Serological evidence for the association of Bartonella henselae infection with arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in young adults. On the basis of histopathological findings its pathogenesis may involve both a genetic origin and an inflammatory process. Bartonella henselae may cause endomyocarditis and was detected in myocardium from a young male who succumbed to sudden cardiac death. HYPOTHESIS: We hypothesized that chronic infection with Bartonella henselae could contribute to the pathogenesis of ARVC. METHODS: We investigated sera from 49 patients with ARVC for IgG antibodies to Bartonella henselae. In this study, 58 Swiss blood donors tested by the same method served as controls. RESULTS: Six patients with ARVC (12%) had positive (>1:256) IgG titres in the immunofluorescence test with Bartonella henselae. In contrast, only 1 elevated titre was found in 58 controls (p < or = 0.05). Interestingly, all patients with increased titres had no familial occurrence of ARVC. CONCLUSIONS: Further studies in larger patient cohorts seem justified to investigate a possible causal link between chronic Bartonella henselae and ARVC, in particular its sporadic (nonfamilial) form.

Successful treatment of Bartonella henselae endocarditis in a cat

This report describes the clinical presentation, diagnosis and treatment of a cat with vegetative valvular endocarditis temporally associated with natural infection with Bartonella henselae. Lethargy, abnormal gait and weakness were the main clinical signs that resulted in referral for diagnostic evaluation. Using a novel and sensitive culture approach, B henselae was isolated from the blood. Following antibiotic therapy there was total resolution of clinical signs, the heart murmur, the valvular lesion by echocardiography, and no Bartonella species was isolated or amplified from a post-treatment blood culture. In conjunction with previous case reports, infective endocarditis can be associated with natural B henselae infection in cats; however, early diagnosis and treatment may result in a better prognosis than previously reported.

Molecular and serological diagnosis of Bartonella infection in 61 dogs from the United States

Molecular diagnosis of canine bartonellosis can be extremely challenging and often requires the use of an enrichment culture approach followed by PCR amplification of bacterial DNA. HYPOTHESES: (1) The use of enrichment culture with PCR will increase molecular detection of bacteremia and will expand the diversity of Bartonella species detected. (2) Serological testing for Bartonella henselae and Bartonella vinsonii subsp. berkhoffii does not correlate with documentation of bacteremia. ANIMALS: Between 2003 and 2009, 924 samples from 663 dogs were submitted to the North Carolina State University, College of Veterinary Medicine, Vector Borne Diseases Diagnostic Laboratory for diagnostic testing with the Bartonella α-Proteobacteria growth medium (BAPGM) platform. Test results and medical records of those dogs were retrospectively reviewed. METHODS: PCR amplification of Bartonella sp. DNA after extraction from patient samples was compared with PCR after BAPGM enrichment culture. Indirect immunofluorescent antibody assays, used to detect B. henselae and B. vinsonii subsp. berkhoffii antibodies, were compared with PCR. RESULTS: Sixty-one of 663 dogs were culture positive or had Bartonella DNA detected by PCR, including B. henselae (30/61), B. vinsonii subsp. berkhoffii (17/61), Bartonella koehlerae (7/61), Bartonella volans-like (2/61), and Bartonella bovis (2/61). Coinfection with more than 1 Bartonella sp. was documented in 9/61 dogs. BAPGM culture was required for PCR detection in 32/61 cases. Only 7/19 and 4/10 infected dogs tested by IFA were B. henselae and B. vinsonii subsp. berkhoffii seroreactive, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs were most often infected with B. henselae or B. vinsonii subsp. berkhoffii based on PCR and enrichment culture, coinfection was documented, and various Bartonella species were identified. Most infected dogs did not have detectable Bartonella antibodies.

An unmatched case controlled study of clinicopathologic abnormalities in dogs with Bartonella infection

We compared clinicopathologic findings in dogs with Bartonella infection to Bartonella spp. negative dogs suspected of a vector-borne disease. Cases (n=47) and controls (n=93) were selected on the basis of positive or negative enrichment culture PCR results, respectively. Signalment, clinicopathologic findings and treatments were extracted from medical records. DNA sequencing identified Bartonella henselae (n=28, 59.6%), Bartonella vinsonii subsp. berkhoffii (n=20, 42.6%), Bartonella koehlerae (n=3, 6.4%), Bartonella volans-like (n=3, 6.4%) and Bartonella bovis (n=1, 2.1%). There were no significant differences in age, breed, size, sex or neuter status between cases and controls. Dogs infected with Bartonella sp. often had a history of weight loss [OR=2.82; 95% CI: 1.08-7.56] and were hypoglobulinemic [OR=4.26; 95% CI: 1.31-14.41]. With the exception of weight loss and hypoglobulinemia, clinicopathologic abnormalities in Bartonella-infected dogs in this study were similar to dogs suspected of other vector-borne infections.

