on 09-May-2025 (Fri)

With a fully modularized code base registered in Git, each of them can check out a feature branch from the master, make small edits to the modules that are part of their features, write new tests (if needed), run their tests, and submit a pull request. Once their work is complete—because of the configuration-based code and the capability of the methods in each module class to act upon the data for their project through leveraging the job configuration—each feature branch will not impact the other and should just work as designed. Julie and Joe can cut a release branch of both of their changes in a single build, run a full integration test, and safely merge to the master, confident that their work is correct. They can, in effect, work efficiently together on the same code base, greatly minimizing the chance of errors and reducing the amount of time spent debugging code.

Before the introduction of the measles vaccine, over two million deaths occurred annually.

Measles occurs predominantly in areas with low vaccination rates, particularly resource-limited settings [9]

However, even in resource-rich settings, outbreaks of measles have occurred in settings where vaccination uptake has declined, allowing for transmission of imported measles virus from unvaccinated and infected travelers [ 10-12]

Individuals at risk for measles include children too young to be vaccinated, those who have not been vaccinated for medical or other reasons, those who have not received a second dose of measles vaccine, and those for whom the vaccine failed to elicit a protective immune response (a very small fraction of those immunized with two doses of vaccine)

Measles is highly contagious; the attack rate in a susceptible individual exposed to measles is 90 percent [14,15]

Transmission occurs via person-to-person contact as well as airborne spread.

Infectious droplets from the respiratory secretions of a patient with measles can remain airborne for up to two hours [ 15,16]

The incubation period for measles is 6 to 21 days (median 13 days) [20]. Subclinical illness is unusual. The period of contagiousness is estimated to be from five days before the appearance of rash to four days afterward. The period of maximum contagiousness is thought to be during the late prodrome phase, when the patient is febrile and has respiratory symptoms.

Patients with measles-associated subacute sclerosing panencephalitis are not contagious [ 21].

In temperate areas, the peak incidence of measles occurs in the late winter and early spring. However, cases occur throughout the year and, in some regions, no seasonal incidence is apparent.

Natural measles infection is thought to confer lifelong immunity.

Immunity due to measles vaccination is also highly protective against clinical infection [ 23]. During an outbreak in the Netherlands, for example, unvaccinated individuals were 224 times more likely to become infected compared with vaccinated individuals [24]

Children of mothers vaccinated against measles have lower concentrations of transplacentally acquired maternal antibodies to measles (and therefore lose protection afforded by maternal antibodies at an earlier age) than children born to mothers with immunity acquired from natural infection [25-28]. As a result, measles occurs more commonly among children <12 months in countries with high measles vaccine coverage [6,29].

Adults with measles are at increased risk of mortality compared with older children, and measles in pregnancy is associated with premature labor and spontaneous abortion [3].

It is rare for immunocompetent individuals to not be fully immune after two doses of MMR (table 1)

Measles vaccination usually leads to long-term immunity. In the United States, measles antibodies develop in 96 percent of individuals vaccinated at age 12 months and in 98 percent of individuals vaccinated at age 15 months [3,5]. For the small percentage of nonresponders to the first vaccine dose, a second dose will result in seroconversion in 90 percent of cases [6], resulting in 99 percent immunity among individuals who have received two doses of measles vaccine [7]. Thus, the second vaccine dose generally provides immunity among nonresponders to the first dose. There are no compelling data to support a routine third dose of MMR vaccine for the prevention of measles [8].

Measles can occur in previously vaccinated individuals. As an example, in one study including 232 cases of measles in California between 2000 and 2015, 13 individuals (11 percent) had received ≥2 doses of measles vaccine [9].

In another study of over 4000 measles cases, 12 percent were breakthrough infections, defined as an infection in an individual who has received at least one dose of the MMR vaccine [ 10]. Most patients with breakthrough infections were ≥20 years old. Individuals with breakthrough infections have milder disease.

Measles antibody titers have been shown to decrease over time [ 11-14]. Most people with waning antibody titers after vaccination have an anamnestic response to revaccination, suggesting continued immunity [7], although at least one analysis has suggested that waning immunity contributes to lower vaccine efficacy [15].

