Q fever is the infection caused by the Gram-negative bacteria Coxiella burnetii. Derrick named it in 1937 as Q (for query) fever, "until fuller knowledge should allow a better name".
C. burnetti is an obligate intracellular parasite related to the genus Rickettsia.
Q fever is an highly infectious zoonosis where the main reservoir is either arthropods (mainly ticks) or farm animals, eg cattle, sheep, goats, although pets (dogs, rabbits and particularly cats) may be the reservoir in urban areas, and wild rats have been shown to be a potential reservoir in the UK.
- Animals are infected by inhaling or ingesting infected material:
- It produces spores that can last in the soil for up to 150 days.
- They shed bacteria in urine, faeces or milk.
- They rarely become ill, but the bacteria localise in the uterus and mammary glands and become reactivated during pregnancy.
- It can cause abortion in sheep and reproductive problems in cattle.
- Very high concentrations of C. burnetii are found in the placenta.
- Humans usually become infected from domestic animals:
- This is through inhaling the organism, although occasionally by ingesting raw milk.
- The incubation period is approximately 2 weeks (2-29 days) following inhalation.
An occupational disease of slaughterhouse, animal husbandry and animal research workers.
Q fever is endemic in every part of the world except New Zealand. Cases of Q fever have been reported in 45 countries on 5 continents and it is a significant problem in Australia.
In June 2006, the United Kingdom experienced its largest outbreak of Q fever with 138 cases associated with a slaughterhouse near Stirling in Scotland. The slaughterhouse had been processing post-parturition ewes, that were thought to be the likely source. There is an ongoing outbreak in The Netherlands.
It has been designated a category B bioterrorism agent, as an incapacitating agent:
- The incubation period depends on the dose.
- It is usually 2 to 3 weeks, but 4 days and 6 weeks have been reported.
- Although it has a low case fatality rate, it meets criteria such as ease of manufacture, stability in the environment, and ability to cause disease.
- Treatment should be delayed until 8-12 days after exposure and continued for 10 days.
NB: up to 50% of cases may be asymptomatic.
Acute Q fever
This can present with any combination of the following:
- Most commonly, a self-limiting flu-like illness:
- It lasts for 1-3 weeks
- There is sudden-onset high fever, headache, fatigue, and muscle aches
- Atypical pneumonia:
- Usually mild, with a dry cough, fever, and minimal chest signs
- Very occasionally, it can present with acute respiratory distress or pleural effusion
- CXR changes are usually nonspecific
- Symptoms usually last 10-90 days
- May be clinically asymptomatic
- Alternatively, presents similarly to infective hepatitis with hepatomegaly and (rarely) jaundice
- Or, presents as a chronic pyrexia of unknown origin (PUO) with granulomas on liver biopsy
Rarer features include:
- Maculopapular or purpuric rash (5-20%)
- Erythema annulare centrifugum
- Erythema nodosum
- Pericarditis and/or myocarditis
- Aseptic meningitis/encephalitis, Guillain-Barré syndrome, neuritis (including optic, brachial, and mononeuritis multiplex), myelitis and peripheral neuropathy, polyradiculopathy, extrapyramidal neurological disease
Q fever in pregnancy can cause miscarriage, premature deliveries, and stillbirths. Antibiotic treatment can reduce miscarriage rate. Transplacental transmission has been reported.
The clinician suspecting Q fever must check for heart valve disease and immunosuppression because these conditions predispose to the development of endocarditis.
Chronic Q fever
This appears as culture-negative endocarditis, almost exclusively affecting patients with abnormal or prosthetic heart valves.
- Fever (70%)
- Hepatomegaly ± splenomegaly (50%)
- Clubbing (30%)
- Purpuric rash (vasculitic) is found in 20% cases
In the acute phase:
- WCC raised in 1/3 cases
- Liver enzymes raised at 2-3 x normal; alkaline phosphatase raised in 70% of cases
- Plasma sodium reduced in 28% of cases
- Reactive thrombocytosis and microscopic haematuria are common
- Hyperglobulinaemia of up to 60 g/L is commonly found and a useful diagnostic sign
- Serology - paired acute and convalescent phase show >4 x changes in IgG or IgM (immunofluoresence antibody)
- Elevated antibody response to C. burnetii phase-I or phase-II antigens (phase-II antigen >phase-I antigen in acute Q fever, converse in chronic Q fever)
- Other techniques include polymerase chain reaction (PCR) or immunohistochemical staining:
- The sensitivity of serum PCR has been disappointing.
- Of 100 patients with Q fever, only 18 were PCR positive.
- There is also ongoing controversy over PCR methods, with some tests branded insensitive and claims that others produce false positives through cross-contamination.
