1. BARTONELLOSIS

2. Bartonella spp. Fastidious genus of hemotropic organisms Small, curved, gram-negative bacteria Long-lasting intraerythrocytic bacteremia Vector transmitted

3. Feline Bartonellosis 4 species can infect cats – B. henselae – B. clarridgeiae – B. kohlerae – B. bovis Exposure is prevalent among U.S. cats and throughout temperate regions of the world Greatest prevalence in warmer, humid regions

4. Feline Bartonellosis Higher prevalence of seroreactivity with: – Age – Warmer temperatures – Higher humidity – Feral populations – Cats with fleas

5. Prevalence B. henselae bacteremia affect ~5-40% of cats in the U.S. B. clarridgeiae affects ~10% of U.S. cats with Bartonella bacteremia B. koehlerae was isolated from 2 cats in CA B. bovis was isolated from 2 cats in UT and 2 cats in IL

6. Reservoirs Domestic cats are major reservoir and vector for human infections for B. henselae and B. clarridgeiae Cattle are the reservoir for B. bovis The reservoir for B. koehlerae is unknown Co-infection with henselae and clarridgeae is possible

7. Transmission Naturally transmitted among cats by fleas – Exact role of flea unknown – Transmission involves flea excrement, not saliva – Ticks may also play a role – Transmission does not occur between cats in a flea- free environment Transmissable with blood transfusions Not shed in urine Not passed during breeding, gestation, or lactation

8. Pathogenesis Bacteremia chronically waxes and wanes – Periods of undectable disease Bacteremia long-lived – Up to 454 days in experimentally infected – Up to 3 years in naturally infected Re-infection possible as complete protection is highly specific Intracellular location is protective for the organism – May be within RBCs and vascular endothelial cells

9. Clinical Findings Few infected cats have clinical signs Clinical signs in experimentally infected are mild and transient Severity of signs may vary with strain Endocarditis reported in two cats Potential role in chronic diseases – Stomatitis, gingivitis, urinary tract disorders, uveitis

10. Clinical Findings

11. Diagnosis Expect normal CBC/Chem/UA – Early transient anemia, persistent eosinophilia, mature neutrophilia possible Unlikely to find it on blood smear Special confocal microscopy staining has been used Extracellular organisms have been documented in blood with immunocytochemical and immunohistochemical methods

12. Diagnosis Serologic testing – Better for initial screening but overestimates the # of infected cats – Not useful to determine if sick cat has active infection – IgG persists for prolonged periods after clearance – Positive predictive value for bacteremia ~39-46% – Negative predictive value ~92-97% Negative result is more useful

13. Diagnosis Culture of blood or tissue is the most reliable for diagnosis of active infection – Insensitive due to relapsing nature of infection – Ineffective as a screening test Nucleic acid testing – Standard PCR just as sensitive as blood culture for detecting active infection – Can determine species/strain – Technique may induce false positives Necropsy – Hyperplasia of lymphoid ograns – Lymphocytic, pyogranulomatous, or neutrophilic inflammation in multiple tissues

14. Therapy No antibiotic has been proven effective Documentation of clearance difficult due to prolonged relapsing bacteremia High dose Baytril (5-7mg/kg BID) for 14-28 days (unsafe) High dose (10mg/kg BID) doxycycline for 28 days Azithromycin has shown improvement in clinical signs but proof of clearance lacking – May be more immunomodulatory and antiinflammatory effects of the drug

15. Therapy Treated and untreated cats may become culture negative after the same period of time Follow up blood cultures after treatment at 4- 8 week intervals Only treat cats with clinical signs Has been shown to decrease bacteremia but no evidence that it will decrease probability of transmission to owner

16. Prevention Avoid exposure to infected animals and their fleas Avoid transfusing donor blood of unknown cats or seropositive cats No vaccine available – Significant genetic variation exists amongst B. henselae

17. Public Health People are susceptible to at least 9 different species or subspecies – B. quintana – B. bacilliformis – B. henselae* – B. clarridgeiae* – B. vinsonii subsp berkhoffii* – B. vinsonii subsp arupensis* – B. grahamii* – B. elizabethae* – B. washoensis*

18. Public Health Cats are reservoir and vector for B. henselae and clarridgeiae Coyotes are reservoir for B. vinsonii subsp berkhoffii Rodents may be reservoirs for other zoonotic species Role of fleas, ticks, and flies in transmission to people is unknown

19. Cat Scratch Disease (CSD) Transmission to people through contamination of cat scratches and bites with flea excrement Clinical syndromes – Encephalopathies in children – Bacillary angiomatosis and peliosis – Relapsing fever with bacteremia – Endocarditis – Optic neuritis – Pulmonary, hepatic, and splenic granulomas – Osteomyelitis

