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Q Fever: Epidemiology, Diagnosis, and Treatment

  • Joshua D. Hartzell
    Correspondence
    Individual reprints of this article are not available. Address correspondence to Joshua D. Hartzell, MD, Infectious Diseases Service, Walter Reed Army Medical Center, BLD 2, Ward 63, 6900 Georgia Ave NW, Washington, DC 20307
    Affiliations
    Infectious Diseases Service, Department of Internal Medicine, Walter Reed Army Medical Center, Washington, DC, and Uniformed Services University of the Health Sciences, Bethesda, MD
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  • Robert N. Wood-Morris
    Affiliations
    Infectious Diseases Service, Department of Internal Medicine, Walter Reed Army Medical Center, Washington, DC, and Uniformed Services University of the Health Sciences, Bethesda, MD
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  • Luis J. Martinez
    Affiliations
    Infectious Diseases Service, Department of Internal Medicine, Walter Reed Army Medical Center, Washington, DC, and Uniformed Services University of the Health Sciences, Bethesda, MD
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  • Richard F. Trotta
    Affiliations
    Infectious Diseases Service, Department of Internal Medicine, Walter Reed Army Medical Center, Washington, DC, and Uniformed Services University of the Health Sciences, Bethesda, MD
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      Q fever, a zoonosis caused by Coxiella burnetii, is seen throughout the world. Recent reports suggest that its incidence in the United States is increasing, with more than 30 cases reported in the US military. The disease has many acute and chronic manifestations. Endocarditis is the most common form of chronic disease, and recent studies have led to substantial changes in the approach to its diagnosis and treatment. Military and civilian health care professionals need to consider Q fever when evaluating patients with appropriate geographic exposures and clinical presentations to prevent delays in diagnosis and treatment.
      FQ (fluoroquinolone), TTE (transthoracic echocardiography)
      First described in 1937 by E. H. Derrick in Queensland, Australia,
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      Q fever is a zoonotic infection caused by Coxiella burnetii, an obligate, intracellular, gram-negative organism. This article reviews recent findings related to the epidemiology, diagnosis, and treatment of chronic forms of the disease that have important clinical implications.

      EPIDEMIOLOGY

      Q fever infects a variety of hosts, including humans, ruminants (cattle, sheep, goats), pets, and, rarely, reptiles, birds, and ticks. A sturdy organism, C burnetii can survive in the environment for weeks. It is highly infectious; a single or a few organisms can cause disease.
      • Raoult D
      • Marrie T
      • Mege J
      Natural history and pathophysiology of Q fever.
      Humans are exposed to the disease as other animals shed the organism in feces, urine, milk, and products of conception. These products, specifically parturient products, contain large numbers of bacteria that become aerosolized after drying and remain virulent for months.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      Infection can also be acquired via ingestion or direct skin penetration. Despite the wellknown association of Q fever with ruminants, direct exposure is unnecessary for infection, as was shown in recently reported cases in which patients had no obvious risk factors for disease other than being in an endemic area.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      • Hartzell JD
      • Peng SW
      • Wood-Morris RN
      • et al.
      Atypical Q fever in US soldiers.
      • Leung-Shea C
      • Danaher PJ
      Q fever in members of the United States armed forces returning from Iraq.
      Although Q fever affects people worldwide, certain countries have higher incidences of disease. The rates in France (500 cases per million persons) and Australia (38 cases per million persons) are greater than those in the United States (0.28 cases per million persons), most likely reflecting the difference in importance of animal hosts between countries.
      • McQuiston JH
      • Holman RC
      • McCall CL
      • Childs JE
      • Swerdlow DL
      • Thompson HA
      National surveillance and the epidemiology of human Q fever in the United States, 1978-2004.
      Since Q fever became a reportable disease in the United States in 1999, the number of cases has increased dramatically. According to a recent study, the cases of Q fever in the United States have increased from 21 cases per year (1978-1999) to 51 cases per year (2000-2004). The states with the highest incidence are in the Midwest; however, California reported the largest total number of cases.
      • McQuiston JH
      • Holman RC
      • McCall CL
      • Childs JE
      • Swerdlow DL
      • Thompson HA
      National surveillance and the epidemiology of human Q fever in the United States, 1978-2004.
      These data indicate that Q fever should no longer be considered a disease of occupational hazard (farmers, slaughterhouse workers, or veterinarians) in the United States but rather an endemic environmental disease.
      More than 30 cases of Q fever have been reported among US military personnel recently deployed to Iraq and Afghanistan.
      • Hartzell JD
      • Peng SW
      • Wood-Morris RN
      • et al.
      Atypical Q fever in US soldiers.
      • Leung-Shea C
      • Danaher PJ
      Q fever in members of the United States armed forces returning from Iraq.
      Several of these patients had no obvious exposures other than environmental exposure in an endemic area. Some initially presented to civilian physicians, and Q fever was not considered in the diagnostic evaluation. Given the increased reporting of the disease in the United States, the increase in international travel, and the increased number of military personnel returning from endemic areas, all health care professionals (military and civilian) should consider the diagnosis when confronted with the appropriate clinical presentation.

