Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JCM
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Journal of Clinical Microbiology
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JCM
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Clinical Veterinary Microbiology

Bartonella vinsonii subsp.berkhoffii and Related Members of the Alpha Subdivision of the Proteobacteria in Dogs with Cardiac Arrhythmias, Endocarditis, or Myocarditis

Edward B. Breitschwerdt, Clarke E. Atkins, Talmage T. Brown, Dorsey L. Kordick, Patti S. Snyder
Edward B. Breitschwerdt
Departments of Clinical Sciences and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clarke E. Atkins
Departments of Clinical Sciences and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Talmage T. Brown
Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dorsey L. Kordick
Departments of Clinical Sciences and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patti S. Snyder
College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/JCM.37.11.3618-3626.1999
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Cardiac arrhythmias, endocarditis, or myocarditis was identified in 12 dogs, of which 11 were seroreactive to Bartonella vinsonii subspecies berkhoffii antigens. Historical abnormalities were highly variable but frequently included substantial weight loss, syncope, collapse, or sudden death. Fever was an infrequently detected abnormality. Cardiac disease was diagnosed following an illness of short duration in most dogs, but a protracted illness of at least 6 months' duration was reported for four dogs. Valvular endocarditis was diagnosed echocardiographically or histologically in eight dogs, two of which also had moderate to severe multifocal myocarditis. Four dogs lacking definitive evidence of endocarditis were included because of seroreactivity to B. vinsonii antigens and uncharacterized heart murmurs and/or arrhythmias. Alpha proteobacteria were not isolated from the blood by either conventional or lysis centrifugation blood culture techniques. Using PCR amplification and DNA sequencing of a portion of the 16S rRNA gene, B. vinsonii was identified in the blood or heart valves of three dogs. DNA sequence alignment of PCR amplicons derived from blood or tissue samples from seven dogs clustered among members of the alpha subdivision of the Proteobacteria and suggested the possibility of involvement of one or more alpha proteobacteria; however, because of the limited quantity of sequence, the genus could not be identified. Serologic or molecular evidence of coinfection with tick-transmitted pathogens, including Ehrlichia canis,Babesia canis, Babesia gibsonii, or spotted fever group rickettsiae, was obtained for seven dogs. We conclude thatB. vinsonii subsp. berkhoffii and closely related species of alpha proteobacteria are an important, previously unrecognized cause of arrhythmias, endocarditis, myocarditis, syncope, and sudden death in dogs.

There is increasing evidence thatBartonella species and other closely related members of the alpha subdivision of the Proteobacteria are important cardiac pathogens in both dogs and people. During 1993,Bartonella quintana (35), Bartonella elizabethae (9), and Bartonella henselae(15) were identified for the first time as causal agents of endocarditis in human patients. In 1993, our laboratory isolated from a dog with endocarditis a novel Bartonella subspecies (6) that was subsequently designated Bartonella vinsonii subspecies berkhoffii (American Type Culture Collection type strain 51672) (22). In 1997, a new alpha-2 proteobacterium, provisionally designated Rasbo bacterium, was isolated from a chronically febrile patient with pericardial effusion and clinical evidence of myocardial disease (5). Because these organisms are highly fastidious, molecular diagnosis by PCR amplification and direct sequencing, as reported in recent studies of human endocarditis (references 13 and19 and this study), may be necessary to confirm alpha-proteobacterial infection. Based on these recent observations, continued research efforts should be directed at clarifying the role of alpha proteobacteria in cardiovascular disease in dogs, man, and potentially other animal species.

Since its first association with endocarditis in 1993,Bartonella infection has become known as an important cause of culture-negative endocarditis in man (10, 19, 33, 36). Of microbiological and clinical importance, B. quintana orB. henselae was ultimately identified as the cause of endocarditis in nine human patients previously diagnosed with chlamydia endocarditis by seroreactivity to Chlamydia antigens. It is now known that Bartonella infection induces antibodies that cross-react with Chlamydia species (33). AlthoughBartonella quintana, which is transmitted by the human body louse, caused epidemics of trench fever during World War I, the clinical association of this fastidious organism with endocarditis was not reported until nearly a century later. More recently, it has been determined that B. quintana endocarditis can be associated with alcoholism, homelessness, and presumably body louse infestations (10, 33, 37). B. henselae endocarditis can be associated with cat contact, since cats throughout the world serve as a major reservoir for B. henselae and Bartonella clarridgeiae (21, 26, 33). Although a human pathogen,B. clarridgeiae has not yet been associated with endocarditis (25).

