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Canine Bartonellosis Peer Consultant on Call ZOONOTIC DISEASE Reviewed Edward B. Breitschwerdt, DVM, Diplomate ACVIM North Carolina State University Canine Bartonellosis PROFILE Definition Bartonella species are emerging zoonotic bacterial pathogens that are of increasing medical impor - tance in veterinary and human medicine. 1-3 Approximately 11 species have been identified as pathogenic for human disease, and 6 of these have been isolated from pet cats and dogs. 1 Bar - tonella henselae and Bartonella vinsonii subspecies berkhoffii are the most commonly identified species in sick dogs and have been isolated from the blood of immunocompetent human patients. 4 Systems. These intraerythrocytic, endothelio- 1 tropic bacteria have been associated with a spec - trum of disease manifestations involving the as reservoir hosts for B vinsonii subspecies berk - Bartonella henselae sero - lymph nodes, heart (valves and myocardium), hoffii , and tick transmission of this subspecies is prevalence by state based vasculature, liver, joints, and central nervous suspected. 7 In nontropical areas, dogs appear to upon tick-borne disease 4 1 panel results (9030 samples system. be accidental hosts for several Bartonella species. from sick dogs tested from 2004–2007) from the North Genetic Implications. As is true of other com - Geographic Distribution. The geographic distri - Carolina State University panion animal infectious diseases, a genetic pre - butions of the various species vary College of Veterinary Medi - Bartonella cine, Vector-Borne Diseases disposition may exist. Bartonella species have greatly (likely reflecting the distribution of their Diagnostic Laboratory. An been found in 18% of healthy golden retrievers; hosts and vectors), but B henselae and B vinsonii antibody titer of 1:64 was although U.S. data are scarce, some research sug - subspecies berkhoffii have worldwide distribution. considered seroreactive, and individual requests for B gests that overall seroprevalence is less than Prevalence is higher in regions where flea and henselae serology are not 5%. 1,5 In 1 study involving 1872 working dogs tick infestations are more likely. 1-3,7 On the basis included in the data sum - owned by the U.S. government, German shep - of seroprevalence data, dogs are exposed to B mary. herd dogs were significantly less likely to be henselae and B vinsonii subspecies berkhoffii seropositive for B vinsonii subspecies berkhoffii throughout the U.S., but some research has than other breeds. 6 Acquired or therapeutically demonstrated that B vinsonii seropositivity may induced immunosuppression enhances disease be more likely in tropical and coastal areas receiv - expression. ing high levels of precipitation. 1,8,9 (Figures 1 and 2 ). Incidence/Prevalence. Cats are the primary reservoir host for B henselae , which is transmitted Signalment among cats and potentially dogs by fleas. Canids, Species. B hensela e and B vinsonii subspecies including coyotes, dogs, and gray foxes can serve berkhoffii have caused endocarditis in dogs and CONTINUES Consultant on Call / NAVC Clinician’s Brief / July 2010 ......................................................................................................................................................................... 13 Consultant on Call CONTINUED seroreactivity. 7 Under standably, these bacteria pose an occupa tional risk for animal health profession - als. 12,13 Pathophysiology Presumably complex, the pathophysiology of Bartonella species infection is incompletely understood. 3,4 Following transmission, bacteria localize to erythrocytes, endothelial cells, and, based upon in vitro data, macrophages and den - dritic, microglial, and CD34 bone marrow pro - genitor cells. Lymphoid hyperplasia, granulo- matous inflammation in a variety of tissues, vas - culitis, and vasoproliferative lesions are among the reported pathologic lesions. 2 Signs Bartonella vinsonii subspecies people. To date, 7 Bartonella species have caused History. Due to the highly adaptive nature of berkhoffii seroprevalence by endocarditis in dogs. 4 these vector-borne bacteria, most dogs experience state based upon tick-borne an acute illness that may or may not be associ - disease panel results (9030 ated with fever or evidence of a systemic inflam - samples from sick dogs tested Breed Predilection. Epidemiologically, B henselae from 2004–2007) from the and B vinsonii subspecies berkhoffii seropreva - matory response, followed by a chronic, insidious North Carolina State Univer - lences correlate with midsize and large-breed course of illness spanning months to years. sity Vector-Borne Diseases Lameness, intermittent lethargy or fever, epis - Diagnostic Laboratory. An dogs that are allowed to roam. 10,11 antibody titer of 1:64 was