Q fever

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See also: Coxiella burnetii for the pathogen of this disease

Q fever is a febrile illness, sometimes presenting as chronic endocarditis, caused by Coxiella burnetti. It has presented worldwide, with New Zealand as an exception. The disease was first described after a 1935 outbreak among Australian slaughterhouse workers. Since the disease proved so hard to track, the Q comes from query. Burnet and Freeman isolated the organism from blood samples and identified it as a Rickettsia species in 1937, although it is now categorized as of the Legionella family. Although primarily disseminated as an aerosol via inhalation or ingestion, Cox and Davis identified vector transmission when the organism was isolated from ticks at Nine Mile Creek in Montana in 1938.[1] There may be immunologic cross-reactivity with Legionella pneumophilia, or concurrent infection with both agents. [2]

Outbreaks of the disease, without an obvious association with animal or laboratory exposure, may be bioterrorism. It was known to have been weaponized before the Biological Weapons Convention went into effect, and is liste, as an overlap agent in the Select Agent Program and as a Category B organism in CDC Bioterrorism Agents-Disease list.


Prevention

Preventive actions need to be directed against people with exposure to animals and ticks in the wild, to meat processing, and in laboratories (especially working with sheep). Unpasteurized dairy products are also a risk factor.

Immunization

A commercial human Q fever vaccine (Q-Vax) is manufactured in Australia but is not available in the United States; it is available on an investigational basis from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland .[1]

Chemoprophylaxis

Postexposure prophylaxis for 5 days by using tetracycline or doxycycline is effective if initiated within 8-12 days of exposure. Treatment with tetracycline during the incubation period may delay but not prevent the onset of symptoms.

Clinical Presentation

The disease has both an acute and a chronic form. In the acute form, however, there are different major presentations of pneumonia versus gastrointestinal disease.

Acute disease

The overall presentation is "flulike", with fever of sudden onset, headache and muscle pain. Respiratory involvement is common, with pneumonia in most U.S. cases, while hepatitis is more common in Europe. Nausea is not uncommon, along with right upper quadrant pain.

Cardiovascular involvement correlates to the height of the fever. Myocarditis and pericarditis are seen in the acute form.

Several forms of rash may be seen, along with meningitis and encephalitis.

Forms of the disease

Canadian researchers hypothesized that the route of infection, known to include inhalation, tick bite, and contaminated food, could determine the the form of the clinical disease. Mice in one group were given C. burnetti by a nasal route, and another group by intraperitoneal ijection. While both groups had pneumonia, the group that inhaled the pathogen had a statistically higher level of airway changes. "It was concluded that the route of infection is one determinant of the manifestations of acute Q fever."[3]

Chronic disease

Chronic disease usually presents as endocarditis, especially of abnormal (e.g., aneurysm) or prosthetic heart valves; endocarditis usually coexists with chronic hepatitis. It may also present with bone disease such septic arthritis or osteomyelitis, especially when there are risk factors such as prosthetic joints.

Differential diagnosis

Infections to rule out
Chlamydial Infections Ehrlichiosis Endocarditis, Bacterial
Hepatitis B Hepatitis C Legionellosis
Lyme disease Myocarditis, Nonviral Pericarditis, Bacterial
Pneumonia, viral Pneumonia, mycoplasma Tularemia
Rickettsial Infection Rocky Mountain Spotted Fever

Also consider aseptic meningitis and granulomatous hepatitis

Physical examination

Fever, while it may be low-grade, is almost always present. With respiratory involvement, look for dry cough, dyspnea and pleuritic chest pain. Gastrointestinal involvem

  • Acute Q fever
    • Hepatitis - Fever, malaise, abdominal pain (right upper quadrant), hepatomegaly, jaundice
    • Pneumonia - Fever, dry cough, pleuritic chest pain, dyspnea
    • Isolated fever (may be low grade but usually as high as 40°C)
    • Meningitis or encephalitis (rare, approximately 1%) - Severe headache, stiff neck, fever
  • Chronic Q fever - Endocarditis (vegetations, clubbing, embolization, rash, hepatosplenomegaly)

Laboratory presentation

Immunologic testing is definitive, although some general findings may be suggestive. In most laboratories, the indirect immunofluorescence assay (IFA) is the most dependable and widely used method. Coxiella burnetii may also be identified in infected tissues by using immunohistochemical staining and DNA detection methods.[4]

A platelet count may be suggestive because persons with Q fever may show a transient thrombocytopenia. Confirming a diagnosis of Q fever requires serologic testing to detect the presence of antibodies to Coxiella burnetii antigens. C. burnetii is acid-fast and can be visualized, in tissue samples with Stamp, modified Ziehl-Neelsen, Gimenez, Giemsa or modified Koster stains. Microscopic examination is more a veterinary than a human medical technique, used to determine if the organism is present in a herd. [5]

