Q Fever

Coxiella burnetti is an obligate intracellular parasite related to the genus Rickettsia, that was first described in Australian abattoir workers in 1937.¹
Q fever is an highly infectious zoonosis where the main reservoir are either arthropods (mainly ticks) or farm animals e.g. 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.²

• 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.³

Occupational disease of slaughterhouse, animal husbandry, and animal research workers.

Incidence

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 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.⁴ The slaughterhouse had been processing post-parturition ewes, that were thought to be the likely source.

Bioterrorism

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.⁵
• 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.⁶

Acute Q fever

Can present with any combination of the following:³

• Most commonly a self-limiting flu-like illness:
  • Lasts for 1-3 weeks
  • Sudden onset high fever, headache, fatigue, and muscle aches
• Atypical pneumonia:
  • Usually mild, with dry cough, fever, and minimal chest signs
  • Very occasionally can present with acute respiratory distress or pleural effusion
  • CXR changes are usually non-specific
  • Symptoms usually last 10-90 days
  • Mortality rate 0.5-1.5%
• Hepatitis:
  • May be clinically asymptomatic
  • Alternatively presents similarly to infective hepatitis with hepatomegaly and (rarely) jaundice
  • Or as a chronic PUO with granulomas on liver biopsy

Rarer features include:

• Maculopapular or purpuric rash (10%)
• Erythema annulare centrifugum
• Erythema nodosum
• Pericarditis and/or myocarditis
• Aseptic meningitis/encephalitis⁷

Q fever in pregnancy can cause miscarriage, premature deliveries, and stillbirths. Antibiotic treatment can reduce miscarriage rate.⁸ 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

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:

• WBC raised in 1/3 cases
• Liver enzymes raised at 2-3x normal; alkaline phosphatase raised in 70% of cases
• Plasma sodium reduced in 28% cases
• Reactive thrombocytosis and microscopic haematuria are common
• Hyperglobulinaemia of up to 60g/l is commonly found and a useful diagnostic sign
• Serology - paired acute and convalescent phase show >4x changes in IgG or IgM (immunofluoresence antibody)
• Elevated antibody response to C. burnetii phase I or II antigens (phase-II antigen > phase-I antigen in acute Q fever, converse in chronic Q fever)
  • Significant titres may take 3 to 4 weeks to appear.^2,5
  • Treatment should be started as soon as a clinician suspects the disease to be present.
  • Only 39 of 100 people presenting with Q fever were positive on their first test.⁹
• Other techniques include polymerase chain reaction or immunohistochemical staining:
  • The sensitivity of serum PCR has been disappointing.
  • Of 100 patients with Q fever, only 18 were PCR positive.⁹
  • There is also on-going 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.⁸
• Antibiotic treatment lessens the time in which the patient has fever and hastens recovery from pneumonia.¹⁰
• In studies, doxycycline outperforms other antibiotics including erythromycin.^10,11
• Starting antibiotic therapy after the third day of fever might not change the clinical outcome.¹²
• 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

• Life-long 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.¹²
• 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.³
• 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.^13,14
• Mortality <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 e.g. 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.