Acute Q fever in nonpregnant patients

INTRODUCTION — 

Acute Q fever is the clinical syndrome in the early period following acquisition of Coxiella burnetii. It can present as various syndromes, most commonly a flu-like illness, community-acquired pneumonia, or hepatitis.

The clinical manifestations, diagnosis, and treatment of acute Q fever in nonpregnant patients are discussed in this topic.

Chronic Q fever, Q fever in pregnancy, and the epidemiology of Q fever are discussed in detail separately. (See "Chronic Q fever, including endocarditis" and "Q fever in pregnancy" and "Q fever: Epidemiology, microbiology, and diagnostic tests".)

CLINICAL MANIFESTATIONS — 

Clinical presentations of acute Q fever can vary markedly among patients.

Onset of symptoms (incubation period) — 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]. (See "Chronic Q fever, including endocarditis".)

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

Clinical syndromes — Acute Q fever can present with various clinical syndromes as described below.

Flu-like illness — 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]. (See "Fever of unknown origin in adults: Etiologies".)

Pneumonia — 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 — Hepatitis has been reported in series of acute Q fever; in a series from the United States, 29 percent of patients had acute hepatitis [5].

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].

Less common manifestations — Other clinical findings or syndromes include the following:

●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 endocarditis 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].

Special populations

Children — Q fever in children usually manifests with an acute, mild, nonspecific, febrile illness. However, rare serious cases of chronic Q fever have been reported [27]. (See "Chronic Q fever, including endocarditis".)

Q fever is less commonly reported in children than adults, but the true incidence of infection in children is unknown, as discussed separately [27]. (See "Q fever: Epidemiology, microbiology, and diagnostic tests", section on 'Risk factors'.)

Pregnant patients — 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].

Acute fever in pregnancy may also be associated with increased risk for progression to chronic Q fever after delivery [28].

Detailed discussion of Q fever in pregnancy is found separately. (See "Q fever in pregnancy".)

Geographic variability — 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].

Examples of geographic differences in the presentation of acute Q fever include the following:

●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].

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

●French Guinea – Pneumonia in 83 percent and hepatitis in 3 percent (115 patients) [34].

●South Korea – Pneumonia in 10 percent and hepatitis in 23 percent (48 patients) [15].

●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].

DIAGNOSIS

When to suspect acute Q fever — 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]. (See 'Clinical syndromes' above.)

In pregnant patients, there is a much lower threshold for considering the diagnosis, as discuss separately. (See "Q fever in pregnancy".)

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. (See "Q fever: Epidemiology, microbiology, and diagnostic tests", section on 'Risk factors'.)

Confirming the diagnosis — For clinical purposes, the diagnosis of acute Q fever should be based on clinical criteria, epidemiologic context, and microbiologic laboratory tests. Case definitions have been created for Q fever and vary by country or region [37].

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]). (See "Q fever: Epidemiology, microbiology, and diagnostic tests", section on 'Diagnostic tests'.)

Serology — 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. The initial "acute" test is performed at the time of clinical presentation, and 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].

More in-depth discussion of serologic testing for Q fever is found separately. (See "Q fever: Epidemiology, microbiology, and diagnostic tests", section on 'Serology'.)

Polymerase chain reaction — 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) [38,39].

Further discussion of PCR for the diagnosis of Q fever is found separately. (See "Q fever: Epidemiology, microbiology, and diagnostic tests", section on 'Polymerase chain reaction'.)

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis is broad and depends on the specific clinical syndrome. Infectious and noninfectious conditions should be considered, with appropriate serologic and nucleic acid amplification testing targeted toward the most probable infectious conditions.

●Flu-like illness

•Viral infection – 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). (See "Seasonal influenza in adults: Clinical manifestations and diagnosis" and "COVID-19: Evaluation and management of adults with acute infection in the outpatient setting" and "Acute and early HIV infection: Clinical manifestations and diagnosis".)

•Arthropod-borne infections – 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. (See "Human ehrlichiosis and anaplasmosis" and "Diagnosis of Lyme disease" and "Epidemiology, clinical manifestations, and diagnosis of Rocky Mountain spotted fever" and "Other spotted fever group rickettsial infections" and "Dengue virus infection: Clinical manifestations and diagnosis".)

•Zoonoses – 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. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Pneumonia – Infectious and noninfectious etiologies should be considered.

•Infectious – Bacterial and viral causes of pneumonia, including atypical pathogens (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella spp), should be considered. (See "Overview of community-acquired pneumonia in adults", section on 'Microbiology'.)

