on 26-Aug-2026 (Wed)

Approximately one-half of patients who acquire the infection develop symptoms; the other half develop asymptomatic seroconversion [1,2]

Among symptomatic patients, most (over 90 percent) present with acute Q fever, and the remainder present with chronic Q fever [3].

Among patients with symptomatic acute Q fever, the time interval between exposure and onset of symptoms (iе, incubation period) ranges from one to five weeks, with a median of 18 days [4]

A febrile syndrome similar to influenza is common; in a series from the United States, 25 percent of patients presented with flu-like illness [5]. Along with fever, patients typically experience severe headache, myalgia, fatigue, chills, cough, and night sweats [5-8]. Onset of symptoms is often abrupt with high fever. In untreated patients, the illness typically persists for one to three weeks, but it can last longer [9]. In patients with fever of unknown origin (ie, unexplained fever that lasts longer than three weeks), Q fever should be included in the differential diagnosis, particularly in the endemic regions or if a known exposure exists [6,10].

Q fever is a documented cause, albeit rare, of community-acquired pneumonia. Among patients with acute Q fever, pneumonia is not uncommon; it was reported in 16 percent of patients in a series from the United States [5].

Most cases of Q fever pneumonia are mild with a nonproductive cough and fever, but severe cases can occur [11].

Radiologic findings vary and may include rounded opacities (with or without a halo sign); interstitial, ground-glass, or lobar infiltrates; necrotizing pneumonia; or a tumor-like mass [1].

In a retrospective study comparing radiographic findings of Q fever pneumonia with pneumonia due to Streptococcus pneumoniae, ground-glass opacities and lymphadenopathy were predictors of Q fever pneumonia; alveolar consolidation was common in both infections [12]

Q fever pneumonia may be accompanied by extrapulmonary manifestations, including elevated liver enzymes

Hepatitis in acute Q fever manifests with fever and mild elevation of liver enzymes, mainly aminotransferases [13]. In some patients, severe acute hepatitis may occur. Jaundice and cholestatic hepatitis may rarely occur [14]. Fevers may be prolonged. If liver biopsy is performed, a fibrin ring doughnut-like granuloma is a characteristic feature in patients with severe hepatitis [6]

Cutaneous – Rashes have been reported in 1 to 10 percent of cases in case series of acute Q fever [1,15]

Neurologic – Aseptic meningitis, encephalitis, myelitis, and peripheral neuropathy have been reported [16]. ● Cardiac – Pericarditis, myocarditis, and atrioventricular conduction block have been reported [17-19]. ● In a case series from France, acute еոԁοϲarditiѕ was described and was associated with increased anticardiolipin levels; it was unclear whether the valvular vegetations noted on echocardiogram were sterile (due to anticardiolipin deposition) or infected by C. burnetii [20]. Inflammatory or malignant – Hemophagocytic lymphohistiocytosis, lymphoma, and lymphadenitis have all been associated with Q fever [21-24]. ● Ophthalmic – Optic neuritis and chorioretinitis have been reported in case reports [25,26]

Acute Q fever during pregnancy is asymptomatic in 90 percent [28]. However, symptomatic and asymptomatic acute infections are associated with fetal complications including miscarriage, intrauterine fetal death, intrauterine growth retardation, and premature labor [3]

Clinical manifestations may depend, among other factors, on where the patient acquired the infection. Geographic differences in clinical presentation may reflect different genotypes of the bacterium in certain locales and genetic variations in patients with infections [29,30]

Australia – Hepatitis in 63 percent and pneumonia in 3 percent (73 patients) [31]

France – Hepatitis in 40 percent, pneumonia in 17 percent, and pneumonia with hepatitis in 20 percent (1070 patients) [32].

Spain – Northern region: pneumonia in 71 percent and hepatitis in 13 percent; Central/Southern regions: isolated fever in 40 percent, hepatitis in 38 percent, and pneumonia in 17 percent [35].