- Plain X-ray shows typical signs of bacterial pneumonia but rounded opacities are suggestive of Q fever
- Chronic Q fever cases may test positive for rheumatoid factor, anti-smooth muscle, antinuclear or antimitochondrial antibodies, or circulating anticoagulant antibodies
Acute Q fever
- Doxycycline 100 mg twice-daily for 14 days is recommended for acute illness.
- Antibiotic treatment lessens the time in which the patient has fever and hastens recovery from pneumonia.
- In studies, doxycycline outperforms other antibiotics, including erythromycin.
- Starting antibiotic therapy after the third day of fever might not change the clinical outcome.
- Co-trimoxazole is recommended for children younger than 8 years, and the newer macrolides might also prove useful.
- Anti-inflammatory agents could be useful when symptoms do not respond to antibiotics.
Chronic Q fever
- Lifelong antibiotic treatment has been recommended for endocarditis, but 18 months of doxycycline (100 mg twice-daily) and hydroxychloroquine (200 mg three times daily) could be enough.
- Concomitant treatment with chloroquine raises the pH in the phagolysosome, increasing the efficacy of doxycycline.
- Most patients treated with this regimen have photosensitivity, and regular heart and eye examinations are needed.
- Antibody titres should be measured every 6 months for first 2 years with progressive decline (anti-phase I IgG) showing successful treatment.
Q fever during pregnancy
- This is treated with co-trimoxazole until delivery.
- Serology to detect recrudescence is needed in subsequent pregnancies.
- A year of doxycycline and chloroquine after delivery may prevent recrudescence.
- Mothers should be advised that both C. burnetii and doxycycline are excreted in breast milk.
- Follow-up for life might be needed.
- Haemodynamic problems could require valve replacement, and pericarditis can cause cardiac tamponade and require urgent intervention.
- A third of patients with a valvulopathy could develop endocarditis if left untreated.
- May show long-term fatigue syndrome.
- Mortality of <1%, but has been reported up to 2.4%.
- In the chronic form, mortality is much higher, at about 25%.
- Education about sources of infection, eg appropriate hygiene measures and disposal of sheep/goat birth products when farming.
- Vaccination of those whose occupation places them at high risk.
- Only those who are skin test negative are vaccinated to avoid side-effects.
- Side-effects include local reactions, sterile abscesses with draining sinuses.
Further reading & references
- Q fever deliberate release guidelines, Health Protection Agency (2007)
- Q Fever, Centers for Disease Control & Prevention
- Dhawan VK, Q fever, eMedicine, Jan 2010
- Fournier PE, Marrie TJ, Raoult D; Diagnosis of Q fever. J Clin Microbiol. 1998 Jul;36(7):1823-34.
- Raoult D, Fenollar F, Stein A; Q fever during pregnancy: diagnosis, treatment, and follow-up. Arch Intern Med. 2002 Mar 25;162(6):701-4.
- Pollock KG, Mellor DJ, Browning LM, et al; Q Fever in migrant workers, Scotland. Emerg Infect Dis. 2007 Dec;13(12):1963-4.
- Q Fever, Health Protection Agency
- Raoult D, Marrie T; Q fever. Clin Infect Dis. 1995 Mar;20(3):489-95; quiz 496.
- Parker NR, Barralet JH, Bell AM; Q fever. Lancet. 2006 Feb 25;367(9511):679-88.
- Ravid S, Shahar E, Genizi J, et al; Acute Q fever in children presenting with encephalitis. Pediatr Neurol. 2008 Jan;38(1):44-6.
- Fournier PE, Raoult D; Comparison of PCR and serology assays for early diagnosis of acute Q fever. J Clin Microbiol. 2003 Nov;41(11):5094-8.
- Gikas A, Kofteridis DP, Manios A, et al; Newer macrolides as empiric treatment for acute Q fever infection. Antimicrob Agents Chemother. 2001 Dec;45(12):3644-6.
- Sobradillo V, Zalacain R, Capelastegui A, et al; Antibiotic treatment in pneumonia due to Q fever. Thorax. 1992 Apr;47(4):276-8.
- Maurin M, Raoult D; Q fever. Clin Microbiol Rev. 1999 Oct;12(4):518-53.
- Wildman MJ, Smith EG, Groves J, et al; Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort. QJM. 2002 Aug;95(8):527-38.
- Ledina D, Bradaric N, Milas I, et al; Chronic fatigue syndrome after Q fever. Med Sci Monit. 2007 Jul;13(7):CS88-92.
|Original Author: Dr Huw Thomas||Current Version: Dr Hayley Willacy|
|Last Checked: 16/07/2010||Document ID: 2692 Version: 21||© EMIS|
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