      CLINICAL MANIFESTATIONS

      The presentation of Q fever is extremely variable: infection can lead to asymptomatic seroconversion, acute disease (ranging from a flulike syndrome to severe pneumonia), or chronic disease (manifesting mainly as endocarditis).
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      • Raoult D
      • Marrie T
      • Mege J
      Natural history and pathophysiology of Q fever.
      Host factors, including age, sex, and certain medical conditions, are thought to play a role in disease presentation. Patients older than 15 years are more likely to present with clinical symptoms.
      • Raoult D
      • Marrie T
      • Mege J
      Natural history and pathophysiology of Q fever.
      Although Q fever is thought to occur rarely in children, it could be underreported because of its nonspecific presentation. When symptoms do occur in children, they have a similar presentation to those in adults, whether the manifestation of the disease is acute or chronic.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      • Raoult D
      • Marrie T
      • Mege J
      Natural history and pathophysiology of Q fever.
      Male sex is a risk factor for symptomatic disease.
      • Raoult D
      • Marrie T
      • Mege J
      Natural history and pathophysiology of Q fever.
      In Australia and France, males are 5-fold and 2.5-fold more likely than females to develop disease, respectively.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      In a recent report on the incidence of Q fever in the United States, men accounted for 77% of cases.
      • McQuiston JH
      • Holman RC
      • McCall CL
      • Childs JE
      • Swerdlow DL
      • Thompson HA
      National surveillance and the epidemiology of human Q fever in the United States, 1978-2004.
      Although the precise reasons for such differences are unknown, sex hormones have been suggested to have a role.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      • Raoult D
      • Marrie T
      • Mege J
      Natural history and pathophysiology of Q fever.
      In pregnant women with Q fever, recrudescence of infection as well as premature birth, low birth weight, and spontaneous abortion have been reported. Chronic disease can also be associated with recurrent miscarriages.
      • Raoult D
      • Marrie T
      • Mege J
      Natural history and pathophysiology of Q fever.
      Immunosuppressed hosts are at risk of severe disease or development of chronic infection. Of the chronic infections, endocarditis poses the greatest risk, and pneumonia occurs frequently as well.

