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Cat -borne in humans – is the dog to blame? Rebecca J Traub Assoc. Prof. in Parasitology Faculty of Veterinary and Agricultural Sciences

Introduction- felis

 Emerging zoonoses globally  -flea or flea- borne spotted fever  Transitional group ‘cat-flea’ Ctenocephalides felis  Serological cross-reactivity typhus  Flea vector cf  Lack of ompA gene - SFG

Clinical manifestations

 Fever, malaise, myalgia, macular rash*, eschar*  Non-specific: gastrointestinal, respiratory or nurological 1  Fevers of unknown origin (6-7% in Africa)2,3  Significant correlation between R. felis and malaria (av. 23% co-infected)4  Re-infection / relapses4

1Nilsson et al., 2013; 2 Maina et al., 2012;3 Socolovschi et al., 2010; 4 Mediannikov et al., 2013 Williams et al., 2010

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Grossly misdiagnosed?

 Indistinguishable from other spotted fevers  Cross-reactivity with typhus group  R. prowazekii (louse-borne typhus)  R. typhi ()  Non-specific febrile illness  Lack of awareness / Low index of suspicion

Grossly misdiagnosed?

Cat-flea typhus in Australia

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Rickettsia felis life cycle

MAMMALIAN RESERVOIR Cats5? Opossums 6 Rattus spp.?7 Dogs?8

Ctenocephaledes felis

15-80% +ve VECTOR

Trans-ovarial and trans-stadial transmission (12 generations for C. felis)

5Wedincamp & Foil, 2000; 6 Schriefer et al, 1994; 7Abramowicz et al, 2011; ACCIDENTAL HOST 8Oteo et al, 2006; 9 5Wedincamp & Foil, 2002

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The role of dogs?

Whole blood sampled from:  100 healthy pound dogs from SE QLD  130 healthy dogs from Indigenous community in Maningrida, NT (Dog Health Program by AMRRIC)

Results of R. felis PCRs (ompB and gltA):  9 SE QLD dogs POSITIVE (9%)9  3 Indigenous community dogs POSITIVE (2.3%)10

9Hii et al., 2011; 10Hii et al., 2012 Image courtesy Dr Ted Donelan

Dogs are likely natural mammalian reservoirs for R. felis infection

Serosurvey of R. felis in dogs

Antigen production – a pivotal advantage (AARL)  Culturing Rickettsia felis in XTC-2 cell lines  Specific diagnosis using MIF

Study design  Serum from 292 pound, rescued and client- owned dogs from SE QLD and the NT  MIF test using R. felis antigen R. felis infected  Age, gender, and ectoparasite control status of XTC-2 cell all dogs were collected

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Antibody titre Total positive / 292 % positive

1≥64 148 50.7 1:64 94 32.3 1:128 42 14.4 1:256 10 3.4 1≥512 1 0.3 1≥8192 1 0.3  Dogs receiving no ectoparasite control (odds ratio 2.6; P = 0.014) were more likely to have antibodies to R. felis at titres of ≥ 64

Current AIMS (ARC-Linkage)

 Confirm the role of dogs as primary mammalian reservoirs  Horizontal transmission of R. felis between feeding FOLLOWED BY  Successive transovarial transmission  Identify ‘misdiagnosed’ clinical cases  Epidemiology of R. felis exposure in humans  Role of wild rats as reservoirs?  Vector-endosymbiont relationship among cat flea strains from Europe, Asia and Australia

Role of feral rats in Australia?

Study design  Splenic tissue from 250 feral rats from Qld (Mahdis Aghazadeh, QIMR Berghofer MRI)  PCR for spotted fever group Rickettsia OmpB and 17kDA protein genes

Preliminary results:  None were found positive for R. felis  A further 200 rats to be tested  Rats unlikely mammalian reservoirs

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Retrospective diagnosis of cat-flea borne spotted fever in humans in Australia Selection criteria:  Serum from patients suspect of spotted fever disease referred to the AARL for testing between Jan 2010 - Jan 14 AND  Initially diagnosed with R. typhi

 In total 118 serum samples tested for IgM/IgG antibody titres to R. felis (and R. typhi) using MIF

POSITIVE NEGATIVE

Preliminary results:

Western Blot to confirm those with comparable antibody titres to R. typhi

Correlated with patient data – history and presenting signs, location

Take home message – Medical doctors

Cat flea-borne spotted fever is a grossly underestimated zoonosis in Australia

Spectrum of clinical disease Low index of suspicion Advocates for history of domestic flea exposure be collected Included in panel for febrile illnesses of unknown origin?

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Take home message - Vets

Dogs are likely primary mammalian reservoirs for cat-flea borne spotted fever

Adds significance to flea control Would breaking the cycle at the level of the dog mitigate risk?  Products that insecticidal prior to feeding (e.g. topical vs. systemic insecticides?  Potential development for a vaccine for R. felis in dogs?

Acknowledgements

Sze Fui Hii

Mahdis Aghazadeh – QIMR Berghoffer Thomas Teoh

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