Evolving evidence indicates that B. vinsonii is a potentially important canine pathogen, and it has been implicated as a cause of endocarditis (6), granulomatous lymphadenitis, and granulomatous rhinitis (32). A seroepidemiological survey of sick dogs from North Carolina and Virginia identified tick exposure as a risk factor for the detection of B. vinsonii antibodies (30). Compared to a seroprevalence of 3.6% in the North Carolina State University Veterinary Teaching Hospital population,B. vinsonii antibodies were found in 36% of dogs that were seroreactive to Ehrlichia canis antigens, further supporting the potential of tick transmission of B. vinsonii subsp.berkhoffii. Examination of sera from dogs experimentally infected with Rickettsia rickettsii or E. canisdid not identify cross-reactivity to B. vinsonii antigens (32). In a more recent prospective study of dogs from North Carolina naturally infected with E. canis, Ehrlichia chaffeensis, Ehrlichia equi, and/or Ehrlichia ewingii, serologic or molecular evidence of Bartonellainfection was detected in 7 of 12 animals (7). Based on these observations, the extent to which coinfection with B. vinsonii influences the pathophysiologic consequences of E. canis infection in dogs deserves additional investigation.

The initial purpose of this study was to identify additional cases of endocarditis caused by infection with B. vinsonii subsp.berkhoffii in dogs. During the course of the investigation, definitive molecular evidence of B. vinsonii subsp.berkhoffii infection was obtained for three dogs. Unexpectedly, molecular evidence of infection with one or more alpha proteobacteria spp. was found in seven dogs. The remaining two dogs had serologic evidence of Bartonella infection, but DNA could not be amplified from blood or tissue samples.

MATERIALS AND METHODS

Dogs.Since definitive diagnostic criteria forBartonella species infection in dogs have not been established, inclusion in this study required electrocardiographic evidence of arrhythmias or conduction defects, echocardiographic evidence of endocarditis, or histopathologic evidence of endocarditis or myocarditis. In addition, one or more of the following conditions had to be met: a reciprocal indirect fluorescent antibody (IFA) antibody titer of ≥128 to B. vinsonii antigens, culture ofB. vinsonii from blood, or PCR amplification of DNA from EDTA-treated blood samples or from tissues obtained at necropsy, using primers originally designed to detect Bartonella species (4). Eleven dogs were evaluated at North Carolina State University, and one dog was evaluated at the University of Florida Veterinary Teaching Hospital.

Clinical and pathologic findings.The medical records of dogs meeting the above inclusion criteria were reviewed by two authors (E.B.B. and C.E.A.). Clinical, hematologic, serum biochemical, and urinalysis findings, available for all dogs, were summarized. When requested by the attending clinician, blood coagulation profiles, blood culture results, and all other ancillary diagnostic test results were reviewed. Cardiovascular findings, including the electrocardiogram and echocardiogram, were reviewed by a veterinary cardiologist (C.E.A.). Histopathologic analysis of biopsy samples or tissues obtained at necropsy was performed by a pathologist (T.T.B.).

Serology.When serologic testing for tick-transmitted diseases had not been requested by the attending clinician and serum was stored in our research laboratory, frozen samples from these dogs were analyzed by indirect fluorescent antibody (IFA) testing for reactivity to B. vinsonii subsp. berkhoffii,E. canis, Babesia canis, and R. rickettsii antigens, using previously published procedures (6, 7).