Culture

It can be grown in conventional cell cultures or embryonated chicken yolk sacs or laboratory animals. Culture is not routinely done, but can be useful in isolating the organism from contaminated tissue samples, or to obtain phase I antigens. Inoculation of laboratory animals (guinea-pig, mouse, hamster) is helpful in cases requiring isolation from tissues contaminated with various microorganisms or in order to the [[#antigenic variation|phase I antigen.[5]

Tests

Confirming a diagnosis of Q fever requires immunologic testing to detect the presence of antibodies to Coxiella burnetii antigens. Refinements of this testing can determine if a case is acute or chronic.

Immunologic methods

In most laboratories, the indirect immunofluorescence assay (IFA) is the most dependable and widely used method. PCR and ELISA also are used. PCR offers the advantage of being useful in herd screening, and also allowing heat inactivation of the organism to protect laboratory workers.

Recent studies have shown that greater accuracy in the diagnosis of Q fever can be achieved by looking at specific levels of classes of antibodies other than IgG, namely IgA and IgM. Combined detection of IgM and IgA in addition to IgG improves the specificity of the assays and provides better accuracy in diagnosis. IgM levels are helpful in the determination of a recent infection. In acute Q fever, patients will have IgG antibodies to phase II and IgM antibodies to phases I and II. Increased IgG and IgA antibodies to phase I are often indicative of Q fever endocarditis.

Antigenic variation

Coxiella burnetii exists in two antigenic phases called phase I and phase II. This antigenic difference is important in diagnosis.

  • Acute Q fever: Phase II antibodies are much greater than Phase I
  • Chronic Q fever: Phase I antibodies predominate; it takes longer for them to appear.

The continued presence of Phase I suggests continuing exposure. Both types can persist for months or years. To confirm chronic disease, high Phase I levels are detectable along with general markers of an inflammatory process.

Treatment and prognosis

Different approaches are needed for the acute and chronic forms of the disease.

Treatment of acute Q fever

Doxycycline, especially when started within the first 3 days and continued twice daily for 15-21 days, is a common regimen. Fluoroquinolone antibiotics also have demonstrated efficacy. There may be a relapse, which calls for another course of antibiotics.

Treatment of chronic Q fever

Chronic Q fever endocarditis is much more difficult to treat effectively and often requires the use of multiple drugs.

  1. doxycycline in combination with fluoroquinolones for at least 4 years
  2. doxycycline in combination with hydroxychloroquine for 1.5 to 3 years. The second therapy leads to fewer relapses, but requires routine eye exams to detect accumulation of chloroquine.

Surgery to remove damaged valves may be required for some cases of C. burnetii endocarditis.

Prognosis

Acute Q fever is generally a self-limited disease (in 38% of cases); more than one half of patients are asymptomatic, and only 2-4% require hospitalization. The mortality rate for symptomatic patients is less than 1%.

Chronic Q fever, which is practically synonymous with Q fever endocarditis, is more difficult to treat than acute Q fever. Mortality is almost universal if untreated, but the mortality rate is less than 10% with appropriate treatment.

Significant outbreaks

In 1983, 415 confirmed cases took place in Switzerland, 3 weeks after 12 flocks of sheep, totaling 850 to 900 animals, came into a populated valley from mountain patures. 21.1 percent of the human population of the village along the road that the sheep followed contracted the disease, while there was only 2.9 percent infection in the villages away from the road.[6]

References

  1. 1.0 1.1 Migala, Alexandre F & Leah Neumann, "Q fever", eMedicine
  2. Finidori JP, Raoult D, Bornstein N, Fleurette J. (1992 Oct), "Study of cross-reaction between Coxiella burnetii and Legionella pneumophila using indirect immunofluorescence assay and immunoblotting.", Acta Virol. 36(5): 459-65
  3. Marrie TJ, Stein A, Janigan D, Raoult D. (1996 Feb), "Route of infection determines the clinical manifestations of acute Q fever.", J Infect Dis. 173(2): 484-7.
  4. Viral and Rickettsial Zoonoses Branch, Centers for Disease Control, Q fever
  5. 5.0 5.1 World Organisation for Animal Health, CHAPTER 2.2.10. Q FEVER url = http://www.oie.int/eng/normes/mmanual/A_00049.htm, Manual of Diagnostic Tests and Vaccines for Terrestrial Animals
  6. Dupuis G, Petite J, Péter O, Vouilloz M. (1987 Jun), "An important outbreak of human Q fever in a Swiss Alpine valley.", Int J Epidemiol 16(2): 282-7