QF Fever: Where Does it Come From?

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QF Fever: Where Does it Come From? Katrina Bosward FACULTY OF VETERINARY SCIENCE

Animal Sources of Coxiella burnetii for Humans Animals typically acquire Q fever through exposure to other infected animals by direct contact with body fluids or aerosols They subsequently undergo mild or sub-clinical infection which re-emerges in females during late pregnancy - There is massive multiplication of the organism in the placenta and foetal fluids resulting in large no s of bacteria being shed into the environment - Concentrations of C. burnetii of up to 10 9 /gram of tissue - Suggested that < 10 organisms are required to establish infection via the respiratory route www.123rf.com 2

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Animal Sources of Coxiella burnetii for Humans Organisms can also be shed in faeces, urine, milk & other body fluids (e.g. vaginal mucus, saliva) and these, too, can potentially be a source of finfection for humans C. burnetii is very resistant to chemical & physical agents, heat, UV rays, desiccation last in environment up to 5 months (150 days) - People may be infected via fomites: e.g. from handling contaminated wool, clothes contaminated with faeces or foetal/placental fluids, or exposure to contaminated manure used as a fertiliser Image: http://nla.gov.au/nla.pic-an23398070 5

Q Fever: Where Does it Come From? Production Animals Companion Animals Wildlife.birds, fish, reptiles & arthropods

Traditional view of the common sources of Coxiella for humans Goats, cattle, sheep Q fever in humans livestock industry (vets, farmers, shearers, people yarding or transporting ruminants, dairy workers) meat tindustry (abattoir workers and meat inspectors) IMAGES: http://www.biolinklimited.co.uk/; www.superstock.com

Goats Production Animals - The source of the outbreak in humans in The Netherlands was largely attributed to dairy goats (abortion storms) - Along with chronic reproductive problems including serial abortions, birth of weak kids the goats themselves can also develop pneumonia - Organisms persist in mammary glands shedding in milk for up to 52 days - In many countries, goats are a common source of human infection - Seroprevalence detected in Africa, America, Asia and Europe - No recent studies on prevalence in Australia - Prevalence studies in feral goats at abattoir SA - 51.5% - method not specified (Hein and Cargill, AVJ, 1981) Qld 2/20 (10%) CFT Phase I (McKenzie et al AVJ, 1979) 8

Production Animals Sheep Sheep can undergo (late) abortion/still birth & birth of weak lambs however they don t end up with the chronicity observed with goats Infected sheep shed bacteria in vaginal secretions, urine, faeces & milk (toalesser extent & shorter duration ~ 8 days). Identified as a source of infection in Europe (Spain & France; & Bulgarian outbreak in 2004) Paucity of prevalence studies in Australian sheep French report of human infection associated with ovine manure used as a garden fertilizer (Berri et al 2003) 9

Production Animals Beef and Dairy Cattle Infection in cattle is associated with metritis, infertility and mastitis - Less likely to manifest abortion, still birth & weak calves - Cattle shed C. burnetii in milk for several months - 13 months in one study Prevalence around the world varies with geographical location & method of testing - Guatteo (2011) examined 69 selected publications on prevalence in ruminants & came up with a seroprevalence of 20% worldwide in cattle vs 15% in sheep & goats Lower prevalence in Australia by comparison????? Image: 123rf 10

Prevalence in Australian Cattle Country Prevalence Method Reference Northern & NW Qld Beef cattle 16.8% serum ELISA developed Cooper et al, Aust Vet against Phase I & II of J. (2011) an Australian isolate 89 (7): 260-264 264 Western Australia Sheep (50) & Beef cattle (329) Antibodies 2/379 (0.5%) PCR Indirect ELISA designed for study, IDEXX CHEKiT Q Fever ELISA and CFT 41/379 (~11%) two PCR assays Banazis et al (2010) Veterinary Microbiology 143 (2/4): 337-345. 345 Northern SA Beef cattle (617 head on 10 properties) 1991-92 a single positive found on CFT Durham & Paine 1997 only 1 property Aust Vet J, 75, 139

Prevalence in Australian Cattle Country Prevalence Method Reference Victoria Dairy cattle (1,576 cattle from 49 herds) 8/1576 cows (0.5%) in 6/49 herds CFT serum Hore & Kovesdy (1972) Aust Vet J. 143: 337-345. NSW Beef or dairy cattle (617 head on 10 properties) 1991-92 No positives CFT Forbes et al (1954) Aust Vet J, 30, 266

What about milk? 13

Milk In ruminants, milk is the most frequent route of C. burnetii shedding c.f. faeces & vaginal mucus - In addition, shedding in milk can be intermittent & unassociated with parturition While inhalation is considered the major route of infection for humans & animals, the possibility of the oral route (unpasteurised milk & goats cheese) being a source of infection has been proposed: - e.g. Studies involving Idaho prison (Benson et al 1963) and patients and staff of a French psychiatric hospital (Fishbein i & Raoult 1992) However, difficult to demonstrate that the subjects in these studies were not exposed to contaminated dusts or aerosols Production Animals 14