Fic domain-catalyzed adenylylation: insight provided by the structural analysis of the type IV secretion system effector BepA

Numerous bacterial pathogens subvert cellular functions of eukaryotic host cells by the injection of effector proteins via dedicated secretion systems. The type IV secretion system (T4SS) effector protein BepA from Bartonella henselae is composed of an N-terminal Fic domain and a C-terminal Bartonella intracellular delivery domain, the latter being responsible for T4SS-mediated translocation into host cells. A proteolysis resistant fragment (residues 10-302) that includes the Fic domain shows autoadenylylation activity and adenylyl transfer onto Hela cell extract proteins as demonstrated by autoradiography on incubation with α-[(32)P]-ATP. Its crystal structure, determined to 2.9-Å resolution by the SeMet-SAD method, exhibits the canonical Fic fold including the HPFxxGNGRxxR signature motif with several elaborations in loop regions and an additional β-rich domain at the C-terminus. On crystal soaking with ATP/Mg(2+), additional electron density indicated the presence of a PP(i) /Mg(2+) moiety, the side product of the adenylylation reaction, in the anion binding nest of the signature motif. On the basis of this information and that of the recent structure of IbpA(Fic2) in complex with the eukaryotic target protein Cdc42, we present a detailed model for the ternary complex of Fic with the two substrates, ATP/Mg(2+) and target tyrosine. The model is consistent with an in-line nucleophilic attack of the deprotonated side-chain hydroxyl group onto the α-phosphorus of the nucleotide to accomplish AMP transfer. Furthermore, a general, sequence-independent mechanism of target positioning through antiparallel β-strand interactions between enzyme and target is suggested.

Spontaneous onset of complex regional pain syndrome Type I in a woman infected with Bartonella koehlerae

After a short-term fever, complex regional pain syndrome, characterized by hyperalgesia, intermittent swelling, erythema and cyanosis of both feet, was diagnosed in a female veterinarian. The woman was infected with Bartonella koehlerae and she was also Bartonella vinsonii subsp. berkhoffii seroreactive. Having failed other treatments, symptoms resolved following initiation of antibiotics.

Molecular detection of Bartonella spp. in deer ked pupae, adult keds and moose blood in Finland

SUMMARY The deer ked (Lipoptena cervi) is a haematophagous ectoparasite of cervids that harbours haemotrophic Bartonella. A prerequisite for the vector competence of the deer ked is the vertical transmission of the pathogen from the mother to its progeny and transstadial transmission from pupa to winged adult. We screened 1154 pupae and 59 pools of winged adult deer keds from different areas in Finland for Bartonella DNA using PCR. Altogether 13 pupa samples and one winged adult deer ked were positive for the presence of Bartonella DNA. The amplified sequences were closely related to either B. schoenbuchensis or B. bovis. The same lineages were identified in eight blood samples collected from free-ranging moose. This is the first demonstration of Bartonella spp. DNA in a winged adult deer ked and, thus, evidence for potential transstadial transmission of Bartonella spp. in the species.

Geographic distribution and molecular diversity of Bartonella infections in moose, Alces alces, in Finland.

Moose, Alces alces (Artiodactyla: Cervidae) in Finland are heavily infested with deer keds, Lipoptena cervi (Diptera: Hippoboschidae). The deer ked, which carries species of the genus Bartonella, has been proposed as a vector for the transmission of bartonellae to animals and humans. Previously, bartonella DNA was found in deer keds as well as in moose blood collected in Finland. We investigated the prevalence and molecular diversity of Bartonella spp. infection from blood samples collected from free-ranging moose. Given that the deer ked is not present in northernmost Finland, we also investigated whether there were geographic differences in the prevalence of bartonella infection in moose. The overall prevalence of bartonella infection was 72.9% (108/148). Geographically, the prevalence was highest in the south (90.6%) and lowest in the north (55.9%). At least two species of bartonellae were identified by multilocus sequence analysis. Based on logistic regression analysis, there was no significant association between bartonella infection and either age or sex; however, moose from outside the deer ked zone were significantly less likely to be infected (P<0.015) than were moose hunted within the deer ked zone.

Survey of selected tick-borne diseases in dogs in Finland

BACKGROUND: Due to climate changes during the last decades, ticks have progressively spread into higher latitudes in northern Europe. Although some tick borne diseases are known to be endemic in Finland, to date there is limited information with regard to the prevalence of these infections in companion animals. We determined the antibody and DNA prevalence of the following organisms in randomly selected client-owned and clinically healthy hunting dogs living in Finland: Ehrlichia canis (Ec), Anaplasma phagocytophilum (Ap), Borrelia burgdorferi (Bb) and Bartonella. METHODS: Anti-Ap, -Bb and -Ec antibodies were determined in 340 Finnish pet dogs and 50 healthy hunting dogs using the 4DX Snap(R)Test (IDEXX Laboratories). In addition, PCRs for the detection of Ap and Bartonella DNA were performed. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with seropositivity to a vector borne agent. RESULTS: The overall seroprevalence was highest for Ap (5.3%), followed by Bb (2.9%), and Ec (0.3%). Seropositivities to Ap and Bb were significantly higher in the Aland Islands (p <0.001), with prevalence of Ap and Bb antibodies of 45 and 20%, respectively. In healthy hunting dogs, seropositivity rates of 4% (2/50) and 2% (1/50) were recorded for Ap and Bb, respectively. One client-owned dog and one hunting dog, both healthy, were infected with Ap as determined by PCR, while being seronegative. For Bartonella spp., none of the dogs tested was positive by PCR. CONCLUSIONS: This study represents the first data of seroprevalence to tick borne diseases in the Finnish dog population. Our results indicate that dogs in Finland are exposed to vector borne diseases, with Ap being the most seroprevalent of the diseases tested, followed by Bb. Almost 50% of dogs living in Aland Islands were Ap seropositive. This finding suggests the possibility of a high incidence of Ap infection in humans in this region. Knowing the distribution of seroprevalence in dogs may help predict the pattern of a tick borne disease and may aid in diagnostic and prevention efforts.

Multiple infections of rodents with zoonotic pathogens in Austria

Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host–pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans.