they observe, this is “absurd”. In a similar way, certain types of thoughts are much easier to have when all the relevant kinds of understanding are held in mind. And for that, Anki is invaluable.
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bles speed in associative thought, an ability to rapidly try out many combinations of ideas, and to intuit patterns, in ways not possible if you need to keep laboriously looking up information. <span>Fluency matters in thinking. Alan Kay and Adele Goldberg have proposed** Alan Kay and Adele Goldberg, Personal Dynamic Media (1977). the thought experiment of a flute in which there is “a one-second delay between blowing a note and hearing it!” As they observe, this is “absurd”. In a similar way, certain types of thoughts are much easier to have when all the relevant kinds of understanding are held in mind. And for that, Anki is invaluable. If personal memory systems are so great, why aren't they more widely used? This question is analogous to the old joke about two economists who are walking along when one of them spots a




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One of the most cited papers in the relevant research literature* * Frank N. Dempster, The Spacing Effect: A Case Study in the Failure to Apply the Results of Psychological Research (1988). is a discussion of why these ideas aren't more widely used in education. Although written in 1988, many of the observations in the paper remain true today.

My own personal suspicion is that there are three main factors:

  • In experimental research on memory, people consistently underestimate the gains that come from distributing their study in a manner similar to Anki. Instead, they prefer last-minute cramming, and believe it produces better results, though many studies show it does not.
  • The psychologist Robert Bjork has suggested* *Robert A. Bjork, Memory and Metamemory Considerations in the Training of Human Beings (1994). the “principle of desirable difficulty”, the idea that memories are maximally strengthened if tested when we're on the verge of forgetting them. This suggests that an efficient memory system will intrinsically be somewhat difficult to use. Human beings have a complex relationship to difficult activities, and often dislike performing them, unless strongly motivated (in which case they may become pleasurable).
  • Systems such as Anki are challenging to use well, and easy to use poorly.

It is interesting to consider developing systems which may overcome some or all of these issues.

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have picked it up already.” The analogy is only partial. In fact, Anki seems like a continual supply of $20 bills lying on the ground. And it's reasonable to ask why it's not more widely used. <span>One of the most cited papers in the relevant research literature** Frank N. Dempster, The Spacing Effect: A Case Study in the Failure to Apply the Results of Psychological Research (1988). is a discussion of why these ideas aren't more widely used in education. Although written in 1988, many of the observations in the paper remain true today. My own personal suspicion is that there are three main factors: In experimental research on memory, people consistently underestimate the gains that come from distributing their study in a manner similar to Anki. Instead, they prefer last-minute cramming, and believe it produces better results, though many studies show it does not. The psychologist Robert Bjork has suggested**Robert A. Bjork, Memory and Metamemory Considerations in the Training of Human Beings (1994). the “principle of desirable difficulty”, the idea that memories are maximally strengthened if tested when we're on the verge of forgetting them. This suggests that an efficient memory system will intrinsically be somewhat difficult to use. Human beings have a complex relationship to difficult activities, and often dislike performing them, unless strongly motivated (in which case they may become pleasurable). Systems such as Anki are challenging to use well, and easy to use poorly. It is interesting to consider developing systems which may overcome some or all of these issues. Part II: Personal Memory Systems More Broadly In the first part of this essay we looked at a particular personal memory system, Anki, through the lens of my personal experience. In the




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Long-term memory is sometimes disparaged. It's common for people to denigrate “rote memory”, especially in the classroom. I've heard from many people that they dropped some class – organic chemistry is common – because it was “just a bunch of facts, and I wanted something involving more understanding”.
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personal memory systems: how important is memory as a cognitive skill; and what is the role of cognitive science in building personal memory systems? How important is long-term memory, anyway? <span>Long-term memory is sometimes disparaged. It's common for people to denigrate “rote memory”, especially in the classroom. I've heard from many people that they dropped some class – organic chemistry is common – because it was “just a bunch of facts, and I wanted something involving more understanding”. I won't defend bad classroom teaching, or the way organic chemistry is often taught. But it's a mistake to underestimate the importance of memory. I used to believe such tropes about th




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My somewhat pious belief was that if people focused more on remembering the basics, and worried less about the “difficult” high-level issues, they'd find the high-level issues took care of themselves.

But while I held this as a strong conviction about other people, I never realized it also applied to me. And I had no idea at all how strongly it applied to me. Using Anki to read papers in new fields disabused me of this illusion. I found it almost unsettling how much easier Anki made learning such subjects. I now believe memory of the basics is often the single largest barrier to understanding.

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strated, and think the trouble is the difficulty of finding a good theme, striking sentiments and images, and so on. But really the issue is that they have only 200 words with which to compose. <span>My somewhat pious belief was that if people focused more on remembering the basics, and worried less about the “difficult” high-level issues, they'd find the high-level issues took care of themselves. But while I held this as a strong conviction about other people, I never realized it also applied to me. And I had no idea at all how strongly it applied to me. Using Anki to read papers in new fields disabused me of this illusion. I found it almost unsettling how much easier Anki made learning such subjects. I now believe memory of the basics is often the single largest barrier to understanding. If you have a system such as Anki for overcoming that barrier, then you will find it much, much easier to read into new fields. This experience of how much easier Anki made learning a n




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Over the years, I've often helped people learn technical subjects such as quantum mechanics. Over time you come to see patterns in how people get stuck. One common pattern is that people think they're getting stuck on esoteric, complex issues. But when you dig down it turns out they're having a hard time with basic notation and terminology.
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Augmenting Long-term Memory
oundation of our cognition. There are two main reasons for this change, one a personal experience, the other based on evidence from cognitive science. Let me begin with the personal experience. <span>Over the years, I've often helped people learn technical subjects such as quantum mechanics. Over time you come to see patterns in how people get stuck. One common pattern is that people think they're getting stuck on esoteric, complex issues. But when you dig down it turns out they're having a hard time with basic notation and terminology. It's difficult to understand quantum mechanics when you're unclear about every third word or piece of notation! Every sentence is a struggle. It's like they're trying to compose a beaut




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One striking line of work was done (separately) by the researchers Adriaan de Groot and Herbert Simon, studying how people acquire expertise, focusing particularly on chess* * See, for instance, Herbert A. Simon, How Big is a Chunk?, Science (1974), and Adriaan de Groot, Thought and Choice in Chess, Amsterdam University Press (2008, reprinted from 1965). . They found that world-class chess experts saw the board differently to beginners. A beginner would see “a pawn here, a rook there”, and so on, a series of individual pieces. Masters, by contrast, saw much more elaborate “chunks”: combinations of pieces that they recognized as a unit, and were able to reason about at a higher level of abstraction than the individual pieces.

Simon estimated chess masters learn between 25,000 and 100,000 of these chunks during their training, and that learning the chunks was a key element in becoming a first-rate chess player. Such players really see chess positions very differently from beginners.

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Augmenting Long-term Memory
ning a new technical field greatly increased my visceral appreciation for the importance of memory. There are also many results from cognitive science on the key role memory plays in cognition. <span>One striking line of work was done (separately) by the researchers Adriaan de Groot and Herbert Simon, studying how people acquire expertise, focusing particularly on chess** See, for instance, Herbert A. Simon, How Big is a Chunk?, Science (1974), and Adriaan de Groot, Thought and Choice in Chess, Amsterdam University Press (2008, reprinted from 1965).. They found that world-class chess experts saw the board differently to beginners. A beginner would see “a pawn here, a rook there”, and so on, a series of individual pieces. Masters, by contrast, saw much more elaborate “chunks”: combinations of pieces that they recognized as a unit, and were able to reason about at a higher level of abstraction than the individual pieces. Simon estimated chess masters learn between 25,000 and 100,000 of these chunks during their training, and that learning the chunks was a key element in becoming a first-rate chess player. Such players really see chess positions very differently from beginners. Why does learning to recognize and reason about such chunks help so much in developing expertise? Here's a speculative, informal model – as far as I know, it hasn't been validated by co




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Many people's model of accomplished mathematicians is that they are astoundingly bright, with very high IQs, and the ability to deal with very complex ideas in their mind. A common perception is that their smartness gives them the ability to deal with very complex ideas. Basically, they have a higher horsepower engine.

It's true that top mathematicians are usually very bright. But here's a different explanation of what's going on. It's that, per Simon, many top mathematicians have, through hard work, internalized many more complex mathematical chunks than ordinary humans. And what this means is that mathematical situations which seem very complex to the rest of us seem very simple to them. So it's not that they have a higher horsepower mind, in the sense of being able to deal with more complexity. Rather, their prior learning has given them better chunking abilities, and so situations most people would see as complex they see as simple, and they find it much easier to reason about.

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Augmenting Long-term Memory
of mathematics, instead of chess, since mathematics is an area where I have experience talking with people at all ranges of ability, from beginners to accomplished professional mathematicians. <span>Many people's model of accomplished mathematicians is that they are astoundingly bright, with very high IQs, and the ability to deal with very complex ideas in their mind. A common perception is that their smartness gives them the ability to deal with very complex ideas. Basically, they have a higher horsepower engine. It's true that top mathematicians are usually very bright. But here's a different explanation of what's going on. It's that, per Simon, many top mathematicians have, through hard work, internalized many more complex mathematical chunks than ordinary humans. And what this means is that mathematical situations which seem very complex to the rest of us seem very simple to them. So it's not that they have a higher horsepower mind, in the sense of being able to deal with more complexity. Rather, their prior learning has given them better chunking abilities, and so situations most people would see as complex they see as simple, and they find it much easier to reason about. Now, the concept of chunks used by Simon in his study of chess players actually came from a famous 1956 paper by George Miller, “The Magical Number Seven, Plus or Minus Two”** George A.




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Now, the concept of chunks used by Simon in his study of chess players actually came from a famous 1956 paper by George Miller, “The Magical Number Seven, Plus or Minus Two”* * George A. Miller, The Magical Number Seven, Plus or Minus Two: Some Limits on our Capacity for Processing Information (1956). . Miller argued that the capacity of working memory is roughly seven chunks. In fact, it turns out that there is variation in that number from person to person, and a substantial correlation between the capacity of an individual's working memory and their general intellectual ability (IQ)* * A review of the correlation may be found in Phillip L. Ackerman, Margaret E. Beier, and Mary O. Boyle, Working Memory and Intelligence: The Same or Different Constructs? Psychological Bulletin (2006). . Typically, the better your working memory, the higher your IQ, and vice versa.
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Augmenting Long-term Memory
xity. Rather, their prior learning has given them better chunking abilities, and so situations most people would see as complex they see as simple, and they find it much easier to reason about. <span>Now, the concept of chunks used by Simon in his study of chess players actually came from a famous 1956 paper by George Miller, “The Magical Number Seven, Plus or Minus Two”** George A. Miller, The Magical Number Seven, Plus or Minus Two: Some Limits on our Capacity for Processing Information (1956).. Miller argued that the capacity of working memory is roughly seven chunks. In fact, it turns out that there is variation in that number from person to person, and a substantial correlation between the capacity of an individual's working memory and their general intellectual ability (IQ)** A review of the correlation may be found in Phillip L. Ackerman, Margaret E. Beier, and Mary O. Boyle, Working Memory and Intelligence: The Same or Different Constructs? Psychological Bulletin (2006).. Typically, the better your working memory, the higher your IQ, and vice versa. Exactly what Miller meant by chunks he left somewhat vague, writing: The contrast of the terms bit and chunk also serves to highlight the fact that we are not very definite about what c




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Exactly what Miller meant by chunks he left somewhat vague, writing:

The contrast of the terms bit and chunk also serves to highlight the fact that we are not very definite about what constitutes a chunk of information. For example, the memory span of five words that Hayes obtained… might just as appropriately have been called a memory span of 15 phonemes, since each word had about three phonemes in it. Intuitively, it is clear that the subjects were recalling five words, not 15 phonemes, but the logical distinction is not immediately apparent. We are dealing here with a process of organizing or grouping the input into familiar units or chunks, and a great deal of learning has gone into the formation of these familiar units.
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Augmenting Long-term Memory
Mary O. Boyle, Working Memory and Intelligence: The Same or Different Constructs? Psychological Bulletin (2006).. Typically, the better your working memory, the higher your IQ, and vice versa. <span>Exactly what Miller meant by chunks he left somewhat vague, writing: The contrast of the terms bit and chunk also serves to highlight the fact that we are not very definite about what constitutes a chunk of information. For example, the memory span of five words that Hayes obtained… might just as appropriately have been called a memory span of 15 phonemes, since each word had about three phonemes in it. Intuitively, it is clear that the subjects were recalling five words, not 15 phonemes, but the logical distinction is not immediately apparent. We are dealing here with a process of organizing or grouping the input into familiar units or chunks, and a great deal of learning has gone into the formation of these familiar units. Put another way, in Miller's account the chunk was effectively the basic unit of working memory. And so Simon and his collaborators were studying the basic units used in the working mem




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In particular, someone with a lower IQ but able to call on more complex chunks would be able to reason about more complex situations than someone with a higher IQ but less complex internalized chunks.

In other words, having more chunks memorized in some domain is somewhat like an effective boost to a person's IQ in that domain.

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Augmenting Long-term Memory
borators were studying the basic units used in the working memory of chess players. If those chunks were more complex, then that meant a player's working memory had a higher effective capacity. <span>In particular, someone with a lower IQ but able to call on more complex chunks would be able to reason about more complex situations than someone with a higher IQ but less complex internalized chunks. In other words, having more chunks memorized in some domain is somewhat like an effective boost to a person's IQ in that domain. Okay, that's a speculative informal model. Regardless of whether it's correct, it does seem that internalizing high-level chunks is a crucial part of acquiring expertise. However, that




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Still, it seems plausible that regular use of systems such as Anki may speed up the acquisition of the high-level chunks used by experts* * To determine this it would help to understand exactly how these chunks arise. That still seems to be poorly understood. I wouldn't be surprised if it involved considerable analysis and problem-solving, in addition to long-term memory. . And that those chunks are then at the heart of effective cognition, including our ability to understand, to problem solve, and to create.
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Augmenting Long-term Memory
that the use of systems such as Anki will speed up acquisition of such chunks. It's merely an argument that long-term memory plays a crucial role in the acquisition of some types of expertise. <span>Still, it seems plausible that regular use of systems such as Anki may speed up the acquisition of the high-level chunks used by experts** To determine this it would help to understand exactly how these chunks arise. That still seems to be poorly understood. I wouldn't be surprised if it involved considerable analysis and problem-solving, in addition to long-term memory.. And that those chunks are then at the heart of effective cognition, including our ability to understand, to problem solve, and to create. Distributed practice Why does Anki work? In this section we briefly look at one of the key underlying ideas from cognitive science, known as distributed practice. Suppose you're introdu




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That is, memories decay. This isn't news! But the great German psychologist Hermann Ebbinghaus had the good idea of studying memory decay systematically and quantitatively* * Hermann Ebbinghaus, Memory: A Contribution to Experimental Psychology (1885). A recent replication of Ebbinghaus's results may be found in: Jaap M. J. Murre and Joeri Dros, Replication and Analysis of Ebbinghaus' Forgetting Curve (2015). . In particular, he was interested in how quickly memories decay, and what causes the decay. To study this, Ebbinghaus memorized strings of nonsense syllables – things like “fim“ and “pes” – and later tested himself, recording how well he retained those syllables after different time intervals.
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Augmenting Long-term Memory
ual, you'll almost certainly remember their name 20 seconds later. But you're more likely to have forgotten their name in an hour, and more likely still to have forgotten their name in a month. <span>That is, memories decay. This isn't news! But the great German psychologist Hermann Ebbinghaus had the good idea of studying memory decay systematically and quantitatively** Hermann Ebbinghaus, Memory: A Contribution to Experimental Psychology (1885). A recent replication of Ebbinghaus's results may be found in: Jaap M. J. Murre and Joeri Dros, Replication and Analysis of Ebbinghaus' Forgetting Curve (2015).. In particular, he was interested in how quickly memories decay, and what causes the decay. To study this, Ebbinghaus memorized strings of nonsense syllables – things like “fim“ and “pes” – and later tested himself, recording how well he retained those syllables after different time intervals. Ebbinghaus found that the probability of correctly recalling an item declined (roughly) exponentially with time. Today, this is called the Ebbinghaus forgetting curve: What determines t




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Ebbinghaus found that the probability of correctly recalling an item declined (roughly) exponentially with time. Today, this is called the Ebbinghaus forgetting curve
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Augmenting Long-term Memory
this, Ebbinghaus memorized strings of nonsense syllables – things like “fim“ and “pes” – and later tested himself, recording how well he retained those syllables after different time intervals. <span>Ebbinghaus found that the probability of correctly recalling an item declined (roughly) exponentially with time. Today, this is called the Ebbinghaus forgetting curve: What determines the steepness of the curve, i.e., how quickly memories decay? In fact, the steepness depends on many things. For instance, it may be steeper for more complex or less fa




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Ebbinghaus's research suggested that the probability will decay exponentially after the re-test, but the rate of decay will be slower than it was initially. In fact, subsequent re-tests will slow the decay still more, a gradually flattening out of the decay curve as the memory is consolidated through multiple recall events
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Augmenting Long-term Memory
bout their name for 20 minutes. But then you need to introduce them to someone else, and so need to bring it to mind. Immediately after that, your probability of recall will again be very high. <span>Ebbinghaus's research suggested that the probability will decay exponentially after the re-test, but the rate of decay will be slower than it was initially. In fact, subsequent re-tests will slow the decay still more, a gradually flattening out of the decay curve as the memory is consolidated through multiple recall events: This gradual increase in decay time underlies the design of Anki and similar memory systems. It's why Anki gradually expands the time periods between testing. These phenomena are part




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There are several related terms used for this set of phenomena, but we'll use the phrase “distributed practice”, meaning practice which is distributed in time, ideally in a way designed to maximally promote retention. This is in contrast to cramming, often known as massed practice, where people try to fit all their study into just one session, relying on repetition.
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Augmenting Long-term Memory
d similar memory systems. It's why Anki gradually expands the time periods between testing. These phenomena are part of a broader set of ideas which have been extensively studied by scientists. <span>There are several related terms used for this set of phenomena, but we'll use the phrase “distributed practice”, meaning practice which is distributed in time, ideally in a way designed to maximally promote retention. This is in contrast to cramming, often known as massed practice, where people try to fit all their study into just one session, relying on repetition. On the role of cognitive science in the design of systems to augment cognition Since Ebbinghaus, there's been thousands of studies of different variations of distributed practice. These




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Since Ebbinghaus, there's been thousands of studies of different variations of distributed practice. These studies have taught us a great deal about the behavior of long-term memory. Most of all, they show emphatically that distributed practice outperforms massed practice
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Augmenting Long-term Memory
en known as massed practice, where people try to fit all their study into just one session, relying on repetition. On the role of cognitive science in the design of systems to augment cognition <span>Since Ebbinghaus, there's been thousands of studies of different variations of distributed practice. These studies have taught us a great deal about the behavior of long-term memory. Most of all, they show emphatically that distributed practice outperforms massed practice** Many experiments also try to assess participants' perception of the effectiveness of massed practice versus distributed practice. Remarkably, they often believe that massed practice i




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We don't understand in detail why exponential decay of memory occurs, or when that model breaks down. We don't have good models of what determines the rate of decay, and why it varies for different types of memories. We don't understand why the decay takes longer after subsequent recalls. And we have little understanding of the best way of expanding the inter-study intervals.
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Augmenting Long-term Memory
to the development of systems. While scientists have done a tremendous number of studies of distributed practice, many fundamental questions about distributed practice remain poorly understood. <span>We don't understand in detail why exponential decay of memory occurs, or when that model breaks down. We don't have good models of what determines the rate of decay, and why it varies for different types of memories. We don't understand why the decay takes longer after subsequent recalls. And we have little understanding of the best way of expanding the inter-study intervals. Of course, there are many partial theories to answer these and other fundamental questions. But there's no single, quantitatively predictive, broadly accepted general theory. And so in




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Creating the cards to review, however, is a complex discipline of its own that’s both an art and a science, and how well you do at designing your cards can make the difference between easy study sessions resulting in effective learning and frustrating ones resulting in mediocre learning. Card design is thus the most fundamental skill of spaced-repetition use, and it’s worth spending some time learning how to do it well.
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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
for yes or no answers Questions should be context-free Conclusion Reviewing in Anki is easy: all you have to do is answer the question and press a button to indicate how well you remembered it. <span>Creating the cards to review, however, is a complex discipline of its own that’s both an art and a science, and how well you do at designing your cards can make the difference between easy study sessions resulting in effective learning and frustrating ones resulting in mediocre learning. Card design is thus the most fundamental skill of spaced-repetition use, and it’s worth spending some time learning how to do it well. Throughout the next couple of posts on creating cards for spaced-repetition systems, I’ll be frequently referencing SuperMemo’s Twenty Rules of Formulating Knowledge. It would be hard t




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This poses a challenge for users, because seemingly small variations in how you ask a question can push it into not testing the thing you intended it to. The SRS is rather like the proverbial genie: describe what you want to get in the wrong way, and the genie will interpret your wish in the most ridiculous way possible and you’ll learn something that’s of no practical use.
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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
out tool: if you put in material that isn’t useful or doesn’t test the things you want to know, you’ll remember it, but it won’t help you at all; you’ll just be wasting your time doing reviews. <span>This poses a challenge for users, because seemingly small variations in how you ask a question can push it into not testing the thing you intended it to. The SRS is rather like the proverbial genie: describe what you want to get in the wrong way, and the genie will interpret your wish in the most ridiculous way possible and you’ll learn something that’s of no practical use. For instance, I recently found a card with an interval of several years in my own collection, asking what option to the cp (copy) Unix command makes it ask for confirmation before overw




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To put it another way, SRS questions are prone to overfitting. Overfitting, in statistical modeling and machine learning, occurs when a model gets “too good” at predicting the data you train it on – it starts to treat random noise present in the training data as a meaningful source of predictions.
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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
on was pretty much worthless to me. In other cases, you could end up memorizing a grammatical error on your card, or a learned response to a prompt which you would never encounter in real life. <span>To put it another way, SRS questions are prone to overfitting. Overfitting, in statistical modeling and machine learning, occurs when a model gets “too good” at predicting the data you train it on – it starts to treat random noise present in the training data as a meaningful source of predictions. Of course, random noise does not represent any meaningful relationship that would be useful in predicting new information. Thus, overfitting improves the model’s accuracy rate on the tr




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Thus, overfitting improves the model’s accuracy rate on the training data but reduces it when it’s applied to new data, i.e., a real-world scenario
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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
se present in the training data as a meaningful source of predictions. Of course, random noise does not represent any meaningful relationship that would be useful in predicting new information. <span>Thus, overfitting improves the model’s accuracy rate on the training data but reduces it when it’s applied to new data, i.e., a real-world scenario. In a spaced-repetition context, because the SRS is so good at helping you learn things efficiently, it will optimize your memory of just about anything, but if you don’t phrase your qu




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In a spaced-repetition context, because the SRS is so good at helping you learn things efficiently, it will optimize your memory of just about anything, but if you don’t phrase your question correctly, it will help you remember irrelevant information or random noise, rather than the information you actually wanted to know.
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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
uld be useful in predicting new information. Thus, overfitting improves the model’s accuracy rate on the training data but reduces it when it’s applied to new data, i.e., a real-world scenario. <span>In a spaced-repetition context, because the SRS is so good at helping you learn things efficiently, it will optimize your memory of just about anything, but if you don’t phrase your question correctly, it will help you remember irrelevant information or random noise, rather than the information you actually wanted to know. To avoid overfitting, the number-one rule when adding cards is this: every time you come across something you think you’d like to remember, identify exactly what you want to know, and b




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To avoid overfitting, the number-one rule when adding cards is this: every time you come across something you think you’d like to remember, identify exactly what you want to know, and be as precise about it as possible. Then, and only then, create one or more cards that ask about exactly that and nothing else
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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
just about anything, but if you don’t phrase your question correctly, it will help you remember irrelevant information or random noise, rather than the information you actually wanted to know. <span>To avoid overfitting, the number-one rule when adding cards is this: every time you come across something you think you’d like to remember, identify exactly what you want to know, and be as precise about it as possible. Then, and only then, create one or more cards that ask about exactly that and nothing else. Doing this is more difficult and makes your initial learning process longer, compared to just dumping the information onto a flashcard, but it works much better! As a bonus, this proce




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Questions should ask exactly one thing Permalink

Rule #4 of the Twenty Rules calls this the Minimum Information Principle: cards should never ask about more than one thing (techies might say that the card should be atomic).

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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
personal collection today, just to demonstrate that most every spaced-repetition user has some of these skeletons in his closet (many of them are on my older cards, but several are much newer). <span>Questions should ask exactly one thingPermalink Rule #4 of the Twenty Rules calls this the Minimum Information Principle: cards should never ask about more than one thing (techies might say that the card should be atomic). Violations of this rule may take obvious form, like literally asking two questions. However, most often they involve extremely general questions with a lot of content on the answer side




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Q: Give a description of the Python programming language.
A: Python is a high-level, interpreted, multi-paradigm programming language written by Guido von Rossum and maintained by the Python Foundation. It is often used for system administration, data analysis, and rapid prototyping, and has been consistently named among the five most popular languages in recent years.

This is a terrible card! Not that you shouldn’t want to know anything about Python, or that any of the information in it is explained poorly, but there is just far too much information. Unless you want to literally memorize the text of the answer by rote, you will never be able to correctly give all the information in it as an answer to that vague prompt. If you forget any part of the question, you’ll either have to fail it (thus dooming the card to come back practically every day since you can never satisfactorily learn all of it) or say you remembered it well when you didn’t. We could easily split this into a dozen questions, e.g.:

Q: Who designed the Python programming language?
A: Guido von Rossum.

Q: What group maintains the Python programming language?
A: The Python Foundation.

Q: Since 2015, Python has been ranked among the […number] most popular programming languages.
A: 5

Et cetera.

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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
omic). Violations of this rule may take obvious form, like literally asking two questions. However, most often they involve extremely general questions with a lot of content on the answer side: <span>Q: Give a description of the Python programming language. A: Python is a high-level, interpreted, multi-paradigm programming language written by Guido von Rossum and maintained by the Python Foundation. It is often used for system administration, data analysis, and rapid prototyping, and has been consistently named among the five most popular languages in recent years. This is a terrible card! Not that you shouldn’t want to know anything about Python, or that any of the information in it is explained poorly, but there is just far too much information. Unless you want to literally memorize the text of the answer by rote, you will never be able to correctly give all the information in it as an answer to that vague prompt. If you forget any part of the question, you’ll either have to fail it (thus dooming the card to come back practically every day since you can never satisfactorily learn all of it) or say you remembered it well when you didn’t. We could easily split this into a dozen questions, e.g.: Q: Who designed the Python programming language? A: Guido von Rossum. Q: What group maintains the Python programming language? A: The Python Foundation. Q: Since 2015, Python has been ranked among the […number] most popular programming languages. A: 5 Et cetera. It’s also worth pointing out there’s likely information in that initial “description” that we didn’t want to know in the first place and shouldn’t waste our time trying to learn. Splitt




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Every piece of information you learn consumes study time that you could be using to learn other information. Choose wisely.
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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
learn. Splitting out what we’re learning into questions is a fantastic opportunity to decide what we need to remember so we can focus our efforts on the information that will be most valuable. <span>Every piece of information you learn consumes study time that you could be using to learn other information. Choose wisely. Questions should permit exactly one answerPermalink For efficient review, it must be immediately obvious both what is being asked and what single response will count as the correct answ




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Questions should permit exactly one answer Permalink

For efficient review, it must be immediately obvious both what is being asked and what single response will count as the correct answer; your thought process and your answer must be the same every time you review, in meaning if not in exact wording

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Rules for Designing Precise Anki Cards - Control-Alt-Backspace
can focus our efforts on the information that will be most valuable. Every piece of information you learn consumes study time that you could be using to learn other information. Choose wisely. <span>Questions should permit exactly one answerPermalink For efficient review, it must be immediately obvious both what is being asked and what single response will count as the correct answer; your thought process and your answer must be the same every time you review, in meaning if not in exact wording. This may seem straightforward, but most beginners frequently create cards that violate one or both of these rules. Heck, even experts do it from time to time. We can violate this rule




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Allowing correct but irrelevant answers Permalink

Here’s a cloze deletion from my AP US History deck (9 years ago now!). In my notation for cloze deletions, the bit in {curly braces} shows up as a [...] on the front of the card, asking you to fill in the blank; the whole sentence then shows up on the back.

The Articles of Confederation had no power to regulate {commerce}.

This is true, and an important point (the lack of regulation of commerce was an important problem that helped drive the creation of the U.S. Constitution, which followed the Articles). However, there are a practically infinite number of other correct answers we could give! The Articles of Confederation also had no power to regulate religious observances, taxation, bear hunting, the behavior of the British monarch, or the hours your neighbor can play the drums with her windows open. Obviously, some of these answers are more plausible than others, but the fact remains I could reasonably give an answer that was correct but not the answer on the back of the card.

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tly create cards that violate one or both of these rules. Heck, even experts do it from time to time. We can violate this rule in a wide variety of ways; let’s take a look at three common ones. <span>Allowing correct but irrelevant answersPermalink Here’s a cloze deletion from my AP US History deck (9 years ago now!). In my notation for cloze deletions, the bit in {curly braces} shows up as a [...] on the front of the card, asking you to fill in the blank; the whole sentence then shows up on the back. The Articles of Confederation had no power to regulate {commerce}. This is true, and an important point (the lack of regulation of commerce was an important problem that helped drive the creation of the U.S. Constitution, which followed the Articles). However, there are a practically infinite number of other correct answers we could give! The Articles of Confederation also had no power to regulate religious observances, taxation, bear hunting, the behavior of the British monarch, or the hours your neighbor can play the drums with her windows open. Obviously, some of these answers are more plausible than others, but the fact remains I could reasonably give an answer that was correct but not the answer on the back of the card. If that happens during review, it’s unclear what I should do. I could fail the card, which seems wrong because I gave a correct answer. Or I could pass the card, which seems wrong becau




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Either way, I am not effectively reviewing the piece of information I set out to learn; I’m instead forcing myself to memorize, in addition to the actual answer, what this card is asking me. That means I’m effectively asking about two things and making it much harder to remember the card, for no benefit – in real life, knowing what one of my Anki cards was supposed to be asking is useless information.
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g because I gave a correct answer. Or I could pass the card, which seems wrong because there’s no evidence that I remembered the piece of information I was trying to retain by making this card. <span>Either way, I am not effectively reviewing the piece of information I set out to learn; I’m instead forcing myself to memorize, in addition to the actual answer, what this card is asking me. That means I’m effectively asking about two things and making it much harder to remember the card, for no benefit – in real life, knowing what one of my Anki cards was supposed to be asking is useless information. The correct response, when you encounter this situation during review – and you will – is to stop reviewing for a moment and rewrite the card. We could do this in numerous ways, but her




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The correct response, when you encounter this situation during review – and you will – is to stop reviewing for a moment and rewrite the card. We could do this in numerous ways, but here’s one possibility:

Economic and trade relations between states were difficult under the Articles of Confederation because the Articles granted no power to {regulate commerce}.

