Q Fever

Q FEVER

SUMMARY

Signs and Symptoms: Fever, cough, and pleuritic chest pain may occur as early as ten days after exposure. Patients are not generally critically ill, and the illness lasts from 2 days to 2 weeks.

Diagnosis: Q fever is not a clinically distinct illness and may resemble a viral illness or other types of atypical pneumonia. The diagnosis is confirmed serologically.

Treatment: Q fever is generally a self-limited illness even without treatment. Tetracycline or doxycycline are the treatments of choice and are given orally for 5 to 7 days. Q fever endocarditis (rare) is much more difficult to treat.

Prophylaxis: Treatment with tetracycline during the incubation period may delay but not prevent the onset of symptoms. An inactivated whole cell IND vaccine is effective in eliciting protection against exposure, but severe local reactions to this vaccine may be seen in those who already possess immunity.

Isolation and Decontamination: Standard Precautions are recommended for healthcare workers. Person-to-person transmission is rare. Patients exposed to Q fever by aerosol do not present a risk for secondary contamination or re-aerosolization of the organism. Decontamination is accomplished with soap and water or after a 30 minute contact time with 5% microchem plus (quaternary ammonium compound) or 70% ethyl alcohol.

OVERVIEW

The endemic form of Q fever is a zoonotic disease caused by a rickettsia, Coxiella burnetii. Its natural reservoirs are sheep, cattle and goats, and grows to especially high concentrations in placental tissues. Exposure to infected animals at parturition is an important risk factor for endemic disease. The organisms are also excreted in animal milk, urine, and feces. Humans acquire the disease by inhalation of aerosols contaminated with the organisms. Farmers and abattoir workers are at greatest risk occupationally. A biological warfare attack with Q fever would cause a disease similar to that occurring naturally. Q fever is also a significant hazard in laboratory personnel who are working with the organism.

HISTORY AND SIGNIFICANCE

Q fever was first described in Australia: it was called "Query fever" because the causative agent was initially unknown. Coxiella burnetii, the causative agent, was discovered in 1937. This organism is a rickettsial agent that is resistant to heat and desiccation and highly infectious by the aerosol route. A single inhaled organism may produce clinical illness. For all of these reasons, Q fever could be used as a biological warfare agent. This organism could be employed by an adversary as an incapacitating agent due to its highly infectious nature and likelihood of causing disease if delivered by the respiratory route.

CLINICAL FEATURES

Following the usual incubation period of 10-40 days, Q fever generally occurs as a self-limiting febrile illness lasting 2 days to 2 weeks. The incubation period varies according to the numbers of organisms inhaled, with longer periods between exposure and illness with lower numbers of inhaled organisms (up to forty days in some cases). The disease generally presents as an acute nondifferentiated febrile illness, with headaches, fatigue, and myalgias as prominent symptoms. Pneumonia manifested by an abnormal chest X-ray occurs in half of all patients, but only half of these, or 25 percent of patients, will have a cough (usually non-productive) or rales. Pleuritic chest pain occurs in about one-fourth of patients with Q fever pneumonia. Chest radiograph abnormalities, when present, are patchy infiltrates that may resemble viral or mycoplasma pneumonia. Rounded opacities and adenopathy have also been described.

Uncommon complications include chronic hepatitis, culture-negative endocarditis, aseptic meningitis, encephalitis and osteomyelitis. Most patients who develop endocarditis have pre-existing valvular heart disease.

DIAGNOSIS

Routine Laboratory Findings: The white blood cell count is elevated in one third of patients. Most patients with Q fever have a mild elevation of hepatic transaminase levels.

Differential Diagnosis: As Q fever usually presents as an undifferentiated febrile illness, or a primary atypical pneumonia, it may be difficult to distinguish from viral illnesses and must be differentiated from pneumonia caused by Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia psittaci, and Chlamydia pneumoniae (TWAR). More rapidly progressive forms of Q fever pneumonia may look like bacterial pneumonias such as tularemia or plague. Significant numbers of soldiers (from the same geographic area) presenting over a one to two week period with a nonspecific febrile illness, with associated pneumonic symptoms in about half of cases, should trigger the possibility of an attack with aerosolized Q fever in the minds of the treating physicians. The diagnosis will often rest on the clinical and epidemiologic picture in the setting of a possible biowarfare attack.

Specific Laboratory Diagnosis: Identification of organisms by examination of the sputum is not helpful. Isolation of the organism is impractical, as the organism is difficult to culture and a significant hazard to laboratory workers. Serological tests for Q fever include identification of antibody to C. burnetii by indirect fluorescent antibody (IFA), enzyme-linked immunosorbent assay (ELISA), and complement fixation. Specific IgM antibodies may be detectable as early as the second week after onset of illness. ELISA testing is available at USAMRIID. A single serum specimen can be used to reliably diagnose acute Q fever with this test as early as 1 1/2 - 2 weeks into the illness. The most commonly available serologic test is the complement fixation test (CF) which is relatively insensitive and may not be useful if sera have intrinsic anti-complement activity.

MEDICAL MANAGEMENT

Standard Precautions are recommended for healthcare workers. Most cases of acute Q fever will eventually resolve without antibiotic treatment. Tetracycline 500 mg every 6 hr or doxycycline 100 mg every 12 hr for 5-7 days will shorten the duration of illness, and fever usually disappears within one to two days after treatment is begun. Successful treatment of Q fever endocarditis is much more difficult. Tetracycline or doxycycline given in combination with trimethoprim-sulfamethoxazole (TMP-SMX) or rifampin for 12 months or longer has been successful in some cases. However, valve replacement is often required to achieve a cure.

PROPHYLAXIS

Vaccine: A formalin-inactivated whole cell IND vaccine is available for immunization of at-risk personnel on an investigational basis, although a Q fever vaccine is licensed in Australia. Vaccination with a single dose of this killed suspension of C. burnetii provides complete protection against naturally occurring Q fever, and greater than 95 percent protection against aerosol exposure. Protection lasts for at least 5 years. Administration of this vaccine in immune individuals may cause severe local induration, sterile abscess formation, and even necrosis at the inoculation site. This observation led to the development of an intradermal skin test using 0.02 mg of specific formalin-killed whole-cell vaccine to detect presensitized or immune individuals.

Antibiotics: Tetracycline or doxycycline given prophylactically after exposure can delay the onset of disease, or even prevent symptoms if administered late in the incubation period. When prophylaxis is started one day after exposure and continued for 5 days, clinical disease has been shown to occur about three weeks after stopping therapy. If prophylaxis is begun 8 to 12 days post-exposure and continued for 5 days, clinical disease will not occur after treatment is discontinued.