Approach Considerations
As with any patient with a febrile illness, the physician should maintain a sufficient level of suspicion about any patient with fever to exclude other potentially life-threatening diseases, which, in the case of tick-borne disease, involves presumptive antibiotic therapy.
Although specific antimicrobial therapy is indicated, most patients improve spontaneously. However, when Q fever is diagnosed, the administration of antibiotics is appropriate to prevent progression to chronic disease, which is far more resistant to treatment. In addition, supportive care with fluids, antitussives, and antipyretics may improve patient comfort. Patients should avoid ingestion of unpasteurized dairy products as well.
Surgical intervention may be necessary in some cases; for example, surgical treatment can affect survival in endovascular complications such as mycotic aneurysm or vascular graft infections. [12] Valvular replacement is indicated for intractable heart failure. C burnetii can persist on endocardial tissue even after valve replacement; therefore, antibiotics should be continued following surgery. Surgical debridement is also recommended for osteoarticular infections. [12]
Consultations
Consultation with an infectious diseases specialist is warranted, particularly in cases of suspected chronic Q fever. In addition, consult an internist for admission and management of patients who are immunocompromised, elderly, or who have endocarditis.
In pregnant women, an obstetric consultation should be considered. Cardiothoracic, vascular, and orthopedic surgeons as well as a cardiologist may be consulted in selected cases.
Management of Acute Q Fever
As many as 60% of patients with Q fever are asymptomatic. The disease is self-limiting and spontaneously resolves within 2 weeks in 38% of the remaining patients. However, antibiotic treatment has been shown to reduce the duration of disease, especially if initiated within 3 days of illness onset. The optimal duration of treatment has not been adequately studied, but antibiotics are generally given for 14-21 days, usually in an outpatient setting.
Doxycycline has been the agent most frequently investigated, [39] and it is the treatment of choice.
Fluoroquinolones can be used as alternative antibiotic agents. Ofloxacin and pefloxacin have been used with success in patients. Ciprofloxacin demonstrated higher minimum inhibitory concentration (MIC) values than other fluoroquinolones and doxycycline. Levofloxacin showed bacteriostatic activity in vitro. [39]
Fluoroquinolones may offer a theoretical advantage in meningoencephalitis, because these agents possess better cerebrospinal fluid (CSF) penetration. A literature review demonstrated that the choice of antimicrobial therapy (doxycycline vs fluoroquinolones) did not affect resolution of acute disease or severity of neurologic sequelae. [12]
Macrolides, especially azithromycin and clarithromycin, can be used as alternative agents, but some strains of C burnetii show resistance. [12] Trimethoprim-sulfamethoxazole (TMP-SMZ) also has been used. [3, 12]
No reliable regimen is available for children (< 8 y) or pregnant women. Macrolides or TMP-SMZ may be options in these populations. [12, 19]
Adjuvant corticosteroid treatment has been used in antimicrobial-nonresponsive hepatitis.
Management of Chronic Q Fever
Chronic C burnetii infections are very difficult to treat. A prolonged combined antimicrobial regimen is recommended. Hospitalization may be warranted for intractable heart failure.
No drug used alone has been shown to be bactericidal against C burnetii. Therefore, prolonged combination therapy is recommended because of the high rate of relapse with treatment of shorter duration. No consensus on the ideal duration of therapy has been reached, but serial measurement of antibody titers should likely be used as a guide to duration of therapy.
The most current recommendation for endocarditis is combination treatment with doxycycline and hydroxychloroquine for at least 18 months to eradicate any remaining C burnetii and prevent relapses. An alternative option is combination of doxycycline and a fluoroquinolone for at least 3-4 years. Other proposed alternatives include doxycycline or fluoroquinolones with rifampin therapy, although significant drug interactions could limit these regimens. [12]
The use of hydroxychloroquine is based on the assumption that it will elevate the pH within the phagolysosome vacuole of the monocyte, where C burnetii resides. This might affect the metabolism of the organism, rendering it more susceptible to the effects of doxycycline.