      Acute Disease

      Most patients (50%-60%) who are infected with Q fever are asymptomatic; for symptomatic patients, more than 30 different clinical syndromes have been described.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      • Raoult D
      • Marrie T
      • Mege J
      Natural history and pathophysiology of Q fever.
      The classic presentation is a flulike illness manifested by fevers, sweats, cough (productive at times), myalgias, and arthralgias. A high percentage of patients also have pneumonia and hepatitis. Pneumonia is typically mild, but progression to acute respiratory distress syndrome can occur.
      • Hartzell JD
      • Peng SW
      • Wood-Morris RN
      • et al.
      Atypical Q fever in US soldiers.
      Patients with both acute and chronic disease can have hepatosplenomegaly and hepatitis; when hepatitis is present, it is usually manifested by mild elevations in transaminase levels. Acute acalculous cholecystitis associated with Q fever has been described rarely in the literature; however, 2 cases in returning US soldiers have been reported recently.
      • Hartzell JD
      • Peng SW
      • Wood-Morris RN
      • et al.
      Atypical Q fever in US soldiers.
      Physicians should consider the diagnosis of Q fever when caring for patients with the clinical triad of fever, hepatitis, and atypical pneumonia. If cholecystitis is present, antibiotics alone may be sufficient for treatment.
      • Hartzell JD
      • Peng SW
      • Wood-Morris RN
      • et al.
      Atypical Q fever in US soldiers.
      Other manifestations of acute disease, which can affect almost any organ system, are well described in a recent review.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      Physicians must be aware of these varying presentations in the appropriate clinical setting to avoid delays in diagnosis and treatment. In most patients, acute disease has a self-limited course or responds to appropriate therapy. When diagnosed, however, acute disease must be treated promptly to avoid chronic manifestations of disease.

      Chronic Disease

      People with certain conditions, including pregnancy, immunosuppression, heart valve lesions, and vascular abnormalities, are more susceptible to developing chronic Q fever.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      Endocarditis, the most common form of chronic Q fever (60%-70%), represents 3% to 5% of all endocarditis cases
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      • Fenollar F
      • Fournier PE
      • Carrieri MP
      • Habib G
      • Messana T
      • Raoult D
      Risk factors and prevention of Q fever endocarditis.
      and is estimated to occur in 0.76% of acute Q fever cases.
      • Fenollar F
      • Fournier PE
      • Carrieri MP
      • Habib G
      • Messana T
      • Raoult D
      Risk factors and prevention of Q fever endocarditis.
      The clinical and echocardiographic findings are dissimilar to those of typical acute bacterial endocarditis, and blood cultures are negative, often resulting in delays in diagnosis. The clinical presentation ranges from no symptoms to congestive heart failure. Fever may be absent in up to 18% of patients. The vegetations of Q fever tend to be sub-endothelial and smaller than those in other forms of bacterial endocarditis.
      • Gami AS
      • Antonios VS
      • Thompson RL
      • Chaliki HP
      • Ammash NM
      Q fever endocarditis in the United States.
      Recent publications have increased our understanding of endocarditis in Q fever. Immunosuppression has been considered a risk factor for some time, but evidence currently suggests that underlying valvulopathies pose an even higher risk.
      • Fenollar F
      • Fournier PE
      • Carrieri MP
      • Habib G
      • Messana T
      • Raoult D
      Risk factors and prevention of Q fever endocarditis.
      One study showed that the risk of endocarditis after acute Q fever in patients with an underlying valvular abnormality approached 40%.
      • Fenollar F
      • Fournier PE
      • Carrieri MP
      • Habib G
      • Messana T
      • Raoult D
      Risk factors and prevention of Q fever endocarditis.
      Another suggested that even minor valvular abnormalities (ie, mitral valve prolapse, bicuspid aortic valve, and minor valvular leak) could be associated with endocarditis.
      • Fenollar F
      • Thuny F
      • Xeridat B
      • Lepidi H
      • Raoult D
      Endocarditis after acute Q fever in patients with previously undiagnosed valvulopathies.
      In patients with untreated underlying valvulopathies, the risk of developing endocarditis is reported to be 75%.
      • Fenollar F
      • Fournier PE
      • Carrieri MP
      • Habib G
      • Messana T
      • Raoult D
      Risk factors and prevention of Q fever endocarditis.
      Patients who received doxycycline alone (2 weeks to 6 months) had a 50% chance of developing endocarditis, whereas those treated with doxycycline and hydroxychloroquine (12 patients) for 1 to 15 months did not develop endocarditis.
      • Fenollar F
      • Fournier PE
      • Carrieri MP
      • Habib G
      • Messana T
      • Raoult D
      Risk factors and prevention of Q fever endocarditis.
      These findings led to new recommendations regarding treatment and follow-up of patients with acute Q fever (see Treatment section).
      Vascular infections are the second most common form of chronic disease. Aortic aneurysms or vascular grafts are frequently involved, as evidenced by the report of 30 cases in France.
      • Botelho-Nevers E
      • Fournier PE
      • Richet H
      • et al.
      Coxiella burnetii infection of aortic aneurysms or vascular grafts: report of 30 new cases and evaluation of outcome.
      Mortality is high (25%); however, surgical treatment is associated with improved outcomes.
      • Botelho-Nevers E
      • Fournier PE
      • Richet H
      • et al.
      Coxiella burnetii infection of aortic aneurysms or vascular grafts: report of 30 new cases and evaluation of outcome.
      Rare manifestations of chronic Q fever include osteomyelitis, granulomatous hepatitis, and chronic pulmonary infections.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      In addition, chronic fatigue syndrome has been reported in patients after infection with acute Q fever,
      • Hickie I
      • Davenport T
      • Wakefield D
      • Dubbo Infection Outcomes Study Group
      • et al.
      Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study.
      with most cases in Europe and Australia. Few papers have been written on this topic, and future research is needed in patients with post-Q fever fatigue syndrome.

