Introduction- Rickettsia felis

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Wilfrid Pearson
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Cat flea-borne spotted fever in humans is the dog to blame? Rebecca J Traub Assoc. Prof.

Emerging zoonoses globally Cat-flea typhus or fleaborne spotted fever cat-flea Ctenocephalides

- SFG Clinical manifestations Fever, malaise, myalgia, macular rash*, eschar* Non-specific:

Significant correlation between R. felis and malaria (av.

1 Cat flea-borne spotted fever in humans is the dog to blame? Rebecca J Traub Assoc. Prof. in Parasitology Faculty of Veterinary and Agricultural Sciences Introduction- Rickettsia felis Emerging zoonoses globally Cat-flea typhus or fleaborne spotted fever cat-flea Ctenocephalides felis Transitional group Serological cross-reactivity typhus Flea vector cf tick 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 / relapses 4 1 Nilsson et al., 2013; 2 Maina et al., 2012; 3 Socolovschi et al., 2010; 4 Mediannikov et al., 2013 Williams et al.,

misdiagnosed? Cat-flea typhus in Australia Rickettsia felis life cycle MAMMALIAN RESERVOIR Cats 5?

2 5 5/08/2014 Grossly misdiagnosed? Indistinguishable from other spotted fevers Cross-reactivity with typhus group R. prowazekii (louse-borne typhus) R. typhi (murine typhus) Non-specific febrile illness Lack of awareness / Low index of suspicion Grossly misdiagnosed? Cat-flea typhus in Australia Rickettsia felis life cycle MAMMALIAN RESERVOIR Cats 5? Opossums 6 Rattus spp.? 7 Dogs? 8 Ctenocephaledes felis VECTOR 15-80% +ve Trans-ovarial and trans-stadial transmission (12 generations for C. felis) ACCIDENTAL HOST 5 Wedincamp & Foil, 2000; 6 Schriefer et al, 1994; 7 Abramowicz et al, 2011; 8 Oteo et al, 2006; 9 5 Wedincamp & Foil,

community in Maningrida, NT (Dog Health Program by AMRRIC) Results of R.

3%) 10 9 Hii et al., 2011; 10 Hii et al.

3 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 9 Hii et al., 2011; 10 Hii 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 clientowned dogs from SE QLD and the NT MIF test using R. felis antigen Age, gender, and ectoparasite control status of all dogs were collected R. felis infected XTC-2 cell 3

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.

felis between feeding fleas FOLLOWED BY Successive transovarial transmission Identify misdiagnosed clinical cases Epidemiology of R. felis exposure in humans Role of wild rats as reservoirs?

4 Antibody titre Total positive / 292 % positive : : : 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 fleas 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 4

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

typhi) using MIF POSITIVE NEGATIVE Preliminary results: Western Blot to confirm those with comparable antibody titres to R.

5 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 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? 5

Take home message - Vets Dogs are likely primary mammalian reservoirs

Would breaking the cycle at the level of the dog mitigate risk?

systemic insecticides? Potential development for a vaccine for R.

6 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 Thomas Teoh Mahdis Aghazadeh QIMR Berghoffer 6

Seroprevalence and risk factors for Rickettsia felis exposure in dogs from Southeast Queensland and the Northern Territory, Australia

Hii et al. Parasites & Vectors 2013, 6:159 RESEARCH Open Access Seroprevalence and risk factors for Rickettsia felis exposure in dogs from Southeast Queensland and the Northern Territory, Australia Sze-Fui