DNA extraction and sequencing.DNA was extracted from EDTA-treated blood or fixed tissues as specimens became available during the investigation period. DNA was extracted from 200 μl of stored, frozen (−70°C), EDTA-treated blood sample with phenol-chloroform after proteinase K digestion (27). Cultured B. vinsonii was used as the positive control. PCR amplification of Bartonella DNA was performed in a 100-μl reaction volume containing 1 μg of DNA template, 0.2 μM each primer (Bh16SF [AGAGTTTGATCCTGGCTCAG] and Bh16SR [CCGATAAATCTTTCTCCCTAA], and 1.25 U of Taqpolymerase, using a previously described procedure (4). Amplification cycles included denaturation at 95°C for 30 s, annealing at 54°C for 1 min, and chain extension at 72°C for 45 s. This was repeated for 35 cycles and was followed by a final chain extension at 72°C for 5 min. When the specimen was obtained by necropsy or biopsy, PCR was performed to amplify a portion of the 16S rRNA gene from formalin-fixed, paraffin-embedded heart valve tissue, myocardium, or other tissues. In all instances, the DNA sequence of the amplicons was obtained through the North Carolina State University DNA Sequencing Facility.

RESULTS

Dogs.The states of origin, signalments, approximate dates of onset, durations of illness, historical abnormalities, and cardiac abnormalities of animals in this study are summarized in Table1. All dogs resided in North Carolina, South Carolina, or Florida. Dogs ranged in age from 6 months to 12 years (median age, 5.5 years), were predominantly male (9 of 12), and included only medium or large breeds. Historical abnormalities were highly variable but frequently included fever (n = 5), substantial weight loss (n = 5), syncope or collapse (n = 4), vomiting or diarrhea (n = 4), lameness (n = 2), ataxia (n = 3), hemorrhage (n = 2), and/or sudden death (n = 2). In nearly all instances, illness was severe, necessitating intensive care management and/or prolonged hospitalization or resulting in death.

View this table:
  • View inline
  • View popup
Table 1.

Selected clinical findings in 12 dogs with cardiac abnormalities and evidence of alpha-proteobacterial infection

Cardiovascular findings.Clinical signs that were attributable to the cardiovascular system included heart murmurs (n = 6), syncope or collapse (n = 4), heart failure (n = 4), and exercise intolerance (n = 1). However, four dogs were presented for evaluation of abnormalities other than cardiac. At the time of initial presentation, eight dogs were in sinus rhythm, three had ventricular ectopy, and one had a complete atrioventricular block. Dog 3 subsequently developed atrial fibrillation. Endocarditis involved the aortic valve in four dogs, the mitral valve in two dogs, and both the aortic and mitral valves in two additional dogs. Based on echocardiographic and/or postmortem findings, two dogs had preexisting aortic stenosis.

Clinical and pathologic findings.Hematologic parameters were highly variable, and frequently values were within laboratory reference ranges (Table 2). Hematologic abnormalities included anemia (hematocrit <36%; n = 6), thrombocytopenia (platelet count <200,000/μl; n = 5), and neutrophilia (segmented neutrophil count >11,500/μl; n = 10), rarely accompanied by a substantial left shift but occasionally accompanied by mild neutrophil toxicity, monocytosis (monocyte count >1,350/μl; n = 7), and eosinophilia (eosinophil count >750/μl; n = 1). Antierythrocyte antibodies were detected in dog 8, the only dog examined by Coombs' testing. Of the three dogs tested, antinuclear antibodies were detected only in dog 3 (reciprocal titer, 1,280). When present, hypoalbuminemia (serum albumin <2.8 g/dl; n = 9 of 12) and hyperglobulinemia (serum globulin >3.8 g/dl; n = 8 of 12) were of mild to moderate severity. With the exception of dog 4, in which there was chronic renal failure secondary to chronic renal fibrosis, hypercreatinemia (serum creatinine >1.8 mg/dl; n = 4) was usually associated with dehydration or decreased cardiac output and resolved if initial therapeutic interventions were successful. Four dogs were hyperglycemic (serum glucose >115 mg/dl), presumably a function of severe systemic stress or bacteremia-induced hyperglycemia. Hemoglobinuria, proteinuria, and bilirubinuria, as determined by urine dipstick quantitation (trace to 4+), were identified in 12 dogs.

View this table:
  • View inline
  • View popup
Table 2.

Selected laboratory findings from 12 dogs with cardiac abnormalities and evidence of alpha-proteobacterial infection

Blood cultures and serology.Conventional blood cultures from 10 dogs and lysis centrifugation blood cultures from 5 dogs failed to result in bacterial growth (Table 3).

View this table:
  • View inline
  • View popup
Table 3.