Netherlands – Pneumonia in 86 percent and mildly elevated alanine aminotransferase in 32 percent (183 patients) [33].

In nonpregnant patients, we suspect the diagnosis of acute Q fever in individuals who have risk factors for infection and a compatible syndrome (febrile illness, community-acquired pneumonia, hepatitis, etc). The diagnosis is also considered in patients without risk factors since some patients do not have an identified epidemiologic risk [36].

Risk factors for infection include direct exposure to livestock (eg, veterinarians, farmers, slaughterhouse workers), laboratory exposure to C. burnetii, or living near livestock. Further details regarding geographic epidemiology and risk factors are found separately.

Because C. burnetii does not grow in standard blood cultures, the microbiologic diagnosis relies on detection of antibodies against C. burnetii (serology tests) and molecular detection of the pathogen in blood (eg, polymerase chain reaction [PCR]).

Serologic diagnosis of acute infection is based on detection of antibodies against phase II C. burnetii. For suspected acute Q fever, we recommend obtaining acute and convalescent antibody immunoglobulin M (IgM) and immunoglobulin (IgG) titers.

a repeat "convalescent" test is obtained 2 to 10 weeks later. A conversion of phase II IgG from negative to positive or a fourfold change in titer confirms the diagnosis of acute Q fever. The same test kit or manufacturer should be used to allow accurate comparison of results

A probable test result is defined as a positive phase II IgM plus a simultaneous phase II IgG ≥128 (or 200 depending on the specific kit). In an endemic setting, this combination of test results is challenging to interpret because high titers of phase II IgG can persist for many years, and IgM antibodies can be falsely positive; a convalescent sample provides clarification [37]

Polymerase chain reaction (PCR) is particularly useful for diagnosis of acute Q fever early in the illness, before serologic tests become positive. The test is most sensitive between days 3 and 7 of illness and declines once IgG phase II antibodies become detectable ( figure 1)

Patients with risk factors for Q fever (eg, farm exposure) are often at risk for tick-borne and mosquito-borne infections that cause flu-like symptoms. Such infections depend on geographic locale and include ehrlichiosis, anaplasmosis, Lyme disease, rickettsial infections, malaria, Dengue virus, Zika virus, chikungunya virus, Oropouche virus, and others.

Viral infections can mimic Q fever, including influenza, coronavirus disease 2019 (COVID-19), acute human immunodeficiency virus (HIV), and other common respiratory pathogens (eg, cytomegalovirus, enterovirus, adenovirus).

Outdoor exposure, particularly in agricultural settings, is a risk factor for infections such as brucellosis and leptospirosis. These conditions have a broad range of presentations that may mimic Q fever.

Bacterial and viral causes of pneumonia, including atypical pathogens (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella spp), should be considered

Fungal and mycobacterial infections, including histoplasmosis, blastomycosis, coccidioidomycosis, and tuberculosis, may present with imaging findings sometimes found in Q fever (eg, round mass-like infiltrates, halo phenomenon).

Malignancy may have clinical and imaging features similar to Q fever. Malignancy should especially be considered if clinical findings fail to resolve with appropriate antibiotic therapy.

Viral hepatitis (hepatitis A, B, C, or E) should be considered in patients with fever and abnormal liver function tests. In addition, many of the above infectious etiologies can cause liver test abnormalities, including cytomegalovirus, ehrlichiosis, anaplasmosis, brucellosis, leptospirosis, and atypical pneumonia pathogens.