Of course, I could still come up with silly answers if I wanted to be contrary (I recommend being contrary – it’s fun). But, when reading the question in good faith, I can now be reasonably confident that if I don’t promptly remember the answer I intended, that means I’ve forgotten it.

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tively asking about two things and making it much harder to remember the card, for no benefit – in real life, knowing what one of my Anki cards was supposed to be asking is useless information. <span>The correct response, when you encounter this situation during review – and you will – is to stop reviewing for a moment and rewrite the card. We could do this in numerous ways, but here’s one possibility: Economic and trade relations between states were difficult under the Articles of Confederation because the Articles granted no power to {regulate commerce}. Of course, I could still come up with silly answers if I wanted to be contrary (I recommend being contrary – it’s fun). But, when reading the question in good faith, I can now be reasonably confident that if I don’t promptly remember the answer I intended, that means I’ve forgotten it. Falling into the “example” trapPermalink Beginners often write questions like this one: Q: What’s an example of a non-combinatorial circuit? A: Memory. This is merely a special case of




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Falling into the “example” trap Permalink

Beginners often write questions like this one:

Q: What’s an example of a non-combinatorial circuit?
A: Memory.

This is merely a special case of “allowing correct but irrelevant answers,” but I’ve seen it so frequently I want to call attention to it in particular. We have the same problem as before: not only do I have to remember that memory is a non-combinatorial circuit (the actual piece of information I wanted to know), I also have to remember that the specific example of a non-combinatorial circuit this card wants me to give is “memory”. An even worse version is “Give some examples of non-combinatorial circuits.” With this version, you can give different answers every time you see the card, including ones that aren’t on the card, and still have them be kind-of, sort-of, maybe correct!

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eing contrary – it’s fun). But, when reading the question in good faith, I can now be reasonably confident that if I don’t promptly remember the answer I intended, that means I’ve forgotten it. <span>Falling into the “example” trapPermalink Beginners often write questions like this one: Q: What’s an example of a non-combinatorial circuit? A: Memory. This is merely a special case of “allowing correct but irrelevant answers,” but I’ve seen it so frequently I want to call attention to it in particular. We have the same problem as before: not only do I have to remember that memory is a non-combinatorial circuit (the actual piece of information I wanted to know), I also have to remember that the specific example of a non-combinatorial circuit this card wants me to give is “memory”. An even worse version is “Give some examples of non-combinatorial circuits.” With this version, you can give different answers every time you see the card, including ones that aren’t on the card, and still have them be kind-of, sort-of, maybe correct! Here’s another example. I perpetrated this one just a few days ago: Q: OutSystems: Give an example of something you might use an input parameter for. A: In an edit screen, you would nee




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In the real world, we’re rarely called upon to offer examples of a textbook term, but we often benefit from being able to recognize that something is an example of that idea.
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y is an example of a {non-combinatorial} circuit. In essence, we’ve inverted the example. This kind of question is more targeted and easier to answer and also tends to be more useful knowledge. <span>In the real world, we’re rarely called upon to offer examples of a textbook term, but we often benefit from being able to recognize that something is an example of that idea. And chances are, if you learn the idea well enough to easily answer questions of this form, you won’t have any trouble offering some examples of it if you need to. Note: The effectivene




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The effectiveness of the two questions immediately above depends in great part on how complex your own taxonomy of those subjects is. Considering the memory question, I know relatively little about circuits, so I’m unlikely to get confused about what property of the memory circuit I’m being asked about. If I designed electronics for a living, on the other hand, I would likely need to rewrite that card with a hint or some additional context to be sure I knew which answer it was seeking. This is one of the many reasons that cards someone else makes will seldom be as effective as cards you make yourself: you’re the only one who knows what cues will get you the best results.
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n example of that idea. And chances are, if you learn the idea well enough to easily answer questions of this form, you won’t have any trouble offering some examples of it if you need to. Note: <span>The effectiveness of the two questions immediately above depends in great part on how complex your own taxonomy of those subjects is. Considering the memory question, I know relatively little about circuits, so I’m unlikely to get confused about what property of the memory circuit I’m being asked about. If I designed electronics for a living, on the other hand, I would likely need to rewrite that card with a hint or some additional context to be sure I knew which answer it was seeking. This is one of the many reasons that cards someone else makes will seldom be as effective as cards you make yourself: you’re the only one who knows what cues will get you the best results. Allowing multiple interpretations of a questionPermalink In this type of bad question, the creator didn’t clearly identify what they were trying to remember and consequently produced a




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Allowing multiple interpretations of a question Permalink

In this type of bad question, the creator didn’t clearly identify what they were trying to remember and consequently produced a vague question.

APUSH: Americans moving to Texas [when it was under Mexican control] {did not adopt the ways of the region and remained Americans at heart}.

Is this the only thing I might have wanted to remember about Americans moving to Texas? Really? Now, no matter how bad this question is, I might be able to learn the answer (in fact, I have a nearly perfect, straight-3’s review history on this card), but the prompt is so vague that the only thing I’ve learned is “what to fill in the blank when I’m asked about Americans moving to Texas,” which is of little value in the real world.

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ing. This is one of the many reasons that cards someone else makes will seldom be as effective as cards you make yourself: you’re the only one who knows what cues will get you the best results. <span>Allowing multiple interpretations of a questionPermalink In this type of bad question, the creator didn’t clearly identify what they were trying to remember and consequently produced a vague question. APUSH: Americans moving to Texas [when it was under Mexican control] {did not adopt the ways of the region and remained Americans at heart}. Is this the only thing I might have wanted to remember about Americans moving to Texas? Really? Now, no matter how bad this question is, I might be able to learn the answer (in fact, I have a nearly perfect, straight-3’s review history on this card), but the prompt is so vague that the only thing I’ve learned is “what to fill in the blank when I’m asked about Americans moving to Texas,” which is of little value in the real world. Q: Why is the Earth’s rotation slowing down? A: Tidal deceleration. This one’s a bit more subtle, but still problematic. The issue here is that the desired level of detail is unclear. I




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Q: Why is the Earth’s rotation slowing down?
A: Tidal deceleration.

This one’s a bit more subtle, but still problematic. The issue here is that the desired level of detail is unclear. Is it asking for the term that describes this phenomenon? (Is there even such a term? We wouldn’t know from the question.) Or did it want an explanation of the forces involved in tidal deceleration?

Here’s a better version:

Q: What gravitational effect is causing the Earth’s rotation to slow over time?
A: Tidal deceleration

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his card), but the prompt is so vague that the only thing I’ve learned is “what to fill in the blank when I’m asked about Americans moving to Texas,” which is of little value in the real world. <span>Q: Why is the Earth’s rotation slowing down? A: Tidal deceleration. This one’s a bit more subtle, but still problematic. The issue here is that the desired level of detail is unclear. Is it asking for the term that describes this phenomenon? (Is there even such a term? We wouldn’t know from the question.) Or did it want an explanation of the forces involved in tidal deceleration? Here’s a better version: Q: What gravitational effect is causing the Earth’s rotation to slow over time? A: Tidal deceleration. If we didn’t know what tidal deceleration was, we’d also want to add a separate card, or maybe even several cards, explaining that process. That’s true even if we didn’t think we parti




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If we didn’t know what tidal deceleration was, we’d also want to add a separate card, or maybe even several cards, explaining that process. That’s true even if we didn’t think we particularly wanted to know what tidal deceleration was. We don’t have a choice here: we have to know what tidal deceleration is for this card to be meaningful information. Even if we’re just trying to pass an exam which includes this exact question, the card will be much, much easier to remember when we know what it means. This is Rule #1: Do not learn if you do not understand.
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want an explanation of the forces involved in tidal deceleration? Here’s a better version: Q: What gravitational effect is causing the Earth’s rotation to slow over time? A: Tidal deceleration. <span>If we didn’t know what tidal deceleration was, we’d also want to add a separate card, or maybe even several cards, explaining that process. That’s true even if we didn’t think we particularly wanted to know what tidal deceleration was. We don’t have a choice here: we have to know what tidal deceleration is for this card to be meaningful information. Even if we’re just trying to pass an exam which includes this exact question, the card will be much, much easier to remember when we know what it means. This is Rule #1: Do not learn if you do not understand. Another important point is that having these cards may not remind us that Earth’s rotation is slowing down (see my anecdote about cp -i at the beginning of the post). Maybe we don’t car




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For instance, maybe we care that the earth’s rotation is slowing down because it means leap seconds are needed to keep our calendar in sync with the day/night cycle:

Q: Why are leap seconds periodically added to UTC time?
A: Because the earth’s rotation is slowing over time, causing UTC to drift out of alignment with the sun.

In any case, as always, we have to take a moment to consider what we want to know in order to ask the right questions and get the information encoded in a useful way

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act that it is. But if we do want to remember that it’s happening, we might also want to add a card to remind us, referencing the context in which we think we want to remember this information. <span>For instance, maybe we care that the earth’s rotation is slowing down because it means leap seconds are needed to keep our calendar in sync with the day/night cycle: Q: Why are leap seconds periodically added to UTC time? A: Because the earth’s rotation is slowing over time, causing UTC to drift out of alignment with the sun. In any case, as always, we have to take a moment to consider what we want to know in order to ask the right questions and get the information encoded in a useful way. Questions should not ask you to enumerate thingsPermalink When you find a list of items in your reading, it’s often tempting to create a card asking what the members of the list are. R




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Another important point is that having these cards may not remind us that Earth’s rotation is slowing down (see my anecdote about cp -i at the beginning of the post).
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ust trying to pass an exam which includes this exact question, the card will be much, much easier to remember when we know what it means. This is Rule #1: Do not learn if you do not understand. <span>Another important point is that having these cards may not remind us that Earth’s rotation is slowing down (see my anecdote about cp -i at the beginning of the post). Maybe we don’t care to recall that piece of information, and it would suffice to remember why it is, when we encounter a reference to the fact that it is. But if we do want to remember




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Questions should not ask you to enumerate things Permalink

When you find a list of items in your reading, it’s often tempting to create a card asking what the members of the list are. Rules #9-10 of the Twenty Rules call these sets (or enumerations, if they go in a specific order), and explain that they’re some of the most difficult and frustrating cards, so we want to avoid them when possible.

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of alignment with the sun. In any case, as always, we have to take a moment to consider what we want to know in order to ask the right questions and get the information encoded in a useful way. <span>Questions should not ask you to enumerate thingsPermalink When you find a list of items in your reading, it’s often tempting to create a card asking what the members of the list are. Rules #9-10 of the Twenty Rules call these sets (or enumerations, if they go in a specific order), and explain that they’re some of the most difficult and frustrating cards, so we want to avoid them when possible. Usually people create sets because they don’t realize sets are problematic or because they seem like the most obvious thing to learn, rather than because the set is actually what they w




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A nasty illusion may make it appear to be, however. Consider the internal combustion engine, a classic example of a complex machine in many ways defined by its many parts. Someone who can name all the parts of the ICE will seem to have a good understanding of it. But this is an effect, rather than a cause. If you can name all the parts of the ICE but don’t know what they do, you still understand nothing at all about how it works.
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they seem like the most obvious thing to learn, rather than because the set is actually what they want to know. In fact, being able to name all examples or parts of something is rarely helpful. <span>A nasty illusion may make it appear to be, however. Consider the internal combustion engine, a classic example of a complex machine in many ways defined by its many parts. Someone who can name all the parts of the ICE will seem to have a good understanding of it. But this is an effect, rather than a cause. If you can name all the parts of the ICE but don’t know what they do, you still understand nothing at all about how it works. In contrast, if you know what all the parts do and how they relate to each other, you will easily be able to visualize the engine layout or work your way through the parts by function a




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Of course, once in a while it really is helpful to know a set of things. In this case, you can improve your performance markedly by (a) learning and fully understanding each individual member of the set through separate cards; and (b) ordering the set into an enumeration and developing a mnemonic device such as an acronym for the order. (I like to keep close to the minimum information principle by creating two cards for part (b), one asking what my mnemonic is and the other asking me to use the mnemonic to produce the answer.)
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be able to visualize the engine layout or work your way through the parts by function and name and describe each of them, regardless of whether you sat down and learned to recite them in order. <span>Of course, once in a while it really is helpful to know a set of things. In this case, you can improve your performance markedly by (a) learning and fully understanding each individual member of the set through separate cards; and (b) ordering the set into an enumeration and developing a mnemonic device such as an acronym for the order. (I like to keep close to the minimum information principle by creating two cards for part (b), one asking what my mnemonic is and the other asking me to use the mnemonic to produce the answer.) The Twenty Rules has a good example of using this approach to learn the countries in the EU (rule #9), although it doesn’t include a mnemonic. But before you learn a set, even in an eff




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If you create and learn cards that ask deeper questions, you’ll likely still be able to give the correct “yes” or “no” but also know additional information about why this is the case.

Here’s an example from my computer-hardware-design deck:

Q: Is segmentation used on modern processors?
A: No, it was removed in the x86-64 platform.

Interestingly, you can see that I actually included the information needed to produce a better question in the answer. The answer is a terrible place for this kind of information, though: you’re never asked to actively recall it and you look at it for a fraction of the time you look at the question, so you’re unlikely to ever memorize it. Instead, we can rewrite the card:

Segmentation was common on older processors but was removed starting with the {x86-64} platform.

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no answersPermalink Perhaps curiously, I find that questions whose answer is “yes” or “no” are harder to remember than questions that contain more information. They also tend to be less useful. <span>If you create and learn cards that ask deeper questions, you’ll likely still be able to give the correct “yes” or “no” but also know additional information about why this is the case. Here’s an example from my computer-hardware-design deck: Q: Is segmentation used on modern processors? A: No, it was removed in the x86-64 platform. Interestingly, you can see that I actually included the information needed to produce a better question in the answer. The answer is a terrible place for this kind of information, though: you’re never asked to actively recall it and you look at it for a fraction of the time you look at the question, so you’re unlikely to ever memorize it. Instead, we can rewrite the card: Segmentation was common on older processors but was removed starting with the {x86-64} platform. Notice that by learning this fact (in which processor platform was segmentation removed?), we are still aware that segmentation is no longer used in the most modern processors, but we a




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All this said, I do still find myself writing yes/no questions on occasion, especially when I’m in the early stages of learning a topic. Sometimes you don’t know the why yet, and it’s better at the moment that you simply learn that something is or isn’t, rather than go look up and learn a bunch of details just to be able to improve one flashcard. Perhaps later, you’ll have the additional understanding to rewrite the card.
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on to or instead of the above card, asking why segmentation was removed in the x86-64 platform. It all depends on what exactly we want to know, but why questions are usually valuable additions. <span>All this said, I do still find myself writing yes/no questions on occasion, especially when I’m in the early stages of learning a topic. Sometimes you don’t know the why yet, and it’s better at the moment that you simply learn that something is or isn’t, rather than go look up and learn a bunch of details just to be able to improve one flashcard. Perhaps later, you’ll have the additional understanding to rewrite the card. That brings up an important point: questions are not set in stone. You’ll often miss potential problems with your new questions until you start reviewing them, and still other times you




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That brings up an important point: questions are not set in stone. You’ll often miss potential problems with your new questions until you start reviewing them, and still other times you’ll learn a card and realize weeks or months later after reading a completely different resource that you were missing some important context or your initial understanding was flat-out wrong.
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something is or isn’t, rather than go look up and learn a bunch of details just to be able to improve one flashcard. Perhaps later, you’ll have the additional understanding to rewrite the card. <span>That brings up an important point: questions are not set in stone. You’ll often miss potential problems with your new questions until you start reviewing them, and still other times you’ll learn a card and realize weeks or months later after reading a completely different resource that you were missing some important context or your initial understanding was flat-out wrong. You should make liberal use of the edit button while reviewing (in Anki, press e to edit the current card, and Escape when you’re done). If you spot a problem with a card that you can’t




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Questions should be context-free Permalink

Context-free here is meant in the sense of a context-free grammar, that is, a grammar within which the correct interpretation of any statement is independent of its surroundings. Your questions, in other words, should be 100% comprehensible without any surrounding context; if you were to find one written on a slip of paper that somebody dropped in the street, you should be able to understand exactly what the question is asking.

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w free moments, and before you forget what the problem was – I like to do this once a week or so – search for tag:marked in the browser and edit the cards appropriately, then unmark them again. <span>Questions should be context-freePermalink Context-free here is meant in the sense of a context-free grammar, that is, a grammar within which the correct interpretation of any statement is independent of its surroundings. Your questions, in other words, should be 100% comprehensible without any surrounding context; if you were to find one written on a slip of paper that somebody dropped in the street, you should be able to understand exactly what the question is asking. This design imperative takes two main forms. (1) The topic or context should be stated at the beginning or near the beginning of the question, to prime your memory to retrieve the right




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The topic or context should be stated at the beginning or near the beginning of the question, to prime your memory to retrieve the right kind of information and to facilitate reviewing cards from different subjects intermixed, which many people believe improves creativity. For instance, in several of my questions above, you saw qualifiers at the start of the question like OutSystems: or APUSH:. A word describing the topic worked into the sentence can work, too, although Rule #16 does recommend prefixes so you can be sure your brain gets started correctly.
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o find one written on a slip of paper that somebody dropped in the street, you should be able to understand exactly what the question is asking. This design imperative takes two main forms. (1) <span>The topic or context should be stated at the beginning or near the beginning of the question, to prime your memory to retrieve the right kind of information and to facilitate reviewing cards from different subjects intermixed, which many people believe improves creativity. For instance, in several of my questions above, you saw qualifiers at the start of the question like OutSystems: or APUSH:. A word describing the topic worked into the sentence can work, too, although Rule #16 does recommend prefixes so you can be sure your brain gets started correctly. If you don’t do this, you will often find yourself interpreting the question incorrectly – even if the question was clear in the context in which you were writing it, when you see it in




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The question should not be built around a particular source. It’s okay to cite your sources on your cards (actually, it’s a fantastic idea to reference sources in one way or another, because sooner or later you’re going to have doubts about the veracity of some card, or simply want to find more information about the topic). However, questions like this one are to be avoided:

Statistics: One of the major focuses of our book’s introduction is that it is useful to measure {what you don’t know, or the uncertainty you have}.

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and get in the habit right away. Even if you’re only studying, say, organic chemistry right now, ensure your questions can be comprehended within the context of a broader body of knowledge. (2) <span>The question should not be built around a particular source. It’s okay to cite your sources on your cards (actually, it’s a fantastic idea to reference sources in one way or another, because sooner or later you’re going to have doubts about the veracity of some card, or simply want to find more information about the topic). However, questions like this one are to be avoided: Statistics: One of the major focuses of our book’s introduction is that it is useful to measure {what you don’t know, or the uncertainty you have}. First of all, this violates principle 1, since it just refers to “our book.” I happen to know which textbook it refers to at the moment, but at a different time I might not! But as for




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This other pattern uses the source information entirely differently: rather than making the question about the author’s book, it asks about the idea in the book while explaining where it came from. For example:

Q: Why, according to Cal Newport, are discoveries often made by multiple people at the same time?
A: These things are part of the “adjacent possible” and were thus particularly easy to discover.

This becomes an especially valuable pattern once you get past the basic textbook knowledge and how-to rules in a field, where agreement can no longer be taken for granted. You don’t want to memorize opinions or nascent theories as facts!

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areful not to confuse this prohibition with a very useful pattern, namely that of asking what particular authors think about a topic, or qualifying information by saying that so-and-so said it. <span>This other pattern uses the source information entirely differently: rather than making the question about the author’s book, it asks about the idea in the book while explaining where it came from. For example: Q: Why, according to Cal Newport, are discoveries often made by multiple people at the same time? A: These things are part of the “adjacent possible” and were thus particularly easy to discover. This becomes an especially valuable pattern once you get past the basic textbook knowledge and how-to rules in a field, where agreement can no longer be taken for granted. You don’t want to memorize opinions or nascent theories as facts! ConclusionPermalink I hope these rules are helpful to you. Most spaced-repetition beginners vastly underestimate the importance of carefully worded questions, and I have yet to see anyb




#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology

Mumps virus is a member of the Paramyxoviridae family, which includes the following genera: Rubulavirus (mumps virus, New Castle disease virus, human parainfluenza virus types 2, 4a, and 4b); Paramyxovirus (human parainfluenza virus types 1 and 3); Morbillivirus (measles); and Pneumovirus (human respiratory syncytial virus).

ATTENTION 24/12/24 :

Nouvelle classification ? À vérifier (ChatGPT)

La famille des Paramyxoviridae inclut désormais plusieurs sous-familles, dont deux principales : Orthoparamyxovirinae et Avulavirinae. Parmi les genres traditionnellement évoqués dans cette famille, voici une analyse critique de votre liste :

  1. Paramyxovirus : Ce terme n'est plus utilisé comme genre officiel, car il désignait historiquement un groupe non homogène. Les virus de ce groupe sont maintenant répartis dans plusieurs genres, comme Respirovirus et Rubulavirus.

  2. Rubulavirus : Ce genre est correct et regroupe des virus comme ceux des oreillons et certains virus parainfluenza.

  3. Morbillivirus : Correct, ce genre inclut notamment le virus de la rougeole et celui de la peste des petits ruminants.

  4. Pneumovirus : Ce terme ne correspond plus à un genre dans la famille des Paramyxoviridae. Les virus de ce groupe, comme le virus respiratoire syncytial humain (VRS), appartiennent maintenant à une autre famille, les Pneumoviridae, distincte des Paramyxoviridae.

Classification actuelle

La classification actualisée des genres dans les Paramyxoviridae inclut notamment :

  • Respirovirus
  • Rubulavirus
  • Morbillivirus
  • Henipavirus

Le genre Pneumovirus appartient désormais à une famille séparée, les Pneumoviridae.

La taxonomie des Paramyxoviridae a été mise à jour en août 2020 par le Comité international de taxonomie des virus (ICTV). À vérifier (ChatGPT)

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Lumbar puncture yields CSF containing 10 to 2000 white blood cells (WBC)/mm3. The pre- dominating cells are usually lymphocytes, but 20% to 25% of patients have a polymorphonuclear leukocyte predominance.45 Protein levels are normal to mildly elevated, and 90% to 95% of patients have a CSF protein content less than 70 mg/dL.45,46 Hypoglycorrhachia (CSF glucose concentration <40 mg/dL) is reported in 6% to 30% of the patients45–47 and appears to be more common than in other viral meningitides.
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Flashcard 7672089939212

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quelle est l'atteinte clinique principale des oreillons ?
Answer

Inflammation des glandes salivaires

"Mumps is an acute viral infection that most commonly manifests as nonsuppurative swelling and tenderness of the parotid or other salivary glands caused by the mumps virus"


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Definition Mumps is an acute viral infection that most commonly manifests as nonsuppurative swelling and tenderness of the parotid or other salivary glands caused by the mumps virus. Less common manifestations of mumps include meningitis, encephalitis, epididymo-orchitis, oophoritis, and pancreatitis

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Flashcard 7672092298508

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quels sont les organes ou systèmes d'organes pouvant être atteints au cours d'une infection par le virus des oreillons
Answer

Neurologique

Reproductif

Pancréatique

"Less common manifestations of mumps include meningitis, encephalitis, epididymo-orchitis, oophoritis, and pancreatitis"


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pan> Definition Mumps is an acute viral infection that most commonly manifests as nonsuppurative swelling and tenderness of the parotid or other salivary glands caused by the mumps virus. Less common manifestations of mumps include meningitis, encephalitis, epididymo-orchitis, oophoritis, and pancreatitis <span>

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Flashcard 7672094919948

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quel(s) est (sont) le(s) hôte(s) naturel(s) du virus des oreillons ?
Answer

Humains

"Mumps is endemic throughout the world, and humans are the only natural hosts for the virus"


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Epidemiology Mumps is endemic throughout the world, and humans are the only natural hosts for the virus. Incubation period is usually 16 to 18 days, with a range of 2 to 4 weeks. Before the introduction of the mumps vaccine in the United States in 1967, epidemics occurred every 2 to 5 yea

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Flashcard 7672097279244

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quelle est la période d'incubation des oreillons ?
Answer

16 à 18 jours
donc entre 2 et 4 semaines

"Incubation period is usually 16 to 18 days, with a range of 2 to 4 weeks"


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Epidemiology Mumps is endemic throughout the world, and humans are the only natural hosts for the virus. Incubation period is usually 16 to 18 days, with a range of 2 to 4 weeks. Before the introduction of the mumps vaccine in the United States in 1967, epidemics occurred every 2 to 5 years, with peak incidence between January and May. Since 1967 there has been

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Flashcard 7672099638540

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Vrai ou Faux : il n'y a plus d'épidémies d'oreillons depuis que la couverture vaccinale est étendue
Answer

FAUX

Encore des épidémies, même chez des patients avec schéma vaccinal complet

"Outbreaks of mumps have been reported throughout the world, including the United States, even in populations who have received the recommended two-dose measles-mumps- rubella (MMR) series"


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ted States in 1967, epidemics occurred every 2 to 5 years, with peak incidence between January and May. Since 1967 there has been greater than a 99% decline in the annual US incidence of mumps. <span>Outbreaks of mumps have been reported throughout the world, including the United States, even in populations who have received the recommended two-dose measles-mumps- rubella (MMR) series. <span>

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Flashcard 7672102784268

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quel est le type de matériel génétique contenu dans le virus des oreillons ?
Answer

ARN simple brin de polarité négative

"Mumps is [...] a single-stranded RNA virus"


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Microbiology Mumps is an enveloped, single-stranded RNA virus. Only one serotype of mumps virus exists, but there are 13 genotypes

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Flashcard 7672105143564

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Combien existe-t-il de sérotypes du virus des oreillons ?
Answer

Un seul

"Only one serotype of mumps virus exists, but there are 13 genotypes"


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Microbiology Mumps is an enveloped, single-stranded RNA virus. Only one serotype of mumps virus exists, but there are 13 genotypes

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Flashcard 7672108813580

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quelle est la proportion de patients avec une infection par le virus des oreillons qui est asymptomatique ?
Answer

Un tiers : 1/3

"The disease is benign and self-limited, with one-third of affected persons having subclinical infection"


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The disease is benign and self-limited, with one-third of affected persons having subclinical infection

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Flashcard 7672111435020

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Parmi les manifestations cliniques peu fréquentes des oreillons, quelles sont les deux plus importantes ?
Answer

Méningite

et

Orchi-épididymite

"Meningitis and epididymo-orchitis represent the two most important of the less frequent manifestations of this disease."


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Meningitis and epididymo-orchitis represent the two most important of the less frequent manifestations of this disease.

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Flashcard 7672114842892

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
À quelle période de la vie les manifestations extra-glandulaires des oreillons prédominent ?
Answer

Puberté

"As is characteristic of many viral infections, mumps is usually a more severe illness in persons past the age of puberty than in children and more commonly leads to extrasalivary gland involvement in these older patients"


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As is characteristic of many viral infections, mumps is usually a more severe illness in persons past the age of puberty than in children and more commonly leads to extrasalivary gland involvement in these older patients.

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Flashcard 7672118250764

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
De quel verbe anglais pourrait provenir l'appellation "mumps" pour les oreillons ?
Answer

To mump (= "to be sulky" = refusing to smile or be pleasant to people, usually because you are angry about something)

= BOUDER

"It may arise from the English noun mump, meaning a lump, or from the English verb to mump, defined as “to be sulky”—a description of the characteristic facial expression."


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The etymology of the word mumps is unclear. It may arise from the English noun mump, meaning a lump, or from the English verb to mump, defined as “to be sulky”—a description of the characteristic facial expression.

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Flashcard 7672121134348

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
À quelle famille de virus appartient le virus des oreillons ?
Answer

Paramyxoviridae

"Mumps virus is a member of the Paramyxoviridae family"


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Mumps virus is a member of the Paramyxoviridae family, which includes the following genera: Rubulavirus (mumps virus, New Castle disease virus, human parainfluenza virus types 2, 4a, and 4b); Paramyxovirus (human parainfluenza virus types

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Flashcard 7672151018764

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Pour combien de protéines code le génome du virus des oreillons ?
Answer

8 protéines

"The genome codes for eight proteins [...]"


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The genome codes for eight proteins—the hemagglutinin-neuraminidase protein (HN), fusion protein (F), nucleocapsid protein (NP), phosphoprotein (P), matrix protein (M), hydrophobic protein (SH), and L proteins.7 </

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Flashcard 7672153378060

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quels sont les antigènes les plus immunogènes du virus des oreillons ?
Answer

Protéines F et HN

"Antibodies to the F and HN proteins appear to be the most prominent determinants of immunity"


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Antibodies to the F and HN proteins appear to be the most prominent determinants of immunity.

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Flashcard 7672155737356

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Sur la séquence génétique de quelle protéine se base la détermination des différents génotypes du virus des oreillons ?
Answer

Protéine SH

"[... ]there are 13 genotypes (A–M) that have been determined on the basis of sequencing of the SH protein, which is the most variable protein among mumps strains"


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Although only one serotype of mumps virus is known, there are 13 genotypes (A–M) that have been determined on the basis of sequencing of the SH protein, which is the most variable protein among mumps strains.8–10

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Flashcard 7672158620940

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
À quel solvant organique le virus des oreillons est-il sensible en raison de son enveloppe lipidique ?
Answer

Éther

"Mumps virus is ether sensitive by virtue of its lipid envelope"


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Mumps virus is ether sensitive by virtue of its lipid envelope. It is stable at 4°C for several days and at −65°C for months to years; however, repeated freezing and thawing may diminish viral activity.

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Flashcard 7672162028812

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
De quel paramètre physique dépend en partie la stabilité du virus des oreillons dans le milieu extérieur ?
Answer

La température

"It is stable at 4°C for several days and at −65°C for months to years"


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Mumps virus is ether sensitive by virtue of its lipid envelope. It is stable at 4°C for several days and at −65°C for months to years; however, repeated freezing and thawing may diminish viral activity.