Milk Lack of conclusive studies further research required Nevertheless, OIE advises against drinking unpasteurised milk from infected farms Heating temps in pasteurisation have increased over the years to account for the resistance to heat demonstrated by C. burnetii Production Animals 15

Traditional view of the common sources of Coxiella for humans Goats, cattle, sheep Q fever in humans IMAGES: http://www.biolinklimited.co.uk/; www.superstock.com

Sources of Coxiella for humans Goats, cattle, sheep Study out of the UK (1995) examined seroprevalence in Wild Brown rat populations: 7% - captive enclosure pop n 53% on dairy farms with sheep present Companion Animals Q fever in humans Study in The Netherlands (2011) detected 15.8% seropositive rats on 50% of goat farms Peripartiuent cats + dogs and their offspring IMAGES: http://www.biolinklimited.co.uk/; http://commons.wikimedia.org/wiki/file:russian_riding_horse.jpg; http://www.catadvice.co.uk/; http://www.globalpet.com.br/camasecasas.htm; www.telegraph.co.uk; www.elsevier.nl www.superstock.com wild brown rat (Rattus norvegicus)

Reported Prevalence in Cats Many prevalence studies in cats worldwide - Huge variation in the results of these studies & in the methodology as well as the validation of the tests used - In the order of 15-30% coming out of some studies in Japan & parts of Canada - indicates that in some countries (e.g. Japan, Canada) cats are one of the most important reservoirs of Coxiella But what about Australia? - Until recently, the idea that cats are a source of infection for C. burnetii hasn t been at the forefront of the minds of Australians including the veterinary profession 18

Case Cluster: associated with a Sydney SA vet clinic that also saw a lot of birds Cats A queen What presented about with in dystocia Australia? following the birth of one kitten at home 8am arrived in 9 cat staff members cage, examined in were exposed to consult room by a vet and nurse Coxiella 9am-10am caesarean (2 kittens) 12pm discharged from hospital Image kindly provided by S. Ferguson 19

The Consult Room Nurse 1 + Vet ta examine cat Presented in cat cage Examined in consult room NURSE 1 36 yr F Sick (fever, malaise, headaches, night sweats) VET A 55 yr F Sick (fever, malaise, headaches, night sweats)

The Caesarean Two Nurses + Vet B NURSE 2 26 yr F Revived kittens Sick (hospitalised 2-3 weeks) CLINICAL NURSE 3 26 yr F Revived kittens Sick (hospitalised 2-3 weeks) Long recovery Kittens survived but were weak & discoloured green/grey. Revived by nurse using mouth to nose 2kitt kittens Psittacosis i red herring Non- CLINICAL VET B 56 yr F Surgeon (no clinical signs, seroconverted) www.123rf.com

Other Staff with NO DIRECT exposure to cat NURSE 4 64 yr F CLINICAL Arrived at clinic 5 30pm 5.30pm Sick (headaches, fever) VET C 42 yr F Arrived at clinic NEXT DAY Sick (headaches, fever) Non-CLINICAL TAFE NURSING STUDENT 20 yr F In clinic at same time as cat but no clinical signs, seroconverted NURSE 5 40 yr F Arrived at clinic 12pm Sick (headaches, fever) Degree off clinical D li i l disease correlated with known exposure to the cat & its kittens

Study into the Seroprevalence of Coxiella burnetii in Domestic and Feral Cats in NSW Amanda Shapiro, Jacqui Norris, Katrina Bosward Modified a commercially available sensitive and specific indirect IFA against phase I and II Coxiella burnetii antibodies for use in cats Preliminary results (stats not yet performed): - Five unique subpopulations of cats (n=708) from NSW (centred on Sydney) were screened: - Overall seroprevalence in cats to date = 6.9% - Pet cats = 5.1% (n=198) - Feral cats = 4% (n=50) - Shelter cats = 0% (n=87) - Cattery-confined breeding cats = 9.3% (n=343) - Cats from cattery at centre of 2010 Q fever outbreak = 16.6% 6% (n=30) Poster No. 7: Kopecny, Bosward, Shapiro & Norris Using Serological Assays & Fluorescent In Situ Hybridisation to Investigate C. burnetii Infection in a Breeding Cattery

Reported Prevalence in Dogs Dogs infrequently implicated in the transmission of Q fever to humans Seroprevalence detected in dogs in Africa, Egypt, France & USA - Case reports out of Canada, Japan But what about Australia? - Until recently, like cats, dogs were not a well known source of Q fever infection in Australia Poster no. 5: Gibbons and White Q Fever in a Veterinary Hospital 25