Because 1 to 5 percent of patients with acute Q fever eventually develop chronic Q fever, including еոԁοсаrditiѕ, risk stratification using echocardiography has been proposed by some experts [1,3,22,40-42]

We obtain echocardiography for all patients with acute Q fever who have any of the following risk factors for acute or chronic Q fever еոԁοсаrԁitis [1,3,40,41,43]

History of known or suspected valvulopathy● Findings consistent with еոԁοϲаrditis on physical examination (eg, heart murmur, heart failure, potential embolic events such as stroke, Janeway lesions) (see "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Clinical manifestations') ● Prosthetic heart valve● Vascular aneurysm or graft● Pregnancy● Immunosuppression● Age >50 years

Some experts obtain echocardiography for all patients with acute Q fever, regardless of risk factors

French experience with universal echocardiography for all patients with acute Q fever – Data from France arose from a referral center that managed patients with Q fever for decades. Their protocol was to obtain screening echocardiography in all patients with acute Q fever and to provide one year of prophylaxis to patients with valvulopathy. They reported high rates of subsequent еոԁοcаrditiѕ (up to 39 percent) in patients with valvulopathy [40]. Screening echocardiography led to the discovery of unsuspected valvulopathy in some patients [43] and rare cases of acute еոԁοϲаrditis in others [20].

Potential sources of uncertainty from the French experience include the selection bias inherent in data from a referral center, including the possibility of more severely ill patients. Also, the severity of valvulopathy and treatment regimens for acute fever were unclear in some case series

Dutch experience with limited echocardiography for patients with acute Q fever – Data from the Netherlands arose from an outbreak of over 4000 cases of Q fever from 2007 to 2010. During 2007 and 2008, screening echocardiography was recommended for all patients with acute Q fever [44-46]. The largest case series evaluated 509 patients with acute Q fever over an eight-year period, of whom 306 received a screening echocardiogram [46]. After treatment for acute Q fever following a specific protocol, subsequent development of chronic Q fever (including еոԁοсаrditiѕ) was not dependent on whether an echocardiogram was performed or its results [47]. No antibiotic prophylaxis was given to any patients, regardless of the presence or severity of valvulopathy. Overall, development of chronic Q fever occurred in 26 of 509 patients (5 percent); most cases were vascular infection as opposed to еոԁοсаrԁitiѕ. After the first year of the outbreak, screening echocardiography was discontinued due to limited efficacy and high resource cost

A potential source of uncertainty from the Dutch experience is the low proportion of moderate or severe valvulopathy (18) and prosthetic valves (1) in case patients; in countries with high baseline rates of severe valvular disease (eg, rheumatic fever), the results may not be applicable.

For nonpregnant patients with asymptomatic infection (ie, recent seroconversion) or resolved symptoms, we do not provide treatment. This approach is in alignment with the CDC guidelines for management of Q fever [3]

The most consistently reported advantage of antimicrobial treatment is shortening the duration of symptoms [48]. Without treatment, the median time to defervescence is 9 to 14 days, which is reduced to around three days with effective treatment [9,48,49].

Early treatment also reduces hospitalization. In a retrospective study from the Netherlands that included 388 patients with acute Q fever, appropriate antibiotics reduced risk of hospitalization compared with ineffective antibiotics (odds ratio [OR] 0.04, 95% CI 0.01-0.22). Treatment delay of more than seven days was associated with increased risk of hospitalization [50]

Observational studies suggest that treatment may decrease the likelihood of progression to chronic Q fever, but the studies lack statistical power to make definitive conclusions [41,48,50].

There is no evidence that treatment reduces the likelihood of post-Q fever fatigue syndrome

Our preferred regimen for acute Q fever in nonpregnant adults without acute еոԁοϲаrditis is oral doxycycline (100 mg twice daily) for 14 days.

Clinical experience with doxycycline is more extensive than with other antibiotics, but there are no randomized trials comparing doxycycline treatment with other antibiotic regimens. Limited observational data suggest that doxycycline may more effectively reduce symptoms than other antibiotics [3,9,48-50].

Management of acute Q fever еոԁοϲаrditiѕ has not been studied given the extreme rarity of this entity. Most experts would treat with the regimens used for chronic Q fever еոԁοсаrԁitis.

Alternative regimens – For patients unable to take doxycycline, alternative regimens include 14 days of one of the following: trimethoprim-sulfamethoxazole (1 double- strength tablet twice daily) [3,51], moxifloxacin (400 mg once daily) [50], or clarithromycin (500 mg twice daily) [48,49]. Azithromycin is considered to be less effective [50]. Although accumulating in vitro and in vivo data suggest that levofloxacin is effective, clinical data are limited [52].