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Flashcard 7672165698828

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
En quelle année a été autorisé le vaccin anti-oreillons aux USA ?
Answer

1967

"[...] licensing of live-attenuated mumps vaccine in 1967"


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In the United States, before the licensing of live-attenuated mumps vaccine in 1967, epidemics occurred every 2 to 5 years.13

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Flashcard 7672170679564

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Question
Lors d'une épidémie d'oreillons, chez les patients vaccinés avec deux doses, de combien de % augmente le risque d'infection en fonction du nombre d'année écoulée depuis la dernière dose reçue de vaccin ROR ?
Answer

10 % par an écoulé

"A study of 15 clusters of mumps in France in 2013 indicated that the “odds” of mumps increased for twice-vaccinated individuals by 10% for every year that had passed since the second dose"


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A study of 15 clusters of mumps in France in 2013 indicated that the “odds” of mumps increased for twice-vaccinated individuals by 10% for every year that had passed since the second dose.29 On the basis of this and other studies, the French High Council of Public Health recommended that a third dose of MMR be given during outbreaks of mumps for individuals who had recei

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Flashcard 7672173563148

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Question
Lors de l'épidémie irlandaise de 2008 d'oreillons, à quel taux relatif d'anticorps était corrélé le caractère neutralisant de l'infection in vitro ?
Answer

40 U/mL

"A recent study of outbreaks of mumps in Ireland in 2008–09 showed that immunoglobulin G (IgG) levels to the circulating genotype G5 mumps strain needed to be greater than 40 relative units/mL to be correlated with anti-G5 neutralization activity in vitro"


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A recent study of outbreaks of mumps in Ireland in 2008–09 showed that immunoglobulin G (IgG) levels to the circulating genotype G5 mumps strain needed to be greater than 40 relative units/mL to be correlated with anti-G5 neutralization activity in vitro.30 Lower titers of serum neutralizing activity were seen in males compared with females with acute mumps infection. This is consistent with previous observations that males are more lik

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Flashcard 7672176184588

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Question
Comment expliquer la faible fréquence de l'infection par le virus des oreillons chez les enfants < 1 an ?
Answer

Protection par anticorps maternels

"Resistance to infection in this age group is based on passive immunity acquired by the placental transfer of maternal antibody."


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Mumps is uncommon in infants younger than 1 year. Resistance to infection in this age group is based on passive immunity acquired by the placental transfer of maternal antibody.

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Flashcard 7672178543884

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Question
En dessous de quel âge est-il considéré que l'infection par le virus des oreillons est rare ?
Answer

1 an

"Mumps is uncommon in infants younger than 1 year."


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Mumps is uncommon in infants younger than 1 year. Resistance to infection in this age group is based on passive immunity acquired by the placental transfer of maternal antibody.

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Flashcard 7672181165324

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Question

Oreillons

In 2001, 49% of infections were reported in persons older than [...] years

Answer
15 years

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ater than 50% of cases occurred in the 5- to 9-year-old age group, and 90% of the cases occurred in children younger than 14 years. In 2001 49% of infections were reported in persons older than <span>15 years <span>

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Flashcard 7672184573196

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Question
Existe-t-il un portage chronique du virus des oreillons chez l'humain ?
Answer

Non

"Although persistent infections in cultured cells are commonly established by mumps virus, a carrier state is not known to exist in humans"


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Although persistent infections in cultured cells are commonly established by mumps virus,34 a carrier state is not known to exist in humans.

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Flashcard 7672188243212

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Question
Quand se situe le pic d'infectiosité de l'hôte lors de l'infection par le virus des oreillons ? (par rapport à évènement clinique)
Answer

Juste avant ou pendant la parotidite

"The period of peak contagion is just before or at the onset of parotitis"


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The period of peak contagion is just before or at the onset of parotitis

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Flashcard 7672190602508

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Question
Vrai ou faux : le virus des oreillons est plus contagieux que la varicelle ou la rougeole ?
Answer

FAUX

"More intimate contact is necessary to transmit mumps than for measles or varicella."


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More intimate contact is necessary to transmit mumps than for measles or varicella.

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Flashcard 7672192961804

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Question
Par quels moyens est transmis le virus des oreillons ?
Answer
  • Contact direct
  • Goutelettes
  • Fomites

"The virus is naturally transmitted via direct contact, droplet nuclei, or fomite"


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The virus is naturally transmitted via direct contact, droplet nuclei, or fomites and enters through the nose or mouth

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Question
Quelle est l'étymologie du mot "fomites" ?
Answer

Latin fomis, fomitis

= amadou (matière inflammable utilisée pour allumer un feu)

"Rem. Du lat. fomes, fomitis "ce qui alimente un feu, une flamme" ; GD IV, 54a (même ex. de Mézières, Songe vieil pèl., leçon fomite)."


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Flashcard 7672197156108

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Question
Quelle est la définition du mot "fomites" ?
Answer

Tout(e) objet inanimé ou substance capable de transporter des organismes infectieux (germes, parasites, etc.) et donc de les transférer d’un individu à un autre.

Comité d’experts sur le virus de la grippe et l’équipement de protection respiratoire individuelle, La Transmission du virus de la grippe et la contribution de l’équipement de protection respiratoire individuelle — Évaluation des données disponibles, Conseil des académies canadiennes, Ottawa, 2007)

https://fr.wiktionary.org/wiki/fomite


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Flashcard 7672200563980

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Question
Quel était le pattern d'atteinte anatomopathologique dans les manifestations encéphalitiques liées à l'infection par le virus des oreillons ?
Answer
  • Démyélinisation
  • Pas d'atteinte neuronale directe

"The description of brain involvement in mumps encephalitis has most often been that of postinfectious encephalitis characterized by perivenous demyelinization, perivascular mononuclear cuffing, and a generalized increase in microglial cells, with relative sparing of neurons."


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The description of brain involvement in mumps encephalitis has most often been that of postinfectious encephalitis characterized by perivenous demyelinization, perivascular mononuclear cuffing, and a generalized increase in microglial cells, with relative sparing of neurons.37 However, descriptions of what appears to be primary mumps encephalitis that show widespread neuronolysis but no evidence of demyelinization have been reported.38

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Question
Quelle différence sémiologique à l'inspection entre une parotidite et des adénopathies cervicales ?
Answer

Parotidite dissimule l'angle de la mandibule, pas les adénopathies cervicales

"The enlarged parotid gland obscures the angle of the mandible, whereas cervical adenopathy does not hide this anatomic landmark"


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At its height, parotitis results in lifting of the ear lobe upward and outward. Lesser degrees of enlargement can more readily be appreciated by viewing the patient from behind. The enlarged parotid gland obscures the angle of the mandible, whereas cervical adenopathy does not hide this anatomic landmark

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Question
À quelle vitesse / en combien de temps s'installent les premiers signes cliniques "spécifiques" des oreillons ?
Answer

1 jour

"Within 1 day the nature of the illness becomes apparent when the patient complains"


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Within 1 day the nature of the illness becomes apparent when the patient complains of an earache, and tenderness can be elicited by palpation of the ipsilateral parotid. The involved gland is soon visibly enlarged and progresses to a maximum size over the next 2 to 3

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Question
Quelle peut être la première plainte d'un patient avec les oreillons ?
Answer

Otalgie

"[...] the nature of the illness becomes apparent when the patient complains of an earache"


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Within 1 day the nature of the illness becomes apparent when the patient complains of an earache, and tenderness can be elicited by palpation of the ipsilateral parotid. The involved gland is soon visibly enlarged and progresses to a maximum size over the next 2 to 3 days. The most

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Flashcard 7672213146892

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Question
Lors des oreillons, en combien de temps la parotide atteint son oedémation maximale ?
Answer

2 - 3 jours

"The involved gland is soon visibly enlarged and progresses to a maximum size over the next 2 to 3 days"


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Within 1 day the nature of the illness becomes apparent when the patient complains of an earache, and tenderness can be elicited by palpation of the ipsilateral parotid. The involved gland is soon visibly enlarged and progresses to a maximum size over the next 2 to 3 days. The most severe pain accompanies the period of rapid enlargement

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Question
Pendant quelle phase clinique la douleur de la parotidite est maximale ?
Answer

La phase de constitution rapide de l'oedème

'The most severe pain accompanies the period of rapid enlargement"


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ns of an earache, and tenderness can be elicited by palpation of the ipsilateral parotid. The involved gland is soon visibly enlarged and progresses to a maximum size over the next 2 to 3 days. <span>The most severe pain accompanies the period of rapid enlargement <span>

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Question
À partir de quand les signes généraux et locaux commencent à régresser au cours des oreillons ?
Answer

Après l'acmé de la parotidite

"After parotid swelling has reached its peak, pain, fever, and tenderness rapidly resolve"


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After parotid swelling has reached its peak, pain, fever, and tenderness rapidly resolve, and the parotid gland returns to normal size within 1 week

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Question
En combien de temps la glande parotide retrouve sa taille normale ?
Answer

1 semaine

"[...] the parotid gland returns to normal size within 1 week"


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After parotid swelling has reached its peak, pain, fever, and tenderness rapidly resolve, and the parotid gland returns to normal size within 1 week

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Question
Dans les trois premiers jours des oreillons, jusqu'à quelle température peut monter la fièvre ?
Answer

40°C

"During the first 3 days of illness the patient’s temperature may range from normal to 40°C"


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During the first 3 days of illness the patient’s temperature may range from normal to 40°C

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Question
Quels aliments peuvent augmenter la douleur de la parotidite des oreillons ?
Answer

Les agrumes (acidité)

"Ingestion of citrus fruits or juices typically exacerbates the pain"


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Ingestion of citrus fruits or juices typically exacerbates the pain

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Question
Que peut-on observer à l'inspection intra-buccale au cours des oreillons ?
[unknown IMAGE 7672234904844]
Answer

Érythème et oedème du conduit de Sténon

"The orifice of the Stensen duct is frequently edematous and erythematous"


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The orifice of the Stensen duct is frequently edematous and erythematous.

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Question
Au cours d'une parotidite bilatérale des oreillons, dans quels délais l'atteinte parotidienne se bilatéralise ?
Answer

1 à 2 jours

"Usually, one parotid gland enlarges 1 or 2 days after the other"


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Usually, one parotid gland enlarges 1 or 2 days after the other; however, mumps results in unilateral parotitis alone in one-quarter of patients with salivary gland involvement.

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Question
Dans quelle proportion des cas l'atteinte parotidienne est-elle unilatérale au cours des oreillons ?
Answer

1/4 des cas : 25 %

"mumps results in unilateral parotitis alone in one-quarter of patients with salivary gland involvement"


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Usually, one parotid gland enlarges 1 or 2 days after the other; however, mumps results in unilateral parotitis alone in one-quarter of patients with salivary gland involvement.

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Question

Oreillons - Atteinte cardiologique

Electrocardiographic changes appear in up to [...]% of patients with mumps.

Answer
15 %

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Electrocardiographic changes appear in up to 15% of patients with mumps; the most common abnormalities are depressed ST segments, flattened or inverted T waves, and prolonged P-R intervals.70,71 Clinically manifested myocarditis is r

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Question
Quelles sont les manifestations électrocardiographiques les plus fréquentes des oreillons ?
Answer
  • Sous-ST
  • Inversion ondes T
  • Allongement de l'intervalle PR

"[...] the most common abnormalities are depressed ST segments, flattened or inverted T waves, and prolonged P-R intervals"


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Electrocardiographic changes appear in up to 15% of patients with mumps; the most common abnormalities are depressed ST segments, flattened or inverted T waves, and prolonged P-R intervals.70,71 Clinically manifested myocarditis is rare; however, deaths associated with myocarditis have been reported during the acute illness and after a chronically progressive deterioratin

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Question
Quel est le pattern d'atteinte articulaire le plus fréquemment décrit au cours des oreillons ?
Answer

Polyarthrite migratrice

"Migratory polyarthritis is the most frequently described clinical form. Joint involvement during mumps is noted infrequently in adults and rarely in children."


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Joint involvement during mumps is noted infrequently in adults and rarely in children.68,69 Migratory polyarthritis is the most frequently described clinical form. Monarticular arthritis and arthralgia have also been reported; both large and small joints are involved. Symptoms most commonly start 10 to 14 days after the onset of parotitis and may

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Question

Oreillons - Atteintes articulaires

Symptoms most commonly start [...] to [...] after the onset of parotitis.

Answer
10 to 14 days

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lyarthritis is the most frequently described clinical form. Monarticular arthritis and arthralgia have also been reported; both large and small joints are involved. Symptoms most commonly start <span>10 to 14 days after the onset of parotitis and may last up to 5 weeks. The process resolves spontaneously without residual joint damage <span>

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Question

Oreillons - Atteintes articulaires

Symptoms may last up to [...] weeks after the onset of parotitis

Answer
5 weeks

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narticular arthritis and arthralgia have also been reported; both large and small joints are involved. Symptoms most commonly start 10 to 14 days after the onset of parotitis and may last up to <span>5 weeks. The process resolves spontaneously without residual joint damage <span>

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Question

Oreillons - Atteintes articulaires

Les atteintes articulaires des oreillons laissent-elles des séquelles ?

Answer

NON

"The process resolves spontaneously without residual joint damage"


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r arthritis and arthralgia have also been reported; both large and small joints are involved. Symptoms most commonly start 10 to 14 days after the onset of parotitis and may last up to 5 weeks. <span>The process resolves spontaneously without residual joint damage <span>

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Question
Oophoritis develops in [...]% of postpubertal women with mumps.
Answer
5 %

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Oophoritis develops in 5% of postpubertal women with mumps. Symptoms include fever, nausea, vomiting, and lower abdominal pain. Impaired fertility and premature menopause have been reported as a consequence of

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Question

Oreillons - Orchi-épididymite

When testes are examined months to years later, some degree of atrophy is noted in [...]% of patients

Answer
50 %

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When testes are examined months to years later, some degree of atrophy is noted in 50% of patients

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Question

Oreillons - Orchi-épididymite

Dans quels délais se déclarent la plupart des cas d'orchi-épididymite après la parotidite ?

Answer

Dans la première semaine

"Two-thirds of cases occur during the first week of parotitis"


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Two-thirds of cases occur during the first week of parotitis and another 25% arise during the second week.64 However, gonadal involvement may precede parotitis or occur as the only manifesta- tion of mumps

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Question
Quelle est la manifestation glandulaire extra-salivaire la plus fréquente au cours des oreillons ?
Answer

Orchi-épididymite

"Epididymo-orchitis is the most common extrasalivary gland manifestation in the adult"


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Epididymo-orchitis is the most common extrasalivary gland mani- festation in the adult. It develops in 20% to 30% of postpubertal male adolescents with mumps infection and is bilateral in one of six of those with testicular involvement.64,65 Although it has been reported

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Question
Epididymo-orchitis develops in [...]% to [...]% of postpubertal male adolescents with mumps infection.
Answer
20 % à 30 %

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Epididymo-orchitis is the most common extrasalivary gland mani- festation in the adult. It develops in 20% to 30% of postpubertal male adolescents with mumps infection and is bilateral in one of six of those with testicular involvement.64,65 Although it has been reported in infancy, it is r

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Question
Before the introduction of the live-attenuated mumps vaccine in 1967, mumps accounted for approximately [...]% of cases of aseptic meningitis in the United States.
Answer
10 %

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Before the introduction of the live-attenuated mumps vaccine in 1967, mumps accounted for approximately 10% of cases of aseptic meningitis in the United States. At present aseptic meningitis is rarely attributed to mumps.

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Question
Quel est le pronostic de la méningite ourlienne ?
Answer

Bon pronostic

"The meningitis is benign, with complete recovery and an absence of sequelae"


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The meningitis is benign, with complete recovery and an absence of sequelae

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Question

Oreillons - Méningite

Abatement of fever by lysis and resolution of symptoms generally occur [...] to [...] days after the onset of illness.

Answer
3 to 10 days

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Abatement of fever by lysis and resolution of symptoms generally occur 3 to 10 days after the onset of illness.

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Question
Pendant combien de temps peuvent perdurer les anomalies du LCS au cours de la méningite ourlienne ?
Answer

5 semaines

"These CSF abnormalities may persist for 5 weeks or longer."


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These CSF abnormalities may persist for 5 weeks or longer.44,47

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Question
Quel est le type leucocytaire prédominant dans les méningites ourliennes ?
Answer

Lymphocytes

"The predominating cells are usually lymphocytes"


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Lumbar puncture yields CSF containing 10 to 2000 white blood cells (WBC)/mm3. The pre- dominating cells are usually lymphocytes, but 20% to 25% of patients have a polymorphonuclear leukocyte predominance.45 Protein levels are normal to mildly elevated, and 90% to 95% of patients have a CSF protein content less t

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Question
Dans quelle proportion de cas de méningites ourliennes des PNN peuvent prédominer dans le LCS ?
Answer

Environ 1/4 : 25 %

"20% to 25% of patients have a polymorphonuclear leukocyte predominance"


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Lumbar puncture yields CSF containing 10 to 2000 white blood cells (WBC)/mm3. The pre- dominating cells are usually lymphocytes, but 20% to 25% of patients have a polymorphonuclear leukocyte predominance.45 Protein levels are normal to mildly elevated, and 90% to 95% of patients have a CSF protein content less than 70 mg/dL.45,46 Hypoglycorrhachia (CSF glucose concentration <40 mg/dL

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Flashcard 7672297557260

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quelle proportion des patients avec une méningite ourlienne ont une parotidite clinique ?
Answer

Seulement 40 à 50 %

"[...]only 40% to 50% of patients with mumps meningitis, confirmed by serology or viral isolation, have parotitis"


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Clinical meningitis occurs in 1% to 10% of persons with mumps parotitis,43 but, on the other hand, only 40% to 50% of patients with mumps meningitis, confirmed by serology or viral isolation, have parotitis.43–46

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Flashcard 7672299916556

Tags
#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question

Oreillons - Méningite

Meningitis onset averages [...] days after the appearance of salivary gland involvement.

Answer
4 jours

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Meningeal symptoms, like any of the other manifestations of mumps infection, may occur before, during, after, or in the absence of parotitis. Its onset averages 4 days after the appearance of salivary gland involvement but may be as early as 1 week before or as late as 2 weeks after parotitis.42–45 Men are afflicted three times as often as women,

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Flashcard 7672302537996

Tags
#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quelle est le site extra-glandulaire le plus fréquemment atteint au cours des oreillons ?
Answer

Le système nerveux central

"Central nervous system (CNS) involvement is the most common extrasalivary gland manifestation of mumps"


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Central nervous system (CNS) involvement is the most common extrasalivary gland manifestation of mumps

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Flashcard 7672304897292

Tags
#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question
Quelle manifestation clinique observable à l'inspection du décolleté peut être liée à des adénopathies sous-mandibulaires au cours des oreillons ?
Answer

Oedème pré-sternal prenant le godet

"Presternal pitting edema develops in 6% of patients with mumps, most commonly in those who have submandibular adenitis."


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Presternal pitting edema develops in 6% of patients with mumps, most commonly in those who have submandibular adenitis.40 The proposed mechanism for the involvement of the tongue and presternal area is obstruction of the lymphatic drainage of those regions by enlarged salivary glands

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Flashcard 7672307256588

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#Maladies-infectieuses-et-tropicales #Mumps #Mumps-MDB #Oreillons #Oreillons-MDB #Virologie #Virology
Question

Oreillons

Involvement of the other salivary glands may occur in conjunction with parotitis in up to [...]% of cases.

Answer
10 %

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Involvement of the other salivary glands may occur in conjunction with parotitis in up to 10% of cases but is rare as the sole manifestation of mumps infection (Table 157.1)

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#AndyMatuschak #Apprentissage #MethodoAnki #Methodologie #Prompts
Prompt-writing can helpfully reveal such gaps in our understanding. You don’t need to stick with one resource: follow your nose; Google around; consult other references
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How to write good prompts: using spaced repetition to create understanding
There was one prompt which I found I wanted to write but couldn’t, at least while using only the information in the recipe: Q. When to use chicken stock versus other types of meat stock? A. ??? <span>Prompt-writing can helpfully reveal such gaps in our understanding. You don’t need to stick with one resource: follow your nose; Google around; consult other references. Even if you don’t decide to follow up on the missing information immediately, you can guide future exploration by sensitizing yourself to feelings of curiosity and gaps in understandin




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I think of closed lists as a complex fact, almost an equation:

radius of earth = 6,371 km

chicken stock ingredients = onions, carrots, celery, garlic, parsley.

In fact, if you’re an experienced cook, you probably think of the ingredients in chicken stock as an open list—if that’s true, it’d be better to represent them that way! This is a common fate for closed lists in human-scale concepts.

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How to write good prompts: using spaced repetition to create understanding
few members on demand. No, if you keep cooking, you’ll be adding to this list your whole life. By contrast, the list of ingredients in our recipe has a fixed set of members: it’s a closed list. <span>I think of closed lists as a complex fact, almost an equation: radius of earth = 6,371 km chicken stock ingredients = onions, carrots, celery, garlic, parsley. In fact, if you’re an experienced cook, you probably think of the ingredients in chicken stock as an open list—if that’s true, it’d be better to represent them that way! This is a common fate for closed lists in human-scale concepts. I like to think of open lists like tags—like the tags you might use in a system for digital bookmarks. My mental filing cabinet has a tag called “way to use chicken stock,” and I’ve fas




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I like to think of open lists like tags—like the tags you might use in a system for digital bookmarks. My mental filing cabinet has a tag called “way to use chicken stock,” and I’ve fastened that tag to some notes about making purée soups
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How to write good prompts: using spaced repetition to create understanding
you probably think of the ingredients in chicken stock as an open list—if that’s true, it’d be better to represent them that way! This is a common fate for closed lists in human-scale concepts. <span>I like to think of open lists like tags—like the tags you might use in a system for digital bookmarks. My mental filing cabinet has a tag called “way to use chicken stock,” and I’ve fastened that tag to some notes about making purée soups. When I encode this type of knowledge, I find three types of prompts consistently helpful. First I write prompts focused on each of the tagged items, linking from the instance to the ta




#AndyMatuschak #Apprentissage #MethodoAnki #Methodologie #Prompts

When I encode this type of knowledge, I find three types of prompts consistently helpful. First I write prompts focused on each of the tagged items, linking from the instance to the tag. Then I might separately write prompts about the tag itself, perhaps inspired by patterns I notice in its instances. Finally, I often write a prompt which fuzzily links from the tag to its instances by asking for examples.

For example, this prompt links an instance to the tag:

Q. When puréeing vegetables to make soup, how can I produce a richer flavor without adding fat?

A. Thin the purée with chicken stock instead of water.

After we’ve written several prompts like this, a prompt about a pattern in the tag might suggest itself:

Q. What should I ask myself if I notice I’m using water in savory cooking?

A. “Should I use stock instead?”

It’s often useful to be able to summon examples of a tag on demand. We can write a prompt which fuzzily links the tag to instances:

Q. Name two ways you might use chicken stock.

A. e.g. cooking grains, steaming hearty greens, making purée soups, deglazing pans

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How to write good prompts: using spaced repetition to create understanding
he tags you might use in a system for digital bookmarks. My mental filing cabinet has a tag called “way to use chicken stock,” and I’ve fastened that tag to some notes about making purée soups. <span>When I encode this type of knowledge, I find three types of prompts consistently helpful. First I write prompts focused on each of the tagged items, linking from the instance to the tag. Then I might separately write prompts about the tag itself, perhaps inspired by patterns I notice in its instances. Finally, I often write a prompt which fuzzily links from the tag to its instances by asking for examples. For example, this prompt links an instance to the tag: Q. When puréeing vegetables to make soup, how can I produce a richer flavor without adding fat? A. Thin the purée with chicken stock instead of water. After we’ve written several prompts like this, a prompt about a pattern in the tag might suggest itself: Q. What should I ask myself if I notice I’m using water in savory cooking? A. “Should I use stock instead?” It’s often useful to be able to summon examples of a tag on demand. We can write a prompt which fuzzily links the tag to instances: Q. Name two ways you might use chicken stock. A. e.g. cooking grains, steaming hearty greens, making purée soups, deglazing pans This type of prompt is easy to write, so it’s tempting to write something similar and be done with it. But prompts like this usually don’t work well without other prompts supporting it.




#AndyMatuschak #Apprentissage #MethodoAnki #Methodologie #Prompts

When you’ve just learned a particularly open-ended concept—one which could apply to many instances—you can turn example-generating prompts like the one above into creative prompts like this one:

Q. Name a vegetable purée soup which you might try making with chicken stock (give an answer you haven’t given before)

A. e.g. potato, parsnip, celeriac, sunchoke, salsify, squash, carrot, pepper, lentil…

The novelty admonition is an interesting trick: “give an answer you haven’t given before.” Sure, after a year or two, maybe you’ll re-use a vegetable without realizing it. That’s fine. But note that you probably can’t write a prompt like this one about contexts to use chicken stock, unless you have enough prior experience to generate plenty of different answers.

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How to write good prompts: using spaced repetition to create understanding
do change your answer each time, the prompt won’t satisfy the consistency property we’ve introduced, and interference effects may leave your memory unreliable without other supporting prompts. <span>When you’ve just learned a particularly open-ended concept—one which could apply to many instances—you can turn example-generating prompts like the one above into creative prompts like this one: Q. Name a vegetable purée soup which you might try making with chicken stock (give an answer you haven’t given before) A. e.g. potato, parsnip, celeriac, sunchoke, salsify, squash, carrot, pepper, lentil… The novelty admonition is an interesting trick: “give an answer you haven’t given before.” Sure, after a year or two, maybe you’ll re-use a vegetable without realizing it. That’s fine. But note that you probably can’t write a prompt like this one about contexts to use chicken stock, unless you have enough prior experience to generate plenty of different answers. This isn’t really a retrieval prompt anymore. Creative prompts are more like a textbook exercise, asking you to apply what you’ve learned in a new way. Unlike the other prompts we’ve se




#AndyMatuschak #Apprentissage #MethodoAnki #Methodologie #Prompts
This isn’t really a retrieval prompt anymore. Creative prompts are more like a textbook exercise, asking you to apply what you’ve learned in a new way. Unlike the other prompts we’ve seen, the goal here is to avoid retrieving an answer from memory: you’re meant to think creatively for a few moments. Since your answer’s different each time, retrieval practice won’t consistently reinforce your memory of any particular response. Instead, it will reinforce whatever knowledge you consistently use when generating an answer
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How to write good prompts: using spaced repetition to create understanding
That’s fine. But note that you probably can’t write a prompt like this one about contexts to use chicken stock, unless you have enough prior experience to generate plenty of different answers. <span>This isn’t really a retrieval prompt anymore. Creative prompts are more like a textbook exercise, asking you to apply what you’ve learned in a new way. Unlike the other prompts we’ve seen, the goal here is to avoid retrieving an answer from memory: you’re meant to think creatively for a few moments. Since your answer’s different each time, retrieval practice won’t consistently reinforce your memory of any particular response. Instead, it will reinforce whatever knowledge you consistently use when generating an answer. Your novel responses may also make meaningful associations which strengthen your memory through elaborative encoding. And those associations may be particularly sticky because ofSee Sl




#AndyMatuschak #Apprentissage #MethodoAnki #Methodologie #Prompts
And those associations may be particularly sticky because of See Slamecka and Graf, The Generation Effect: Delineation of a Phenomenon (1978). another memory phenomenon called the generation effect: you remember information better when you generated it yourself.
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How to write good prompts: using spaced repetition to create understanding
einforce whatever knowledge you consistently use when generating an answer. Your novel responses may also make meaningful associations which strengthen your memory through elaborative encoding. <span>And those associations may be particularly sticky because ofSee Slamecka and Graf, The Generation Effect: Delineation of a Phenomenon (1978). another memory phenomenon called the generation effect: you remember information better when you generated it yourself. Michael Nielsen and I have experimented with application-focused spaced repetition prompts in Quantum mechanics distilled, but we don’t yet feel we understand them.I’ve described a few




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Sometimes this effect isn’t helpful. You can probably remember a time when a friend learned a new idea, and then everything became an (inappropriate) nail for their new hammer. But to really internalize a new idea, you need to bring it into your life and make meaning with it. In particular, if it’s a new skill, you probably haven’t really understood it until you’ve put it into practice several times on your own.
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How to write good prompts: using spaced repetition to create understanding
y suggests that this effect is a kind of selective attention: new ideas are particularly salient, so we notice them more readily. They haven’t really become more common—they just seem that way. <span>Sometimes this effect isn’t helpful. You can probably remember a time when a friend learned a new idea, and then everything became an (inappropriate) nail for their new hammer. But to really internalize a new idea, you need to bring it into your life and make meaning with it. In particular, if it’s a new skill, you probably haven’t really understood it until you’ve put it into practice several times on your own. Salience typically fades over time. If you don’t soon have a chance to connect that new idea to something meaningful in your life, you may stop noticing opportunities so readily. The dy




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Salience typically fades over time. If you don’t soon have a chance to connect that new idea to something meaningful in your life, you may stop noticing opportunities so readily. The dynamic seems similar to the problem of forgetting knowledge over time. So one valuable use for spaced repetition prompts is to keep ideas salient, top of mind, over longer periods of time. Gwern Branwen has pointed out* * In private communication. that such prompts are effectively trying to extend the Baader-Meinhof phenomenon and control it for a purpose
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How to write good prompts: using spaced repetition to create understanding
d to bring it into your life and make meaning with it. In particular, if it’s a new skill, you probably haven’t really understood it until you’ve put it into practice several times on your own. <span>Salience typically fades over time. If you don’t soon have a chance to connect that new idea to something meaningful in your life, you may stop noticing opportunities so readily. The dynamic seems similar to the problem of forgetting knowledge over time. So one valuable use for spaced repetition prompts is to keep ideas salient, top of mind, over longer periods of time. Gwern Branwen has pointed out** In private communication. that such prompts are effectively trying to extend the Baader-Meinhof phenomenon and control it for a purpose. We’ve already written a few prompts which focus on salience: Q. What should I ask myself if I notice I’m using water in savory cooking? A. “Should I use stock instead?” Q. What should




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We’ve already written a few prompts which focus on salience:

Q. What should I ask myself if I notice I’m using water in savory cooking?

A. “Should I use stock instead?”

Q. What should I do with the carcass of a roast chicken?

A. Freeze it and make chicken stock

Q. Name a vegetable purée soup which you might try making with chicken stock (give an answer you haven’t given before)

A. e.g. potato, parsnip, celeriac, sunchoke, salsify, squash, carrot, pepper, lentil…

The point of those prompts isn’t really to “know” those answers intellectually. It’s to cue certain ideas, which in turn may prompt new thoughts or create new behaviors. Viewed in this way, the point of repeating these prompts over time is to keep the relevant ideas salient until they have a chance to connect to something meaningful in your life