taxis, and neurologic abnormalities, including considered seroreactive, and Age & Range. Exposure is more likely in middle lack of coordination or seizures, can develop pro - individual requests for B vin - gressively in chronically infected dogs. 4,14-16 sonii subspecies berkhoffii age to older dogs residing in rural environments serology are not included in with frequent flea and tick exposure. the data summary. Physical Examination. Chronically infected dogs 17 Gender. Female sex predilection is suspected in may not exhibit clinical signs of illness. Dogs human patients. No sex predilection has been with neutrophilic polyarthritis may exhibit a mild identified in dogs. shifting leg lameness or severe debilitating joint pain. Causes & Risk Factors DIAGNOSIS Bartonella species can be transmitted to humans via a bite or scratch (cat, dog, or rabbit scratch Definitive Diagnosis disease). Research in cats has shown that claws contaminated with flea feces are the predominant As is true for other intracellular pathogens that source of infection, whereas reports of B henselae induce chronic infection in dogs after vector- shedding in cat saliva are inconclusive. 1 borne transmission, diagnostic confirmation of active infection with a Bartonella species can be Less is known about risk factors for canine bar - extremely challenging. Due to cost and duration tonellosis, but dogs are most likely infected of therapy, the diagnosis of bartonellosis should through animal scratches and bites from fleas, be confirmed by culturing the organism from ticks, and other arthropod vectors. In particular, blood; cerebrospinal, aqueous, or joint fluids; BAPGM = Bartonella alpha- thoracic, pericardial, or abdominal effusions; or Proteobacteria growth there is increasing interest in the role of tick bites medium; IFA = indirect in transmitting Bartonella infection because some tissue biopsy samples. immunofluorescent antibody; PCR = polymerase chain correlation has been found between high tick reaction burden and B vinsonii subspecies berkhoffi 14 ......................................................................................................................................................................... NAVC Clinician’s Brief / July 2010 / Consultant on Call PCR Assay Sample DNA When blood culturing cats, B henselae and B clar - ridgeae can be readily isolated; however, isolation from dog, horse, or human blood samples using BAPGM Culture DNA PCR the same approach is very insensitive. 18 There - fore, to increase diagnostic sensitivity, we com - bined enrichment culture in a specialized growth Plate Isolates DNA – + medium (designated Bartonella alpha-Proteobac - teria growth medium or BAPGM) with a highly Sequence sensitive polymerase chain reaction (PCR) assay. Currently, BAPGM (galaxydx.com) provides the 3 A diagram depicting the steps involved in the BAPGM platform. PCR is per - most sensitive (98% at 1 bacterium/mcL) modal - formed following extraction of DNA from the original patient sample, enrich - ment incubation in BAPGM, and subculture onto a blood agar plate. BAPGM is a ity to confirm active infection with a Bartonella patented insect cell culture-based liquid growth medium that was optimized to species in companion animal or human patient facilitate the growth of Bartonella species and other fastidious bacteria. 18 The samples ( Figure 3 ). enrichment process increases the quantity of Bartonella species DNA so as to enhance the sensitivity of the PCR assay. All PCR-positive samples are sequenced to determine the Bartonella species and strain. Alternatively, PCR can be used to amplify bar - tonella DNA from paraffin-embedded lymph nodes, heart valves, or other tissues, but PCR with preenrichment culture is reportedly 2 to 3 4 times more sensitive than direct PCR alone. 19,20 Immunosuppressive drugs appear to increase the An example of Bartonella quantity of Bartonella in blood, whereas adminis - vinsonii subspecies berkhoffii immunofluorescent organ - tration of antibiotics prior to obtaining samples isms (serum antibody titer of for BAPGM culture will decrease detection. 1:2048) using the IFA sero - logic assay in the North Car - olina State University IFA Testing Vector-Borne Diseases Diag - By indirect immunofluorescent antibody (IFA) nostic Laboratory. The test testing, antibody reactivity to the Bartonella serum was from a military working dog with B vinsonii species antigens is detected in only 50% of dogs subspecies berkhoffii geno - and humans in which active infection with B type III endocarditis. Bacter- vinsonii subspecies berkhoffii and B henselae can antibodies in dogs with bartonellosis, infection emia was confirmed using the BAPGM platform. 4 be documented ( Figure 4 ). Therefore, antibody with these bacteria
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