Selected microbiological, serologic, and PCR-DNA sequencing results from 12 dogs with cardiac abnormalities and evidence of alpha-proteobacterial infection

Seroreactivity (reciprocal titers of ≥128) to B. vinsonii antigens, as determined by IFA testing, was documented in 11 of 12 dogs (Table 3). There was also serologic evidence of exposure to several other tick-transmitted pathogens. Seroreactivity to spotted fever group rickettsiae was documented for four dogs (reciprocal titers to R. rickettsii antigens, ≥64), seroreactivity to E. canis was evident for three dogs (reciprocal titers, ≥80), and seroreactivity to Babesia canis or Babesia gibsonii was found for dogs 3 and 10 (reciprocal titers, ≥80).Babesia canis organisms were observed on the blood smear of dog 10. Dog 3 had a reciprocal titer to Babesia gibsoniiantigens of 160, and Babesia gibsonii DNA was subsequently amplified from a stored EDTA-treated blood sample. Retrospectively, based on DNA sequence similarity to Brucella canis (see below), stored frozen sera from 10 of 12 dogs (available for all except dogs 4 and 10) were tested by rapid slide agglutination for antibodies to Brucella canis antigens by Leland Carmichael, Cornell University. Brucella canis antibodies were not detected in any serum sample.

PCR and DNA sequencing.DNA obtained from stored EDTA-treated blood samples or formalin-fixed, paraffin-embedded heart valve, myocardium, or other tissue was amplified by using 16S rRNA primers originally described as specific for the genus Bartonella(4). PCR performed at low stringency allowed amplification of a product of appropriate size (approximately 185 bp) from the blood of seven dogs, the heart valve or myocardium of five dogs, the kidney of one dog, and a preputial mass removed from dog 10 4 months prior to evaluation of fever and collapse (Table 3). Between 99 and 146 nucleotides of DNA sequence were derived from the 185-bp PCR products. A similarity search of GenBank sequence data indicated that three samples derived from dogs 1 to 3 were identical to B. vinsonii subsp. berkhoffii (Table4). Amplicons derived from seven other dogs (cases 4 to 10) clustered among several alpha proteobacteria, including Rhizobium, Agrobacterium,Brucella, Methylobacterium, and the currently unnamed Rasbo agent (5). Given the lack of a bacterial isolate and the limited quantity of DNA available, it was not possible to definitively identify the bacteria in these seven dogs. However, when compared with the corresponding nucleotide sequences of blood culture isolates or of common contaminants (Staphylococcus aureus or Staphylococcus intermedius), other organisms associated with cardiac disease or bacteremia (Capnocytophaga canis or Chlamydia spp.), or bacteria, rickettsia, or bloodborne protozoa that some of these dogs were apparently exposed to or coinfected with (Serratia marcescens, E. canis, or Babesia canis), minimal sequence alignment was achieved. Bacterial DNA was not amplified from the available blood of dogs 11 and 12, despite the presence ofBartonella-reactive immunoglobulin G (IgG) and clinical signs compatible with bacteremia.

View this table:
  • View inline
  • View popup
Table 4.

Comparative alignment of partial 16S rRNA gene sequences of B. henselae, B. vinsonii subsp.berkhoffii, and amplicons derived from dogs 1 to 3

Treatment.Regimens differed considerably among individual dogs but included antibiotics in all cases (amoxicillin, enrofloxacin, cephalexin, doxycycline, and amikacin), diuretics for congestive heart failure for five dogs (furosemide), and various combinations of cardiovascular drugs (enalapril, digoxin, nitroglycerin, and diltiazem). Eight dogs were euthanized or died within the first month following presentation, two died within 2 to 7 months of presentation, 1 was lost to follow-up, and 1 remains alive. Dog 6, diagnosed with endocarditis during May 1996, has been treated continuously with enrofloxacin since that time. Sequential reciprocal B. vinsonii antibody titers were 8,192 (May 1996), 512 (November 1997), 512 (January 1998), and 256 (May 1998). The dog was still alive in November 1998 but had developed congestive heart failure.