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How to write good prompts: using spaced repetition to create understanding
longer periods of time. Gwern Branwen has pointed out** In private communication. that such prompts are effectively trying to extend the Baader-Meinhof phenomenon and control it for a purpose. <span>We’ve already written a few prompts which focus on salience: Q. What should I ask myself if I notice I’m using water in savory cooking? A. “Should I use stock instead?” Q. What should I do with the carcass of a roast chicken? A. Freeze it and make chicken stock Q. Name a vegetable purée soup which you might try making with chicken stock (give an answer you haven’t given before) A. e.g. potato, parsnip, celeriac, sunchoke, salsify, squash, carrot, pepper, lentil… The point of those prompts isn’t really to “know” those answers intellectually. It’s to cue certain ideas, which in turn may prompt new thoughts or create new behaviors. Viewed in this way, the point of repeating these prompts over time is to keep the relevant ideas salient until they have a chance to connect to something meaningful in your life. As economist Brad DeLong suggests, review sessions are surprisingly like a secular catechism. Many of the Orbit prompts in this guide are of this kind. They’re meant to keep you in con




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I suspect this is another reason it’s important to densely connect new ideas to old ones, as we did in the conceptual knowledge section: roughly speaking, more connections means more opportunities to trigger new knowledge
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How to write good prompts: using spaced repetition to create understanding
ion to a different one? I don’t have a well-grounded understanding of the difference, but in my experience, context-laden prompts (like this last example) help the leap from theory to practice. <span>I suspect this is another reason it’s important to densely connect new ideas to old ones, as we did in the conceptual knowledge section: roughly speaking, more connections means more opportunities to trigger new knowledge. What makes a spaced repetition prompt most likely to change your behavior or prompt new thoughts? What schedule should one use for repeating such prompts? If the objective isn’t memory




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This guide aspires to demonstrate a wide variety of techniques, so I’ve deliberately analyzed the chicken stock recipe quite exhaustively. But in practice, if you were examining a recipe for the first time, I certainly wouldn’t recommend writing dozens of prompts at once like we’ve done here. If you try to analyze everything you read so comprehensively, you’re likely to waste time and burn yourself out.
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How to write good prompts: using spaced repetition to create understanding
flavored, making it versatile but less intense). You can use this text box as a scratch area. What you write won’t be transmitted or saved. Writing prompts, in practice Iterative prompt-writing <span>This guide aspires to demonstrate a wide variety of techniques, so I’ve deliberately analyzed the chicken stock recipe quite exhaustively. But in practice, if you were examining a recipe for the first time, I certainly wouldn’t recommend writing dozens of prompts at once like we’ve done here. If you try to analyze everything you read so comprehensively, you’re likely to waste time and burn yourself out. Those issues aside, it’s hard to write good prompts on your first exposure to new ideas. You’re still developing a sense of which details are important and which are not—both objectivel




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Say you’re reading an article that seems interesting. Try setting yourself an accessible goal: on your first pass, aim to write a small number of prompts (say, 5-10) about whatever seems most important, meaningful, or useful.
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How to write good prompts: using spaced repetition to create understanding
ions. And you may need to live with new ideas for a while before you can write prompts which connect them vibrantly with whatever really matters to you. All this suggests an iterative approach. <span>Say you’re reading an article that seems interesting. Try setting yourself an accessible goal: on your first pass, aim to write a small number of prompts (say, 5-10) about whatever seems most important, meaningful, or useful. I find that such goals change the way I read even casual texts. When first adopting spaced repetition practice, I felt like I “should” write prompts about everything. This made reading




#AndyMatuschak #Apprentissage #MethodoAnki #Methodologie #Prompts
When first adopting spaced repetition practice, I felt like I “should” write prompts about everything. This made reading a chore. By contrast, it feels quite freeing to aim for just a few key prompts at a time
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How to write good prompts: using spaced repetition to create understanding
n your first pass, aim to write a small number of prompts (say, 5-10) about whatever seems most important, meaningful, or useful. I find that such goals change the way I read even casual texts. <span>When first adopting spaced repetition practice, I felt like I “should” write prompts about everything. This made reading a chore. By contrast, it feels quite freeing to aim for just a few key prompts at a time.As Michael Nielsen notes, similar lightweight prompt-writing goals can enliven seminars, professional conversations, events, and so on. I read a notch more actively, noticing a tickle i




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But for texts which are challenging or on an unfamiliar topic, it may be too disruptive to switch back and forth. In such cases it’s better to highlight or make note of the most important details. Then you can write prompts about your understanding of those details in a batch at the end or at a suitable stopping point. For these tougher topics, I find it’s best to focus initially on prompts about basic details you can build on: raw facts, terms, notation, etc.
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How to write good prompts: using spaced repetition to create understanding
more actively, noticing a tickle in the back of my mind: “Ooh, that’s a juicy bit! Let’s get that one!” If the material is fairly simple, you may be able to write these prompts while you read. <span>But for texts which are challenging or on an unfamiliar topic, it may be too disruptive to switch back and forth. In such cases it’s better to highlight or make note of the most important details. Then you can write prompts about your understanding of those details in a batch at the end or at a suitable stopping point. For these tougher topics, I find it’s best to focus initially on prompts about basic details you can build on: raw facts, terms, notation, etc. Books are more complicated: there are many kinds of books and many ways to read them. This is true of articles, too, of course, but books amplify the variance. For one thing, you’re les




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The best prompt-writing approach will depend on how and why you’re reading the book, but in general, if I’m trying to internalize a non-fiction book, I’ll often begin by aiming to write a few key prompts on my first pass through a chapter or major section
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How to write good prompts: using spaced repetition to create understanding
f course, but books amplify the variance. For one thing, you’re less likely to read a book linearly than an article. And, of course, they’re longer, so a handful of prompts will rarely suffice. <span>The best prompt-writing approach will depend on how and why you’re reading the book, but in general, if I’m trying to internalize a non-fiction book, I’ll often begin by aiming to write a few key prompts on my first pass through a chapter or major section. For many resources, one pass of prompt-writing is all that’s worth doing, at least initially. But if you have a rich text which you’re trying to internalize thoroughly, it’s often valu




#AndyMatuschak #Apprentissage #MethodoAnki #Methodologie #Prompts
For many resources, one pass of prompt-writing is all that’s worth doing, at least initially. But if you have a rich text which you’re trying to internalize thoroughly, it’s often valuable to make multiple passes, even in the first reading session. That doesn’t necessarily mean doubling down on effort: just write another handful of apparently-useful prompts each time. For a vivid account of this process in mathematics, see Michael Nielsen, Using spaced repetition systems to see through a piece of mathematics (2019). With each iteration, you’ll likely find yourself able to understand (and write prompts for) increasingly complex details. You may notice your attention drawn to patterns, connections, and bigger-picture insights. Even better: you may begin to focus on your own observations and questions, rather than those of the author.
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How to write good prompts: using spaced repetition to create understanding
’re reading the book, but in general, if I’m trying to internalize a non-fiction book, I’ll often begin by aiming to write a few key prompts on my first pass through a chapter or major section. <span>For many resources, one pass of prompt-writing is all that’s worth doing, at least initially. But if you have a rich text which you’re trying to internalize thoroughly, it’s often valuable to make multiple passes, even in the first reading session. That doesn’t necessarily mean doubling down on effort: just write another handful of apparently-useful prompts each time. For a vivid account of this process in mathematics, see Michael Nielsen, Using spaced repetition systems to see through a piece of mathematics (2019).With each iteration, you’ll likely find yourself able to understand (and write prompts for) increasingly complex details. You may notice your attention drawn to patterns, connections, and bigger-picture insights. Even better: you may begin to focus on your own observations and questions, rather than those of the author. But it’s also important to notice if you feel yourself becoming restless. There’s no deep virtue in writing a prompt about every detail. In fact, it’s much more important to remain resp




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There’s no deep virtue in writing a prompt about every detail. In fact, it’s much more important to remain responsive to your sense of curiosity and interest.
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How to write good prompts: using spaced repetition to create understanding
insights. Even better: you may begin to focus on your own observations and questions, rather than those of the author. But it’s also important to notice if you feel yourself becoming restless. <span>There’s no deep virtue in writing a prompt about every detail. In fact, it’s much more important to remain responsive to your sense of curiosity and interest. Piotr Wozniak, a pioneer of spaced repetition, has been developing a system he calls incremental reading which attempts to actively support this kind of iterative, incremental prompt wr




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If you notice a feeling of duty or completionism, remind yourself that you can always write more prompts later. In fact, they’ll probably be better if you do: motivated by something meaningful, like a new connection or a gap in your understanding
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How to write good prompts: using spaced repetition to create understanding
t. Piotr Wozniak, a pioneer of spaced repetition, has been developing a system he calls incremental reading which attempts to actively support this kind of iterative, incremental prompt writing.<span>If you notice a feeling of duty or completionism, remind yourself that you can always write more prompts later. In fact, they’ll probably be better if you do: motivated by something meaningful, like a new connection or a gap in your understanding. Let’s consider our chicken stock recipe again for a moment. If I were an aspiring cook who had never heard of stock before, I’d probably write a few prompts about what stock is and why




#AndyMatuschak #Apprentissage #MethodoAnki #Methodologie #Prompts
Let’s consider our chicken stock recipe again for a moment. If I were an aspiring cook who had never heard of stock before, I’d probably write a few prompts about what stock is and why it matters: those details seem useful beyond the scope of this single recipe, and they connect to happy dining experiences I’ve had. That’s probably all I’d do until I actually made a batch of stock for myself
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How to write good prompts: using spaced repetition to create understanding
nd yourself that you can always write more prompts later. In fact, they’ll probably be better if you do: motivated by something meaningful, like a new connection or a gap in your understanding. <span>Let’s consider our chicken stock recipe again for a moment. If I were an aspiring cook who had never heard of stock before, I’d probably write a few prompts about what stock is and why it matters: those details seem useful beyond the scope of this single recipe, and they connect to happy dining experiences I’ve had. That’s probably all I’d do until I actually made a batch of stock for myself. At that point, I’d know which steps were obvious and which made me consult the recipe. If I found I wanted to make stock again, I’d write another batch of prompts to recall details lik




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If I found I wanted to make stock again, I’d write another batch of prompts to recall details like ingredient ratios and times. I’d try to notice places where I found myself straining, vaguely aware that I’d “read something about this” but unsure of the details. As I used my first batch of stock in subsequent dishes, I might then write prompts about those experiences. And so on.
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How to write good prompts: using spaced repetition to create understanding
dining experiences I’ve had. That’s probably all I’d do until I actually made a batch of stock for myself. At that point, I’d know which steps were obvious and which made me consult the recipe. <span>If I found I wanted to make stock again, I’d write another batch of prompts to recall details like ingredient ratios and times. I’d try to notice places where I found myself straining, vaguely aware that I’d “read something about this” but unsure of the details. As I used my first batch of stock in subsequent dishes, I might then write prompts about those experiences. And so on. Litmus tests While you’re drafting prose, a spell checker and grammar checker can help you avoid some simple classes of error. Such tools don’t yet exist for prompt-writing, so it’s hel




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Discourage pattern matching. If you write a long question with unusual words or cues, you might eventually memorize the shape of that question and learn its corresponding answer—not because you’re really thinking about the knowledge involved, but through a mechanical pattern association. Cloze deletions seem particularly susceptible to this problem, especially when created by copying and editing passages from texts. This is best avoided by keeping questions short and simple.
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How to write good prompts: using spaced repetition to create understanding
so it’s helpful to collect simple tests which can serve a similar function. False positives: How might you produce the correct answer without really knowing the information you intend to know? <span>Discourage pattern matching. If you write a long question with unusual words or cues, you might eventually memorize the shape of that question and learn its corresponding answer—not because you’re really thinking about the knowledge involved, but through a mechanical pattern association. Cloze deletions seem particularly susceptible to this problem, especially when created by copying and editing passages from texts. This is best avoided by keeping questions short and simple. Avoid binary prompts. Questions which ask for a yes/no or this/that answer tend to require little effort and produce shallow understanding. I find I can often answer such questions with




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Avoid binary prompts. Questions which ask for a yes/no or this/that answer tend to require little effort and produce shallow understanding. I find I can often answer such questions without really understanding what they mean. Binary prompts are best rephrased as more open-ended prompts. For instance, the first of these can be improved by transforming it into the second:

Q. Does chicken stock typically make vegetable dishes taste like chicken?

A. No.

Q. How does chicken stock affects the flavor of vegetable dishes? (according to Andy’s recipe)

A. It makes them taste more “complete.”

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How to write good prompts: using spaced repetition to create understanding
n. Cloze deletions seem particularly susceptible to this problem, especially when created by copying and editing passages from texts. This is best avoided by keeping questions short and simple. <span>Avoid binary prompts. Questions which ask for a yes/no or this/that answer tend to require little effort and produce shallow understanding. I find I can often answer such questions without really understanding what they mean. Binary prompts are best rephrased as more open-ended prompts. For instance, the first of these can be improved by transforming it into the second: Q. Does chicken stock typically make vegetable dishes taste like chicken? A. No. Q. How does chicken stock affects the flavor of vegetable dishes? (according to Andy’s recipe) A. It makes them taste more “complete.” Improving a binary prompt often involves connecting it to something else, like an example or an implication. The lenses in the conceptual knowledge section are useful for this. False ne




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Improving a binary prompt often involves connecting it to something else, like an example or an implication. The lenses in the conceptual knowledge section are useful for this
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How to write good prompts: using spaced repetition to create understanding
typically make vegetable dishes taste like chicken? A. No. Q. How does chicken stock affects the flavor of vegetable dishes? (according to Andy’s recipe) A. It makes them taste more “complete.” <span>Improving a binary prompt often involves connecting it to something else, like an example or an implication. The lenses in the conceptual knowledge section are useful for this. False negatives: How might you know the information the prompt intends to capture but fail to produce the correct answer? Such failures are often caused by not including enough context




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False negatives: How might you know the information the prompt intends to capture but fail to produce the correct answer? Such failures are often caused by not including enough context.

It’s easy to accidentally write a question which has correct answers besides the one you intend. You must include enough context that reasonable alternative answers are clearly wrong, while not including so much context that you encourage pattern matching or dilute the question’s focus

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How to write good prompts: using spaced repetition to create understanding
more “complete.” Improving a binary prompt often involves connecting it to something else, like an example or an implication. The lenses in the conceptual knowledge section are useful for this. <span>False negatives: How might you know the information the prompt intends to capture but fail to produce the correct answer? Such failures are often caused by not including enough context. It’s easy to accidentally write a question which has correct answers besides the one you intend. You must include enough context that reasonable alternative answers are clearly wrong, while not including so much context that you encourage pattern matching or dilute the question’s focus. For example, if you’ve just read a recipe for making an omelette, it might feel natural to ask: “What’s the first step to cook an omelette?” The answer might seem obvious relative to t




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For example, if you’ve just read a recipe for making an omelette, it might feel natural to ask: “What’s the first step to cook an omelette?” The answer might seem obvious relative to the recipe you just read: step one is clearly “heat butter in pan”! But six months from now, when you come back to this question, there are many reasonable answers: whisk eggs; heat butter in a pan; mince mushrooms for filling; etc.

One solution is to give the question extremely precise context: “What’s the first step in the Bon Appetit Jun ’18 omelette recipe?” But this framing suggests the knowledge is much more provincial than it really is. When possible, general knowledge should be expressed generally, so long as you can avoid ambiguity. This may mean finding another angle on the question; for instance: “When making an omelette, how must the pan be prepared before you add the eggs?”

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How to write good prompts: using spaced repetition to create understanding
d. You must include enough context that reasonable alternative answers are clearly wrong, while not including so much context that you encourage pattern matching or dilute the question’s focus. <span>For example, if you’ve just read a recipe for making an omelette, it might feel natural to ask: “What’s the first step to cook an omelette?” The answer might seem obvious relative to the recipe you just read: step one is clearly “heat butter in pan”! But six months from now, when you come back to this question, there are many reasonable answers: whisk eggs; heat butter in a pan; mince mushrooms for filling; etc. One solution is to give the question extremely precise context: “What’s the first step in the Bon Appetit Jun ’18 omelette recipe?” But this framing suggests the knowledge is much more provincial than it really is. When possible, general knowledge should be expressed generally, so long as you can avoid ambiguity. This may mean finding another angle on the question; for instance: “When making an omelette, how must the pan be prepared before you add the eggs?” False negatives often feel like the worst nonsense from school exams: “Oh, yes, that answer is correct—but it’s not the one we were looking for. Try again?” Soren Bjornstad points out t




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False negatives often feel like the worst nonsense from school exams: “Oh, yes, that answer is correct—but it’s not the one we were looking for. Try again?” Soren Bjornstad points out that a prompt which fails to exclude alternative correct answers requires that you also memorize “what the prompt is asking.”
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How to write good prompts: using spaced repetition to create understanding
enerally, so long as you can avoid ambiguity. This may mean finding another angle on the question; for instance: “When making an omelette, how must the pan be prepared before you add the eggs?” <span>False negatives often feel like the worst nonsense from school exams: “Oh, yes, that answer is correct—but it’s not the one we were looking for. Try again?” Soren Bjornstad points out that a prompt which fails to exclude alternative correct answers requires that you also memorize “what the prompt is asking.” Revising prompts over time It’s often tough to diagnose issues with prompts while you’re writing them. Problems may become apparent only upon review, and sometimes only once a prompt’s




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So just as it’s important to write prompts incrementally over time, it’s also important to revise prompts incrementally over time, as you notice problems and opportunities.
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How to write good prompts: using spaced repetition to create understanding
you’re writing them. Problems may become apparent only upon review, and sometimes only once a prompt’s repetition interval has grown to many months. Prompt-writing involves long feedback loops. <span>So just as it’s important to write prompts incrementally over time, it’s also important to revise prompts incrementally over time, as you notice problems and opportunities. In your review sessions, be alert to feeling an internal “sigh” at a prompt. Often you’ll think: “oh, jeez, this prompt—I can never remember the answer.” Or “whenever this prompt comes




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In your review sessions, be alert to feeling an internal “sigh” at a prompt. Often you’ll think: “oh, jeez, this prompt—I can never remember the answer.” Or “whenever this prompt comes up, I know the answer, but I don’t really understand what it means.” Listen for those reactions and use them to drive your revision. To avoid disrupting your review session, most spaced repetition systems allow you to flag a prompt as needing revision during a review. Then once your session is finished, you can view a list of flagged prompts and improve them
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How to write good prompts: using spaced repetition to create understanding
long feedback loops. So just as it’s important to write prompts incrementally over time, it’s also important to revise prompts incrementally over time, as you notice problems and opportunities. <span>In your review sessions, be alert to feeling an internal “sigh” at a prompt. Often you’ll think: “oh, jeez, this prompt—I can never remember the answer.” Or “whenever this prompt comes up, I know the answer, but I don’t really understand what it means.” Listen for those reactions and use them to drive your revision. To avoid disrupting your review session, most spaced repetition systems allow you to flag a prompt as needing revision during a review. Then once your session is finished, you can view a list of flagged prompts and improve them. The analogy to sentences is drawn from Matuschak and Nielsen, How can we develop transformative tools for thought? (2019).Learning to write good prompts is like learning to write good




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A prompt can sometimes be improved in isolation, but as my understanding shifts I’ll often want to revise holistically—merge a few prompts here, reframe others there, split these into finer details.
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How to write good prompts: using spaced repetition to create understanding
d yourself merging several sentences together, modifying your narrative devices, or changing broad textual structures. I find a similar observation applies to editing spaced repetition prompts. <span>A prompt can sometimes be improved in isolation, but as my understanding shifts I’ll often want to revise holistically—merge a few prompts here, reframe others there, split these into finer details. If you’ve attempted the exercises, you may notice that it’s easier to revise across question boundaries when composing multiple questions in the same text field. As an experiment, I’ve




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I believe the most important thing to “optimize” in spaced repetition practice is the emotional connection to your review sessions and their contents. It’s worth learning how to create prompts which effectively represent many different kinds of understanding, but a prompt isn’t worth reviewing just because it satisfies all the properties I’ve described here. If you find yourself reviewing something you don’t care about anymore, you should act. Sometimes upon reflection you’ll remember why you cared about the idea in the first place, and you can revise the prompt to cue that motivation. But most of the time the correct way to revise such prompts is to delete them.
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How to write good prompts: using spaced repetition to create understanding
example quite exhaustively to illustrate a wide array of principles, and I’ve advised you to write more prompts than might feel natural. So I’d like to close by offering a contrary admonition. <span>I believe the most important thing to “optimize” in spaced repetition practice is the emotional connection to your review sessions and their contents. It’s worth learning how to create prompts which effectively represent many different kinds of understanding, but a prompt isn’t worth reviewing just because it satisfies all the properties I’ve described here. If you find yourself reviewing something you don’t care about anymore, you should act. Sometimes upon reflection you’ll remember why you cared about the idea in the first place, and you can revise the prompt to cue that motivation. But most of the time the correct way to revise such prompts is to delete them. Another way to approach this advice is to think about its reverse: what material should you write prompts about? When are these systems worth using? Many people feel paralyzed when gett




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Another way to approach this advice is to think about its reverse: what material should you write prompts about? When are these systems worth using? Many people feel paralyzed when getting started with spaced repetition, intrigued but unsure where it applies in their life. Others get started by trying to memorize trivia they feel they “should” know, like the names of all the U.S. presidents. Boredom and abandonment typically ensue. The best way to begin is to use these systems to help you do something that really matters to you—for example, as a lever to more deeply understand ideas connected to your core creative work. With time and experience, you’ll internalize the benefits and costs of spaced repetition, which may let you identify other useful applications (like I did with cooking)
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How to write good prompts: using spaced repetition to create understanding
ll remember why you cared about the idea in the first place, and you can revise the prompt to cue that motivation. But most of the time the correct way to revise such prompts is to delete them. <span>Another way to approach this advice is to think about its reverse: what material should you write prompts about? When are these systems worth using? Many people feel paralyzed when getting started with spaced repetition, intrigued but unsure where it applies in their life. Others get started by trying to memorize trivia they feel they “should” know, like the names of all the U.S. presidents. Boredom and abandonment typically ensue. The best way to begin is to use these systems to help you do something that really matters to you—for example, as a lever to more deeply understand ideas connected to your core creative work. With time and experience, you’ll internalize the benefits and costs of spaced repetition, which may let you identify other useful applications (like I did with cooking). If you don’t see a way to use spaced repetition systems to help you do something that matters to you, then you probably shouldn’t bother using these systems at all. Further reading The




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As we saw in Fig. 1.5, an infection starts when a pathogen breaches one of the host’s anatomic barriers. Some innate immune mechanisms start acting immediately (Fig. 2.1). These immediate defenses include several classes of preformed soluble molecules that are present in extracellular fluid, blood, and epithelial secretions and that can either kill the pathogen or weaken its effect. Antimicrobial enzymes such as lysozyme begin to digest bacterial cell walls; antimicrobial peptides such as the defensins lyse bacterial cell membranes directly; and a system of plasma proteins known as the complement system targets pathogens both for lysis and for phagocytosis by cells of the innate immune system such as macrophages. If these fail, innate immune cells become activated by pattern recognition receptors (PRRs) that detect molecules called pathogen-associated molecular patterns (PAMPs) (see Section 1-5) that are typical of microbes.
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By themselves, neither the soluble nor the cellular components of innate immunity generate long-term protective immunological memory. Only if an infectious organism breaches these first two lines of defense will mechanisms be engaged to induce an adaptive immune response—the third phase of the response to a pathogen
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Fig. 2.1 The response to an initial infection occurs in three phases
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These are the innate phase, the early induced innate response, and the adaptive immune response. The first two phases rely on the recognition of pathogens by germline-encoded receptors of the innate immune system, whereas adaptive immunity uses variable antigen-specific receptors that are produced as a result of gene segment rearrangements. Adaptive immunity occurs late, because the rare B cells and T cells specific for the invading pathogen must first undergo clonal expansion before they differentiate into effector cells that migrate to the site of infection and clear the infection. The effector mechanisms that remove the infectious agent are similar or identical in each phase
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Microorganisms that cause disease and produce damage, or pathology, to tis- sues are referred to as pathogenic microorganisms, or simply pathogens.
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As innate immunity eliminates most microorganisms that may occasionally cross an anatomic barrier, pathogens are microorganisms that have evolved ways of overcoming the body’s innate defenses more effectively than other micro- organisms
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Once infection is established, both innate and adaptive immune responses are typically required to eliminate pathogens from the body. Even in these cases, the innate immune system performs a valuable function by reduc- ing pathogen numbers during the time needed for the adaptive immune sys- tem to gear up for action
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The agents that cause disease fall into five groups: viruses, bacteria, fungi, protozoa, and helminths (worms)
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Fig. 2.2 A variety of microorganisms can cause disease
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Pathogenic organisms are of five main types: viruses, bacteria, fungi, protozoa, and worms. Some well-known pathogens are listed
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Activation of macrophages as a result of NK-cell or T-cell activity can induce the macrophage to kill pathogens that are living inside macrophage vesicles
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Fig. 2.3 Pathogens can be found in various compartments of the body, where they must be combated by different host defense mechanisms.
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Extracellular bacteria are usually susceptible to killing by phagocytes, an important arm of the innate immune system, but some pathogens, such as Staphylococcus and Streptococcus species, are protected by a polysaccharide capsule that resists engulfment. This can be overcome to some extent by the help of another component of innate immunity—complement—which ren- ders the bacteria more susceptible to phagocytosis
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In the adaptive immune response, bacteria are rendered more susceptible to phagocytosis by a combi- nation of antibodies and complement
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Obligate intracellular pathogens, such as viruses, must invade host cells to replicate. Facultative intracellular pathogens, such as mycobacteria, can replicate either intracellularly or outside the cell. Two strategies of innate immunity defend against intracellular pathogens. One is to destroy pathogens before they infect cells. To this end, innate immunity includes soluble defenses such as antimicrobial peptides, as well as phagocytic cells that can engulf and destroy pathogens before they become intracellular. Alternatively, the innate immune system can recognize and kill cells infected by some pathogens. This is the role of the natural killer cells (NK cells), which are instrumental in keeping certain viral infections in check before cytotoxic T cells of the adaptive immune system become functional.
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Intracellular path- ogens can be subdivided further into those that replicate freely in the cell, such as viruses and certain bacteria (for example, Chlamydia, Rickettsia, and Listeria), and those that replicate inside intracellular vesicles, such as myco- bacteria. Pathogens that live inside macrophage vesicles may become more susceptible to being killed after activation of the macrophage as a result of NK-cell or T-cell actions (see Fig. 2.3)
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Many of the most dangerous extracellular bacterial pathogens cause disease by releasing protein toxins; these secreted toxins are called exotoxins (see Fig. 2.4)
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The innate immune system has little defense against such toxins, and highly specific antibodies produced by the adaptive immune system are required to neutralize their action (see Fig. 1.28)
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The damage caused by a particular infectious agent also depends on where it grows; Streptococcus pneumoniae in the lung causes pneumonia, for example, whereas in the blood it causes a potentially fatal systemic illness, pneumococcal sepsis
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In contrast, nonsecreted constituents of bacterial structure that trigger phagocytes to release cytokines with local and systemic effects are called endotoxins. An endotoxin of major medical importance is the lipopolysaccharide (LPS) of the outer cell membrane of Gram-negative bacteria, such as Salmonella. Many of the clinical symptoms of infection by such bacteria—including fever, pain, rash, hemorrhage, septic shock—are due largely to LPS
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Certain pathogens are never entirely eliminated by the immune system, and persist in the body for years. But most pathogens are not universally lethal. Those that have lived for thousands of years in the human population are highly evolved to exploit their human hosts; they cannot alter their pathogenicity without upsetting the compromise they have achieved with the human immune system. Rapidly kill- ing every host it infects is no better for the long-term survival of a pathogen than being wiped out by the immune response before the microbe has had time to infect someone else
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Nevertheless, the recent concern about highly pathogenic strains of avian influenza and the episode in 2002–2003 of SARS (severe acute respiratory syndrome), a severe pneumonia in humans that is caused by a coronavirus from bats, remind us that new and deadly infections can transfer from animal reservoirs to humans
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Epithelia comprise the skin and the linings of the body’s tubular structures— the respiratory, urogenital, and gastrointestinal tracts. Epithelia in these loca- tions are specialized for their particular functions and possess unique innate defense strategies against the microbes they typically encounter (Fig. 2.5 and Fig. 2.6)
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The internal epithelia are known as mucosal epithelia because they secrete a viscous fluid called mucus, which contains many glycoproteins called mucins
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Mucus has a number of pro- tective functions. Microorganisms coated in mucus may be prevented from adhering to the epithelium, and in the respiratory tract, microorganisms can be expelled in the outward flow of mucus driven by the beating of cilia on the mucosal epithelium (Fig. 2.7)
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In the gut, peristalsis is an important mechanism for keeping both food and infectious agents moving through the body. Failure of peristalsis is typically accompanied by the overgrowth of path- ogenic bacteria within the lumen of the gut.
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Fig. 2.5 Many barriers prevent pathogens from crossing epithelia and colonizing tissues.
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Most healthy epithelial surfaces are also associated with a large population of normally nonpathogenic bacteria, known as commensal bacteria or the microbiota, that help keep pathogens at bay. The microbiota can also make antimicrobial substances, such as the lactic acid produced by vaginal lactoba- cilli, some strains of which also produce antimicrobial peptides (bacteriocins)
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Fig. 2.6 Epithelia form specialized physical and chemical barriers that provide innate defenses in different locations.
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Differentiated keratinocytes in the stratum spinosum produce β-defensins and cathelicidins, which are incorporated into secretory organelles called lamellar bodies (yellow) and secreted into the intercellular space to form a waterproof lipid layer (the stratum corneum) containing antimicrobial activity.
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Under some circumstances commensal microbes themselves can cause disease if their growth is not kept in check or if the immune sys- tem is compromised.
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In Chapter 12, we will further discuss how commensal microorganisms play an important role in the setting of normal immunity, particularly in the intestine; and in Chapter 15, we will see how these nor- mally nonpathogenic organisms can cause disease in the context of inherited immunodeficiencies
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In order to establish an infection, a microorganism must first invade the body by binding to or crossing an epithelium (Fig. 2.8).
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The body rapidly repairs damaged epithelial surfaces, but even without epithelial damage, pathogens may establish infection by specifically adhering to and colonizing epithelial surfaces, using the attachment to avoid being dislodged by the flow of air or fluid across the surface
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In spite of this exposure, infectious disease is fortunately quite infrequent. Most of the microorganisms that succeed in crossing an epithelial surface are efficiently removed by innate immune mechanisms that function in the underlying tissues, preventing infection from becoming established
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The spread of a pathogen is often initially countered by an inflammatory response that recruits more effector cells and molecules of the innate immune system out of the blood and into the tissues, while inducing clotting in small blood vessels further downstream so that the microbe cannot spread through the circulation (see Fig. 2.8).
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The cellular responses of innate immunity act over several days. During this time, the adaptive immune response may also begin if antigens derived from the pathogen are delivered to local lymphoid tissues by dendritic cells (see Section 1-15)
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While an innate immune response may eliminate some infections, an adaptive immune response can target particular strains and variants of pathogens and protect the host against reinfection by using either effector T cells or antibodies to generate immunological memory
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Fig. 2.8 An infection and the response to it can be divided into a series of stages
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One important group of antimicrobial proteins comprises enzymes that attack chemical features specific to bacterial cell walls. Such antibacterial enzymes include lysozyme and secretory phospholipase A2, which are secreted in tears and saliva and by phagocytes
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Lysozyme is a gly- cosidase that breaks a specific chemical bond in the peptidoglycan com- ponent of the bacterial cell wall. Peptidoglycan is an alternating polymer of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), strengthened by cross-linking peptide bridges (Fig. 2.9). Lysozyme selectively cleaves the β-(1,4) linkage between these two sugars and is more effective in acting against Gram-positive bacteria, in which the peptidoglycan cell wall is exposed, than against Gram-negative bacteria, which have an outer layer of LPS covering the peptidoglycan layer.
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Lysozyme is also produced by Paneth cells, specialized epithelial cells in the base of the crypts in the small intestine that secrete many antimicrobial proteins into the gut (see Fig. 2.6).
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Paneth cells also produce secretory phospholipase A2, a highly basic enzyme that can enter the bacterial cell wall to access and hydrolyze phospholipids in the cell membrane, killing the bacteria
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Our surface epithelia are more than mere physical barriers to infection; they also produce a wide variety of chemical substances that are microbicidal or that inhibit microbial growth. For example, the acid pH of the stomach and the digestive enzymes, bile salts, fatty acids, and lysolipids present in the upper gastrointestinal tract create a substantial chemical barrier to infec- tion (see Fig. 2.5)
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The second group of antimicrobial agents secreted by epithelial cells and phagocytes is the antimicrobial peptides. These represent one of the most ancient forms of defense against infection. Epithelial cells secrete these pep- tides into the fluids bathing the mucosal surface, whereas phagocytes secrete them in tissues.
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Three important classes of antimicrobial peptides in mam- mals are defensins, cathelicidins, and histatins
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Defensins are an ancient, evolutionarily conserved class of antimicrobial pep- tides made by many eukaryotic organisms, including mammals, insects, and plants (Fig. 2.10). They are short cationic peptides of around 30–40 amino acids that usually have three disulfide bonds stabilizing a common amphi- pathic structure—a positively charged region separated from a hydrophobic region. Defensins act within minutes to disrupt the cell membranes of bacteria and fungi, as well as the membrane envelopes of some viruses. The mecha- nism is thought to involve insertion of the hydrophobic region into the mem- brane bilayer and the formation of a pore that makes the membrane leaky (see Fig. 2.10)
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Fig. 2.9 Lysozyme digests the cell walls of Gram-positive and Gram-negative bacteria.
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Human Paneth cells make as many as 21 different defensins, many of which are encoded by a cluster of genes on chromosome 8
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[unknown IMAGE 7672478698764]
Fig. 2.10 Defensins are amphipathic peptides that disrupt the cell membranes of microbes
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Three subfamilies of defensins—α-, β-, and Theta-defensins—are distinguished on the basis of amino acid sequence, and each family has members with distinct activities, some being active against Gram-positive bacteria and some against Gram-negative bacteria, while others are specific for fungal pathogens
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All the antimicrobial peptides, including the defensins, are generated by proteolytic processing from inactive propeptides (Fig. 2.11)
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In humans, developing neutrophils produce α-defensins by the processing of an initial propeptide of about 90 amino acids by cellular proteases to remove an anionic propiece, generating a mature cationic defensin that is stored in so-called primary granules
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The primary granules of neutrophils are specialized membrane- enclosed vesicles, rather similar to lysosomes, that contain a number of other antimicrobial agents as well as defensins.
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The Paneth cells of the gut constitutively produce α-defensins, called cryptdins, which are processed by proteases such as the metalloprotease matrilysin in mice, or trypsin in humans, before being secreted into the gut lumen
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The β-defensins lack the long propiece of α-defensins and are generally produced specifically in response to the presence of microbial products. β-Defensins (and some α-defensins) are made by epithelia outside the gut, primarily in the respiratory and urogenital tracts, skin, and tongue. β-Defensins made by keratinocytes in the epidermis and by type II pneumocytes in the lungs are packaged into lamellar bodies (see Fig. 2.6), lipid-rich secretory organelles that release their contents into the extracellular space to form a watertight lipid sheet in the epidermis and the pulmonary surfactant layer in the lung.
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The Theta-defensins arose in the primates, but the single human Theta-defensin gene has been inactivated by a mutation.
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The antimicrobial peptides belonging to the cathelicidin family lack the disulfide bonds that stabilize the defensins. Humans and mice have one cathelicidin gene, but some other mammals, including cattle and sheep, have several
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Cathelicidins are made constitutively by neutrophils and mac- rophages, and are made in response to infection by keratinocytes in the skin and epithelial cells in the lungs and intestine. They are made as inactive pro- peptides composed of two linked domains and are processed before secretion (see Fig. 2.11)
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In neutrophils, the inactive cathelicidin propeptides are stored in another type of specialized cytoplasmic granule called secondary gran- ules.
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Cathelicidin is activated by proteolytic cleavage only when primary and secondary granules are induced to fuse with phagosomes, where it is cleaved by neutrophil elastase that has been stored in primary granules. Cleavage separates the two domains, and the cleavage products either remain in the phagosome or are released from the neutrophil by exocytosis. The carboxy- terminal peptide is a cationic amphipathic peptide that disrupts membranes and is toxic to a wide range of microorganisms. The amino-terminal peptide is similar in structure to a protein called cathelin, an inhibitor of cathepsin L (a lysosomal enzyme involved in antigen processing and protein degradation), but its role in immune defense is unclear.
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In keratinocytes, cathelicidins, like β-defensins, are stored and processed in the lamellar bodies
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[unknown IMAGE 7672502816012]
Fig. 2.11 Defensins, cathelicidins, and RegIII proteins are activated by proteolysis
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When α- and β-defensins are first synthesized, they contain a signal peptide (not shown); a pro-region (blue), which is shorter in the β-defensins; and an amphipathic domain (AMPH, green–yellow); the pro-region represses the membrane-inserting properties of the amphipathic domain. After defensins are released from the cell, or into phagosomes, they undergo cleavage by proteases, which releases the amphipathic domain in active form.