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). (See "Diagnosis and treatment of pulmonary histoplasmosis" and "Clinical manifestations and diagnosis of blastomycosis" and "Primary pulmonary coccidioidal infection" and "Pulmonary tuberculosis disease in adults: Clinical manifestations and complications".)

•Noninfectious – 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. (See "Diagnostic evaluation of the incidental pulmonary nodule" and "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer".)

●Hepatitis – 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. (See "Hepatitis B virus: Clinical manifestations and natural history" and "Screening and diagnosis of chronic hepatitis C virus infection" and "Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis".)

TREATMENT — 

Treatment of acute Q fever consists of antibiotic therapy and appropriate monitoring and follow-up.

Role of pretreatment echocardiography — Because 1 to 5 percent of patients with acute Q fever eventually develop chronic Q fever, including endocarditis, risk stratification using echocardiography has been proposed by some experts [1,3,22,40-42] (see "Chronic Q fever, including endocarditis"). More recent reports of rare cases of acute endocarditis during acute Q fever infection have led to further discussion of the role of echocardiography during acute infection. (See 'Less common manifestations' above.)

We obtain echocardiography for all patients with acute Q fever who have any of the following risk factors for acute or chronic Q fever endocarditis [1,3,40,41,43] (see "Chronic Q fever, including endocarditis", section on 'Epidemiology and risk factors'):

●History of known or suspected valvulopathy

●Findings consistent with endocarditis 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

This approach allows us to follow patients with these risk factors more closely for progression to endocarditis following treatment (see 'Monitoring and follow-up' below). Some experts obtain echocardiography for all patients with acute Q fever, regardless of risk factors.

Data informing the role of screening echocardiography for patients with acute Q fever are derived from two primary sources, a research group from France and another from the Netherlands:

●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 endocarditis (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 endocarditis 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 endocarditis) 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 endocarditis. 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.

The difference in chronic Q fever manifestations between the French and the Dutch cohorts may limit the comparability of these studies. Specifically, endocarditis was more common in France, whereas vascular infection was more dominant in the Netherlands. The use of echocardiography screening in acute Q fever in a setting in which endocarditis is a less common manifestation of chronic Q fever might have affected the Dutch results and is worth additional investigation in other regions.

In conclusion, the value of screening for valvulopathy with echocardiography is uncertain. The main value is detection of unsuspected valvular disease or acute endocarditis, both of which are rare. We use history and examination findings (eg, known valvular disease, murmur on examination, peripheral stigmata of endocarditis) to help guide our use of echocardiography. This approach is in alignment with the United States Centers for Disease Control and Prevention (CDC) recommendation to use clinical judgment to determine the need for echocardiogram in patients with acute Q fever [3].

Antibiotic regimens — The following antibiotic suggestions are for nonpregnant patients without acute endocarditis; management of pregnant patients is described separately. (See "Q fever in pregnancy", section on 'Treatment'.)

Although acute Q fever is a self-limited disease, treatment is suggested for symptomatic infection. 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. (See 'Post-Q fever fatigue syndrome' below.)

Nonpregnant adults

●Preferred regimen – Our preferred regimen for acute Q fever in nonpregnant adults without acute endocarditis 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 endocarditis has not been studied given the extreme rarity of this entity. Most experts would treat with the regimens used for chronic Q fever endocarditis. (See "Chronic Q fever, including endocarditis", section on 'Treatment'.)

●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].

Children — For children older than eight years of age without acute endocarditis, oral doxycycline (2.2 mg/kg body weight [up to 100 mg] twice daily) for 14 days is appropriate, based on clinical guidelines [3]. The same regimen is suggested for children of any age who have risk factors for progression to chronic Q fever; such risk factors include hospitalization, severe illness, preexisting valvulopathy, immunocompromise, or delayed diagnosis with >14 days of symptoms.

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].

Pregnant patients — Treatment of pregnant patients is discussed in detail separately. (See "Q fever in pregnancy", section on 'Treatment'.)

Monitoring and follow-up — 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. (See "Chronic Q fever, including endocarditis".)

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). Risk factors are described in further detail separately. (See "Chronic Q fever, including endocarditis", section on 'Epidemiology and risk factors'.)

●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].

POST-Q FEVER FATIGUE SYNDROME — 

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].

In a long-term follow-up (>10 years) of over 360 patients with this condition, continued impact on patients' health was observed [65]. Young and middle-aged patients experienced more long-term health consequences compared with older patients (>65 years old).