Q Fever in Dogs in Australia Country Prevalence Method Australia Townville, Nth Qld Cooper et al (2011) Aust Vet J 89 (10): 385-387. 2006-0707 Overall seropositivity ii i 21.8% (n=101) Dogs attending vet practices for ELISA s for routine procedues Phase I and II antigen (samples were positive for 1984-8585 Overall seropositivity phase I and/or phase II 16% (n=100)

Occupational Hazard Veterinary Practice Staff working in veterinary clinics: - Veterinarians, veterinary nurses, students & other staff (e.g. cleaners and receptionists) - Anyone assisting birthing & conducting caesareans - Both large & small animal - Contaminated work clothing may also be a source of infection NSW Public Health Factsheet 8 Feb 2012 - Any staff member that hasn t been vaccinated should not participate in birthing or caesarean sections - Unvaccinated staff members in the vicinity y( (1 metre) of a caesarean or birthing should be given P2 particulate respirator, gloves, eye protection, protective eye wear However as the organism can be airborne, bystanders (days later!) are also at risk 27

Dog & Cat Breeders & Vaccination? Should dog and cat breeders be vaccinated? Not currently listed in the Australian Immunisation Handbook Given the local l case clusters involving i cats & dogs & our preliminary results in cats from NSW ie: - Cattery-confined breeding cats = 9.3% (n=343) - Cats from cattery at centre of 2010 Q fever outbreak = 16.6% (n=30) Perhaps we should consider recommending vaccination against Q fever to this group of people 28

Sources of Coxiella for humans Wildlife Goats, cattle, sheep Kangaroo tick Amblyomma triguttatum triguttatum Companion Animals Q fever in humans Peripartiuent cats + dogs and their offspring IMAGES: http://www.biolinklimited.co.uk/; http://commons.wikimedia.org/wiki/file:russian_riding_horse.jpg; http://www.catadvice.co.uk/; http://www.globalpet.com.br/camasecasas.htm; www.telegraph.co.uk; www.elsevier.nl www.superstock.com wild brown rat (Rattus norvegicus)

Wildlife In the natural lifecycle of C. burnetii transmission occurs between wildlife & birds & their ticks spread to livestock & companion animals source of infection for humans Isolated reports of direct transmission from wild animals to humans Rodents may play a role in the natural maintenance of Q fever among wildlife (as well as in cats). Overseas, antibodies against C. burnetii have been detected in hares, moose, deer, black bears, squirrels & wild rabbits 30

Potential Australian Wildlife Reservoirs of C. burnetii In Australia, bandicoots & macropods are potential reservoirs Agile wallaby Image: Nino Barnieri Tasmanian Bettong Image: JJ Harrison Red Necked Pademelon Gaz images Eastern Barred Bandicoot Image: JJ Harrison Eastern Grey Kangaroos Image: Fir0002/Flagstaffotos 31

Prevalence in Australian Wildlife Country Prevalence Method Reference Western Australia Antibodies 115/343 WG kangaroo positive via ELISA. 2/379 ruminants + PCR 41/379 ruminant (sheep & cattle) 42/343 kangaroo positive for DNA 1,017 WG Kangaroos Serum, faeces and urine collected. Indirect ELISA designed for study, IDEXX CHEKiT Q Fever ELISA and CFT two PCR assays Banazis et al (2010) Veterinary Microbiology 143 (2/4): 337-345. Antibodies (ELISA) Overall 24.1% western grey kangaroo positive PCR 4.1% kangaroo positive for DNA in faeces Blood and faeces ELISA PCR Potter et al (2011) Journal of Wildlife Diseases 47(4): 821-828

Prevalence in Australian Wildlife Country Prevalence Method Reference Examined 500 macropods including kangaroo & wallaby spp, pademelons & bettongs Queensland & Western Overall prevalence Australia of 20.8% 30.4% Nth Qld 13.0% Sth Qld 7.1% West Qld 22.8% SW WA (including an urban area). Serum. A competitive and an indirect ELISA Cooper et al (2012) Veterinary Microbiology 155: 317-323.

Ticks are the natural primary reservoir of C. burnetii >40tickspp spp. are naturally infected Ticks excrete bacteria in saliva & faeces (10 12 per gram) - Faeces are deposited on the skin of hosts - Transmitted among animals via saliva in a tick bite Hypothesised that they play a role in the transmission of C. burnetii among wild vertebrates then transferred to domestic naïve animals & humans However they re often not found on ticks in endemic areas - e.g. The prevalence of C. burnetii in Ixodes ricinus in The Netherlands was 0.2% (Sprong et al 2012) Human infections through tick bites are rarely reported. The Role of Ticks Dermacentor variabilis, female, top Image: http://www.discoverlife.org 34

The Role of Ticks in Q Fever in Australia Amblyomma triguttatum triguttatum The kangaroo tick, found in WA, QLD, SA and NSW, is one tick spp that is of importance in Australia - Parasite of larger macropods, but also found on cattle, horses, sheep, pet cats & dogs, pigs, black rats, wild rabbits & humans Natural reservoir & vector of Q fever to kangaroos & sheep 35