Immunocompetent adults without measles immunity who are exposed to an individual with suspected or confirmed measles should receive a two-dose regimen of the MMR vaccine.

The evidence for the efficacy of the MMR vaccine administered as postexposure prophylaxis for prevention of measles is limited and mixed [16-18]. Prophylactic postexposure vaccination may provide some protection in settings of limited contact such as schools and daycare centers [1]. Efficacy is likely to be diminished in household settings with intense contact because, in these settings, individuals are exposed for prolonged duration during the prodromal period when the index patient is infectious.

Mumps vaccination seroconversion rates range from 84 to 100 percent [19].

A third dose of MMR vaccine may be useful to limit transmission of mumps in outbreak settings that occur in high-density, close-contact settings, given the possibility of two-dose mumps vaccine failure due to waning of vaccine-induced immunity [24,25]. In one mumps outbreak during which 1755 students (80 percent of students in grades 6 to 12) received a third dose of MMR vaccine, mumps attack rates declined from 4.9 percent (three weeks before vaccination) to 0.13 percent (three weeks after vaccination) [25].

In general, immunity to measles and mumps may be presumed for adults born before 1957; health care workers are an exception (see 'Health care workers' below).

In contrast, immunity to rubella is not assured and should be determined by laboratory testing for all women of childbearing age, regardless of birth year.

There is no increase in vaccine-associated adverse reactions in people who are already immune to measles, mumps, and/or rubella [3].

Formal documentation of immunity to measles, mumps, and rubella should be established for adults in the following categories:

• Students in post-secondary educational institutions

• Health care workers (see 'Health care workers' below)

• International travelers

• Individuals with human immunodeficiency virus (HIV) who do not have current evidence of severe immunocompromise (defined as CD4+ T lymphocyte [CD4] percentage <15 percent or CD4 count <200 cells/microL) (see "Immunizations in persons with HIV", section on 'Measles, mumps, and rubella vaccine')

• Hematopoietic cell transplant (HCT) recipients 24 months following HCT who are no longer receiving immunosuppression and do not have active graft-versus-host-disease [45]

Formal documentation of immunity to measles should be established for:

• Individuals at risk for exposure during an outbreak (see 'Outbreak settings' below and "Measles: Epidemiology and transmission", section on 'Transmission')

• Individuals previously vaccinated with attenuated measles vaccine accompanied by immune globulin or high-titer immune globulin

• Individuals previously vaccinated with killed measles vaccine or vaccine of unknown type between 1963 and 1967

• Close contacts of immunocompromised individuals

Pregnant women who do not have evidence of immunity should receive MMR vaccine upon completion or termination of pregnancy and before discharge from the health care facility. Repeat testing for serologic evidence of immunity thereafter is not required.

For health care workers who have no laboratory evidence of immunity to measles or mumps (or laboratory confirmation of disease), two doses of MMR should be given at least four weeks apart. If they only lack laboratory evidence of immunity to rubella, at least one dose of MMR should be given [48].

Health care workers without evidence of immunity who were exposed to an individual with measles should be excluded from the workplace from day 5 through day 21 after exposure. If the case is confirmed, even those who were vaccinated within 72 hours should be excluded [49,50].

In a measles outbreak setting, it is important to determine which individuals are incompletely immunized against measles and to vaccinate all eligible individuals without contraindications. Administration of immune globulin should not be used for outbreak control [3].

For individuals with an incomplete or unknown vaccination history or those with documentation of only one dose of a live measles virus-containing vaccine, we check measles antibody titers. Detectable antibody titers indicate the person has immunity to measles. Individuals with undetectable titers are generally considered not immune.

For nonimmune individuals who have no contraindication to MMR vaccination, we recommend two doses of MMR separated by at least 28 days [1].

Some individuals cannot receive the MMR vaccine due to pregnancy or an immunocompromising condition. These individuals should try to limit their exposure to settings where infected or exposed people may be present as much as feasibly possible. If exposure to measles occurred, postexposure prophylaxis may be indicated. (See 'Postexposure prophylaxis' below.)