20. Cat Scratch Disease (CSD) Localized in immunocompetent Systemic and possibly fatal in immunocompromised Diagnosed by serology or PCR Prevent through parasite control and avoiding bites/scratches – Stray or impounded cats <1 yr old are most likely to be infected – No evidence to show that declawing cats decreases probability of transmission

21. Canine Bartonellosis B. vinsonii subsp berkhoffi – Most frequent disease-causing species in dogs – Only 3.6% of sick dogs had antibodies to it More likely in dogs in a rural environment that are allowed to roam (esp with a history of tick infestation) Rhipicephalus tick may be involved in transmission – 36% of dogs with E. canis also tested positive for this – No crossreactivity between the 2 organisms Amblyomma americanum or Dermacentor may be involved in transmission in the Southeast US Coyote reservoir in western US – 35% of coyotes had antibodies in California Exposure can be found throughout the US

22. Pathogenesis B. vinsonii subsp berkhoffii Presumably transmitted via ticks Thought to cause chronic intraerythrocytic and endothelial cell infections Well tolerated by the dog for extended periods of time – Factors that result in disease are unclear Infection may induce a degree of chronic immunosuppression May contribute to epistaxis tendancy in dogs with ehrlichiosis

23. Clinical Findings B. vinsonii subsp berkhoffii Endocarditis – Large breed dogs – Predilection for aortic valve involvement – Grave prognosis (worse than other types of infectious endocarditis) – Intermittent lameness, bone pain, or FUO may precede dx by several months – Acute cardiopulmonary decompensation possible – Arrhythmias may be found without echocardiographic evidence of disease – Leukocytosis, thrombocytopenia, hypoalbuminemia, azotemia, and proteinuria common

24. Clinical Findings B. vinsonii subsp berkhoffii Granulomatous lymphadenitis – Diagnosed in 1 dog in left mandibular lymph node – Analogous to acute CSD in people Cutaneous vasculitis Anterior uveitis +/- choroiditis Polyarthritis Rhinitis Meningoencephalitis IMHA

25. Clinical Findings Other Bartonellae B. henselae – Peliosis hepatis in 1 dog Generalized weakness and abdominal distension, ALKP elevation, serosanguinous abd effusion, multiple fluid-filled cysts in the liver – Chronic hepatitis in 1 dog Fever, anorexia, weight loss, icterus B. elizabethae – Chronic weight loss and sudden death in 1 dog B. clarridgeiae – Vegetative endocarditis with 3 rd degree AV block and heart failure in 1 dog – Copper storage disease in a Doberman B. washoensis – CHF secondary to endocarditis in 1 dog

26. Clinical Findings

27. Diagnosis Laboratory findings – Thrombocytopenia, anemia, and neutrophilic leukocytosis are most common in seropositive dogs TP and anemia may be immune-mediated TP is found in ~50% of dogs with disease manifestations – Eosinophilia is found in ~1/3 of infected dogs – Monocytosis (esp in those with endocarditis) – Hemoglobinuria +/- hematuria (esp in those with IMHA) – Chemistry changes are usually mild or absent – Positive ANA is possible

28. Diagnosis Imaging – B. henselae Hypoechoic cystic lesions in parenchymal organs possible – B. vinsonii subsp berkhoffii Valvular endocarditis – Left sided heart failure common Necropsy – Endocarditis, myocarditis – Granulomatous lymphadenitis or hepatitis – Peliosis hepatis – Organism can be found in acutely disease tissue

29. Diagnosis Blood culture is insensitive Attempts to isolate the organism from immunocompetant dogs with positive serology has been unsuccessful Serology and PCR amplification are the mainstays of diagnosis – Seroprevalence <4% in sick dogs in endemic regions – Titer of >1:64 is indicative of exposure/infection – PCR best for other species – Seroprevalence of B. henselae in the Southeast is ~10% in healthy dogs and ~26% in sick dogs Co-infection with Ehrlichia, Babesia, Rickettsia, and Bartonella not unocmmon

30. Therapy No established ideal protocol 4-6 weeks of therapy is necessary to eliminate infection Macrolides are thought to be drug of choice Fluoroquinolones +/- amoxicillin possible Doxycycline at high doses possible Titers should fall within 3-6 months of treatment Persistance of antibodies may be indicative of treatment failure Surgical valve replacement used to treat people with Bartonella endocarditis

31. Prevention Minimizing flea and tick exposure is key for people and animals Non-domestic animals (esp coyotes) are the primary reservoir

32. Public Health Extent that dogs serve as reservoir host is poorly characterized Dogs have been implicated in the direct transmission of B. henselae through bites or scratches but not proven B vinsonii subsp berkhoffii has been isolated from a human endocarditis patient

33. Questions?