Endovascular complications should be treated with doxycycline and hydroxychloroquine in combination, although the optimal regimen is not well defined. [12] Osteoarticular infections should also be treated with prolonged antimicrobial combination therapy, along with surgical debridement [40] . A regimen of doxycycline and hydroxychloroquine, with or without rifampin, has been suggested, [12] as has the combination of a fluorquinolone and rifampin. [40]
Long-Term Monitoring
Although not a reportable condition in all 50 states (Delaware, Iowa, Oklahoma, Vermont, and West Virginia are excluded), physicians may consider notifying public health officials, depending on the circumstances and potential risk of others developing Q fever.
Patients should follow up with their primary care provider to confirm complete recovery. Patients with endocarditis or a history of valvular disease may require referral to a cardiologist or cardiothoracic surgeon for possible valve replacement.
Because of the risk for chronic infection, clinical and serologic follow-up for 2 years is recommended, particularly in individuals at risk. Patients with an IgG phase I >1:512 twelve months after treatment should undergo closer serological and clinical follow-up as they may have the highest risk to progress to chronic Q fever. [41]
The following includes a general summary of monitoring in acute and chronic Q fever.
Acute Q fever
Baseline transthoracic echocardiography should be performed to assess for vegetations. [12] Follow-up serology should be performed at least twice over 6 months. If phase I immunoglobulin (IgG) antibodies are found in titers of 1:800 or more, transesophageal echocardiography should be performed along with serum polymerase chain reaction (PCR) measurements, when possible. [12]
Chronic Q fever
Monthly follow-up serology and clinical assessment are recommended during antimicrobial therapy and for the first 6 months following withdrawal, then every 6 months for 2 years, and possibly yearly thereafter. Phase I IgG titers of 1:200 or less are the best predictor of cure.
Perform echocardiography every 3 months during antimicrobial therapy and every 6 months for the first 2 years following drug withdrawal.
High-risk populations should be screened for glucose-6-phosphate dehydrogenase deficiency before receiving hydroxychloroquine. If hydroxychloroquine is used, a yearly ophthalmologic evaluation is required to rule out retinal toxicity.
Patients should be reminded of photosensitivity risk while on doxycycline therapy.
Prevention
C burnetii must be cultured in biosafety level 3 laboratories. Use only seronegative sheep in research facilities.
Isolation and decontamination with standard precautions are recommended for healthcare workers because person-to-person transmission is rare. Decontamination is accomplished with soap and water or after a 30-minute contact time with 5% quaternary ammonium compound (MicroChem plus; National Chemical Laboratories, Inc, Philadelphia, Pa), 5% hydrogen peroxide, or 70% ethyl alcohol.
Postexposure prophylaxis for 5 days by using tetracycline or doxycycline is effective if initiated within 8-12 days of exposure. [42] Treatment with tetracycline during the incubation period may delay but not prevent the onset of symptoms.
If the patient's epidemiologic risk factor suggests that other people may share that risk factor (eg, an abattoir worker's coworkers and family members in a case contracted from a pregnant pet), the physician should notify the appropriate public health authorities.
Vaccine prophylaxis
Vaccine [10, 15, 43] is primarily used in at-risk people, such as veterinarians, abattoir workers, farmers, or others in occupations that require close contact with animals. No vaccine is available for children.
A whole-cell killed vaccine (Q-Vax) has been licensed in Australia since 1989, but it is not available in the United States. [8] Prevaccination screening is essential and includes history, skin testing, and serology, usually by indirect immunofluorescence (IIF). All 3 components must be negative before vaccine administration. Occasionally, large local reactions are reported.
An investigational vaccine is only available in the United States after consultation with the US Army Medical Research Institute of Infectious Diseases (USAMRIID) (Official mailing address: Commander USAMRIID, Attn: MCMR-UIZ-R, 1425 Porter Street, Frederick, MD 21702-5011). The phase II USAMRIID study investigating the vaccine is suspended and has been since May 2011 (clinicaltrials.gov ID:NCT00584454). No other vaccine for Q fever is available in the United States, and there are no other investigation studies pending.
Acellular vaccines include a trichloroacetic-extracted vaccine (Chemovaccine) from the former Czechoslovakia and a chloroform-methanol residue vaccine (CMR) from the United States. They have been promoted to be as effective as Q-Vax, but with fewer side effects. Phase I human trials using CMR proved that vaccination was safe. Although its efficacy has been demonstrated in rodents, sheep, and nonhuman primates, human data are lacking.
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A: Chest radiograph with normal findings. B: Chest radiograph demonstrating Q fever pneumonia.