      DIAGNOSIS

      The diagnosis of Q fever relies mainly on serologic examination. Several laboratory studies are available, but antibody detection by immunofluorescence assay is the most commonly used method because of its high sensitivity and specificity. Polymerase chain reaction, a promising test that may even be able to detect the presence of C burnetii early in disease, is limited to reference laboratories and research studies.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      • Fournier PE
      • Raoult D
      Comparison of PCR and serology assays for early diagnosis of acute Q fever.
      C burnetii can be seen on smears or frozen tissue prepared with a routine Giemsa stain. The presence of doughnut granulomas, ie, fibrin rings, in histopathology specimens is classically associated with Q fever but is not specific for the disease.
      • Fournier PE
      • Marrie TJ
      • Raoult D
      Diagnosis of Q fever.
      Although isolation of the organism provides a definitive diagnosis, several problems exist with culturing or visualizing the organism. Most clinical laboratories do not culture C burnetii because doing so is technically difficult and requires biosafety level 3 containment owing to the organism's extreme infectivity and potential use as a weapon of bioterrorism.
      • Fournier PE
      • Marrie TJ
      • Raoult D
      Diagnosis of Q fever.
      Therefore, isolation of the organism should not be attempted in facilities without adequate safeguards.
      Serologic methods are simpler and safer than isolation attempts and are the diagnostic procedure of choice. Clinically, the most widely used serologic test is the detection of phase I and II antibodies. First described by Bengtson
      • Bengtson IA
      Complement fixation in “Q” fever.
      in 1941, detection of phase I and II antibodies was used by the US Army to describe 8 outbreaks of Q fever in Allied troops between 1944 and 1945.
      • Robbins FC
      • Rustigan R
      • Snyder MJ
      • Smadel JE
      Q fever in the Mediterranean area: report of its occurrence in allied troops. III. the etiologic agent.
      Test results can be confusing to those unfamiliar with Q fever because the phase II antibodies are positive in acute disease, whereas phase I antibodies tend to remain elevated in chronic disease. The antibody response is a result of the phase variation in C burnetii. A titer of 200 or greater for IgG and 50 or greater for IgM against phase II antibodies indicates a recent Q fever infection; an IgG titer of 800 or greater against phase I antibodies suggests chronic infection.
      • Fournier PE
      • Marrie TJ
      • Raoult D
      Diagnosis of Q fever.
      These cutoffs vary among laboratories and defined cutoffs for each individual test should be used.
      • Leung-Shea C
      • Danaher PJ
      Q fever in members of the United States armed forces returning from Iraq.
      Phase II antibodies can be detected within 2 weeks of infection in most patients and within 3 weeks in 90% of patients. A lack of antibodies at 4 weeks suggests another diagnosis. Antibodies typically peak by 2 months and then gradually decrease; however, IgG titers can be persistently elevated.
      • Leung-Shea C
      • Danaher PJ
      Q fever in members of the United States armed forces returning from Iraq.
      Chronic disease (endocarditis) should be suspected if the elevation persists.
      The diagnosis of Q fever endocarditis requires both clinical endocarditis and isolation or serologic evidence of C burnetii. Because Q fever endocarditis is a chronic illness, a single serum specimen is sufficient for diagnosis, and paired sera are not required. A phase I IgG titer of 800 or greater is one of the major modified Duke criteria.
      • Baddour LM
      • Wilson WR
      • Bayer AS
      • Infectious Diseases Society of America
      • et al.
      Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association.
      In cases where clinical suspicion is high and antibody titers are low or negative, the presence of a positive polymerase chain reaction for C burnetii may enable the early diagnosis of acute Q fever endocarditis.
      • Fournier PE
      • Raoult D
      Comparison of PCR and serology assays for early diagnosis of acute Q fever.
      Available recommendations regarding serologic followup of patients diagnosed as having acute Q fever are based primarily on clinical experience in an older population in a single country (Figure).
      • Landais C
      • Fenollar F
      • Thuny F
      • Raoult D
      From acute Q fever to endocarditis: serological follow-up strategy.
      Whether such an approach is appropriate for all patients is uncertain. However, until studies are conducted in different populations, we recommend this algorithm in patients diagnosed as having acute Q fever. Alternative follow-up strategies may be reasonable but should be done in conjunction with infectious disease specialists.
      Figure thumbnail gr1
      FIGUREStrategy for diagnosing Q fever. IE = infective endocarditis; PCR = polymerase chain reaction; TEE = transesophageal echocardiography; TTE = transthoracic echocardiography. Adapted from Clin Infect Dis,
      • Landais C
      • Fenollar F
      • Thuny F
      • Raoult D
      From acute Q fever to endocarditis: serological follow-up strategy.
      with permission from the University of Chicago Press. © 2007 by the Infectious Diseases Society of America. All rights reserved.