For children older than eight years of age without acute еոԁοсаrditis, oral doxycycline (2.2 mg/kg body weight [up to 100 mg] twice daily) for 14 days is appropriate, based on clinical guidelines [3].

We also treat children less than eight years of age who have no risk factors for chronic disease with 14 days of doxycycline. This is in contrast to the 2013 CDC guidelines, which suggest doxycycline for only five days or trimethoprim-sulfamethoxazole for 14 days, based on concern for a possible risk of doxycycline-induced dental staining [3]. However, more recent data have not validated this risk, and most experts believe short-term use (<21 days) in children is safe, regardless of age [53-58].

Clinical and serologic follow-up are recommended after acute Q fever to diagnose progression to chronic infection [3].

Progression to chronic infection should be suspected if the patient develops symptoms consistent with chronic Q fever and/or high titers of phase I IgG, as defined separately.

We base the frequency of follow-up on the patient's risk factors for chronic infection (eg, suspected valvulopathy, vascular aneurysm or graft, pregnancy, immunosuppression, age >50 years)

Patients without risk factors – We perform clinical evaluation shortly after completion of therapy to ensure clinical improvement. We continue to follow the patient clinically and obtain follow-up Q fever serology at 3 months, 6 months, and 12 months after initial diagnosis

Patients with risk factors – We perform clinical evaluation shortly after completion of therapy. We then continue to follow the patient clinically and obtain follow-up Q fever serology at 3 months, 6 months, 12 months, 18 months, 24 months, and then every 6 to 12 months until five years from the initial diagnosis have passed

The United States CDC recommends serologic monitoring for a shorter duration in both groups [3]. Evidence consistently suggests that follow-up serologic testing detects progression to chronic Q fever, but the optimal duration and frequency of serologic follow-up after acute Q fever remains uncertain.

In aggregate, studies suggest that most cases of chronic Q fever will be diagnosed within the first year after diagnosis of acute Q fever, some will occur within years 2 through 5, and rare cases will emerge after five years [41,59-61].

This is the most common complication following acute Q fever. It is estimated to occur in up to 20 percent of patients with symptomatic acute Q fever [62].

A persistent, debilitating fatigue in previously healthy people lasting more than one year after acute infection is the most characteristic feature. Symptoms may be consistent with those of progression to chronic infection, but phase I antibody levels are low or absent, and there is no evidence of focal infection in patients with post-Q fever fatigue syndrome

The pathogenesis of this complication is unknown [63]. The only predictor of development of this condition is the severity of the initial acute infection [31,62]

Prolonged antibiotic treatment is not recommended [3]. Antibiotic treatment, compared with cognitive-behavioral therapy and placebo, was investigated in a randomized controlled trial of 154 patients with post-Q fever fatigue syndrome. Fatigue severity over time was unchanged with doxycycline for three months compared with placebo, while cognitive-behavioral therapy showed improved fatigue compared with placebo [64]

The prognosis of acute Q fever is good. Mortality rate is very low (<1 percent) in most reports [35]; higher rates (up to 5 percent) have been reported in other studies, but small sample size and high rate of severe illness may have affected these results [66]. Death occurs more frequently in older patients with comorbidities

For health care workers caring for patients with Q fever, use of standard precautions is sufficient during routine care. Additional respiratory precautions should be used during aerosol-generating procedures

Post-exposure prophylaxis is not recommended after a known environmental or occupational exposure, but any acute febrile illness that occurs within six weeks of exposure warrants immediate treatment and medical evaluation [3].

Vaccine for humans is available in Australia. It is a whole-cell inactivated vaccine (Q vax) that has an effectiveness of almost 100 percent [69]. It is used for prevention after occupational exposure in Australia. Before vaccination, individuals must undergo a cutaneous test to ascertain for evidence of previous C. burnetii exposure, which has been associated with severe cutaneous reactions