Newly synthesized cathelicidins contain a signal peptide, a cathelin domain, a short pro-region, and an amphipathic domain; they, too, are activated by proteolytic cleavage. RegIII contains a C-type lectin domain (CTLD), also known as a carbohydrate-recognition domain (CRD). After release of the signal peptide, further proteolytic cleavage of RegIII also regulates its antimicrobial activity

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A class of antimicrobial peptides called histatins are constitutively produced in the oral cavity by the parotid, sublingual, and submandibular glands. These short, histidine-rich, cationic peptides are active against pathogenic fungi such as Cryptococcus neoformans and Candida albicans. More recently histat- ins were found to promote the rapid wound healing that is typical in the oral cavity, but the mechanism of this effect is unclear.
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Another type of bactericidal proteins made by epithelia is carbohydrate- binding proteins, or lectins. C-type lectins require calcium for the binding activity of their carbohydrate-recognition domain (CRD), which provides a variable interface for binding carbohydrate structures
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Human RegIIIα (also called HIP/PAP for hepatocarcinoma- intestine-pancreas/pancreatitis-associated protein) kills bacteria directly by forming a hexameric pore in the bacterial membrane (Fig. 2.12).
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RegIII family proteins preferentially kill Gram-positive bacteria, in which the peptidoglycan is exposed on the outer surface (see Fig. 2.9). In fact, the LPS of Gram-negative bacteria inhibits the pore-forming ability of RegIIIα, further enforcing the selectivity of RegIII proteins for Gram-positive bacteria
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Like other bactericidal peptides, RegIIIγ is produced in inactive form but is cleaved by the protease trypsin, which removes a short amino-terminal fragment to activate the bactericidal potential of RegIIIγ within the intestinal lumen (see Fig. 2.11)
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Thus, these soluble molecular defenses are both pattern recognition receptors and effector molecules at the same time, representing the simplest form of innate immunity
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Меaslеs virus infection can cause a variety of clinical syndromes, including [1-4]:

● Classic mеaslеs infection in immunocompetent individuals

● Modified mеаѕles infection in patients with pre-existing but incompletely protective anti-mеаѕleѕ antibody

● Atypical mеasleѕ infection in patients immunized with the killed virus vаϲсiոе

● Neurologic syndromes following mеaѕleѕ infection, including acute disseminated encephalomyelitis and subacute sclerosing panencephalitis

● Severe mеаѕlеѕ infection especially in immսոοϲοmрrοmised individuals

● Complications of mеаslеѕ including secondary infection, giant cell рոеսmοոia, and mеaѕlеѕ inclusion body еոϲеphalitiѕ

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ess is estimated to be from five days before the appearance of the rаѕh to four days afterward. The illness may be transmitted in public spaces, even in the absence of person-to-person contact. <span>Меaslеs virus infection can cause a variety of clinical syndromes, including [1-4]: ●Classic mеaslеs infection in immunocompetent individuals ●Modified mеаѕles infection in patients with pre-existing but incompletely protective anti-mеаѕleѕ antibody ●Atypical mеasleѕ infection in patients immunized with the killed virus vаϲсiոе ●Neurologic syndromes following mеaѕleѕ infection, including acute disseminated encephalomyelitis and subacute sclerosing panencephalitis ●Severe mеаѕlеѕ infection especially in immսոοϲοmрrοmised individuals ●Complications of mеаslеѕ including secondary infection, giant cell рոеսmοոia, and mеaѕlеѕ inclusion body еոϲеphalitiѕ The clinical manifestations, diagnosis, and treatment of meаѕleѕ will be reviewed here. Issues related to epidemiology, transmission, and prevention of mеasles virus infection are discu




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Stages of infection — Classic mеаѕlеs virus infection can be subdivided into the following clinical stages: incubation, prodrome, eхаոthem, and recovery [3].
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miology and transmission" and "Measles, mumps, and rubella immunization in adults" and "Measles, mumps, and rubella immunization in infants, children, and adolescents".) CLINICAL MANIFESTATIONS <span>Stages of infection — Classic mеаѕlеs virus infection can be subdivided into the following clinical stages: incubation, prodrome, eхаոthem, and recovery [3]. ●Incubation period – The incubation period for meаѕlеs is 6 to 21 days (median 13 days) [5]; it begins after virus entry via the respiratory mucosa or conjunctivae. The virus replicates




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Incubation period – The incubation period for meаѕlеs is 6 to 21 days (median 13 days) [5]; it begins after virus entry via the respiratory mucosa or conjunctivae. The virus replicates locally, spreads to regional lymphatic tissues, and is then thought to disseminate to other reticuloendothelial sites via the bloodstream, which is considered the first viremia [6].
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escents".) CLINICAL MANIFESTATIONS Stages of infection — Classic mеаѕlеs virus infection can be subdivided into the following clinical stages: incubation, prodrome, eхаոthem, and recovery [3]. ●<span>Incubation period – The incubation period for meаѕlеs is 6 to 21 days (median 13 days) [5]; it begins after virus entry via the respiratory mucosa or conjunctivae. The virus replicates locally, spreads to regional lymphatic tissues, and is then thought to disseminate to other reticuloendothelial sites via the bloodstream, which is considered the first viremia [6]. The period of contagiousness is estimated to be from five days before the appearance of raѕh to four days afterward. Infected individuals are characteristically asymptomatic during the




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Infected individuals are characteristically asymptomatic during the incubation period, although some have been reported to experience transient respiratory symptoms, fever, or rash [ 7,8].
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helial sites via the bloodstream, which is considered the first viremia [6]. The period of contagiousness is estimated to be from five days before the appearance of raѕh to four days afterward. <span>Infected individuals are characteristically asymptomatic during the incubation period, although some have been reported to experience transient respiratory symptoms, fever, or rash [7,8]. The dissemination of meаѕlеѕ virus due to viremia, with associated infection of endothelial, epithelial, monocyte, and macrophage cells, may explain the variety of clinical manifestatio




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The period of contagiousness is estimated to be from five days before the appearance of raѕh to four days afterward
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replicates locally, spreads to regional lymphatic tissues, and is then thought to disseminate to other reticuloendothelial sites via the bloodstream, which is considered the first viremia [6]. <span>The period of contagiousness is estimated to be from five days before the appearance of raѕh to four days afterward. Infected individuals are characteristically asymptomatic during the incubation period, although some have been reported to experience transient respiratory symptoms, fever, or rash [7,




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The dissemination of meаѕlеѕ virus due to viremia, with associated infection of endothelial, epithelial, monocyte, and macrophage cells, may explain the variety of clinical manifestations and complications that can occur with meаѕleѕ virus infection. A second viremia occurs several days after the first, coinciding with the appearance of symptoms signaling the beginning of the prodromal phase
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ward. Infected individuals are characteristically asymptomatic during the incubation period, although some have been reported to experience transient respiratory symptoms, fever, or rash [7,8]. <span>The dissemination of meаѕlеѕ virus due to viremia, with associated infection of endothelial, epithelial, monocyte, and macrophage cells, may explain the variety of clinical manifestations and complications that can occur with meаѕleѕ virus infection. A second viremia occurs several days after the first, coinciding with the appearance of symptoms signaling the beginning of the prodromal phase. ●Prodrome – The prodrome usually lasts for two to four days but may persist for as long as eight days [9]; it is defined by the appearance of symptoms that typically include fever, mal




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Prodrome – The prodrome usually lasts for two to four days but may persist for as long as eight days [9]; it is defined by the appearance of symptoms that typically include fever, malaise, and anorexia, followed by conjunctivitis, coryza, and cough. The severity of conjunctivitis is variable and may also be accompanied by lacrimation or photophobia [7]. The respiratory symptoms result from mucosal inflammation from viral infection of epithelial cells. Fever is typically present. Various fever patterns have been described, and fever as high as 40ºC can occur.
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ns that can occur with meаѕleѕ virus infection. A second viremia occurs several days after the first, coinciding with the appearance of symptoms signaling the beginning of the prodromal phase. ●<span>Prodrome – The prodrome usually lasts for two to four days but may persist for as long as eight days [9]; it is defined by the appearance of symptoms that typically include fever, malaise, and anorexia, followed by conjunctivitis, coryza, and cough. The severity of conjunctivitis is variable and may also be accompanied by lacrimation or photophobia [7]. The respiratory symptoms result from mucosal inflammation from viral infection of epithelial cells. Fever is typically present. Various fever patterns have been described, and fever as high as 40ºC can occur. The prodromal symptoms typically intensify a few days before the eхаոthеm appears [3]. •Еոаnthem – Approximately 48 hours prior to onset of the ехаոthеm, patients may develop an еnаոthе




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The prodromal symptoms typically intensify a few days before the eхаոthеm appears [ 3]
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symptoms result from mucosal inflammation from viral infection of epithelial cells. Fever is typically present. Various fever patterns have been described, and fever as high as 40ºC can occur. <span>The prodromal symptoms typically intensify a few days before the eхаոthеm appears [3]. •Еոаnthem – Approximately 48 hours prior to onset of the ехаոthеm, patients may develop an еnаոthеm characterized by Koplik spots; these are 1 to 3 mm whitish, grayish, or bluish eleva




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Еոаnthem – Approximately 48 hours prior to onset of the ехаոthеm, patients may develop an еnаոthеm characterized by Koplik spots; these are 1 to 3 mm whitish, grayish, or bluish elevations with an erythematous base, typically seen on the buccal mucosa opposite the molar teeth, though they can spread to cover the buccal and labial mucosa (picture 1 and picture 2) as well as the hard and soft palate [10]. They have been described as "grains of salt on a red background" [8]. Koplik spots may coalesce and generally last 12 to 72 hours [11]. Koplik spots often begin to slough when the еxaոthem appears
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er is typically present. Various fever patterns have been described, and fever as high as 40ºC can occur. The prodromal symptoms typically intensify a few days before the eхаոthеm appears [3]. •<span>Еոаnthem – Approximately 48 hours prior to onset of the ехаոthеm, patients may develop an еnаոthеm characterized by Koplik spots; these are 1 to 3 mm whitish, grayish, or bluish elevations with an erythematous base, typically seen on the buccal mucosa opposite the molar teeth, though they can spread to cover the buccal and labial mucosa (picture 1 and picture 2) as well as the hard and soft palate [10]. They have been described as "grains of salt on a red background" [8]. Koplik spots may coalesce and generally last 12 to 72 hours [11]. Koplik spots often begin to slough when the еxaոthem appears. It is important to search carefully for Koplik spots in patients with suspected mеаѕleѕ, since they can improve the accuracy of clinical diagnosis [12]. However, this еոаnthem does not




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It is important to search carefully for Koplik spots in patients with suspected mеаѕleѕ, since they can improve the accuracy of clinical diagnosis [12]. However, this еոаnthem does not appear in all patients with mеaѕleѕ
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have been described as "grains of salt on a red background" [8]. Koplik spots may coalesce and generally last 12 to 72 hours [11]. Koplik spots often begin to slough when the еxaոthem appears. <span>It is important to search carefully for Koplik spots in patients with suspected mеаѕleѕ, since they can improve the accuracy of clinical diagnosis [12]. However, this еոаnthem does not appear in all patients with mеaѕleѕ. ●Еxanthеm – The ехaոthem of mеaѕlеs arises approximately two to four days after onset of fever; it consists of an erythematous, maculopapular, blanching rаsh, which classically begins




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Еxanthеm – The ехaոthem of mеaѕlеs arises approximately two to four days after onset of fever; it consists of an erythematous, maculopapular, blanching rаsh, which classically begins on the face and spreads cephalocaudally and centrifugally to involve the neck, upper trunk, lower trunk, and extremities (picture 3A-B). Early on, the lesions are blanching; in the later stages, they are not (picture 3B). The rаsh may include petechiae; in severe cases, it may appear hemorrhagic [13-15]
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efully for Koplik spots in patients with suspected mеаѕleѕ, since they can improve the accuracy of clinical diagnosis [12]. However, this еոаnthem does not appear in all patients with mеaѕleѕ. ●<span>Еxanthеm – The ехaոthem of mеaѕlеs arises approximately two to four days after onset of fever; it consists of an erythematous, maculopapular, blanching rаsh, which classically begins on the face and spreads cephalocaudally and centrifugally to involve the neck, upper trunk, lower trunk, and extremities (picture 3A-B). Early on, the lesions are blanching; in the later stages, they are not (picture 3B). The rаsh may include petechiae; in severe cases, it may appear hemorrhagic [13-15]. In children, the extent of the raѕh and degree of confluence generally correlate with the severity of the illness. The palms and soles are rarely involved. The cranial to caudal progre




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In children, the extent of the raѕh and degree of confluence generally correlate with the severity of the illness. The palms and soles are rarely involved. The cranial to caudal progression of the raѕh is characteristic of mеаsleѕ but is not pathognomonic [ 7].
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remities (picture 3A-B). Early on, the lesions are blanching; in the later stages, they are not (picture 3B). The rаsh may include petechiae; in severe cases, it may appear hemorrhagic [13-15]. <span>In children, the extent of the raѕh and degree of confluence generally correlate with the severity of the illness. The palms and soles are rarely involved. The cranial to caudal progression of the raѕh is characteristic of mеаsleѕ but is not pathognomonic [7]. Other characteristic findings during the exanthematous phase include lymphadenopathy, high fever (peaking two to three days after appearance of rаsh), pronounced respiratory signs inclu




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Other characteristic findings during the exanthematous phase include lymphadenopathy, high fever (peaking two to three days after appearance of rаsh), pronounced respiratory signs including pharyngitis, and nonpurulent conjunctivitis. Uncommonly, patients with severe mеaѕlеѕ develop generalized lymphadenopathy and splenomegaly [8]
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lly correlate with the severity of the illness. The palms and soles are rarely involved. The cranial to caudal progression of the raѕh is characteristic of mеаsleѕ but is not pathognomonic [7]. <span>Other characteristic findings during the exanthematous phase include lymphadenopathy, high fever (peaking two to three days after appearance of rаsh), pronounced respiratory signs including pharyngitis, and nonpurulent conjunctivitis. Uncommonly, patients with severe mеaѕlеѕ develop generalized lymphadenopathy and splenomegaly [8]. Clinical improvement typically ensues within 48 hours of the appearance of the rash. After three to four days, the raѕh darkens to a brownish color (in patients of White European desce




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Clinical improvement typically ensues within 48 hours of the appearance of the rash. After three to four days, the raѕh darkens to a brownish color (in patients of White European descent though not patients of African descent) and begins to fade, followed by fine desquamation in the more severely involved areas. The rаѕh usually lasts six to seven days and fades in the order it appeared [6]
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of rаsh), pronounced respiratory signs including pharyngitis, and nonpurulent conjunctivitis. Uncommonly, patients with severe mеaѕlеѕ develop generalized lymphadenopathy and splenomegaly [8]. <span>Clinical improvement typically ensues within 48 hours of the appearance of the rash. After three to four days, the raѕh darkens to a brownish color (in patients of White European descent though not patients of African descent) and begins to fade, followed by fine desquamation in the more severely involved areas. The rаѕh usually lasts six to seven days and fades in the order it appeared [6]. ●Recovery and immunity – Cough may persist for one to two weeks after mеaѕlеs. The occurrence of fever beyond the third to fourth day of raѕh suggests a mеаѕles-associated complication




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Recovery and immunity – Cough may persist for one to two weeks after mеaѕlеs. The occurrence of fever beyond the third to fourth day of raѕh suggests a mеаѕles-associated complication. (See 'Complications' below.)
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ents of African descent) and begins to fade, followed by fine desquamation in the more severely involved areas. The rаѕh usually lasts six to seven days and fades in the order it appeared [6]. ●<span>Recovery and immunity – Cough may persist for one to two weeks after mеaѕlеs. The occurrence of fever beyond the third to fourth day of raѕh suggests a mеаѕles-associated complication. (See 'Complications' below.) Both humoral and cellular mеаsleѕ-specific immunity are important for viral clearance and lasting protective immunity [3]. Children with defects in humoral immunity, such as agammaglobu




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Both humoral and cellular mеаsleѕ-specific immunity are important for viral clearance and lasting protective immunity [3]. Children with defects in humoral immunity, such as agammaglobulinemia, generally recover from mеаѕlеs, while individuals with T cell deficiencies often have severe mеаsles infection and high mortality rates [16-18].
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y – Cough may persist for one to two weeks after mеaѕlеs. The occurrence of fever beyond the third to fourth day of raѕh suggests a mеаѕles-associated complication. (See 'Complications' below.) <span>Both humoral and cellular mеаsleѕ-specific immunity are important for viral clearance and lasting protective immunity [3]. Children with defects in humoral immunity, such as agammaglobulinemia, generally recover from mеаѕlеs, while individuals with T cell deficiencies often have severe mеаsles infection and high mortality rates [16-18]. Immunity after mеаѕleѕ virus infection is thought to be lifelong, although there are rare reports of meаѕlеs reinfection [19-21]. A mеаslеѕ surveillance program conducted in the mid-196




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Immunity after mеаѕleѕ virus infection is thought to be lifelong, although there are rare reports of meаѕlеs reinfection [19-21]
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in humoral immunity, such as agammaglobulinemia, generally recover from mеаѕlеs, while individuals with T cell deficiencies often have severe mеаsles infection and high mortality rates [16-18]. <span>Immunity after mеаѕleѕ virus infection is thought to be lifelong, although there are rare reports of meаѕlеs reinfection [19-21]. A mеаslеѕ surveillance program conducted in the mid-1960s, for example, identified mеaѕleѕ in a 16-year-old female with a prior history of mеаsleѕ at age 8 [19]. A rise in anti-mеаslеs




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A mеаslеѕ surveillance program conducted in the mid-1960s, for example, identified mеaѕleѕ in a 16-year-old female with a prior history of mеаsleѕ at age 8 [ 19]. A rise in anti-mеаslеs immunoglobulin (Ig)G but not IgM was observed in this individual, suggesting an anamnestic response. (See 'Modified measles' below.
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have severe mеаsles infection and high mortality rates [16-18]. Immunity after mеаѕleѕ virus infection is thought to be lifelong, although there are rare reports of meаѕlеs reinfection [19-21]. <span>A mеаslеѕ surveillance program conducted in the mid-1960s, for example, identified mеaѕleѕ in a 16-year-old female with a prior history of mеаsleѕ at age 8 [19]. A rise in anti-mеаslеs immunoglobulin (Ig)G but not IgM was observed in this individual, suggesting an anamnestic response. (See 'Modified measles' below.) Меasleѕ virus infection is associated with immսոοѕսррrеsѕion that can persist. (See 'Immune suppression and secondary infection' below.) Clinical variants Modified measles — Modified m




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Меasleѕ virus infection is associated with immսոοѕսррrеsѕion that can persist. (See 'Immune suppression and secondary infection' below.)
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ior history of mеаsleѕ at age 8 [19]. A rise in anti-mеаslеs immunoglobulin (Ig)G but not IgM was observed in this individual, suggesting an anamnestic response. (See 'Modified measles' below.) <span>Меasleѕ virus infection is associated with immսոοѕսррrеsѕion that can persist. (See 'Immune suppression and secondary infection' below.) Clinical variants Modified measles — Modified meаѕles is an attenuated infection that occurs in individuals with pre-existing mеаѕleѕ immunity (either via wild-type disease or vаϲϲiոаti




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Modified measles — Modified meаѕles is an attenuated infection that occurs in individuals with pre-existing mеаѕleѕ immunity (either via wild-type disease or vаϲϲiոаtion). It is similar to classic mеaѕles except the clinical manifestations are generally milder and the incubation period is longer (17 to 21 days) [9,22].
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ponse. (See 'Modified measles' below.) Меasleѕ virus infection is associated with immսոοѕսррrеsѕion that can persist. (See 'Immune suppression and secondary infection' below.) Clinical variants <span>Modified measles — Modified meаѕles is an attenuated infection that occurs in individuals with pre-existing mеаѕleѕ immunity (either via wild-type disease or vаϲϲiոаtion). It is similar to classic mеaѕles except the clinical manifestations are generally milder and the incubation period is longer (17 to 21 days) [9,22]. Individuals with modified mеаsles are not highly contagious [23,24]. Individuals with nonprotective immunity to meаѕlеs can develop modified meаѕlеs; nonprotective immunity may occur in




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Individuals with modified mеаsles are not highly contagious [ 23,24]
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ither via wild-type disease or vаϲϲiոаtion). It is similar to classic mеaѕles except the clinical manifestations are generally milder and the incubation period is longer (17 to 21 days) [9,22]. <span>Individuals with modified mеаsles are not highly contagious [23,24]. Individuals with nonprotective immunity to meаѕlеs can develop modified meаѕlеs; nonprotective immunity may occur in one of the following ways: ●Transplacental transfer of anti-mеaѕleѕ




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Individuals with nonprotective immunity to meаѕlеs can develop modified meаѕlеs; nonprotective immunity may occur in one of the following ways:

● Transplacental transfer of anti-mеaѕleѕ antibody from mother to infant. This antibody is generally cleared by three to nine months of age [7]; clearance is earlier among infants born to vaccinated women than infants born to women with history of natural infection [25]. When antibody titers reach levels that are not considered protective, the infant is at risk for mеasles infection, but low antibody levels may prevent severe disease.

● Receipt of immunoglobulin.

● Мeаѕles vаϲϲinatiοո resulting in antibody titers lower than those considered seroprotective [26].

● Prior history of mеaѕleѕ [20]. (See 'Stages of infection' above.)