      TREATMENT

      Acute Disease

      Although identified more than 70 years ago, C burnetii remains difficult to treat because of its varied clinical presentations. Most acute infections (60%) are subclinical but should be treated when recognized. Decreased efficacy of therapy has been reported when treatment was not initiated within 3 days of symptom onset; however, rapid improvement has been observed in patients treated up to a week into their presentation. The treatment of choice is 100 mg of oral doxycycline every 12 hours for 14 days.
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      The utility of macrolides remains unclear; erythromycin has been shown to be unreliable,
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      but in vitro
      • Maurin M
      • Raoult D
      In vitro susceptibilities of spotted fever group rickettsiae and Coxiella burnetti to clarithromycin.
      and clinical
      • Gikas A
      • Kofteridis D
      • Manios A
      • Pediatitis J
      • Tselentis Y
      Newer macrolides for empiric treatment of acute Q fever infection.
      evaluation of other macrolide formulations (eg, clarithromycin, roxithromycin) suggest efficacy. The efficacy of fluoroquinolones (FQs) has been shown both in vitro and in acute infection, but clinical data are limited.
      • Yeaman MR
      • Mitscher LA
      • Baca OG
      In vitro susceptibility of Coxiella burnetti to antibiotics, including several quinolones.
      Because of their greater capacity to penetrate the cerebrospinal fluid, FQs have a theoretical advantage in management of meningoencephalitis.
      • Bernit E
      • Pouget J
      • Janbon F
      • et al.
      Neurological involvement in acute Q fever, a report of 29 cases and review of the literature.
      However, in a recent review of 29 cases, the choice of antimicrobial therapy (FQ vs doxycycline) did not affect resolution of acute disease or the severity of neurologic sequelae.
      • Bernit E
      • Pouget J
      • Janbon F
      • et al.
      Neurological involvement in acute Q fever, a report of 29 cases and review of the literature.
      On the basis of available evidence, we recommend doxycycline for acute disease unless patients are allergic to doxycycline, pregnant (see Pregnancy section), or younger than 8 years (cotrimoxazole).

