Chronic Q Fever



Q fever was discovered about 50 years ago in Brisbane, where an outbreak occurred among workers in a meat processing factory. The disease was named Q (query) fever, and the organism isolated was a rickettsia named Coxiella burnetti. Q fever has a worldwide distribution and is the manifestation of overt infection by C burnetti; subclinical infections are common. The majority of cases occur in men of working age, but may occur in either sex and at all ages. C burnetti is a zoonotic infection affecting chiefly cattle, sheep, and goats, but has been found in a large number of species of animals and birds. Although it has also been isolated from various species of ticks, the role of these insects in the spread of the disease is not clear. Human infections generally result from the inhalation of infected aerosols, arising particularly from the products of conception of cattle or sheep, but it is possible that raw milk from infected cows may be responsible for human infections.





C burnetti can be cultured in the yolk sac or monolayers of chick embryo cells, and by the intraperitoneal inoculation of many species of laboratory animals. It has been isolated from the sputum of patients suffering from pneumonia, from infected heart valves from cases of endocarditis, and from the milk of infected animals. The inoculum is injected into the yolk sac of a hen's egg or intraperitoneally into guinea-pigs. The organism can be demonstrated in infected yolk sacs by making impression smears and staining with a Romanovsky stain. After intraperitoneal inoculation of a guinea-pig, antibodies develop which can be detected 2-4 weeks after injection by CFT or other tests. C burnetti has been associated with many laboratory infections and stringent safety precautions should be observed.

      C burnetti undergoes a phase variation somewhat akin to the smooth-rough variation observed in many bacteria. The smooth hydrophilic organisms in phase 1 are stable in suspension and not phagocytosed in the absence of specific antibodies. After repeat­ed passage eg. in yolk sac, they become rough, hydrophobic and agglutinable. These readily phagocytosable organisms are in phase 2. When phase 2 organisms are inoculated into laboratory animals, they rapidly revert to phase 1. Phase 1 organisms are virulent for guinea-pigs, whereas those in phase 2 are avirulent. In the great majority of cases of Q fever, antibodies are produced only against phase 2 antigens. In chronic Q fever, antibodies are produced against both antigens.



C burnetti infection often gives rise to Q fever although inap­parent infections are common. The acute disease is more common in men than women and varies from a trivial febrile illness to a full-blown pneumonia which may be fatal. After an incubation period of 2-3 weeks, a flu-like illness commences with a severe headache, arthralgia, shivering and anorexia. In some cases, the fever subside after 2 or 3 days and the patient recovers. In other cases, the illness progresses and a cough develops. The chest X-ray often shows one or more areas of opacity. The diagnosis is made serologically by the demonstration of a rising titre of antibody in paired sera against the phase 2 antigen of C burnetti. Treatment is symptomatic only but in severe cases, tetracyclines may be given.





1. Endocarditis ;-  this is the most common manifestation of chronic Q fever, amounting to 11% of 839 cases of Q fever in one series in England and Wales. C burnetti causes 2-3% of all cases of infective endocarditis in England and Wales. Q fever endocar­ditis usually presents in men of working age. In the majority of cases, it is not possible to elicit a history of Q fever but this may be due to the fact that the period between infection and the development of endocarditis is very variable and may be as long as 20 years. There is usually a history of previous valvular damage or abnormality. The onset is insidious and the patient presents with signs and symptoms of chronic or subacute endocarditis, usually involving the aortic valve, though the mitral valve may also be attacked. Q fever endocarditis is often diagnosed as "blood culture negative endocarditis" and thus it is important to test all such cases serologically against phase 1 and phase 2 antigens of C burnetti. Untreated disease results in severe valvular destruction, leading to increasing heart failure. Embolic phenomenon are also common.


2. Hepatitis ;- many patients suffering from Q fever endocarditis have abnormal liver function tests without overt evidence of hepatitis, though some develop hepatomegaly. Granulomata and increasing fibrosis may be seen which may rarely lead to cirrho­sis.


3. Glomerular Nephropathy ;- haematuria has been described in many cases of chronic Q fever. 3 cases of endocarditis complicat­ed by glomerular nephropathy had been reported from Spain.


4. Osteomyelitis ;- this has occasionally been observed.


5. Thrombocytopenia ;- this was reported in 12 out of 16 patients in one series, six of whom had purpuric rashes.


6. Encephalitis ;- a case of endocarditis complicated by encepha­litis had been described.







The isolation of the organism is not practicable in the majority of laboratories and is less certain and more time-consuming than serology. CFT is the most widely used test but IF and ELISA techniques are also used. In acute Q fever, phase II antibodies are always present whereas phase I antibodies are usually transient and of low titre. In chronic Q fever, phase I antibodies are always present and are often very high. Phase II antibodies are usually present also, often at a considerably higher titre than phase I anti­bodies. A single serum is usually sufficient to produce the diagnosis; rising titres are rarely found in chronic infections. The differences in antibody responses between acute and chron­ic infections may be because the phase II antigen is more super­ficial, or perhaps because in chronic infections, organisms persist in phase I. There has been much discussion about diagnos­tic levels of phase I antibody in chronic Q fever. Serological tests differ in sensitivity from laboratory to laboratory but most authors accept a phase I CF titre of 1:200 or more as diag­nostic of chronic infection.





The prognosis of Q fever endocarditis is highly variable. There had been many reports of fatal cases. Some patients die within a few months despite appropriate antibiotic treatment. However, most patients respond satisfactorily to antibiotic therapy but treatment needs to be kept up for a long period or even for life. Tetracyclines are the mainstay of treatment, either alone or in combination with other antibiotics. There has been controversy over the duration of antibiotic therapy; some authors suggest that treatment should be continued indefinitely, while others suggest that treatment should be for periods of at least 12 months, or until there is clinical evidence of resolution of endocarditis or the phase I CF antibodies have fallen below 200. Each patient should be treated individually. Patients should be warned that antibiotic treatment should continue for at east 2 years or more. Surgical replacement valves is indicated where the valves are severely damaged. However, numerous cases of infection of prosthetic valves have been recorded.

      The majority of cases of acute Q fever do not require follow-up. They make a rapid clinical recovery with or often without tetracycline treatment. Some of the more severe cases require more careful consideration especially if complications such as myocarditis, hepatitis, encephalitis or haemolysis are seen. In these cases, as well serological testing for phase II antibodies, tests should be carried out for phase I antibodies. Rarely, the antibody persists for months without any signs of chronic infec­tion. To date, little is known about the development of chronic Q fever following the acute attack, and it is not possible to postulate any predisposing factors which may lead to the develop­ment of chronic disease. However, f a patient suffering from a valvular abnormality of the heart develops Q fever, this is clearly an indication for thorough and probably prolonged antibi­otic therapy and follow-up.