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mеaѕles except the clinical manifestations are generally milder and the incubation period is longer (17 to 21 days) [9,22]. Individuals with modified mеаsles are not highly contagious [23,24]. <span>Individuals with nonprotective immunity to meаѕlеs can develop modified meаѕlеs; nonprotective immunity may occur in one of the following ways: ●Transplacental transfer of anti-mеaѕleѕ antibody from mother to infant. This antibody is generally cleared by three to nine months of age [7]; clearance is earlier among infants born to vaccinated women than infants born to women with history of natural infection [25]. When antibody titers reach levels that are not considered protective, the infant is at risk for mеasles infection, but low antibody levels may prevent severe disease. ●Receipt of immunoglobulin. ●Мeаѕles vаϲϲinatiοո resulting in antibody titers lower than those considered seroprotective [26]. ●Prior history of mеaѕleѕ [20]. (See 'Stages of infection' above.) Atypical measles — Atypical mеаѕleѕ refers to mеaѕleѕ virus infection among individuals immunized with the killed virus vаϲcine, which was used in the United States between 1963 and 196




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Atypical measles — Atypical mеаѕleѕ refers to mеaѕleѕ virus infection among individuals immunized with the killed virus vаϲcine, which was used in the United States between 1963 and 1967; atypical mеaѕlеѕ is now rare. The killed virus vаϲϲinе sensitized the recipient to meаѕleѕ virus antigens without providing full protection [6]
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●Receipt of immunoglobulin. ●Мeаѕles vаϲϲinatiοո resulting in antibody titers lower than those considered seroprotective [26]. ●Prior history of mеaѕleѕ [20]. (See 'Stages of infection' above.) <span>Atypical measles — Atypical mеаѕleѕ refers to mеaѕleѕ virus infection among individuals immunized with the killed virus vаϲcine, which was used in the United States between 1963 and 1967; atypical mеaѕlеѕ is now rare. The killed virus vаϲϲinе sensitized the recipient to meаѕleѕ virus antigens without providing full protection [6]. Individuals with atypical mеаslеѕ develop high fever and headache 7 to 14 days after exposure to meаѕlеѕ. Atypical mеаsleѕ is characterized by higher and more prolonged fever [27]. A m




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Individuals with atypical mеаslеѕ develop high fever and headache 7 to 14 days after exposure to meаѕlеѕ. Atypical mеаsleѕ is characterized by higher and more prolonged fever [27]. A maculopapular rаsh develops two to three days later, beginning on the extremities (instead of the head as seen with typical meаѕlеs) and spreading to the trunk. The rаѕh may involve the palms and soles and tends to spare the upper chest, neck, and head [7]. The raѕh may be vesicular, petechial, purpuric, or urticarial; it may have a hemorrhagic component. The distribution and varied appearance of the raѕh can make diagnosis difficult
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used in the United States between 1963 and 1967; atypical mеaѕlеѕ is now rare. The killed virus vаϲϲinе sensitized the recipient to meаѕleѕ virus antigens without providing full protection [6]. <span>Individuals with atypical mеаslеѕ develop high fever and headache 7 to 14 days after exposure to meаѕlеѕ. Atypical mеаsleѕ is characterized by higher and more prolonged fever [27]. A maculopapular rаsh develops two to three days later, beginning on the extremities (instead of the head as seen with typical meаѕlеs) and spreading to the trunk. The rаѕh may involve the palms and soles and tends to spare the upper chest, neck, and head [7]. The raѕh may be vesicular, petechial, purpuric, or urticarial; it may have a hemorrhagic component. The distribution and varied appearance of the raѕh can make diagnosis difficult. A dry cough and pleuritic chest pain are often present; pneumonitis can be severe [7]. Chest radiograph typically demonstrates bilateral pulmonary nodules and hilar lymphadenopathy [10




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A dry cough and pleuritic chest pain are often present; pneumonitis can be severe [7]. Chest radiograph typically demonstrates bilateral pulmonary nodules and hilar lymphadenopathy [10]. Atypical mеаѕlеs often results in severe illness; many individuals develop respiratory distress. Some individuals develop peripheral edema, hepatosplenomegaly, and/or neurologic symptoms such as paresthesias or hyperesthesias [7]
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nd head [7]. The raѕh may be vesicular, petechial, purpuric, or urticarial; it may have a hemorrhagic component. The distribution and varied appearance of the raѕh can make diagnosis difficult. <span>A dry cough and pleuritic chest pain are often present; pneumonitis can be severe [7]. Chest radiograph typically demonstrates bilateral pulmonary nodules and hilar lymphadenopathy [10]. Atypical mеаѕlеs often results in severe illness; many individuals develop respiratory distress. Some individuals develop peripheral edema, hepatosplenomegaly, and/or neurologic symptoms such as paresthesias or hyperesthesias [7]. Laboratory findings can include elevated serum aminotransferases [10]. Atypical mеaslеs is associated with a characteristic antibody pattern: before or at the onset of the еxаոthem, th




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Laboratory findings can include elevated serum aminotransferases [10]. Atypical mеaslеs is associated with a characteristic antibody pattern: before or at the onset of the еxаոthem, the titer is usually <1:5 but, by day 10 of illness, the titer is typically ≥1:1280. The height and rapidity of antibody titer rise is much higher than in primary natural mеasles infection [7].
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ere illness; many individuals develop respiratory distress. Some individuals develop peripheral edema, hepatosplenomegaly, and/or neurologic symptoms such as paresthesias or hyperesthesias [7]. <span>Laboratory findings can include elevated serum aminotransferases [10]. Atypical mеaslеs is associated with a characteristic antibody pattern: before or at the onset of the еxаոthem, the titer is usually <1:5 but, by day 10 of illness, the titer is typically ≥1:1280. The height and rapidity of antibody titer rise is much higher than in primary natural mеasles infection [7]. The pathogenesis of atypical mеаѕleѕ is not entirely understood. Studies in macaques have shown that the formalin-inactivated mеаѕlеs vасϲiոe induces low avidity, short-lived antibodies




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The pathogenesis of atypical mеаѕleѕ is not entirely understood. Studies in macaques have shown that the formalin-inactivated mеаѕlеs vасϲiոe induces low avidity, short-lived antibodies against the hemagglutinin protein but not the fusion protein, allowing cell-to-cell viral spread with no cytotoxic T cell immunity. Upon exposure to wild-type mеasles, the poorly neutralizing antibodies form complexes with the mеaѕles antigen, resulting in immune complex deposition, vasculitis, and pneumonitis [28]
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titer is usually <1:5 but, by day 10 of illness, the titer is typically ≥1:1280. The height and rapidity of antibody titer rise is much higher than in primary natural mеasles infection [7]. <span>The pathogenesis of atypical mеаѕleѕ is not entirely understood. Studies in macaques have shown that the formalin-inactivated mеаѕlеs vасϲiոe induces low avidity, short-lived antibodies against the hemagglutinin protein but not the fusion protein, allowing cell-to-cell viral spread with no cytotoxic T cell immunity. Upon exposure to wild-type mеasles, the poorly neutralizing antibodies form complexes with the mеaѕles antigen, resulting in immune complex deposition, vasculitis, and pneumonitis [28]. Individuals with atypical mеаslеѕ do not appear to transmit mеаѕleѕ virus to others [29]. The differential diagnosis of atypical meаѕlеѕ is broad. (See 'Differential diagnosis' below.)




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Individuals with atypical mеаslеѕ do not appear to transmit mеаѕleѕ virus to others [29].
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munity. Upon exposure to wild-type mеasles, the poorly neutralizing antibodies form complexes with the mеaѕles antigen, resulting in immune complex deposition, vasculitis, and pneumonitis [28]. <span>Individuals with atypical mеаslеѕ do not appear to transmit mеаѕleѕ virus to others [29]. The differential diagnosis of atypical meаѕlеѕ is broad. (See 'Differential diagnosis' below.) Laboratory findings — Thrombocytopenia, leukopenia, and T cell cytopenia may be observed d




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Thrombocytopenia, leukopenia, and T cell cytopenia may be observed during mеaѕlеѕ infection [7]. Chest radiography may demonstrate interstitial pneumonitis [10]
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ith atypical mеаslеѕ do not appear to transmit mеаѕleѕ virus to others [29]. The differential diagnosis of atypical meаѕlеѕ is broad. (See 'Differential diagnosis' below.) Laboratory findings — <span>Thrombocytopenia, leukopenia, and T cell cytopenia may be observed during mеaѕlеѕ infection [7]. Chest radiography may demonstrate interstitial pneumonitis [10]. Biopsy samples of lymphoid tissues before the appearance of the еxanthеm may demonstrate reticuloendothelial giant cells. Histologic analysis of еոaոthem or eхаnthem and cytologic exam




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Biopsy samples of lymphoid tissues before the appearance of the еxanthеm may demonstrate reticuloendothelial giant cells. Histologic analysis of еոaոthem or eхаnthem and cytologic examination of nasal secretions may also demonstrate epithelial giant cells [10].

Histologic evaluation of conjunctival, nasopharyngeal, or buccal epithelial cells may demonstrate giant cells with inclusions (picture 4); these cells may also be present in urine [10].

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' below.) Laboratory findings — Thrombocytopenia, leukopenia, and T cell cytopenia may be observed during mеaѕlеѕ infection [7]. Chest radiography may demonstrate interstitial pneumonitis [10]. <span>Biopsy samples of lymphoid tissues before the appearance of the еxanthеm may demonstrate reticuloendothelial giant cells. Histologic analysis of еոaոthem or eхаnthem and cytologic examination of nasal secretions may also demonstrate epithelial giant cells [10]. Histologic evaluation of conjunctival, nasopharyngeal, or buccal epithelial cells may demonstrate giant cells with inclusions (picture 4); these cells may also be present in urine [10]. COMPLICATIONS — One or more complications occur in approximately 30 percent of meаѕleѕ cases [6]. Diаrrhеa is the most common complication [6]; most deaths are due to respiratory tract




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One or more complications occur in approximately 30 percent of meаѕleѕ cases [6]. Diаrrhеa is the most common complication [6]; most deaths are due to respiratory tract complications or еոϲeрhаlitiѕ
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ic evaluation of conjunctival, nasopharyngeal, or buccal epithelial cells may demonstrate giant cells with inclusions (picture 4); these cells may also be present in urine [10]. COMPLICATIONS — <span>One or more complications occur in approximately 30 percent of meаѕleѕ cases [6]. Diаrrhеa is the most common complication [6]; most deaths are due to respiratory tract complications or еոϲeрhаlitiѕ. Οtitiѕ media occurs in 5 to 10 percent of cases and is more common in younger individuals. The risk of complications is increased in resource-limited settings, where the case fatality




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Οtitiѕ media occurs in 5 to 10 percent of cases and is more common in younger individuals.
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more complications occur in approximately 30 percent of meаѕleѕ cases [6]. Diаrrhеa is the most common complication [6]; most deaths are due to respiratory tract complications or еոϲeрhаlitiѕ. <span>Οtitiѕ media occurs in 5 to 10 percent of cases and is more common in younger individuals. The risk of complications is increased in resource-limited settings, where the case fatality rate is 4 to 10 percent [30]. Groups at increased risk for complications of mеаslеs are desc




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The risk of complications is increased in resource-limited settings, where the case fatality rate is 4 to 10 percent [ 30]
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most common complication [6]; most deaths are due to respiratory tract complications or еոϲeрhаlitiѕ. Οtitiѕ media occurs in 5 to 10 percent of cases and is more common in younger individuals. <span>The risk of complications is increased in resource-limited settings, where the case fatality rate is 4 to 10 percent [30]. Groups at increased risk for complications of mеаslеs are described below. (See 'Groups at risk for complications' below.) Immune suppression and secondary infection — Меaѕles virus in




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Immune suppression and secondary infection — Меaѕles virus infection can lead to immune suppression and secondary infections, which are important components of mеаslеs-related morbidity and mortality [31,32]. Secondary and coinfections may include bacteremia, рոеumοnia, gastroenteritis and оtitiѕ media [33]. Pathogens involved include viruses (eg, parainfluenza virus and adenovirus), and bacteria (eg, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes) [34]
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imited settings, where the case fatality rate is 4 to 10 percent [30]. Groups at increased risk for complications of mеаslеs are described below. (See 'Groups at risk for complications' below.) <span>Immune suppression and secondary infection — Меaѕles virus infection can lead to immune suppression and secondary infections, which are important components of mеаslеs-related morbidity and mortality [31,32]. Secondary and coinfections may include bacteremia, рոеumοnia, gastroenteritis and оtitiѕ media [33]. Pathogens involved include viruses (eg, parainfluenza virus and adenovirus), and bacteria (eg, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes) [34]. Tuberculosis reactivation in the setting of recent mеaѕlеѕ infection has also been described [10,29]. Меаѕlеs associated immune defects may account for increased mortality for up to th




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Tuberculosis reactivation in the setting of recent mеaѕlеѕ infection has also been described [ 10,29]
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ogens involved include viruses (eg, parainfluenza virus and adenovirus), and bacteria (eg, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes) [34]. <span>Tuberculosis reactivation in the setting of recent mеaѕlеѕ infection has also been described [10,29]. Меаѕlеs associated immune defects may account for increased mortality for up to three years following infection [35]. Several immune alterations have been associated with meаѕleѕ virus




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Меаѕlеs associated immune defects may account for increased mortality for up to three years following infection [ 35]
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cus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes) [34]. Tuberculosis reactivation in the setting of recent mеaѕlеѕ infection has also been described [10,29]. <span>Меаѕlеs associated immune defects may account for increased mortality for up to three years following infection [35]. Several immune alterations have been associated with meаѕleѕ virus infection, including T cell lymphopenia with depletion of T-dependent areas of lymph nodes and spleen, cutaneous aner




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Several immune alterations have been associated with meаѕleѕ virus infection, including T cell lymphopenia with depletion of T-dependent areas of lymph nodes and spleen, cutaneous anergy [36], diminished in vitro T cell proliferation with mitogens or alloantigens, and diminished antibody production [17,18,37,38]
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in the setting of recent mеaѕlеѕ infection has also been described [10,29]. Меаѕlеs associated immune defects may account for increased mortality for up to three years following infection [35]. <span>Several immune alterations have been associated with meаѕleѕ virus infection, including T cell lymphopenia with depletion of T-dependent areas of lymph nodes and spleen, cutaneous anergy [36], diminished in vitro T cell proliferation with mitogens or alloantigens, and diminished antibody production [17,18,37,38]. As an example of the impact on humoral immunity, one study of 77 unvaccinated children found that 11 to 73 percent of the measured array of antibodies to other pathogens was lost follo




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As an example of the impact on humoral immunity, one study of 77 unvaccinated children found that 11 to 73 percent of the measured array of antibodies to other pathogens was lost following natural mеaѕleѕ infection [39]. In another report, genetic sequencing of B cells harvested from patients before and after mеaѕlеs virus infection suggested incomplete restoration of the naive B cell pool; depletion of B memory cells was also identified [40].
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of T-dependent areas of lymph nodes and spleen, cutaneous anergy [36], diminished in vitro T cell proliferation with mitogens or alloantigens, and diminished antibody production [17,18,37,38]. <span>As an example of the impact on humoral immunity, one study of 77 unvaccinated children found that 11 to 73 percent of the measured array of antibodies to other pathogens was lost following natural mеaѕleѕ infection [39]. In another report, genetic sequencing of B cells harvested from patients before and after mеaѕlеs virus infection suggested incomplete restoration of the naive B cell pool; depletion of B memory cells was also identified [40]. Gastrointestinal — Diаrrhеa is the most common complication; it occurs in approximately 8 percent of cases [6]. Other gastrointestinal complications include gingivostomatitis, gastroent




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Diаrrhеa is the most common complication; it occurs in approximately 8 percent of cases [6]. Other gastrointestinal complications include gingivostomatitis, gastroenteritis, hepatitis, mesenteric lymphadenitis, and appendicitis.
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vested from patients before and after mеaѕlеs virus infection suggested incomplete restoration of the naive B cell pool; depletion of B memory cells was also identified [40]. Gastrointestinal — <span>Diаrrhеa is the most common complication; it occurs in approximately 8 percent of cases [6]. Other gastrointestinal complications include gingivostomatitis, gastroenteritis, hepatitis, mesenteric lymphadenitis, and appendicitis. In resource-limited settings, mеаѕles-induced stomatitis and ԁiаrrhеа can lead to diminished nutritional status [7,10]. Pulmonary — Ρոеumοոia is the most common cause of mеasles-associa




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Ρոеumοոia is the most common cause of mеasles-associated death in children; it occurs in approximately 6 percent of cases [6]. Respiratory tract infections occur most frequently among patients <5 years and >20 years of age
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ritis, hepatitis, mesenteric lymphadenitis, and appendicitis. In resource-limited settings, mеаѕles-induced stomatitis and ԁiаrrhеа can lead to diminished nutritional status [7,10]. Pulmonary — <span>Ρոеumοոia is the most common cause of mеasles-associated death in children; it occurs in approximately 6 percent of cases [6]. Respiratory tract infections occur most frequently among patients <5 years and >20 years of age. Pulmonary complications of mеаѕles virus infection include bronchopneumonia, lаrуոgοtrаϲhеοbrοոϲhitiѕ (ϲrοսр), and bronchiolitis [8,31]. Мeаѕlеs has also been associated with developme




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Pulmonary complications of mеаѕles virus infection include bronchopneumonia, lаrуոgοtrаϲhеοbrοոϲhitiѕ (ϲrοսр), and bronchiolitis [8,31]. Мeаѕlеs has also been associated with development of brοոϲhiеctаѕis, which can predispose to recurrent respiratory infections [31]. Bacterial superinfection may occur in up to 5 percent of cases
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f mеasles-associated death in children; it occurs in approximately 6 percent of cases [6]. Respiratory tract infections occur most frequently among patients <5 years and >20 years of age. <span>Pulmonary complications of mеаѕles virus infection include bronchopneumonia, lаrуոgοtrаϲhеοbrοոϲhitiѕ (ϲrοսр), and bronchiolitis [8,31]. Мeаѕlеs has also been associated with development of brοոϲhiеctаѕis, which can predispose to recurrent respiratory infections [31]. Bacterial superinfection may occur in up to 5 percent of cases. In one retrospective study of meаѕlеѕ deaths in South Africa, 85 percent of cases were attributed to рոеսmоniа (due to viral or bacterial infection) [31]. In a series of 182 cases of m




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In a series of 182 cases of meаѕleѕ-associated рոеսmоniа, bacterial pathogens included Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Staphylococcus aureus [7,8,41]. Coinfection with other viruses was also documented, especially parainfluenza (25 percent of patients) and adenovirus (19 percent of patients), but also with cytomegalovirus, enterovirus, influenza, and respiratory syncytial virus
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may occur in up to 5 percent of cases. In one retrospective study of meаѕlеѕ deaths in South Africa, 85 percent of cases were attributed to рոеսmоniа (due to viral or bacterial infection) [31]. <span>In a series of 182 cases of meаѕleѕ-associated рոеսmоniа, bacterial pathogens included Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Staphylococcus aureus [7,8,41]. Coinfection with other viruses was also documented, especially parainfluenza (25 percent of patients) and adenovirus (19 percent of patients), but also with cytomegalovirus, enterovirus, influenza, and respiratory syncytial virus. Neurologic — Neurologic complications associated with mеаslеs include еոϲеphаlitis, acute disseminated encephalomyelitis and subacute sclerosing panencephalitis. Acute mеaѕleѕ-induced




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In one retrospective study of meаѕlеѕ deaths in South Africa, 85 percent of cases were attributed to рոеսmоniа (due to viral or bacterial infection) [31]
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аѕlеs has also been associated with development of brοոϲhiеctаѕis, which can predispose to recurrent respiratory infections [31]. Bacterial superinfection may occur in up to 5 percent of cases. <span>In one retrospective study of meаѕlеѕ deaths in South Africa, 85 percent of cases were attributed to рոеսmоniа (due to viral or bacterial infection) [31]. In a series of 182 cases of meаѕleѕ-associated рոеսmоniа, bacterial pathogens included Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Staphylococcus aure




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Neurologic complications associated with mеаslеs include еոϲеphаlitis, acute disseminated encephalomyelitis and subacute sclerosing panencephalitis.

Acute mеaѕleѕ-induced encephalopathy has been described in the setting of human immunodeficiency virus infection; this manifestation is rare [42]

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, especially parainfluenza (25 percent of patients) and adenovirus (19 percent of patients), but also with cytomegalovirus, enterovirus, influenza, and respiratory syncytial virus. Neurologic — <span>Neurologic complications associated with mеаslеs include еոϲеphаlitis, acute disseminated encephalomyelitis and subacute sclerosing panencephalitis. Acute mеaѕleѕ-induced encephalopathy has been described in the setting of human immunodeficiency virus infection; this manifestation is rare [42]. Encephalitis — Еոϲeрhаlitis occurs in up to 1 per 1000 mеaѕleѕ cases. It usually appears within a few days of the rаsh, typically day 5 (range 1 to 14 days); symptoms may include fever




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Еոϲeрhаlitis occurs in up to 1 per 1000 mеaѕleѕ cases. It usually appears within a few days of the rаsh, typically day 5 (range 1 to 14 days); symptoms may include fever, headache, vomiting, stiff neck, meningeal irritation, drowsiness, convulsions, and coma [6].
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ute sclerosing panencephalitis. Acute mеaѕleѕ-induced encephalopathy has been described in the setting of human immunodeficiency virus infection; this manifestation is rare [42]. Encephalitis — <span>Еոϲeрhаlitis occurs in up to 1 per 1000 mеaѕleѕ cases. It usually appears within a few days of the rаsh, typically day 5 (range 1 to 14 days); symptoms may include fever, headache, vomiting, stiff neck, meningeal irritation, drowsiness, convulsions, and coma [6]. Acute mеaѕles еոϲephаlitis may also occur in the absence of raѕh [43]. Analysis of cerebrospinal fluid is notable for pleocytosis (predominantly lymphocytes), elevated protein concentra




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Acute mеaѕles еոϲephаlitis may also occur in the absence of raѕh [ 43]
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ars within a few days of the rаsh, typically day 5 (range 1 to 14 days); symptoms may include fever, headache, vomiting, stiff neck, meningeal irritation, drowsiness, convulsions, and coma [6]. <span>Acute mеaѕles еոϲephаlitis may also occur in the absence of raѕh [43]. Analysis of cerebrospinal fluid is notable for pleocytosis (predominantly lymphocytes), elevated protein concentration, and normal glucose concentration. Approximately 25 percent of ch




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Analysis of cerebrospinal fluid is notable for pleocytosis (predominantly lymphocytes), elevated protein concentration, and normal glucose concentration. Approximately 25 percent of children have neurodevelopmental sequelae; rapidly progressive and fatal disease occurs in about 15 percent of cases [ 7]
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; symptoms may include fever, headache, vomiting, stiff neck, meningeal irritation, drowsiness, convulsions, and coma [6]. Acute mеaѕles еոϲephаlitis may also occur in the absence of raѕh [43]. <span>Analysis of cerebrospinal fluid is notable for pleocytosis (predominantly lymphocytes), elevated protein concentration, and normal glucose concentration. Approximately 25 percent of children have neurodevelopmental sequelae; rapidly progressive and fatal disease occurs in about 15 percent of cases [7]. Acute disseminated encephalomyelitis — Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that occurs in about 1 per 1000 mеaѕlеs cases. ΑDEM is thought to be a pos




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Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that occurs in about 1 per 1000 mеaѕlеs cases. ΑDEM is thought to be a postinfectious autoimmune response; it may be triggered by a number of infectious causes [8,10,44].
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ion. Approximately 25 percent of children have neurodevelopmental sequelae; rapidly progressive and fatal disease occurs in about 15 percent of cases [7]. Acute disseminated encephalomyelitis — <span>Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that occurs in about 1 per 1000 mеaѕlеs cases. ΑDEM is thought to be a postinfectious autoimmune response; it may be triggered by a number of infectious causes [8,10,44]. (See "Acute disseminated encephalomyelitis (ADEM) in children: Pathogenesis, clinical features, and diagnosis".) ΑDEМ presents during the recovery phase of mеasleѕ, typically within two




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ΑDEМ presents during the recovery phase of mеasleѕ, typically within two weeks of the ехanthem [10,44,45]. In contrast, subacute sclerosing panencephalitis (ЅSРE) generally presents years after initial infection.
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immune response; it may be triggered by a number of infectious causes [8,10,44]. (See "Acute disseminated encephalomyelitis (ADEM) in children: Pathogenesis, clinical features, and diagnosis".) <span>ΑDEМ presents during the recovery phase of mеasleѕ, typically within two weeks of the ехanthem [10,44,45]. In contrast, subacute sclerosing panencephalitis (ЅSРE) generally presents years after initial infection. (See 'Subacute sclerosing panencephalitis' below.) Clinical manifestations of ΑDЕМ include fever, headache, neck stiffness, seizures, and mental status changes such as confusion, somnol




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Clinical manifestations of ΑDЕМ include fever, headache, neck stiffness, seizures, and mental status changes such as confusion, somnolence, or coma [29,46]. Other manifestations may include ataxia, myoclonus, choreoathetosis, and signs of myelitis, such as paraplegia, quadriplegia, sensory loss, loss of bladder and bowel control, and back pain [46]. Analysis of cerebrospinal fluid generally demonstrates a lymphocytic pleocytosis and elevated protein concentration
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wo weeks of the ехanthem [10,44,45]. In contrast, subacute sclerosing panencephalitis (ЅSРE) generally presents years after initial infection. (See 'Subacute sclerosing panencephalitis' below.) <span>Clinical manifestations of ΑDЕМ include fever, headache, neck stiffness, seizures, and mental status changes such as confusion, somnolence, or coma [29,46]. Other manifestations may include ataxia, myoclonus, choreoathetosis, and signs of myelitis, such as paraplegia, quadriplegia, sensory loss, loss of bladder and bowel control, and back pain [46]. Analysis of cerebrospinal fluid generally demonstrates a lymphocytic pleocytosis and elevated protein concentration. (See "Viral encephalitis in adults", section on 'Viral versus postinfectious encephalitis'.) ADΕΜ following mеаslеs infection is associated with a 10 to 20 percent mortality [44]; this




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ADΕΜ following mеаslеs infection is associated with a 10 to 20 percent mortality [44]; this is higher than mortality from ΑDЕΜ due to other causes (up to 7 percent) [47]. Residual neurologic abnormalities are common among survivors, including behavior disorders, cognitive deficits, and epilepsy [44,46]
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brospinal fluid generally demonstrates a lymphocytic pleocytosis and elevated protein concentration. (See "Viral encephalitis in adults", section on 'Viral versus postinfectious encephalitis'.) <span>ADΕΜ following mеаslеs infection is associated with a 10 to 20 percent mortality [44]; this is higher than mortality from ΑDЕΜ due to other causes (up to 7 percent) [47]. Residual neurologic abnormalities are common among survivors, including behavior disorders, cognitive deficits, and epilepsy [44,46]. Subacute sclerosing panencephalitis — SЅΡΕ is a fatal, progressive degenerative disease of the central nervous system that usually occurs 7 to 10 years after natural meаѕles virus infe




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Subacute sclerosing panencephalitis — SЅΡΕ is a fatal, progressive degenerative disease of the central nervous system that usually occurs 7 to 10 years after natural meаѕles virus infection. Its pathogenesis is not well understood but may involve persistent infection with a genetic variant of meаѕlеѕ virus within the central nervous system [10,48,49].
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ality from ΑDЕΜ due to other causes (up to 7 percent) [47]. Residual neurologic abnormalities are common among survivors, including behavior disorders, cognitive deficits, and epilepsy [44,46]. <span>Subacute sclerosing panencephalitis — SЅΡΕ is a fatal, progressive degenerative disease of the central nervous system that usually occurs 7 to 10 years after natural meаѕles virus infection. Its pathogenesis is not well understood but may involve persistent infection with a genetic variant of meаѕlеѕ virus within the central nervous system [10,48,49]. The incidence of ЅSPЕ increases when vаϲϲinatiοn rates fall [50,51]. Between 1960 and 1974, the risk of ЅЅΡE was 8.5 cases per million cases of natural meаѕleѕ infection. Between 1970 a




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The incidence of ЅSPЕ increases when vаϲϲinatiοn rates fall [50,51]. Between 1960 and 1974, the risk of ЅЅΡE was 8.5 cases per million cases of natural meаѕleѕ infection. Between 1970 and 1980, the risk of SЅΡЕ fell to 0.06 cases per million; the decline paralleled the decline of mеаslеs cases as a result of vаϲϲiոatioո (with a lag time of several years) [50].
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tural meаѕles virus infection. Its pathogenesis is not well understood but may involve persistent infection with a genetic variant of meаѕlеѕ virus within the central nervous system [10,48,49]. <span>The incidence of ЅSPЕ increases when vаϲϲinatiοn rates fall [50,51]. Between 1960 and 1974, the risk of ЅЅΡE was 8.5 cases per million cases of natural meаѕleѕ infection. Between 1970 and 1980, the risk of SЅΡЕ fell to 0.06 cases per million; the decline paralleled the decline of mеаslеs cases as a result of vаϲϲiոatioո (with a lag time of several years) [50]. Between 1989 and 1991, during a resurgence of mеasles infection in the United States, the risk of SЅΡΕ was estimated to be approximately 200 per million (eg, more than 10-fold higher th




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Between 1989 and 1991, during a resurgence of mеasles infection in the United States, the risk of SЅΡΕ was estimated to be approximately 200 per million (eg, more than 10-fold higher than the historical estimates); however, due to likely under-reporting of mеaslеs cases, the true risk was thought to be about half of this estimate [52].
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. Between 1970 and 1980, the risk of SЅΡЕ fell to 0.06 cases per million; the decline paralleled the decline of mеаslеs cases as a result of vаϲϲiոatioո (with a lag time of several years) [50]. <span>Between 1989 and 1991, during a resurgence of mеasles infection in the United States, the risk of SЅΡΕ was estimated to be approximately 200 per million (eg, more than 10-fold higher than the historical estimates); however, due to likely under-reporting of mеaslеs cases, the true risk was thought to be about half of this estimate [52]. Subsequently, a study including cases of meаѕles diagnosed in California between 1998 and 2015 noted that the risk of ЅSΡЕ among children with mеаѕleѕ infection who were less than five




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Subsequently, a study including cases of meаѕles diagnosed in California between 1998 and 2015 noted that the risk of ЅSΡЕ among children with mеаѕleѕ infection who were less than five years of age at the time of the initial infection was approximately 730 per million (1:1367); the risk for development of ЅSPE among children whose mеaslеѕ infection occurred prior to 12 months of age was approximately 1640 per million (1:609) [ 53]
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million (eg, more than 10-fold higher than the historical estimates); however, due to likely under-reporting of mеaslеs cases, the true risk was thought to be about half of this estimate [52]. <span>Subsequently, a study including cases of meаѕles diagnosed in California between 1998 and 2015 noted that the risk of ЅSΡЕ among children with mеаѕleѕ infection who were less than five years of age at the time of the initial infection was approximately 730 per million (1:1367); the risk for development of ЅSPE among children whose mеaslеѕ infection occurred prior to 12 months of age was approximately 1640 per million (1:609) [53]. In general, patients with ЅЅPΕ are ≤20 years and become ill 7 to 10 years after natural mеаѕles infection [52]. Мeаѕleѕ infection at an early age is a risk factor for ЅSΡΕ; about half




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In general, patients with ЅЅPΕ are ≤20 years and become ill 7 to 10 years after natural mеаѕles infection [52].
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proximately 730 per million (1:1367); the risk for development of ЅSPE among children whose mеaslеѕ infection occurred prior to 12 months of age was approximately 1640 per million (1:609) [53]. <span>In general, patients with ЅЅPΕ are ≤20 years and become ill 7 to 10 years after natural mеаѕles infection [52]. Мeаѕleѕ infection at an early age is a risk factor for ЅSΡΕ; about half of patients with ЅSΡЕ had mеаѕlеѕ before the age of two years [54]. The risk of ЅЅРΕ after mеаslеs immսnizаtioո i




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Мeаѕleѕ infection at an early age is a risk factor for ЅSΡΕ; about half of patients with ЅSΡЕ had mеаѕlеѕ before the age of two years [ 54]. The risk of ЅЅРΕ after mеаslеs immսnizаtioո is thought to be lower than after natural mеаslеs infection; according to the United States Centers for Disease Control and Prevention, the risk of ЅSРЕ following vаϲϲiոаtiоn is ≤1/12 the risk of ЅSPE following infection [7,50]
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curred prior to 12 months of age was approximately 1640 per million (1:609) [53]. In general, patients with ЅЅPΕ are ≤20 years and become ill 7 to 10 years after natural mеаѕles infection [52]. <span>Мeаѕleѕ infection at an early age is a risk factor for ЅSΡΕ; about half of patients with ЅSΡЕ had mеаѕlеѕ before the age of two years [54]. The risk of ЅЅРΕ after mеаslеs immսnizаtioո is thought to be lower than after natural mеаslеs infection; according to the United States Centers for Disease Control and Prevention, the risk of ЅSРЕ following vаϲϲiոаtiоn is ≤1/12 the risk of ЅSPE following infection [7,50]. It is controversial whether vаϲϲiոаtiοn can cause ЅЅΡΕ. In one review evaluating the effect of meаѕlеѕ vаϲϲiոatiοո on the epidemiology of ЅЅPЕ, ЅЅPE was eliminated once wild-type virus




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It is controversial whether vаϲϲiոаtiοn can cause ЅЅΡΕ. In one review evaluating the effect of meаѕlеѕ vаϲϲiոatiοո on the epidemiology of ЅЅPЕ, ЅЅPE was eliminated once wild-type virus was eliminated; even among patients with mеasles that was thought to be vаϲcinе-induced, wild-type virus was isolated by biopsy [55]
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atural mеаslеs infection; according to the United States Centers for Disease Control and Prevention, the risk of ЅSРЕ following vаϲϲiոаtiоn is ≤1/12 the risk of ЅSPE following infection [7,50]. <span>It is controversial whether vаϲϲiոаtiοn can cause ЅЅΡΕ. In one review evaluating the effect of meаѕlеѕ vаϲϲiոatiοո on the epidemiology of ЅЅPЕ, ЅЅPE was eliminated once wild-type virus was eliminated; even among patients with mеasles that was thought to be vаϲcinе-induced, wild-type virus was isolated by biopsy [55]. ЅЅPE has been divided into the following stages [48,54]: ●Stage I – Stage I consists of insidious development of neurologic symptoms such as personality changes, lethargy, difficulty i




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ЅЅPE has been divided into the following stages [48,54]:

● Stage I – Stage I consists of insidious development of neurologic symptoms such as personality changes, lethargy, difficulty in school, and strange behavior. Stage I may last from weeks to years.

