What is Q fever?

Q fever results from infection by C. burnetii (Coxiella burnetii) which is a rickettsia. Q fever is a zoonosis (zoonosis is a disease which is transmitted from animals to man). The major (primary) sources of human infection of Q fever are infected (with Coxiella burnetii) cattle, sheep, and goats. But, cats, rabbits, pigeons, and dogs can also transmit C. burnetii to humans. Coxiella burnetii uses several techniques to escape immune system as well as the harsh environment where it lives. It forms spores to survive in harsh environments and it escapes intracellular killing in macrophages (by immune system) by inhibiting certain steps and adapts to the acidic environment of intracellular environment.

What are the types of Q fever?

Q fever is broadly divided into 2 types according to clinical symptoms, acute Q fever and chronic Q fever. The immune status and the immune response of the host (human) determines the type and severity of Q fever (whether Q fever will be acute or develop into chronic Q fever), not the strain of the infecting organism (Coxiella burnetii). It is proved that C. burnetii can survive in monocytes of patients with chronic Q fever but can not survive in monocytes from patients with acute Q fever or from uninfected persons. The ratio of CD4+ and CD8+ is decreased in Q fever endocarditis. A strong cellular response and very few C. burnetii are observed in patients with acute Q fever, but there are many organisms (C. burnetii) and only a moderate cellular response is seen in chronic Q fever. All the above points prove that the immunity of host is more important in Q fever and severity of the infection.

Epidemiology & incidence of Q fever:

Q fever is seen in almost all over the world except New Zealand and Antarctica. The initial symptoms (manifestations of disease) of Q fever can vary in different geographical area, for example the initial symptom is pneumonia in Nova Scotia of Canada, but is hepatitis in Marseille of France. These differences of initial symptoms may be due to the route of infection e.g. the ingestion of contaminated milk cause hepatitis and inhalation of contaminated aerosols cause pneumonia as initial symptom.

What are the modes of transmission of Q fever?

The wild reservoir (where organisms live naturally before infecting humans) of Q fever is ticks. In the infected female mammal, C. burnetii generally localizes itself to the uterus and the mammary glands (breasts) and infection is reactivated during pregnancy of the infected mammal. High concentrations of C. burnetii are found in the placenta and at the time of parturition (delivery), C. burnetii are released into the air, and human infection follows inhalation of aerosolized organisms by a susceptible human host. Soil is also contaminated during delivery, and C. burnetii aerosols can be generated even months later during windstorms. There are reports that individuals up to 18 km from the source have been infected.

Who are at risk of Q fever?

Abattoir workers, veterinarians, and other individuals who come with direct contact with infected animals, especially newborn animals or products of conception like placenta are at greater risk of getting infection of Q fever. The organisms (C. burnetii) are shed in milk for weeks to months after delivery. The ingestion of contaminated milk (milk without boiling) in some geographic areas probably represents a major route of transmission of Q fever to humans, although the evidence gathered in studies on this point is contradictory (as it is seen that major route of transmission of Q fever is inhalation). Human-to-human transmission can occur during labor and childbirth in an infected woman, autopsy of an infected individual, or blood transfusion, although extremely rare. There are also evidences which suggest that C. burnetii can be sexually transmitted among humans. But, the vast majority of Q fever infections result from inhalation of contaminated aerosols.

Less incidence of Q fever in children and females:

Young age and female sex may be protective against infection with C. burnetii. For example in a large outbreak in Switzerland, infection of Q fever (symptomatic) was five times more among persons more than15 years of age than among those less than 15 years of age. The incidence of Q fever is less among females, may be due to partial protection provided by female sex hormones. For example in France the male-to-female ratio of Q fever infection is 2.45:1, this is despite similar occupational exposure of both the sexes.

What are the clinical manifestations of acute Q fever?

The incubation period (the number of days or hours it takes between the entry of an organism in human body and appearance of first symptoms of disease is known as incubation period) for acute Q fever is 3–30 days. The symptoms of acute Q fever are nonspecific and common symptoms are fever, extreme fatigue, and severe headache. There may be other symptoms like chills, sweating, nausea, vomiting, and diarrhea (these may occur in 5–20% of Q fever patients). In Q fever pneumonia cough is present in half of the patients. Neurological manifestations of acute Q fever are uncommon, but these may be present as was seen in an outbreak in the United Kingdom, where 23% of Q fever patients had neurological signs and symptoms as the major manifestation. Skin rash may be seen in 4–18% of acute Q fever patients. The WBC (White Blood Cell) count is usually normal. Chest X-ray may show an opaque area (multiple rounded opacities) that is indistinguishable from that seen in pneumonia (of other cause).

Hepatitis was the presenting symptom in 40%, pneumonia in 17%, both pneumonia and hepatitis in 20%, isolated fever in 14%, CNS problem in 2%, and pericarditis and myocarditis in 1% of acute Q fever in one study in southern France.

If acute Q fever occurs during pregnancy it can complicate pregnancy (it can cause premature birth in 35% of cases, and 43% in abortion or neonatal death). Among seropositive women a current or previous neonatal death can be as high as three times seronegative for C. burnetii. Studies in Australia and the United Kingdom it was seen that, a fatigue state last 5–10 years in 8–15% of cases of Q fever. Patients who develop Q fever fatigue syndrome have a higher frequency of carriage. Low levels of C. burnetii DNA can be detected in the Q fever patients 0.75–5 years after infection.

