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.
The_Causative_Organism
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.
Acute_Q_Fever
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.
Chronic_Q_Fever
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.