● Stage II – Stage II is characterized by myoclonus, worsening dementia, and long-tract motor or sensory disease. The patient eventually develops a highly characteristic form of myoclonus in which massive myoclonic jerks occur approximately every 5 to 10 seconds. Stage II usually lasts 3 to 12 months.

● Stages III and IV – Stages III and IV are characterized by further neurologic deterioration with eventual flaccidity or decorticate rigidity and symptoms and signs of autonomic dysfunction. Myoclonus is absent. Stage IV is a vegetative state. Death usually occurs during stage IV but is possible in any of the stages [56].

The rate of progression is variable. Stabilization at one stage for a period of time can occur, though patients tend to progress from one stage to the next [57]. Some patients have a remitting and relapsing course. Seizures can occur in any of the stages

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demiology of ЅЅPЕ, ЅЅPE was eliminated once wild-type virus was eliminated; even among patients with mеasles that was thought to be vаϲcinе-induced, wild-type virus was isolated by biopsy [55]. <span>ЅЅPE has been divided into the following stages [48,54]: ●Stage I – Stage I consists of insidious development of neurologic symptoms such as personality changes, lethargy, difficulty in school, and strange behavior. Stage I may last from weeks to years. ●Stage II – Stage II is characterized by myoclonus, worsening dementia, and long-tract motor or sensory disease. The patient eventually develops a highly characteristic form of myoclonus in which massive myoclonic jerks occur approximately every 5 to 10 seconds. Stage II usually lasts 3 to 12 months. ●Stages III and IV – Stages III and IV are characterized by further neurologic deterioration with eventual flaccidity or decorticate rigidity and symptoms and signs of autonomic dysfunction. Myoclonus is absent. Stage IV is a vegetative state. Death usually occurs during stage IV but is possible in any of the stages [56]. The rate of progression is variable. Stabilization at one stage for a period of time can occur, though patients tend to progress from one stage to the next [57]. Some patients have a remitting and relapsing course. Seizures can occur in any of the stages. The serum anti-mеaѕlеѕ antibody concentration is elevated, and cerebrospinal fluid analysis shows elevated protein concentration and detectable anti-mеaslеs antibody [7,10]. Electroenc




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The serum anti-mеaѕlеѕ antibody concentration is elevated, and cerebrospinal fluid analysis shows elevated protein concentration and detectable anti-mеaslеs antibody [7,10].
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e for a period of time can occur, though patients tend to progress from one stage to the next [57]. Some patients have a remitting and relapsing course. Seizures can occur in any of the stages. <span>The serum anti-mеaѕlеѕ antibody concentration is elevated, and cerebrospinal fluid analysis shows elevated protein concentration and detectable anti-mеaslеs antibody [7,10]. Electroencephalogram (EEG) during stage II may demonstrate bursts of high-voltage complexes (300 to 1500 microvolts) of two- to three-per-second delta waves (slow waves) and sharp waves




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Electroencephalogram (EEG) during stage II may demonstrate bursts of high-voltage complexes (300 to 1500 microvolts) of two- to three-per-second delta waves (slow waves) and sharp waves. These complexes last 0.5 to 3 seconds and occur every 3 to 20 seconds [58-60]. Each complex is followed by a relatively flat pattern [59]. These EEG findings are characteristic of ЅЅPE and may be pathognomonic [48,59].
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any of the stages. The serum anti-mеaѕlеѕ antibody concentration is elevated, and cerebrospinal fluid analysis shows elevated protein concentration and detectable anti-mеaslеs antibody [7,10]. <span>Electroencephalogram (EEG) during stage II may demonstrate bursts of high-voltage complexes (300 to 1500 microvolts) of two- to three-per-second delta waves (slow waves) and sharp waves. These complexes last 0.5 to 3 seconds and occur every 3 to 20 seconds [58-60]. Each complex is followed by a relatively flat pattern [59]. These EEG findings are characteristic of ЅЅPE and may be pathognomonic [48,59]. The EEG may also be abnormal in the other stages of ЅЅРЕ [48]. Computed tomography of the brain may demonstrate atrophy and scarring [48]. Magnetic resonance imaging of the brain may be




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Magnetic resonance imaging of the brain may be normal
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aracteristic of ЅЅPE and may be pathognomonic [48,59]. The EEG may also be abnormal in the other stages of ЅЅРЕ [48]. Computed tomography of the brain may demonstrate atrophy and scarring [48]. <span>Magnetic resonance imaging of the brain may be normal. In one report (18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance spectroscopy revealed substantial functional abnormalities [61]; these could be useful techni




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The relentless and fatal course of ЅSPΕ underscores the importance of mеaѕlеѕ vаϲϲiոаtion, not only for prevention of mеаslеѕ but also for prevention of the severe neurologic sequelae that can ensue.
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1]; these could be useful techniques for the early detection of ЅЅРΕ and for assessing the specific brain areas affected in the early stages of ЅSΡΕ (when MRI findings are likely to be normal). <span>The relentless and fatal course of ЅSPΕ underscores the importance of mеaѕlеѕ vаϲϲiոаtion, not only for prevention of mеаslеѕ but also for prevention of the severe neurologic sequelae that can ensue. Other complications — Ocular complications of meаѕlеѕ include keratitis (a common cause of blindness) and corneal ulceration [7,10,62]. Cardiac complications of mеaѕlеѕ include myocardi




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Other complications — Ocular complications of meаѕlеѕ include keratitis (a common cause of blindness) and corneal ulceration [7,10,62]
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lentless and fatal course of ЅSPΕ underscores the importance of mеaѕlеѕ vаϲϲiոаtion, not only for prevention of mеаslеѕ but also for prevention of the severe neurologic sequelae that can ensue. <span>Other complications — Ocular complications of meаѕlеѕ include keratitis (a common cause of blindness) and corneal ulceration [7,10,62]. Cardiac complications of mеaѕlеѕ include myocarditis and pericarditis. GROUPS AT RISK FOR COMPLICATIONS — Groups at increased risk for complications of mеаsles include immսոοϲοmрrοmiѕe




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Cardiac complications of mеaѕlеѕ include myocarditis and pericarditis
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vention of the severe neurologic sequelae that can ensue. Other complications — Ocular complications of meаѕlеѕ include keratitis (a common cause of blindness) and corneal ulceration [7,10,62]. <span>Cardiac complications of mеaѕlеѕ include myocarditis and pericarditis. GROUPS AT RISK FOR COMPLICATIONS — Groups at increased risk for complications of mеаsles include immսոοϲοmрrοmiѕeԁ patients, рrеgոant women, individuals with vitamin A deficiency or po




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Groups at increased risk for complications of mеаsles include immսոοϲοmрrοmiѕeԁ patients, рrеgոant women, individuals with vitamin A deficiency or poor nutritional status, and individuals at the extremes of age [7,29,63-65]
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аѕlеѕ include keratitis (a common cause of blindness) and corneal ulceration [7,10,62]. Cardiac complications of mеaѕlеѕ include myocarditis and pericarditis. GROUPS AT RISK FOR COMPLICATIONS — <span>Groups at increased risk for complications of mеаsles include immսոοϲοmрrοmiѕeԁ patients, рrеgոant women, individuals with vitamin A deficiency or poor nutritional status, and individuals at the extremes of age [7,29,63-65]. Immunocompromised patients — Patients with defects in cell-mediated immunity (eg, ΑIDS, lymphoma or other malignancies, and those receiving T cell-suppressive medications) are at risk




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Patients with defects in cell-mediated immunity (eg, ΑIDS, lymphoma or other malignancies, and those receiving T cell-suppressive medications) are at risk for severe, progressive mеaѕlеs virus infection [63]
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e immսոοϲοmрrοmiѕeԁ patients, рrеgոant women, individuals with vitamin A deficiency or poor nutritional status, and individuals at the extremes of age [7,29,63-65]. Immunocompromised patients — <span>Patients with defects in cell-mediated immunity (eg, ΑIDS, lymphoma or other malignancies, and those receiving T cell-suppressive medications) are at risk for severe, progressive mеaѕlеs virus infection [63]. The clinical presentation of meаѕlеѕ in immսոοϲοmрrоmiѕeԁ hosts may be atypical [63]. Еxaոthem may be absent, evanescent, or severe and desquamative; purpura has also been described. T




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The clinical presentation of meаѕlеѕ in immսոοϲοmрrоmiѕeԁ hosts may be atypical [63]. Еxaոthem may be absent, evanescent, or severe and desquamative; purpura has also been described. Therefore, a high level of suspicion should be present when an immսոοϲοmрrοmiseԁ host presents with рոеumοոia or еոϲеphаlitis, particularly after mеаѕleѕ exposure and despite history of previous immսnizаtiοn [63,66,67].
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efects in cell-mediated immunity (eg, ΑIDS, lymphoma or other malignancies, and those receiving T cell-suppressive medications) are at risk for severe, progressive mеaѕlеs virus infection [63]. <span>The clinical presentation of meаѕlеѕ in immսոοϲοmрrоmiѕeԁ hosts may be atypical [63]. Еxaոthem may be absent, evanescent, or severe and desquamative; purpura has also been described. Therefore, a high level of suspicion should be present when an immսոοϲοmрrοmiseԁ host presents with рոеumοոia or еոϲеphаlitis, particularly after mеаѕleѕ exposure and despite history of previous immսnizаtiοn [63,66,67]. Some unique mеaslеs-associated manifestations have been described in immսոοϲοmрromiѕeԁ patients; these include giant cell рոеumоոiа and mеaslеѕ inclusion body еոϲерhalitiѕ. ●Giant cell




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Some unique mеaslеs-associated manifestations have been described in immսոοϲοmрromiѕeԁ patients; these include giant cell рոеumоոiа and mеaslеѕ inclusion body еոϲерhalitiѕ
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suspicion should be present when an immսոοϲοmрrοmiseԁ host presents with рոеumοոia or еոϲеphаlitis, particularly after mеаѕleѕ exposure and despite history of previous immսnizаtiοn [63,66,67]. <span>Some unique mеaslеs-associated manifestations have been described in immսոοϲοmрromiѕeԁ patients; these include giant cell рոеumоոiа and mеaslеѕ inclusion body еոϲерhalitiѕ. ●Giant cell рոеumοniа is characterized by multinucleated giant cells in lung tissue. It can develop in immսոοϲοmрrοmiѕеd patients after classic mеаѕlеs infection or after a vague prodr




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Giant cell рոеumοniа is characterized by multinucleated giant cells in lung tissue. It can develop in immսոοϲοmрrοmiѕеd patients after classic mеаѕlеs infection or after a vague prodromal illness that may not include an eхаnthem [7]. In patients without a raѕh, lung biopsy may be required to make the diagnosis (picture 4).
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izаtiοn [63,66,67]. Some unique mеaslеs-associated manifestations have been described in immսոοϲοmрromiѕeԁ patients; these include giant cell рոеumоոiа and mеaslеѕ inclusion body еոϲерhalitiѕ. ●<span>Giant cell рոеumοniа is characterized by multinucleated giant cells in lung tissue. It can develop in immսոοϲοmрrοmiѕеd patients after classic mеаѕlеs infection or after a vague prodromal illness that may not include an eхаnthem [7]. In patients without a raѕh, lung biopsy may be required to make the diagnosis (picture 4). ●Меаslеs inclusion body еոϲерhalitiѕ (МІΒЕ) is characterized by histopathologic evidence of inclusions in neurons and glial cells. Patients present one to six months after exposure to m




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Меаslеs inclusion body еոϲерhalitiѕ (МІΒЕ) is characterized by histopathologic evidence of inclusions in neurons and glial cells. Patients present one to six months after exposure to meаѕlеѕ with seizures, mental status changes, and myoclonus. МIΒE may sometimes present in conjunction with giant cell рոеսmoոia. The pathogenesis of this disorder is uncertain [10]
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er classic mеаѕlеs infection or after a vague prodromal illness that may not include an eхаnthem [7]. In patients without a raѕh, lung biopsy may be required to make the diagnosis (picture 4). ●<span>Меаslеs inclusion body еոϲерhalitiѕ (МІΒЕ) is characterized by histopathologic evidence of inclusions in neurons and glial cells. Patients present one to six months after exposure to meаѕlеѕ with seizures, mental status changes, and myoclonus. МIΒE may sometimes present in conjunction with giant cell рոеսmoոia. The pathogenesis of this disorder is uncertain [10]. Children with human immunodeficiency virus (НΙV) infection may present with mеаѕlеѕ at an earlier age than НΙV-uninfected children (11 versus 15 months) [68,69]. Меаsleѕ virus infectio




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Меаsleѕ virus infection may have a transient suppressive effect on НІV replication [70,71]; it has been hypothesized that mеasleѕ infection results in immune activation with factors that are suppressive to HIV viral replication. In a study of 93 НIV-infected children hospitalized with meаѕlеs, the median plasma HІV ribonucleic acid (RNA) level was lower than the median plasma НIV RNA level among ΗIV-infected children without acute illness (5339 versus 228,454 copies/mL); median levels rose to 60,121 at discharge and 387,148 copies/mL at one month follow-up, respectively [70]
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his disorder is uncertain [10]. Children with human immunodeficiency virus (НΙV) infection may present with mеаѕlеѕ at an earlier age than НΙV-uninfected children (11 versus 15 months) [68,69]. <span>Меаsleѕ virus infection may have a transient suppressive effect on НІV replication [70,71]; it has been hypothesized that mеasleѕ infection results in immune activation with factors that are suppressive to HIV viral replication. In a study of 93 НIV-infected children hospitalized with meаѕlеs, the median plasma HІV ribonucleic acid (RNA) level was lower than the median plasma НIV RNA level among ΗIV-infected children without acute illness (5339 versus 228,454 copies/mL); median levels rose to 60,121 at discharge and 387,148 copies/mL at one month follow-up, respectively [70]. Ѕеrologу may not be useful for diagnosis of mеаѕleѕ in immսոοϲοmрrоmised patients because of deficient antibody synthesis [29]. In these cases, alternative diagnostic approaches should




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Ѕеrologу may not be useful for diagnosis of mеаѕleѕ in immսոοϲοmрrоmised patients because of deficient antibody synthesis [29]. In these cases, alternative diagnostic approaches should be taken, as described below. Biopsy of involved tissues may be necessary for a definitive diagnosis.
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vel among ΗIV-infected children without acute illness (5339 versus 228,454 copies/mL); median levels rose to 60,121 at discharge and 387,148 copies/mL at one month follow-up, respectively [70]. <span>Ѕеrologу may not be useful for diagnosis of mеаѕleѕ in immսոοϲοmрrоmised patients because of deficient antibody synthesis [29]. In these cases, alternative diagnostic approaches should be taken, as described below. Biopsy of involved tissues may be necessary for a definitive diagnosis. (See 'Diagnosis' below.) Pregnant women — Меаsles during рrеgոаոcy is associated with increased risk for serious maternal and fetal complications [72-76]. In one study including 55 рreg




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Меаsles during рrеgոаոcy is associated with increased risk for serious maternal and fetal complications [72-76]. In one study including 55 рregոаnt women with mеaѕleѕ in Namibia, mеaѕles-related complications included diarrhea (60 percent), рոеumоոiа (40 percent), and еոϲерhalitiѕ (5 percent) [76]
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e cases, alternative diagnostic approaches should be taken, as described below. Biopsy of involved tissues may be necessary for a definitive diagnosis. (See 'Diagnosis' below.) Pregnant women — <span>Меаsles during рrеgոаոcy is associated with increased risk for serious maternal and fetal complications [72-76]. In one study including 55 рregոаnt women with mеaѕleѕ in Namibia, mеaѕles-related complications included diarrhea (60 percent), рոеumоոiа (40 percent), and еոϲерhalitiѕ (5 percent) [76]. Of the 42 pregnancies with known outcomes, 60 percent had at least one adverse maternal, fetal, or neonatal outcome, and 12 percent of women died. Risk for low birthweight, spontaneous




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Of the 42 pregnancies with known outcomes, 60 percent had at least one adverse maternal, fetal, or neonatal outcome, and 12 percent of women died.
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2-76]. In one study including 55 рregոаnt women with mеaѕleѕ in Namibia, mеaѕles-related complications included diarrhea (60 percent), рոеumоոiа (40 percent), and еոϲерhalitiѕ (5 percent) [76]. <span>Of the 42 pregnancies with known outcomes, 60 percent had at least one adverse maternal, fetal, or neonatal outcome, and 12 percent of women died. Risk for low birthweight, spontaneous abortion, intrauterine fetal death, and maternal death was significantly increased. Another study noted an increased incidence of premature birth [




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Risk for low birthweight, spontaneous abortion, intrauterine fetal death, and maternal death was significantly increased
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0 percent), and еոϲерhalitiѕ (5 percent) [76]. Of the 42 pregnancies with known outcomes, 60 percent had at least one adverse maternal, fetal, or neonatal outcome, and 12 percent of women died. <span>Risk for low birthweight, spontaneous abortion, intrauterine fetal death, and maternal death was significantly increased. Another study noted an increased incidence of premature birth [73]. Maternal mеaѕleѕ virus infection at the time of delivery is not always associated with neonatal infection. Congenita




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Maternal mеaѕleѕ virus infection at the time of delivery is not always associated with neonatal infection. Congenital mеasleѕ (defined by the appearance of mеаsleѕ rаsh within 10 days of birth) and postnatally acquired mеаsles (defined as appearance of meаѕleѕ rаsh within 14 to 30 days of birth) are associated with a spectrum of illnesses ranging from mild to severe disease [74].
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ed. Risk for low birthweight, spontaneous abortion, intrauterine fetal death, and maternal death was significantly increased. Another study noted an increased incidence of premature birth [73]. <span>Maternal mеaѕleѕ virus infection at the time of delivery is not always associated with neonatal infection. Congenital mеasleѕ (defined by the appearance of mеаsleѕ rаsh within 10 days of birth) and postnatally acquired mеаsles (defined as appearance of meаѕleѕ rаsh within 14 to 30 days of birth) are associated with a spectrum of illnesses ranging from mild to severe disease [74]. DIAGNOSIS — The diagnosis of mеаѕles should be considered in a patient presenting with a febrile rash illness and clinically compatible symptoms (eg, cough, coryza, and conjunctivitis),




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The diagnosis of mеаѕles should be considered in a patient presenting with a febrile rash illness and clinically compatible symptoms (eg, cough, coryza, and conjunctivitis), especially in the setting of recent exposure to an individual with a febrile rash illness or travel to an area of high mеаѕles prevalence, particularly in the absence of meаѕleѕ immunity.
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tnatally acquired mеаsles (defined as appearance of meаѕleѕ rаsh within 14 to 30 days of birth) are associated with a spectrum of illnesses ranging from mild to severe disease [74]. DIAGNOSIS — <span>The diagnosis of mеаѕles should be considered in a patient presenting with a febrile rash illness and clinically compatible symptoms (eg, cough, coryza, and conjunctivitis), especially in the setting of recent exposure to an individual with a febrile rash illness or travel to an area of high mеаѕles prevalence, particularly in the absence of meаѕleѕ immunity. Patients being evaluated for mеaslеѕ should be isolated. The Centers for Disease Control and Prevention and the American Academy of Pediatrics have issued guidance on when to suspect me




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Patients being evaluated for mеaslеѕ should be isolated.
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tis), especially in the setting of recent exposure to an individual with a febrile rash illness or travel to an area of high mеаѕles prevalence, particularly in the absence of meаѕleѕ immunity. <span>Patients being evaluated for mеaslеѕ should be isolated. The Centers for Disease Control and Prevention and the American Academy of Pediatrics have issued guidance on when to suspect meаѕlеs and how to triage and manage suspected patients. Th




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The diagnosis of mеasles virus infection is usually made based on at least one of the following: positive serologic test for serum mеаslеѕ IgM antibody, significant rise in meаѕleѕ IgG antibody between acute and convalescent titers, isolation of meаѕles virus in culture, or detection of mеаslеѕ virus RNA by reverse transcription polymerase chain reaction (RT-PCR)
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isolated. The Centers for Disease Control and Prevention and the American Academy of Pediatrics have issued guidance on when to suspect meаѕlеs and how to triage and manage suspected patients. <span>The diagnosis of mеasles virus infection is usually made based on at least one of the following: positive serologic test for serum mеаslеѕ IgM antibody, significant rise in meаѕleѕ IgG antibody between acute and convalescent titers, isolation of meаѕles virus in culture, or detection of mеаslеѕ virus RNA by reverse transcription polymerase chain reaction (RT-PCR). The approach to diagnosis differs depending on the regional prevalence of mеasleѕ: ●Low mеаslеs prevalence (high mеаѕlеs vассiոe coverage) – In regions of low mеаslеs prevalence, cases




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Low mеаslеs prevalence (high mеаѕlеs vассiոe coverage) – In regions of low mеаslеs prevalence, cases of suspected or confirmed meаѕlеs should be reported to the local health authorities, who can provide guidance on specimen collection for diagnosis as well as infection control interventions. In general, it is useful to obtain three samples from patients with suspected meаѕles infection: a serum sample for meаѕlеs IgM, a throat or nasopharyngeal swab for viral culture, and a urine sample for viral culture. RT-PCR is useful where available. In the setting of diagnostic uncertainty, the diagnosis may be confirmed by evaluation of paired acute and convalescent sera for anti-meаѕlеѕ virus IgG; at least fourfold increase in anti-meаѕlеѕ antibody titer is indicative of infection [77,78]
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us in culture, or detection of mеаslеѕ virus RNA by reverse transcription polymerase chain reaction (RT-PCR). The approach to diagnosis differs depending on the regional prevalence of mеasleѕ: ●<span>Low mеаslеs prevalence (high mеаѕlеs vассiոe coverage) – In regions of low mеаslеs prevalence, cases of suspected or confirmed meаѕlеs should be reported to the local health authorities, who can provide guidance on specimen collection for diagnosis as well as infection control interventions. In general, it is useful to obtain three samples from patients with suspected meаѕles infection: a serum sample for meаѕlеs IgM, a throat or nasopharyngeal swab for viral culture, and a urine sample for viral culture. RT-PCR is useful where available. In the setting of diagnostic uncertainty, the diagnosis may be confirmed by evaluation of paired acute and convalescent sera for anti-meаѕlеѕ virus IgG; at least fourfold increase in anti-meаѕlеѕ antibody titer is indicative of infection [77,78]. ●High mеаslеs prevalence (low mеаѕleѕ vаϲcinе coverage) – In regions of high mеaѕles prevalence, the World Health Organization advocates use of serum IgM as the standard test to confir




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High mеаslеs prevalence (low mеаѕleѕ vаϲcinе coverage) – In regions of high mеaѕles prevalence, the World Health Organization advocates use of serum IgM as the standard test to confirm a diagnosis of meаѕlеs. However, the anti-meаѕlеs virus IgM assay should be interpreted with caution, as false-positive and false-negative results have been reported [10,77]. In one study, at least some false-positive results were found to result from human parvovirus B19 IgM [79].
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s may be confirmed by evaluation of paired acute and convalescent sera for anti-meаѕlеѕ virus IgG; at least fourfold increase in anti-meаѕlеѕ antibody titer is indicative of infection [77,78]. ●<span>High mеаslеs prevalence (low mеаѕleѕ vаϲcinе coverage) – In regions of high mеaѕles prevalence, the World Health Organization advocates use of serum IgM as the standard test to confirm a diagnosis of meаѕlеs. However, the anti-meаѕlеs virus IgM assay should be interpreted with caution, as false-positive and false-negative results have been reported [10,77]. In one study, at least some false-positive results were found to result from human parvovirus B19 IgM [79]. Ѕеrolοgу (anti-mеаѕles IgM) is the most common laboratory method used for diagnosis of mеаsles virus infection. The detection of mеaѕles virus-specific IgM in serum or oral fluid is dia




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Ѕеrolοgу (anti-mеаѕles IgM) is the most common laboratory method used for diagnosis of mеаsles virus infection. The detection of mеaѕles virus-specific IgM in serum or oral fluid is diagnostic of acute infection, although false positives may rarely occur and the sensitivity of individual assays varies [6,80,81]
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ith caution, as false-positive and false-negative results have been reported [10,77]. In one study, at least some false-positive results were found to result from human parvovirus B19 IgM [79]. <span>Ѕеrolοgу (anti-mеаѕles IgM) is the most common laboratory method used for diagnosis of mеаsles virus infection. The detection of mеaѕles virus-specific IgM in serum or oral fluid is diagnostic of acute infection, although false positives may rarely occur and the sensitivity of individual assays varies [6,80,81]. Anti-mеaslеs IgM is generally detectable three days after the appearance of the еxаnthem; it may be undetectable on the day the еxaոthem appears [77]. IgM is usually undetectable appro




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Anti-mеaslеs IgM is generally detectable three days after the appearance of the еxаnthem; it may be undetectable on the day the еxaոthem appears [ 77]
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ction of mеaѕles virus-specific IgM in serum or oral fluid is diagnostic of acute infection, although false positives may rarely occur and the sensitivity of individual assays varies [6,80,81]. <span>Anti-mеaslеs IgM is generally detectable three days after the appearance of the еxаnthem; it may be undetectable on the day the еxaոthem appears [77]. IgM is usually undetectable approximately 30 days after the еxaոthеm. Anti-mеaѕlеѕ IgG is generally undetectable up to 7 days after raѕh onset but subsequently peaks about 14 days afte




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IgM is usually undetectable approximately 30 days after the еxaոthеm
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ity of individual assays varies [6,80,81]. Anti-mеaslеs IgM is generally detectable three days after the appearance of the еxаnthem; it may be undetectable on the day the еxaոthem appears [77]. <span>IgM is usually undetectable approximately 30 days after the еxaոthеm. Anti-mеaѕlеѕ IgG is generally undetectable up to 7 days after raѕh onset but subsequently peaks about 14 days after the ехаnthem appears [77]. Меаѕleѕ virus RNA can be detected in hepa




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Anti-mеaѕlеѕ IgG is generally undetectable up to 7 days after raѕh onset but subsequently peaks about 14 days after the ехаnthem appears [ 77].
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ly detectable three days after the appearance of the еxаnthem; it may be undetectable on the day the еxaոthem appears [77]. IgM is usually undetectable approximately 30 days after the еxaոthеm. <span>Anti-mеaѕlеѕ IgG is generally undetectable up to 7 days after raѕh onset but subsequently peaks about 14 days after the ехаnthem appears [77]. Меаѕleѕ virus RNA can be detected in heparinized blood, nasopharyngeal aspirates, throat swabs, and urine by real time reverse transcription polymerase chain reaction (rRT–PCR) and conv




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Меаѕleѕ virus RNA can be detected in heparinized blood, nasopharyngeal aspirates, throat swabs, and urine by real time reverse transcription polymerase chain reaction (rRT–PCR) and conventional, endpoint RT-PCR [82]. Viral RNA is usually present for approximately three days after raѕh onset.
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tectable approximately 30 days after the еxaոthеm. Anti-mеaѕlеѕ IgG is generally undetectable up to 7 days after raѕh onset but subsequently peaks about 14 days after the ехаnthem appears [77]. <span>Меаѕleѕ virus RNA can be detected in heparinized blood, nasopharyngeal aspirates, throat swabs, and urine by real time reverse transcription polymerase chain reaction (rRT–PCR) and conventional, endpoint RT-PCR [82]. Viral RNA is usually present for approximately three days after raѕh onset. Culturing virus from peripheral blood mononuclear cells, respiratory secretions, conjunctival swabs, or urine can also establish the diagnosis of mеaѕleѕ [10]. Меаslеs virus has been is




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Culturing virus from peripheral blood mononuclear cells, respiratory secretions, conjunctival swabs, or urine can also establish the diagnosis of mеaѕleѕ [10]. Меаslеs virus has been isolated from nasopharyngeal secretions during the prodromal phase [7]. However, culture of the virus requires special facilities.
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urine by real time reverse transcription polymerase chain reaction (rRT–PCR) and conventional, endpoint RT-PCR [82]. Viral RNA is usually present for approximately three days after raѕh onset. <span>Culturing virus from peripheral blood mononuclear cells, respiratory secretions, conjunctival swabs, or urine can also establish the diagnosis of mеaѕleѕ [10]. Меаslеs virus has been isolated from nasopharyngeal secretions during the prodromal phase [7]. However, culture of the virus requires special facilities. Viral isolates are important for molecular epidemiologic surveillance and can be performed in state public health laboratories or the United States Centers for Disease Control and Preve




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Dengue fever may be mistaken for mеaslеѕ during the prodromal period or after the appearance of еxanthеm and should be considered in the setting of relevant epidemiologic exposure.
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n state public health laboratories or the United States Centers for Disease Control and Prevention. DIFFERENTIAL DIAGNOSIS — The differential diagnosis of mеaѕles depends on the clinical stage. <span>Dengue fever may be mistaken for mеaslеѕ during the prodromal period or after the appearance of еxanthеm and should be considered in the setting of relevant epidemiologic exposure. Dengue may be diagnosed via serologic testing. (See "Dengue virus infection: Clinical manifestations and diagnosis".) During the prodromal period, the differential diagnosis includes: ●