PROGNOSIS — 

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 those who progress to chronic infection, mortality is higher. (See "Chronic Q fever, including endocarditis", section on 'Prognosis'.)

As described above, approximately 20 percent will develop post-Q fever fatigue syndrome. (See 'Post-Q fever fatigue syndrome' above.)

PREVENTION — 

Prevention of acute Q fever primarily depends on controlling the infection in animals and decreasing shedding of the bacterium into the environment [67,68]. (See "Q fever: Epidemiology, microbiology, and diagnostic tests", section on 'Reservoirs'.)

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.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Q fever".)

SUMMARY AND RECOMMENDATIONS

●Clinical manifestations – Over 90 percent of symptomatic patients present with acute Q fever, and the remainder present with chronic Q fever. The incubation period for acute Q fever ranges from one to five weeks. (See 'Clinical manifestations' above.)

The most common clinical syndromes of acute Q fever include the following (see 'Clinical syndromes' above):

•Flu-like illness – Common symptoms include fever, severe headache, myalgia, fatigue, chills, cough, and night sweats. (See 'Flu-like illness' above.)

•Pneumonia – Most cases of Q fever pneumonia are mild with a nonproductive cough and fever, but severe cases can occur. Radiographic findings vary. (See 'Pneumonia' above.)

•Hepatitis – Hepatitis in acute Q fever manifests with fever and mild elevation of liver aminotransferases; rarely, severe granulomatous hepatitis may occur. (See 'Hepatitis' above.)

●Diagnosis – Diagnosis of acute Q fever is based on clinical criteria, epidemiologic risk factors, and microbiologic laboratory tests. Case definitions have been created for Q fever and vary by country or region. (See 'Diagnosis' above.)

•Serology – The diagnosis can be confirmed by detecting a fourfold change in IgG titers between acute and convalescent phase II antibody tests obtained 2 to 10 weeks apart. 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). (See 'Serology' above.)

•Polymerase chain reaction (PCR) – PCR can confirm the diagnosis of acute Q fever; the test is most sensitive between days 3 and 7 of illness. (See 'Polymerase chain reaction' above.)

●Differential diagnosis – The differential diagnosis is broad and depends on the specific clinical syndrome. Infectious and noninfectious conditions should be considered, with appropriate serologic and nucleic acid amplification testing targeted toward the most probable infectious conditions. (See 'Differential diagnosis' above.)

●Treatment – (See 'Treatment' above.)

•Role of pretreatment echocardiography – Before initiating treatment, we obtain screening echocardiography in patients with the following risk factors for Q fever endocarditis:

-Known or suspected valvulopathy

-Physical examination findings consistent with endocarditis (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

This approach allows us to follow patients with these risk factors more closely for progression to endocarditis following treatment. (See 'Role of pretreatment echocardiography' above.)

•Antibiotic regimens – (See 'Antibiotic regimens' above.)

-Nonpregnant adults and children – Our preferred regimen for acute Q fever in nonpregnant adults and children without endocarditis is doxycycline for 14 days (Grade 2C). Some experts use a shorter course of doxycycline for children under eight years of age with uncomplicated infection. (See 'Nonpregnant adults' above and 'Children' above.)

We treat patients with acute Q fever endocarditis the same as chronic Q fever endocarditis. (See "Chronic Q fever, including endocarditis", section on 'Treatment'.)

-Pregnant patients – Management of pregnant patients with acute Q fever is described separately. (See "Q fever in pregnancy", section on 'Treatment'.)

●Monitoring and follow-up – For patients without risk factors for chronic infection, we perform clinical evaluation shortly after completion of therapy to ensure clinical improvement and obtain follow-up Q fever serology at 3 months, 6 months, and 12 months after initial diagnosis.

For patients with risk factors for chronic infection (eg, valvulopathy, vascular aneurysm or graft, pregnancy, immunosuppression, age >50 years), we add additional serologic follow-up at 18 months, 24 months, and then every 6 to 12 months for five years from the initial diagnosis. (See 'Monitoring and follow-up' above and "Chronic Q fever, including endocarditis", section on 'Epidemiology and risk factors'.)

●Post-Q fever fatigue syndrome – This syndrome is characterized by persistent debilitating fatigue in previously healthy people for more than one year after acute infection. 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. Prolonged antibiotic treatment provides no clinical benefit. (See 'Post-Q fever fatigue syndrome' above.)

●Prevention – 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. A vaccine is available in Australia for individuals at high risk of occupational exposure. (See 'Prevention' above.)