      Chronic Disease

      Endocarditis is the most common form of chronic Q fever, and recommendations for both the treatment and prevention of this complication of acute Q fever havechanged markedly in the past 2 years. Surgery remains an important component of treatment if patients have substantial valvular damage or evidence of heart failure. These decisions should be made in conjunction with infectious disease specialists, cardiologists, and cardiothoracic surgeons.
      Monotherapy decreases symptoms but rarely results in clinical cure because it lacks bactericidal activity. Tetracycline or doxycycline alone is associated with greater than 50% mortality.
      • Raoult D
      • Houpikian P
      • Tissot Dupont H
      • Riss JM
      • Arditi-Djiane J
      • Brouqui P
      Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine.
      In vitro studies have shown that a combination regimen of doxycycline and hydroxychloroquine exhibits bactericidal activity.
      • Maurin M
      • Benoliel AM
      • Bongrand P
      • Raoult D
      Phagolysosomal alkalinzation and the bactericidal effect of antibiotics: the Coxiella burnetti paradigm.
      This regimen was shown to have a greater clinical efficacy than a standard alternative combination (tetracycline plus FQ). Although a 5% mortality was associated with both regimens, patients treated with doxycycline-hydroxychloroquine had shorter treatment duration (by as much as 2.5 years) and fewer relapses.
      • Raoult D
      • Houpikian P
      • Tissot Dupont H
      • Riss JM
      • Arditi-Djiane J
      • Brouqui P
      Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine.
      Combination therapy should be considered standard treatment for patients with Q fever endocarditis.
      The current recommendation for treatment of Q fever endocarditis is oral doxycycline (100 mg twice daily) plus hydroxychloroquine (200 mg 3 times daily)
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      for at least 18 months; however, therapy may need to be prolonged. For patients unable to tolerate hydroxychloroquine, an alternative regimen of doxycycline plus an FQ for a minimum of 3 to 4 years has been proposed.
      • Gami AS
      • Antonios VS
      • Thompson RL
      • Chaliki HP
      • Ammash NM
      Q fever endocarditis in the United States.
      • Levy PY
      • Drancourt M
      • Etienne J
      • et al.
      Comparison of different antibiotic regimens for therapy of 32 cases of Q fever endocarditis.
      Doxycycline plus rifampin has also been suggested as an alternative therapy; however, drug interactions may limit the usefulness of this combination.
      • Landais C
      • Fenollar F
      • Constantin A
      • et al.
      Q fever osteoarticular infection: four new cases and a review of the literature.
      The optimal duration of therapy remains unknown. During therapy, IgA and IgG antibody titers should be obtained every 3 months until they are less than 1:200,
      • Parker NR
      • Barralet JH
      • Bell AM
      Q fever.
      although other cutoffs have been suggested.
      • Gami AS
      • Antonios VS
      • Thompson RL
      • Chaliki HP
      • Ammash NM
      Q fever endocarditis in the United States.
      • Raoult D
      • Houpikian P
      • Tissot Dupont H
      • Riss JM
      • Arditi-Djiane J
      • Brouqui P
      Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine.
      Once therapy has been discontinued, titers should be obtained every 3 months to monitor for a 4-fold increase indicative of relapse. Patients who receive prolonged hydroxychloroquine treatment should have an ophthalmologic examination every 12 months. At-risk populations should be screened for glucose-6-phosphate dehydrogenase deficiency before receiving hydroxychloroquine therapy, and patients who receive treatment with doxycycline should be reminded about photosensitivity.
      Patients with underlying valvulopathies who acquire acute Q fever infection are at a substantially increased risk of developing endocarditis. Transthoracic echocardiography (TTE) is now recommended for all patients with acute Q fever; if a valvulopathy is observed, a 12-month course of doxycycline plus hydroxychloroquine is recommended (Figure).
      • Fenollar F
      • Fournier PE
      • Carrieri MP
      • Habib G
      • Messana T
      • Raoult D
      Risk factors and prevention of Q fever endocarditis.
      • Fenollar F
      • Thuny F
      • Xeridat B
      • Lepidi H
      • Raoult D
      Endocarditis after acute Q fever in patients with previously undiagnosed valvulopathies.
      • Landais C
      • Fenollar F
      • Thuny F
      • Raoult D
      From acute Q fever to endocarditis: serological follow-up strategy.
      Endovascular complications (eg, mycotic aneurysm, vascular graft) are another major group of chronic infections (9%). In a report of 30 cases, surgical treatment (aortic aneurysm repair or graft replacement) at time of Q fever diagnosis was significantly associated with survival (23 of 24 patients who survived underwent surgery; only 2 of 8 patients who died underwent surgery).
      • Botelho-Nevers E
      • Fournier PE
      • Richet H
      • et al.
      Coxiella burnetii infection of aortic aneurysms or vascular grafts: report of 30 new cases and evaluation of outcome.
      Because a variety of antibiotic regimens were used in this series, the optimal regimen could not be determined. However, most patients were treated with combination doxycycline-hydroxychloroquine. Treatment of such cases should be individualized and take into account the actual surgery performed.
      Osteoarticular Q fever infections are exceedingly rare, but, in a report of 4 cases and review of 15 others, surgical debridement was recommended as needed along with at least 18 months of doxycycline (200 mg/d) plus hydroxychloroquine (600 mg/d) and possibly rifampin.
      • Landais C
      • Fenollar F
      • Constantin A
      • et al.
      Q fever osteoarticular infection: four new cases and a review of the literature.