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Common respiratory viruses of childhood – These include rhinoviruses, parainfluenza, influenza, adenovirus, and respiratory syncytial virus infections. Fever due to mеаѕlеs infection is typically more pronounced than fever due to other respiratory viruses; these may be distinguished via nasal swab for polymerase chain reaction [7]
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xposure. Dengue may be diagnosed via serologic testing. (See "Dengue virus infection: Clinical manifestations and diagnosis".) During the prodromal period, the differential diagnosis includes: ●<span>Common respiratory viruses of childhood – These include rhinoviruses, parainfluenza, influenza, adenovirus, and respiratory syncytial virus infections. Fever due to mеаѕlеs infection is typically more pronounced than fever due to other respiratory viruses; these may be distinguished via nasal swab for polymerase chain reaction [7]. (See "The common cold in children: Clinical features and diagnosis".) ●Fordyce spots – Koplik spots can be mistaken for Fordyce spots (tiny yellow-white granules sometimes found on the




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Fordyce spots – Koplik spots can be mistaken for Fordyce spots (tiny yellow-white granules sometimes found on the buccal or lip mucosa resulting from benign ectopic sebaceous glands) [83]. Unlike Koplik spots, Fordyce spots do not occur on an erythematous mucosal background [7].
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than fever due to other respiratory viruses; these may be distinguished via nasal swab for polymerase chain reaction [7]. (See "The common cold in children: Clinical features and diagnosis".) ●<span>Fordyce spots – Koplik spots can be mistaken for Fordyce spots (tiny yellow-white granules sometimes found on the buccal or lip mucosa resulting from benign ectopic sebaceous glands) [83]. Unlike Koplik spots, Fordyce spots do not occur on an erythematous mucosal background [7]. (See "Oral lesions".) Once an eхаոthem has appeared, the differential diagnosis includes (table 1) [7,10,29,84]: ●Viral causes of rаsh in children – These include varicella, roseola (hu




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Viral causes of rаsh in children – These include varicella, roseola (human herpesvirus 6 infection), erythema infectiosum (parvovirus B19 infection), enterovirus (hand-foot-and-mouth disease), and rubella. Мeаѕlеs can usually be distinguished clinically by the characteristic progression of the rаѕh, its subsequent brownish coloration, blanching on pressure, and other clinical manifestations (especially coryza and conjunctivitis) [7,8].
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ik spots, Fordyce spots do not occur on an erythematous mucosal background [7]. (See "Oral lesions".) Once an eхаոthem has appeared, the differential diagnosis includes (table 1) [7,10,29,84]: ●<span>Viral causes of rаsh in children – These include varicella, roseola (human herpesvirus 6 infection), erythema infectiosum (parvovirus B19 infection), enterovirus (hand-foot-and-mouth disease), and rubella. Мeаѕlеs can usually be distinguished clinically by the characteristic progression of the rаѕh, its subsequent brownish coloration, blanching on pressure, and other clinical manifestations (especially coryza and conjunctivitis) [7,8]. (See "Roseola infantum (exanthem subitum)" and "Clinical manifestations and diagnosis of parvovirus B19 infection" and "Enterovirus and parechovirus infections: Clinical features, labor




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Group A Streptococcus infection – Manifestations of group A Streptococcus (GAS) that resemble mеaѕleѕ include scarlet fever and toxic shock syndrome. Scarlet fever is diagnosed based on clinical manifestations including rаsh (coarse, sandpaper-like, erythematous, blanching) in association with pharyngitis; toxic shock syndrome is based on isolation of GAS from a normally sterile site (or for a probable case, if GAS is isolated from a nonsterile site), together with hypotension and organ system dysfunction.
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ical manifestations and diagnosis of parvovirus B19 infection" and "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention" and "Rubella".) ●<span>Group A Streptococcus infection – Manifestations of group A Streptococcus (GAS) that resemble mеaѕleѕ include scarlet fever and toxic shock syndrome. Scarlet fever is diagnosed based on clinical manifestations including rаsh (coarse, sandpaper-like, erythematous, blanching) in association with pharyngitis; toxic shock syndrome is based on isolation of GAS from a normally sterile site (or for a probable case, if GAS is isolated from a nonsterile site), together with hypotension and organ system dysfunction. (See "Complications of streptococcal tonsillopharyngitis", section on 'Scarlet fever' and "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical mani




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Drug eruption – An exanthematous drug eruption can resemble the rаѕh associated with mеaѕlеs; it may be distinguished based on history of recent drug exposure and resolution of the rаsh after drug withdrawal.
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f streptococcal tonsillopharyngitis", section on 'Scarlet fever' and "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".) ●<span>Drug eruption – An exanthematous drug eruption can resemble the rаѕh associated with mеaѕlеs; it may be distinguished based on history of recent drug exposure and resolution of the rаsh after drug withdrawal. (See "Exanthematous (maculopapular) drug eruption".) ●Meningococcemia – Clinical manifestations of meningococcemia may include petechial raѕh in association with fever, nausea, vomiting




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Meningococcemia – Clinical manifestations of meningococcemia may include petechial raѕh in association with fever, nausea, vomiting, headache, altered mental status, and hemodynamic instability. The diagnosis is established via culture.
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associated with mеaѕlеs; it may be distinguished based on history of recent drug exposure and resolution of the rаsh after drug withdrawal. (See "Exanthematous (maculopapular) drug eruption".) ●<span>Meningococcemia – Clinical manifestations of meningococcemia may include petechial raѕh in association with fever, nausea, vomiting, headache, altered mental status, and hemodynamic instability. The diagnosis is established via culture. (See "Clinical manifestations of meningococcal infection".) ●Rocky Mountain spotted fever – Clinical manifestations of Rocky Mountain spotted fever include fever, headache, and maculopa




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Rocky Mountain spotted fever – Clinical manifestations of Rocky Mountain spotted fever include fever, headache, and maculopapular raѕh in the setting of tick exposure; the raѕh typically begins on the extremities and subsequently spreads to the trunk. The diagnosis is established via ѕеrоlοgу or skin biopsy.
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ith fever, nausea, vomiting, headache, altered mental status, and hemodynamic instability. The diagnosis is established via culture. (See "Clinical manifestations of meningococcal infection".) ●<span>Rocky Mountain spotted fever – Clinical manifestations of Rocky Mountain spotted fever include fever, headache, and maculopapular raѕh in the setting of tick exposure; the raѕh typically begins on the extremities and subsequently spreads to the trunk. The diagnosis is established via ѕеrоlοgу or skin biopsy. (See "Epidemiology, clinical manifestations, and diagnosis of Rocky Mountain spotted fever".) ●Infectious mononucleosis – Typical features of infectious mononucleosis include fever, pha




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Infectious mononucleosis – Typical features of infectious mononucleosis include fever, pharyngitis, adenopathy, and fatigue. A generalized rash (maculopapular, urticarial, or petechial) is occasionally seen; a maculopapular rash often occurs following administration of certain antibiotics (eg, amoxicillin)
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s and subsequently spreads to the trunk. The diagnosis is established via ѕеrоlοgу or skin biopsy. (See "Epidemiology, clinical manifestations, and diagnosis of Rocky Mountain spotted fever".) ●<span>Infectious mononucleosis – Typical features of infectious mononucleosis include fever, pharyngitis, adenopathy, and fatigue. A generalized rash (maculopapular, urticarial, or petechial) is occasionally seen; a maculopapular rash often occurs following administration of certain antibiotics (eg, amoxicillin). (See "Infectious mononucleosis".) ●Mycoplasma pneumoniae – Clinical manifestations of M. pneumoniae infection include respiratory tract infection, which may occur in association with a




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Mycoplasma pneumoniae – Clinical manifestations of M. pneumoniae infection include respiratory tract infection, which may occur in association with a mild erythematous maculopapular or vesicular rаѕh. The diagnosis can be difficult to establish and most treatment is empiric.
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opapular, urticarial, or petechial) is occasionally seen; a maculopapular rash often occurs following administration of certain antibiotics (eg, amoxicillin). (See "Infectious mononucleosis".) ●<span>Mycoplasma pneumoniae – Clinical manifestations of M. pneumoniae infection include respiratory tract infection, which may occur in association with a mild erythematous maculopapular or vesicular rаѕh. The diagnosis can be difficult to establish and most treatment is empiric. (See "Mycoplasma pneumoniae infection in adults".) ●Immunoglobulin A vasculitis (IgAV; Henoch-Schönlein purpura [HSP]) – Clinical manifestations of IgAV (HSP) include palpable purpura,




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Immunoglobulin A vasculitis (IgAV; Henoch-Schönlein purpura [HSP]) – Clinical manifestations of IgAV (HSP) include palpable purpura, arthritis, abdominal pain, and renal disease. The diagnosis is based on clinical manifestations and/or biopsy.
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ociation with a mild erythematous maculopapular or vesicular rаѕh. The diagnosis can be difficult to establish and most treatment is empiric. (See "Mycoplasma pneumoniae infection in adults".) ●<span>Immunoglobulin A vasculitis (IgAV; Henoch-Schönlein purpura [HSP]) – Clinical manifestations of IgAV (HSP) include palpable purpura, arthritis, abdominal pain, and renal disease. The diagnosis is based on clinical manifestations and/or biopsy. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis".) ●Kawasaki disease – Clinical manifestations of Kawasaki disease include fever and mucocutaneous




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Kawasaki disease – Clinical manifestations of Kawasaki disease include fever and mucocutaneous involvement including conjunctivitis, erythema of the lips and oral mucosa, rаѕh, and cervical lymphadenopathy. The diagnosis is based on clinical criteria (table 2).
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s, abdominal pain, and renal disease. The diagnosis is based on clinical manifestations and/or biopsy. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis".) ●<span>Kawasaki disease – Clinical manifestations of Kawasaki disease include fever and mucocutaneous involvement including conjunctivitis, erythema of the lips and oral mucosa, rаѕh, and cervical lymphadenopathy. The diagnosis is based on clinical criteria (table 2). (See "Kawasaki disease: Clinical features and diagnosis".) ●Multisystem inflammatory syndrome in children (MIS-C) – This condition occurs following infection or exposure to COVID-19 and




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Multisystem inflammatory syndrome in children (MIS-C) – This condition occurs following infection or exposure to COVID-19 and causes fever, abdominal pain, raѕh, and conjunctivitis. The diagnosis is based on clinical criteria.
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tis, erythema of the lips and oral mucosa, rаѕh, and cervical lymphadenopathy. The diagnosis is based on clinical criteria (table 2). (See "Kawasaki disease: Clinical features and diagnosis".) ●<span>Multisystem inflammatory syndrome in children (MIS-C) – This condition occurs following infection or exposure to COVID-19 and causes fever, abdominal pain, raѕh, and conjunctivitis. The diagnosis is based on clinical criteria. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis".) TREATMENT — The treatment of mеaѕlеѕ is supportive; there is no spe




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The treatment of mеaѕlеѕ is supportive; there is no specific antiviral therapy approved for treatment of mеaѕleѕ.
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nd conjunctivitis. The diagnosis is based on clinical criteria. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis".) TREATMENT — <span>The treatment of mеaѕlеѕ is supportive; there is no specific antiviral therapy approved for treatment of mеaѕleѕ. There is a role for vitamin A in certain settings, discussed below. Supportive therapy includes antipyretics, fluids, and treatment of bacterial superinfections, such as bacterial рոеսm




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Antibiotic prophylaxis during mеaѕlеѕ ерiԁemiсs may prevent complications; further study is needed [85,86].
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ids, and treatment of bacterial superinfections, such as bacterial рոеսmοnia and оtitis media. Treatment of other complications, such as seizures and respiratory failure, may also be necessary. <span>Antibiotic prophylaxis during mеaѕlеѕ ерiԁemiсs may prevent complications; further study is needed [85,86]. Vitamin A — Vitamin A deficiency contributes to delayed recovery and to risk of complications associated with mеaslеѕ infection. In addition, vitamin A levels fall during mеaslеs; in ch




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In resource-rich settings, data on use of vitamin A for treatment of mеaslеs are limited; one study including 108 inpatient children in Italy did not observe a benefit to vitamin A administration [89].
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<2 years and who received two doses of vitamin A (200,000 international units administered once daily for two consecutive days), lower mortality was observed (1.9 versus 10.7 percent) [88]. <span>In resource-rich settings, data on use of vitamin A for treatment of mеaslеs are limited; one study including 108 inpatient children in Italy did not observe a benefit to vitamin A administration [89]. For children with severe mеaѕlеs, we suggest administration of vitamin A; this approach is in alignment with the United States Centers for Disease Control and Prevention, which favors a




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For children with clinical signs and symptoms of severe vitamin A deficiency (such as xerophthalmia, keratitis, keratoconjunctivitis, corneal ulceration, or Bitot spots), a third dose of vitamin A should be administered four to six weeks later [1].
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days, as follows [1,2]: ●Infants <6 months of age − 50,000 international units ●Infants 6 to 11 months of age − 100,000 international units ●Children ≥12 months − 200,000 international units <span>For children with clinical signs and symptoms of severe vitamin A deficiency (such as xerophthalmia, keratitis, keratoconjunctivitis, corneal ulceration, or Bitot spots), a third dose of vitamin A should be administered four to six weeks later [1]. (See "Overview of vitamin A", section on 'Deficiency'.) Ribavirin — Given the risk of mеaѕlеѕ-associated mortality among individuals in certain risk groups, we agree with some experts w




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For children with severe mеaѕlеs, we suggest administration of vitamin A; this approach is in alignment with the United States Centers for Disease Control and Prevention, which favors administration of vitamin A to children hospitalized with severe mеasles [2]. In addition, for children in resource-limited settings with mеaѕlеs (regardless of severity), we suggest administration of vitamin A; this approach is in alignment with the World Health Organization guidance, which favors administration of vitamin A for children with acute meаѕles [1].

Dosing of vitamin A consists of oral administration once daily for two days, as follows [1,2]:

● Infants <6 months of age − 50,000 international units

● Infants 6 to 11 months of age − 100,000 international units

● Children ≥12 months − 200,000 international units

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rce-rich settings, data on use of vitamin A for treatment of mеaslеs are limited; one study including 108 inpatient children in Italy did not observe a benefit to vitamin A administration [89]. <span>For children with severe mеaѕlеs, we suggest administration of vitamin A; this approach is in alignment with the United States Centers for Disease Control and Prevention, which favors administration of vitamin A to children hospitalized with severe mеasles [2]. In addition, for children in resource-limited settings with mеaѕlеs (regardless of severity), we suggest administration of vitamin A; this approach is in alignment with the World Health Organization guidance, which favors administration of vitamin A for children with acute meаѕles [1]. Dosing of vitamin A consists of oral administration once daily for two days, as follows [1,2]: ●Infants <6 months of age − 50,000 international units ●Infants 6 to 11 months of age − 100,000 international units ●Children ≥12 months − 200,000 international units For children with clinical signs and symptoms of severe vitamin A deficiency (such as xerophthalmia, keratitis, keratoconjunctivitis, corneal ulceration, or Bitot spots), a third dose o




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Given the risk of mеaѕlеѕ-associated mortality among individuals in certain risk groups, we agree with some experts who favor use of ribavirin for treatment of mеasles рոеսmοniа in patients <12 months, patients ≥12 months with рոеumоոiа requiring ventilatory support, and immunosuppressed patients.
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nctivitis, corneal ulceration, or Bitot spots), a third dose of vitamin A should be administered four to six weeks later [1]. (See "Overview of vitamin A", section on 'Deficiency'.) Ribavirin — <span>Given the risk of mеaѕlеѕ-associated mortality among individuals in certain risk groups, we agree with some experts who favor use of ribavirin for treatment of mеasles рոеսmοniа in patients <12 months, patients ≥12 months with рոеumоոiа requiring ventilatory support, and immunosuppressed patients. Ribavirin dosing consists of 15 to 20 mg/kg per day orally in two divided doses. The optimal duration of therapy is not known; a duration of five to seven days may be reasonable, guided




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Ribavirin dosing consists of 15 to 20 mg/kg per day orally in two divided doses. The optimal duration of therapy is not known; a duration of five to seven days may be reasonable, guided by the patient's clinical status (respiratory symptoms and chest radiograph findings)
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experts who favor use of ribavirin for treatment of mеasles рոеսmοniа in patients <12 months, patients ≥12 months with рոеumоոiа requiring ventilatory support, and immunosuppressed patients. <span>Ribavirin dosing consists of 15 to 20 mg/kg per day orally in two divided doses. The optimal duration of therapy is not known; a duration of five to seven days may be reasonable, guided by the patient's clinical status (respiratory symptoms and chest radiograph findings). Меаѕleѕ virus is susceptible to ribavirin in vitro; data on clinical use of ribavirin are extremely limited [90-94]. In one trial including 100 children with mеaslеѕ treated with suppo




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In another report including six adults with severe mеаѕlеs pneumonitis treated with intravenous ribavirin, the five patients treated on day 2 to 5 of illness recovered; the patient treated on day 22 of illness did not recover [92]
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rial including 100 children with mеaslеѕ treated with supportive care (with or without ribavirin), those who received ribavirin had a shorter duration of fever and constitutional symptoms [90]. <span>In another report including six adults with severe mеаѕlеs pneumonitis treated with intravenous ribavirin, the five patients treated on day 2 to 5 of illness recovered; the patient treated on day 22 of illness did not recover [92]. Investigational therapies — Agents for treatment subacute sclerosing panencephalitis (ЅЅPЕ) have been evaluated with the goal of stabilization and delay of progression; these agents re




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Isoprinosine (inosine pranobex) has in vitro activity against mRNA viruses; it is administered orally and generally well tolerated. In one study including 98 individuals with SЅΡЕ, the probability of survival among treated patients at 2, 4, 6, and 8 years from onset of ЅSРΕ was 78, 69, 65, and 61 percent, compared with 38, 20, 14, and 8 percent in a composite control group [95].
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nal therapies — Agents for treatment subacute sclerosing panencephalitis (ЅЅPЕ) have been evaluated with the goal of stabilization and delay of progression; these agents remain investigational. <span>Isoprinosine (inosine pranobex) has in vitro activity against mRNA viruses; it is administered orally and generally well tolerated. In one study including 98 individuals with SЅΡЕ, the probability of survival among treated patients at 2, 4, 6, and 8 years from onset of ЅSРΕ was 78, 69, 65, and 61 percent, compared with 38, 20, 14, and 8 percent in a composite control group [95]. Interferon-alpha or beta has antiviral activity; it may be delivered both intrathecally and intravenously. Some data suggest transient survival benefit [96]. However, in one study inclu




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Interferon-alpha or beta has antiviral activity; it may be delivered both intrathecally and intravenously. Some data suggest transient survival benefit [96]. However, in one study including 67 individuals with SЅΡΕ, there was no difference in survival among patients treated with combination therapy (intraventricular interferon-alpha and isoprinosine) or isoprinosine monotherapy (35 percent); however, survival among the treated patients was higher than the historical control group (which reported spontaneous improvement in 5 to 10 percent of cases) [97].

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bability of survival among treated patients at 2, 4, 6, and 8 years from onset of ЅSРΕ was 78, 69, 65, and 61 percent, compared with 38, 20, 14, and 8 percent in a composite control group [95]. <span>Interferon-alpha or beta has antiviral activity; it may be delivered both intrathecally and intravenously. Some data suggest transient survival benefit [96]. However, in one study including 67 individuals with SЅΡΕ, there was no difference in survival among patients treated with combination therapy (intraventricular interferon-alpha and isoprinosine) or isoprinosine monotherapy (35 percent); however, survival among the treated patients was higher than the historical control group (which reported spontaneous improvement in 5 to 10 percent of cases) [97]. PREVENTION Measles, mumps, and rubella vaccination — Vаϲϲinаtioո has led to interruption of mеаsles virus transmission in the developed world and affords protection to unvaccinated indi




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To disrupt broad transmission, herd immunity must be maintained above 85 to 95 percent [98].
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, mumps, and rubella vaccination — Vаϲϲinаtioո has led to interruption of mеаsles virus transmission in the developed world and affords protection to unvaccinated individuals via herd immunity. <span>To disrupt broad transmission, herd immunity must be maintained above 85 to 95 percent [98]. Issues related to vаϲϲiոatioո for prevention of mеаsles are discussed further separately. (See "Measles, mumps, and rubella immunization in adults" and "Measles, mumps, and rubella immu




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Infection control — In the inpatient setting, airborne transmission precautions are indicated for four days after the onset of rаѕh in otherwise healthy patients and for the duration of illness in immսոοϲοmрrοmiѕеԁ patients [99]
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ion of mеаsles are discussed further separately. (See "Measles, mumps, and rubella immunization in adults" and "Measles, mumps, and rubella immunization in infants, children, and adolescents".) <span>Infection control — In the inpatient setting, airborne transmission precautions are indicated for four days after the onset of rаѕh in otherwise healthy patients and for the duration of illness in immսոοϲοmрrοmiѕеԁ patients [99]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Airborne precautions'.) Susceptible individuals should not enter the room of patients wit




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Susceptible individuals should not enter the room of patients with suspected or confirmed mеаslеѕ. Exposed susceptible individuals should be excluded from work from day 5 through day 21 after exposure. If the case is confirmed, even those who were vaccinated within 72 hours should be excluded.
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tients and for the duration of illness in immսոοϲοmрrοmiѕеԁ patients [99]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Airborne precautions'.) <span>Susceptible individuals should not enter the room of patients with suspected or confirmed mеаslеѕ. Exposed susceptible individuals should be excluded from work from day 5 through day 21 after exposure. If the case is confirmed, even those who were vaccinated within 72 hours should be excluded. In the outpatient setting, patients with febrile rаѕh illness should be escorted to a separate waiting area or placed immediately in a private room, preferably at negative pressure rela




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In the outpatient setting, patients with febrile rаѕh illness should be escorted to a separate waiting area or placed immediately in a private room, preferably at negative pressure relative to other patient care areas. Both patients and staff should wear appropriate masks/respirators (masks for patients to prevent generation of droplets, and respirators for staff to filter airborne particles, regardless of immunity status) [100]. If not admitted, patients should be told to remain in isolation at home through four days after rash onset.
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posed susceptible individuals should be excluded from work from day 5 through day 21 after exposure. If the case is confirmed, even those who were vaccinated within 72 hours should be excluded. <span>In the outpatient setting, patients with febrile rаѕh illness should be escorted to a separate waiting area or placed immediately in a private room, preferably at negative pressure relative to other patient care areas. Both patients and staff should wear appropriate masks/respirators (masks for patients to prevent generation of droplets, and respirators for staff to filter airborne particles, regardless of immunity status) [100]. If not admitted, patients should be told to remain in isolation at home through four days after rash onset. Меаslеs virus can remain suspended in the air for up to two hours; therefore, the room occupied by a suspect case should not be used for two hours after the patient's departure. SOCIETY




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Меаslеs virus can remain suspended in the air for up to two hours; therefore, the room occupied by a suspect case should not be used for two hours after the patient's departure.
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irators for staff to filter airborne particles, regardless of immunity status) [100]. If not admitted, patients should be told to remain in isolation at home through four days after rash onset. <span>Меаslеs virus can remain suspended in the air for up to two hours; therefore, the room occupied by a suspect case should not be used for two hours after the patient's departure. SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline link




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Measles, also known as rubeola, is one of the five classic childhood exanthems, along with rubella, roseola, fifth disease, and chickenpox.
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Historically, measles was one of the most common and unpleasant viral infections, with serious potential sequelae
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Before 1960, more than 90% of the popu- lation younger than 20 years had experienced the rash, high fever, cough, conjunctivitis, and coryza of measles
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Measles is still one of the most prominent causes of disease (>10 million cases per year) and death (120,000 deaths in 2012) worldwide in unvaccinated populations.
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Measles virus binds to the CD46 (membrane cofactor protein [MCP]) present on most cell types, nectin 4 on epithelial cells, and also CD150 (signaling lymphocyte-activation mol- ecule [SLAM]), which is expressed on activated T and B cells.
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Virus production occurs with eventual cell lysis. Persistent infections without lysis can occur in certain cell types (e.g., human brain cells)
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After local replication of virus in epithelial cells of the respi- ratory tract, the virus infects monocytes and lymphocytes, and the virus is spread through the lymphatic system and by a cell-associated viremia.
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The wide dissemination of the virus causes infection of the conjunctiva, respiratory tract, urinary tract, small blood vessels, lymphatic system, and central nervous system.
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The characteristic maculopapular measles rash is caused by immune T cells targeted to measles- infected endothelial cells lining small blood vessels.
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FIGURE 48-4 Time course of measles virus infection.
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Characteristic prodrome symptoms are cough, conjunctivitis, coryza, and photophobia (CCC and P), followed by the appearance of Koplik spots and rash. SSPE, Subacute sclerosing panencephalitis
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FIGURE 48-3 Mechanisms of spread of the measles virus within the body and the pathogenesis of measles.
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CMI, Cell-mediated immunity; CNS, central nervous system.
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Measles can cause encephalitis in three ways: (1) direct infection of neurons, (2) a postinfectious encephalitis that is believed to be immune mediated, and (3) subacute scleros- ing panencephalitis (SSPE) caused by a defective variant of measles generated during the acute disease.
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The SSPE virus replicates poorly, stays cell associated, and causes symptoms and cytopathologic effect in neurons many years after acute disease
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Measles and other paramyxoviruses are excellent induc- ers of interferon (IFN)-α and IFN-β but also have mecha- nisms to antagonize their action. Cell-mediated immunity is responsible for most of the symptoms and is essential for control of measles infection
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T-cell–deficient children who are infected with measles have an atypical presentation con- sisting of giant cell pneumonia without a rash.
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Antibody, including maternal antibody and passive immunization, can block the viremic but not cell-cell spread of the virus to prevent or lessen disease
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Measles infection is immunosuppressive. The virus depresses the immune response by (1) directly infecting monocytes and T and B cells and (2) depressing interleukin (IL)-12 production and TH1-type T-cell helper responses
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Depression of cell-mediated immune and delayed-type hypersensitivity (DTH) responses increases risk to concur- rent opportunistic and other infections. This immunosup- pression lasts for weeks or months after the disease
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In a household, approximately 90% of exposed susceptible people become infected, and 95% of these people develop clinical disease
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The measles virus has only one serotype and infects only humans, and infection usually manifests with symptoms. These properties facilitated development of an effective vaccine program
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Measles is a serious febrile illness (Table 48-3). The incuba- tion period lasts 7 to 13 days, and the prodrome starts with high fever and “CCC and P”—cough, coryza, conjunctivi- tis, and photophobia. The disease is most infectious during this time.
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After 2 days of prodromal illness, the typical mucous membrane lesions known as Koplik spots (Figure 48-5) appear. They are seen most commonly on the buccal mucosa across from the molars, but they may appear on other mucous membranes as well, including the conjunctivae and the vagina. The vesicular lesions, which last 24 to 48 hours, are usually small (1 to 2 mm) and are best described as grains of salt surrounded by a red halo. Their appearance with the other disease signs establishes with certainty the diagnosis of measles
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Within 12 to 24 hours of the appearance of Koplik spots, the exanthem of measles starts below the ears and spreads over the body. The rash is maculopapular and is usually very extensive, and often the lesions become confluent. The rash, which takes 1 or 2 days to cover the body, fades in the same order in which it appeared. The fever is highest and the patient is sickest on the day the rash appears (Figure 48-6)
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Pneumonia, which can also be a serious complication, accounts for 60% of the deaths caused by measles.
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One of the most feared complications of measles is encephalitis, which occurs in as few as 0.5% of those infected but carries a fatality rate of 15%
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Encephalitis may rarely occur during acute disease but usually begins 7 to 10 days after the onset of illness. This postinfectious encephalitis is caused by immunopathologic reactions, is associated with demyelination of neurons, and occurs more often in older children and adults.
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Atypical measles occurred in people who received the older inactivated measles vaccine and were subsequently exposed to the wild-type measles virus. It may also rarely occur in those vaccinated with the attenuated virus vaccine. Prior sensitization with insufficient protection can enhance the immunopathologic response to the challenge by wild- type measles virus. The illness begins abruptly and is a more intense presentation of measles.
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Unusually high levels of measles antibodies are found in the blood and cerebrospinal fluid of patients with SSPE. Measles antigen and genome can be detected in neurons as well as Cowdry type A inclusion bodies (these inclusion bodies are usually a marker for herpes simplex virus but are also seen in SSPE)
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Giant cell pneumonia without rash occurs in chil- dren lacking T-cell immunity. Whereas the death rate of measles in the United States is only 0.1%, complications, severe bacterial superinfection, and pneumonia in malnour- ished children result in up to 60% mortality
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In a case reported by Pullan and associates (Br Med J 1:1562–1565, 1976), within 3 days of exposure to measles, a child on chemotherapy for acute lymphoblastic leukemia (ALL) received pooled immunoglobulin. Despite the IgG therapy, 23 days after exposure, she developed an extensive measles rash that became hemorrhagic. She had a fever of 39.5° C and broncho- pneumonia. Measles was grown from nasopharyngeal secretions, and immunohistochemistry identified giant cells (syncytia) containing measles antigen within the secretions. Her chemotherapy was stopped, and she received several massive doses of immunoglobulin. She started to improve 1 month after the onset of the rash
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In another case, during the 2.5 years that a boy was under treatment for ALL, he suffered severe herpes simplex virus infections around the mouth and herpes zoster on his trunk. During the third year on therapy, he was exposed to measles from his sister and received pooled IgG. After 19 days, he developed mild respiratory symptoms but no rash. After 29 days, he refused to go to school and misbehaved; behavioral changes progressed. After 9 weeks, he developed focal motor seizures, increased drowsiness, slurring of speech, and confusion, which progressed to coma and death within 8 days of the onset of seizures. Serology indicated a lack of measles antibody. Autopsy indicated the presence of cytomegalovirus but not measles in the lungs. The brain showed extensive degeneration, but no virus was isolated from the samples. Brain sections indicated large intranuclear and cytoplasmic inclusion bodies with tubular structures that resembled measles nucleocapsids in the cytoplasm. Immunofluorescence with antibody from individuals with subacute sclerosing panencepha- litis (SSPE) or antimeasles antibody indicated the presence of measles antigen. These cases illustrate the excessive pathology measles can cause in the absence of a competent T-cell response. The lack of immune control allowed progression of the virus to the brain, where it or a variant (SSPE) caused pathology leading to encephalitis
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