Immunocompromising conditions include solid organ and/or hematopoietic stem cell transplants, chimeric antigen receptor T cell therapy, B-cell depleting therapy, targeted immunosuppressive biologic and small-molecule therapies, or have HIV-associated immunosuppression (CD4 percentage <15 percent) (table 2). A more complete list can be found on Canada's National Advisory Committee on Immunization (NACI) measles vaccine website.

Individuals unable to produce documentation of measles immunity and cannot get vaccinated should avoid outbreak settings for a minimum of three weeks after the onset of rash in the last measles case.

In a mumps outbreak setting, individuals who are incompletely immunized against mumps should receive two doses of MMR separated by at least 28 days [1]. Individuals who have been previously vaccinated with two doses of MMR vaccine should receive a third dose of mumps virus-containing vaccine [51]

Postexposure prophylaxis following measles exposure depends on whether the individual has any contraindications to the MMR vaccine. MMR vaccination should be administered within 72 hours of exposure [1,52,53].

For nonimmune pregnant individuals and immunocompromised individuals who have been exposed to a person with measles, we suggest immune globulin (intravenous immunoglobulin [IVIG]; 400 mg/kg) within six days of exposure

Immunocompromised individuals should receive IVIG regardless of their measles vaccination status due to their increased susceptibility to measles infection.

Nonimmune individuals should receive the MMR vaccine series when they are no longer immunocompromised/pregnant and at least six to eight months have passed since immune globulin administration (six months for intramuscular [IM] immune globulin, eight months after IVIG).

Immune globulin can prevent or diminish the severity of measles if administered to nonimmune individuals within six days of exposure [1,3,7,54].

Following mumps or rubella exposure, neither postexposure MMR nor immune globulin has been shown to prevent disease or lessen disease severity in the absence of an outbreak [1].

Measles, mumps, and rubella (MMR) and measles, mumps, rubella, and varicella (MMRV) vaccines should not be administered to individuals who have certain conditions (table 2) [1,42]

Severe allergic reaction (eg, anaphylaxis) after a previous dose of MMR or to a vaccine component (eg, neomycin, gelatin).

Pregnancy or attempting to become pregnant – Women should be counseled to avoid becoming pregnant for 28 days after receiving MMR because of the theoretic risk of congenital rubella syndrome [1]

Immunodeficiency – Individuals with immunodeficiency are at risk for severe complications following immunization with live attenuated virus vaccines (eg, encephalitis, pneumonitis) [1,55-60]

Long-term immunosuppressive therapy, including chemotherapy for malignancy, immunosuppression for transplant recipients, or large daily doses of corticosteroids (equivalent to ≥20 mg per day of prednisone) for ≥2 weeks [61]; MMR should be avoided for at least one month after high-dose corticosteroid therapy

Close contacts of patients with contraindications to MMR should receive routine vaccination; secondary transmission associated with MMR vaccination has not been reported [62].

Whether measles, mumps, and rubella (MMR) should be administered to individuals with current illness depends upon the severity of the illness. MMR can be safely administered to individuals with mild illness, with or without fever (eg, upper respiratory infection, otitis media, gastroenteritis); seroconversion is not affected by mild illness [63-65].

It is appropriate to delay administration of MMR in the setting of moderate to severe illness unless the vaccine is being administered for measles exposure.

Receipt of immune globulin or antibody-containing blood products can blunt or block the host response to certain live virus vaccines. The suggested interval between receipt of immune globulin or antibody-containing blood products and administration of MMR varies depending upon the product (table 3) [47,61,66].

MMR may temporarily reduce tuberculin skin test (TST) sensitivity [71]. The effect of MMR vaccination on interferon-gamma release assay (IGRA) is uncertain [1].

If TST or IGRA is warranted for evaluation of tuberculosis, they should be performed before, at the same visit as, or four to six weeks after MMR vaccination [1]

Individuals with a history of thrombocytopenia or thrombocytopenic purpura may have an increased risk of clinically significant thrombocytopenia following immunization with MMR [1].

Decisions regarding administration of the first dose MMR to individuals with a history of thrombocytopenia are made on a case-by-case basis contingent upon the assessment of risks and benefits. In many cases, the benefits outweigh the risks.