In children up to 70% of cases of Q fever are asymptomatic and only a few cases of Q fever endocarditis have been reported among children.

What are the clinical manifestations of chronic Q fever?

Chronic Q fever generally means endocarditis (almost always). Chronic Q fever generally occurs in patients with previous history of valvular heart disease, immunosuppression, or chronic renal insufficiency. Fever is usually absent and if present of low grade. Sometimes diagnosis is made after patients suffer from nonspecific symptoms for up to 1 year. Patients with chronic Q fever may have hepatomegaly (enlargement of liver) and/or splenomegaly (enlargement of spleen). Other manifestations which may be present in chronic Q fever are infection of vascular prostheses, aneurysms, and bone infection. Unusual symptoms of chronic Q fever are chronic thrombocytopenia, mixed cryoglobulinemia etc.

How to diagnose Q fever?

A high index of suspicion is necessary for a correct diagnosis of Q fever and it should be suspected in all patients with culture-negative endocarditis. The most commonly used and method of choice of diagnosis of Q fever is serological test. Indirect immunofluorescence is sensitive as well as specific for diagnosis of Q fever and is the method of choice at present. An IgG titer of more than or equal to 1:800 to phase I antigen is suggestive of chronic Q fever. In acute Q fever the titer of phase II antigen is about fourfold higher than phase I antigen and the reverse is true in chronic Q fever, where titer of phase I antigen is higher. PCR (Polymerase Chain Reaction) detects C. burnetii DNA in tissues, including paraffin-embedded tissues.

Vegetations in the heart valves are detected in only few of patients (approximately 12%) by trans-thoracic echocardiography, but transesophageal echocardiography can increase the detection rate of vegetations. The valvular vegetations of chronic Q fever endocarditis (seen as endothelialized nodules on the valves) are different from those of bacterial endocarditis.

How Q fever is treated?

The drug of choice in treatment of acute Q fever is doxycycline 100 mgs two times a day for 2 weeks (14 days). Treatment with doxycycline is generally successful. Quinolones (ciprofloxacin, ofloxacin, pefloxacin etc.) are also good drugs.

Treatment of chronic Q fever is difficult and need long and careful follow-up. Current treatment regime for chronic Q fever is doxycycline (100 mg 2 times a day) and hydroxychloroquine (200 mg 3 times a day) for 18 months and it is superior regime than doxycycline and ofloxacin combination. Hydroxychloroquine is added to alkalinize the phagolysosome, where C. burnetii lives. For optimal management of chronic Q fever endocarditis the minimal inhibitory concentration (MIC) of doxycycline should be determined for the patient's isolate and measurement of serum doxycycline levels in the patient should be done. The serum level of doxycycline should be more than minimal inhibitory concentration and if the serum level is maintained to more than MIC rapid decline in phase I antibodies occurs. The doxycycline-hydroxychloroquine regimen is also useful in treating chronic Q fever in HIV patients. Photosensitivity and retinal toxicity are the risks and patients should be warned about these side effects. Jarisch-Herxheimer reaction can sometimes complicate the treatment of chronic Q fever. C. burnetii infected aortic aneurysms is treated the same way as that for Q fever endocarditis, but sometimes surgery may be required.

If doxycycline-hydroxychloroquine combination cannot be used (due to hypersensitivity or serious side effects), the treatment should be done with at least 2 antibiotics effective against C. burnetii. In this case rifampin (300 mg once a day) can be used successfully with doxycycline (100 mg 2 times a day) or ciprofloxacin (750 mg 2 times a day).

Q fever during pregnancy:

If a pregnant woman suffers from Q fever, it should be treated with trimethoprim-sulfamethoxazole for the duration of the pregnancy. After pregnancy is over the usual treatment regimen can be given.

How long is the treatment of chronic Q fever?

The optimal duration of treatment of chronic Q fever is still undetermined. Many authorities recommend the duration of treatment should be at least for 3 years and discontinuation of treatment only if the phase I IgA (immunoglobulin A) antibody titer is less than 1:50 and phase I IgG (immunoglobulin G) is less than 1:200.

Treatment of Q fever with biologic modifying agents:

Sometimes treatment with ?-interferon (gamma-interferon) can be successful where conventional regimens with antibiotics for treatment of Q fever fail. Another option of treatment is to use prednisone at the dose of 0.5 mg/kg body weight, if there is prolonged fever not responding to antibiotic therapy, especially in Q fever patients with granulomatous hepatitis. Fever subsides in 2 days to 2 weeks and after that prednisone is withdrawn gradually (tapered) over the next month.

How to prevent Q fever?

Q fever vaccine:

In Australia a whole cell vaccine (Q-vax) is licensed which is used successfully in abattoir workers for prevention of Q fever. The vaccine (Q-vax) is given only to persons with no history of Q fever and who test negative for serologic and skin tests. For this serologic testing and skin testing with intra-dermal diluted C. burnetii vaccine is done before administering the vaccine as well as history of Q fever is obtained.

Good animal husbandry practices should be practiced to prevent Q fever. Good animal husbandry practices include isolating aborting animals for up to 2 weeks, raising feed bunks to prevent contamination of feed by animal excreta, destroying aborted materials (by burning or incinerating and burying fetal membranes and stillborn animals), and wearing of masks and gloves during handling of aborted materials. Only seronegative pregnant animals should be used in research programs, and also only seronegative animals should be kept in zoos.