5/08/2014 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 flea- borne spotted fever Transitional group ‘cat-flea’ Ctenocephalides felis 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 / relapses4 1Nilsson et al., 2013; 2 Maina et al., 2012;3 Socolovschi et al., 2010; 4 Mediannikov et al., 2013 Williams et al., 2010 1 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 5 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 2 5/08/2014 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 3 5/08/2014 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 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 5/08/2014 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? 5 5/08/2014 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 6 .