Q FEVER Australian and global perspectives including the recent Netherlands outbreak

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1 Q FEVER Australian and global perspectives including the recent Netherlands outbreak Coxiella burnetii, the causative bacterium for Q Fever is ubiquitous. Thought to be present in every land mass with the possible exceptions of New Zealand and Tasmania Dr. Stephen Graves Director, Australian Rickettsial Reference Laboratory Director, Division of Microbiology, Pathology North Hunter, NSW Health Pathology 2 C. burnetii is associated with animals Ticks (many species worldwide) Native animals (e.g.. kangaroo) Farm mammals (e.g.. goats) Domestic mammals (e.g.. dogs) Birds Possibly reptiles also and the environment frequented by these animals. C. burnetii exists in two morphological forms 1. A large cell variant (LCV) Grows inside host animals cells Metabolically active Replicates by binary fission Relatively easy to kill 2. A small cell variant (SCV) Survival form ( spore ) Detected in environment Metabolically inactive Converts to LCV when taken into a susceptible host cell e.g.. monocytes in humans (relatively) difficult to kill 3 4 Most countries have background (endemic) human Q Fever. On top of this there are outbreaks (epidemics) that occur from time to time, when certain circumstances occur. Outbreaks may be: Small (e.g.. 6 shearers) Medium (e.g visitors to a farm) Large (e.g s of cases such as the recent Dutch outbreak involving 4000 cases, the largest known outbreak to date) The Dutch Q Fever Epidemic Milking goat farms are located in heavily populated regions Incidence of spontaneous abortions in goats increased (from <5% to 20%) 2 years before any increased incidence in human Q Fever was detected. Veterinary authorities were aware that C. burnetii was causing abortions in goats. But Public Health authorities were unaware of the veterinary situation and were unaware of the risk to the human population

2 The Dutch Q Fever Epidemic (cont.) Goats kept in sheds with straw bedding later used as fertiliser by Dutch farmers This material was contaminated with goat genital secretions, products of abortions, urine and faeces. Hence it contained a high concentration of viable C. burnetii (SCV) SCV were blown by wind from goat dairy farm and fields, especially in dry weather. Inhaled by local residents One-Health issues Animal infection outbreak (2005) Veterinary authorities aware No official mechanisms for (human) population health doctors to be informed Human infection outbreak (2007) The human Q Fever outbreak may well have been anticipated and ameliorated with knowledge of the animal Q Fever outbreak that preceded it Changes in Veterinary Practices Q Fever in goats became notifiable(2008) Vaccination of goats with Coxevax voluntary (2008) and then compulsory (2009) Two weekly testing of bulk goat milk supplies from farms (by C. burnetii PCR) (2009) Results negated by vaccination Culling of (>150,000) pregnant goats (2009) Goat breeding banned on infected farms (2009) Goat shed straw/goat manure composted (stored under plastic) for 90 days (temperature rises to 60 C- 70 C) prior to distribution to farms as fertiliser. This reduces the C. burnetiiload. Changes in Medical Practices PCR used to diagnose acute Q Fever (serology not reliable in early disease) Public health letter to all persons living within 5km of an infected goat farm (2008) Blood donors tested for Q Fever by PCR (2010) Persons with cardiac and vascular disease advised of risk and QVAX recommended via special access scheme. (QVAX notroutinely available in the Netherlands)

3 Useful data from the Dutch Q Fever Outbreak For veterinarians/epidemiologists: 1. Persons living within 2km radius of infected goat farm had 31x risk of infection compared to a person living >5km away. 2. Human infection NOT related to drinking goat milk. 3. Goat vaccination doesn t prevent infection but stops abortions and reduces excretion of C. burnetii, especially in nulliparous goats. 4. Vaccination of goats is not risk-free: Fever Off food Reduced milk production Skin reaction Treating infected goats with tetracycline reduces abortions, but not shedding of C. burnetii 6.Five clones of C. burnetii present in the goat population, but one clone (mst33 genotype 1) predominated; in patients also. This clone is phylogenetically related to a French sheep strain % of goat milk farms were POS by bulk milk PCR testing (CF 5% sheep milk farms). 14 For diagnostic laboratories 1. Q Fever serology not helpful in diagnosing chronic Q Fever Phase I IgG 1024 at 6/12 post infection best correlate with chronic Q Fever (in 73% chronic and 2% recovering patients). Best to diagnose chronic Q Fever clinically. 2. qpcris the best early diagnostic test (49/50 pos); if only ph2 IgMpresent, qpcris still a good test (9/10 pos). After 2 weeks qpcris always negative and must diagnose by serology 3. Post Q Fever serological monitoring recommended at 3, 6 and 12 months. For clinicians Acute Q Fever 1. Pneumonia was main presenting symptom (65%) 2. 21% of patients admitted to hospital CRP (hospitalised): 209 CRP (outpatient): 144 No other differences between groups detected in lab tests 3. No adverse effect of Q Fever on pregnancy despite seroprevalence increasing from 2.6% to 9.0% (within 2 km of infected farm). Products of spontaneous abortions (n=40) were all NEGATIVE for C. burnetii by PCR. 4. Patients with mildacute Q fever were less likely to receive appropriate antibiotics For clinicians Chronic Q Fever % patients developed chronic Q Fever 2. 75% of chronic Q Fever cases appeared within 6 months of 1 infection 3. Patients with mildacute fever were more likely to develop chronic Q Fever 4. Treatment of acute Q Fever (even if mild) with appropriate antibiotics appears to protect against chronic Q Fever. 17 Chronic Q Fever (cont.) 5. Risk factors for chronic Q Fever: Prior vascular surgery (OR=31) Vascular prosthesis (OR=10) Aneurysm (OR=9) Malignancy (OR=4) Endocarditis seen in 27% chronic patients ECHO not recommended in acute Q Fever Only 27% of 1.6% (=0.4%) affected Post Q Fever Fatigue At 1 year post-infection 50% of patients (CF 26% controls) were fatigued. 18 3

4 Q Fever in Australia Endemic disease; epidemics rare NSW and QLD highest incidence Kangaroos may be involved Seropositivityhigher in rural areas (Hunter New England regions of NSW: 22% Guyra; 0.5% Newcastle; 7% overall) Children are infected 19 National QVAX programs targeting at-risk occupational groups have been successful Q Fever in Australia The Future A better vaccine needed; immunogenonly, not whole cell vaccine [no need to pre-test patients by serology and skin test] Need to vaccination of rural population (not just an occupational disease). Many patients have no known animal contact. Q fever is a geographic disease and needs a geographic public health response. 20 Lessons from Dutch outbreak Problem #1 Veterinary authorities and public health authorities did not compare notes! There were no informal channels of communication between veterinarians and human public health doctors There was no formal mechanism for them to be officially informed. Public health authorities were not aware of outbreak in goats Lessons from Dutch outbreak Problem #2 Large, intensive goat farming being undertaken in areas of dense human population Problem #3 Goat farms getting bigger Larger farms have a risk of Q Fever (? reason) Problem #4 Dry weather and severe winds led to dispersal of infected goat manure Problem #5 No human Q Fever vaccine available

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