Gordon E. Schutze
Coxiella burnetii is an obligate intracellular pleomorphic gram-negative coccobacillus that was originally named Rickettsia burnetii. Extensive changes in the taxonomy of rickettsiae based on the sequencing of the 16S rRNA has resulted in the removal of C burnetii from the order Rickettsiales and now finds it in the order Legionellales falling into the gamma group of proteobacteria along with Legionella pneumophila, and Francisella tularensis.1,2 The reader should not become too comfortable with this new classification because as new Coxiella-like organisms are found, the phylogenetic relationships of this group of organisms will be readdressed in the future.
Cattle, sheep, and goats are the primary reservoirs for infections resulting from Coxiella burnetii, although there are an increasing number of cases that have been reported following occasional contact with cats, rabbits, and dogs in an urban setting.3 Infection in humans most often occurs after inhalation of aerosolized organisms or with ingestion of raw milk or fresh goat cheese.4 Reactivation of infection can occur in female mammals during pregnancy where high concentrations of C burnetii can be found in the placenta. Animal-to-human transmission can occur during parturition of such animals by direct aerosol transmission.5 Tick vectors may be important in maintaining animal reservoirs, but are usually not responsible for human disease.6 Q fever is endemic in virtually every country in the world, especially those areas where cattle are raised and sheep and goats are herded. Little is known about the pathologic process associated with infection because most patients recover from their illness. Evidence for human intrauterine infection has also been reported.7
CLINICAL MANIFESTATIONS
The incubation period for Q fever is usually between 14 and 22 days (range 2–6 weeks). The severity of illness in children is varied and difficult to document because published data on infections in children are limited.8,9 Acute illness in older patients is usually manifested by an abrupt onset of fever, chills, weakness, headache, and anorexia. Cough and chest pain should alert the clinician to the possibility of pneumonia that occurs in approximately 50% of patients. Symptoms are exacerbated during temperature spikes, whereas patients frequently feel well during afebrile intervals. In patients younger than age 3 years, the presentation is usually one of persistent fever without respiratory manifestations. Although pneumonitis is a hallmark of this illness, Q fever is a systemic illness. Hepatosplenomegaly and gastrointestinal manifestations (eg, vomiting, abdominal pain) are frequently noted; rash is unusual in adults but may be more likely to develop in children. Most patients with Q fever improve with or without specific antimicrobial therapy.
A small number of patients (< 1% of adults) do not clear the organism and develop a chronic illness.8 The risk for developing chronic infection, however, is correlated with advancing age. Children, therefore, are infrequently diagnosed with chronic illness.8,9 Endocarditis is the major form of chronic Q fever. Endocarditis occurs almost exclusively in patients who have had previous valvular heart disease or immunosuppression. Bone involvement can be demonstrated in patients with chronic Q fever and is more prevalent among children than it is among adults. Chronic Q fever is difficult to treat and often ends in death.
DIAGNOSIS
Q fever should be suspected in febrile patients who live in high-prevalence areas and who are in contact with domestic farm animals. In the United States, animal handlers and laboratory workers make up a significant portion of reported infection. Chest roentgenographic findings for Q fever pneumonia are nonspecific and are similar to those associated with pneumonia caused by viruses, Mycoplasma pneumoniae, or Chlamydia pneumoniae. Multiple round opacities are commonly seen even in patients who are clinically asymptomatic. Q fever endocarditis is rare, vegetations are rarely detected, and blood cultures are usually negative. The diagnostic clue in this situation is valvular heart disease, in association with an unexplained infectious or inflammatory syndrome. Q fever should also be considered in patients with purpuric eruptions, renal insufficiency, stroke, and unexplained hepatosplenomegaly. A normal white blood cell count with thrombocytopenia, and elevated liver function tests are associated with Q fever.10
The approach to the diagnosis of Q fever is serologic.10 Specific phase I and phase II immuno-fluorescent, enzyme immunoassay, complement fixation, and immune adherence hemaggluti-nation antibody tests using paired (acute and convalescent) serum specimens make up the diagnostic method of choice. In acute Q fever, antibody titers to phase II antigens are higher than antibody titers to phase I antigens, whereas in chronic forms, elevated phase I titers are more commonly found. Because patients with previous infection remain seropositive for prolonged periods, single positive titers cannot be used to establish a diagnosis. The use of DNA detection for C burnetii by polymerase chain reaction has been used successfully but is not widely available. Because C burnetii has been transmitted with minimal exposures in laboratory settings, routine isolation by clinical laboratories for diagnostic purposes is not recommended.
TREATMENT
Acute Q fever can be a self-limited disease and many patients recover without the use of antimicrobial therapy. If antimicrobial agents are used, doxycycline is the drug of choice, as treatment can hasten the recovery by several days. It should be noted, however, that the initiation of therapy late in the course of illness has little effect on the course of the acute infection, and in order to prevent complications, antimicrobial therapy needs to be started within 3 days of the onset of symptoms. As with the rickettsial diseases, many experts consider that the benefits of using doxycycline in treating Q fever exceed any potential risk of teeth staining and would use it at any age.11 Trimethoprim-sulfamethoxazole and chloramphenicol can be used as an alternative to doxycycline in the younger patient. Treatment of chronic Q fever is prolonged, lasting a minimum of 18 months and in certain instances as long as 3 years.