Factors to be considered in the decision include:

• Recurrence of thrombocytopenia following MMR in individuals with a history of thrombocytopenia (both vaccine-associated and nonvaccine-associated) has been reported [67-70], but the magnitude of the risk is unknown.

• The likelihood of exposure to MMR (eg, plans for international travel, level of MMR vaccination coverage in the community, etc).

Serologic testing can be performed to determine whether the second dose of MMR is necessary. Individuals with protective levels of antibody to MMR do not need to receive the second dose.

Individuals with a personal or family history of seizures have an increased risk of febrile seizures following MMR, although this does not outweigh the benefits of immunization with MMR or measles, mumps, rubella, and varicella (MMRV) [72,73]; the risk of seizures in children was estimated at one additional seizure per 2300 doses of MMRV versus MMR [74]

MMR vaccine can be administered to patients on antivirals. However, for patients receiving MMRV vaccine, antiviral drugs with activity against herpes viruses (eg, acyclovir, valacyclovir) may interfere with the varicella component of the vaccine; for these patients, the antiviral should be discontinued ≥24 hours before administration of the MMRV vaccine and avoided for 14 days after vaccination.

Adverse reactions to measles, mumps, and rubella (MMR) include fever, rash, lymphadenopathy, joint complaints, hypersensitivity reactions, development of immune thrombocytopenia (ITP), and seizures. These reactions occur more frequently with the first than with the second dose [75].

Fever (>39.4ºC) develops in 5 to 15 percent of MMR recipients, usually within 6 to 12 days after immunization [47].

Rash – Transient rashes also occur in approximately 5 percent of MMR recipients [47]. The combination of fever and rash after MMR immunization generally is attributed to the measles vaccine virus but may be due to wild-type measles or other viral illnesses [76]; virologic studies may be warranted in individuals with potential exposure to wild-type measles (eg, international travel, contact with immigrants).

Lymphadenopathy – Transient lymphadenopathy occurs in 5 percent of children and 20 percent of adults [1].

Joint manifestations – Joint manifestations secondary to the rubella component of the vaccine may occur 7 to 21 days after MMR immunization [47]. Arthralgia occurs in 25 percent of adults, and 10 percent develop arthritis [3].

Hypersensitivity reactions to the MMR are usually minor (wheal and flare or urticaria) and have been attributed to trace amounts of neomycin or gelatin but not to egg antigens since MMR does not contain significant amounts of egg-white cross-reacting proteins [47,77,78]

Thrombocytopenia has been observed in prospective studies (1 case in 25,000 to 40,000 vaccine doses) [3]. In general, it is transient and occurs within two months of the receipt of the vaccine, most commonly at two to three weeks.

Febrile seizure – The incidence of vaccine-associated seizures has been estimated to be 1 in 3000 MMR doses [3] but is increased in individuals with a history of seizures or with a family history in first-degree relatives. Most are simple febrile seizures and in most cases, the benefits of vaccination outweigh the risk of seizures.

Measles, mumps, and rubella (MMR) combination vaccines are supplied as a lyophilized (freeze-dried) powder with a separate diluent. Only the diluent that is supplied with the vaccine should be used to reconstitute it; any dose of vaccine that is reconstituted with the incorrect diluent should be repeated.

Immunogenicity appears to be similar with intramuscular (IM) and subcutaneous administration, and some formulations have also been approved for administration via the IM route; refer to local product information for guidance [80-82]

The dose of MMR is 0.5 mL [61]. All formulations of MMR can be administered subcutaneously with a 5/8 inch (1.6 cm), 23-to 25-gauge needle [80,81]. The site of subcutaneous administration of individuals >12 months of age is usually the upper outer triceps

If a formulation intended for subcutaneous use is administered intramuscularly, the dose need not be repeated.

MMR may be administered at the same clinic visit as other immunizations [83]. However, if live attenuated vaccines (eg, MMR, varicella, live attenuated influenza, yellow fever) are not administered at the same clinic visit, they should be separated by ≥28 days [61]. Administration at <28 days may impair the immune response to one of the vaccines [84-86].

Egg allergy — Egg allergy is not a contraindication or precaution to MMR; vaccination can be administered to individuals with egg allergy without prior skin testing or special protocols [1].