      Pregnancy

      Treating pregnant patients with Q fever is challenging because use of certain medications (doxycycline, FQs, and chloroquine) is unsafe during pregnancy. In the largest reported series to date, 53 cases were evaluated.
      • Carcopino X
      • Raoult D
      • Bretelle F
      • Boubli L
      • Stein A
      Managing Q fever during pregnancy: the benefits of long-term cotrimoxazole therapy.
      Although long-term cotrimoxazole (320 mg/d of trimethoprim and 1600 mg/d of sulfamethoxazole for at least 5 weeks) therapy is often not curative (10 of 17 patients required postpartum therapy for chronic Q fever), it decreased the incidence of spontaneous abortion, intrauterine growth retardation, intrauterine fetal death, premature delivery, and oligohydramnios. The mother's underlying infection can be definitely managed after she gives birth, as discussed previously.
      • Carcopino X
      • Raoult D
      • Bretelle F
      • Boubli L
      • Stein A
      Managing Q fever during pregnancy: the benefits of long-term cotrimoxazole therapy.

      VACCINATION

      No Q fever vaccine has been approved by the Food and Drug Administration. However, vaccine preparations are available in other countries. In 1989, Australia licensed a whole-cell C burnetii vaccine; more than 150,000 doses of the vaccine have been administered with a demonstrated 5-year efficacy of more than 95%.
      • Marmion B
      • Harris R
      • Storm P
      • et al.
      Q Fever Research Group (QRG), Adelaide: activities-exit summary 1980-2004.
      • Ackland JR
      • Worswick DA
      • Marmion BP
      Vaccine prophylaxis of Q fever: a follow-up study of the efficacy of Q-Vax (CSL) 1985-1990.
      People who might benefit from such a vaccine include veterinarians, abattoir workers, and research and reference laboratory personnel who work with the organism.

      CONCLUSION

      The incidence of Q fever is increasing in the United States, including several cases among returning US military personnel. To prevent delays in treatment, military and civilian health care professionals should be familiar with the acute and chronic manifestations of the disease. They should also be aware of the recent recommendations to use TTE to diagnose underlying valvulopathies in all patients with acute Q fever and the need for serologic follow-up (at 6 months) to prevent endocarditis.

      CME Materials

      REFERENCES

        • Parker NR
        • Barralet JH
        • Bell AM
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