Histopathology.Four dogs were necropsied. Endocarditis was confirmed at necropsy in dog 2, infected with B. vinsoniisubsp. berkhoffii, and in dogs 7 and 10, infected with an undetermined alpha proteobacterium. Dogs 2 and 7 also had myocarditis. Dog 2 had a 2-mm-diameter vegetative mass on a mitral valve leaflet (Fig. 1). There were multifocal areas of severe myocardial inflammation widely scattered in both the left and right sides of the heart. These inflammatory foci were often associated with thickened, severely inflamed coronary arteries that were often disrupted by areas of severe fibrinoid necrosis (Fig.2). Inflammatory foci were characterized by myocardial fiber loss, neovascularization, and various numbers of neutrophils and macrophages. In a few areas, a purulent exudate was a prominent component of the inflammatory foci. The mitral valvular mass was a mixture of myxomatous tissue, neutrophils, and macrophages. Warthin Starry staining for bacteria was negative. In dog 4 (infected with an alpha proteobacterium), there were nodular myxomatous thickenings of the mitral valve leaflets, characteristic of valvular endocardiosis rather than endocarditis as suspected from the echocardiogram. Inflammatory cells were not observed in the valvular lesions, but occasional small myocardial inflammatory foci composed of various mixtures of lymphocytes, plasma cells, and macrophages were randomly scattered in the left ventricle. A 1.5-cm-diameter vegetative inflammatory mass was present on a cusp of the aortic valve of dog 7. This mass consisted of a mixture of fibrin, numerous neutrophils, macrophages, and cell debris. Myocardial inflammatory foci composed primarily of neutrophils, fibrin, macrophages, and cell debris were randomly scattered in the left ventricle, interventricular septum, and right atrium. Serratia marcescens was cultured from the aortic cusp mass, Warthin Starry staining was negative, and alignment of the DNA sequence of the PCR amplicon from the valve was consistent with an alpha proteobacterium, not Serratia marcescens. A 1.5-cm-diameter vegetative inflammatory mass was located on the cusps of the aortic valve of dog 10. The mass was composed of a mixture of well- to poorly differentiated mesenchymal tissue. Near the surface, the myxomatous tissue was mixed with cell debris and lymphocytes and was encrusted with amorphous eosinophilic debris containing numerous bacterial colonies and focal areas of mineralization. The bacterial colonies contained short, plump rods, consistent in size and shape withBartonella spp., that stained positive with the Warthin Starry silver stain.

Fig. 1.
  • Open in new tab
  • Download powerpoint
Fig. 1.

Left auricle and base of mitral valve of dog 2, infected with B. vinsonii, distended by inflammatory exudate. Inflammation extends into the adjacent auricular myocardium on the left. Hematoxylin and eosin stain; bar = 268 μm.

Fig. 2.
  • Open in new tab
  • Download powerpoint
Fig. 2.

Coronary artery of dog 2, infected with B. vinsonii. Shown is the coronary artery with an adherent mass of inflammatory exudate bulging into the arterial lumen, with transmural inflammation of the arterial wall beneath the inflammatory exudate. Severe inflammation surrounding inflamed artery effaces the normal tissue architecture. Hematoxylin and eosin stain; bar = 107 μm.

DISCUSSION

In this study, the diagnosis of B. vinsoniiendocarditis in 3 of 12 dogs was suggested by serology and confirmed by PCR and DNA sequencing. The DNA sequences for these three dogs (no. 1 to 3) were essentially identical (Table 4) and included the 12-bp insert that is consistent with B. vinsonii subsp.berkhoffii. Unexpectedly, when the partial 16S rRNA gene sequence derived from blood or other tissue samples from the other seven dogs was compared to GenBank sequences for other, closely related bacteria, including B. henselae, B. vinsonii,Brucella canis, and the alpha proteobacterium provisionally designated Rasbo, all sequences clustered together and were most closely related to Brucella canis and Rasbo bacterium (Fig.3) (5). Although severalBrucella spp. have been associated with endocarditis in human patients (3), Brucella canis has been infrequently associated with endocarditis in dogs (1). Since antibodies to Brucella antigens were not detected in 10 of 12 dogs tested retrospectively, it seems unlikely that the partial sequences are from Brucella spp. Since amplicons were not obtained from blood samples from the remaining two dogs, DNA sequencing could not be performed to determine the infecting bacterial species.

Fig. 3.
  • Open in new tab
  • Download powerpoint
Fig. 3.

Comparative alignment of partial 16S rRNA gene sequences of Brucella canis, Rasbo bacterium, and amplicons derived from dogs 4 to 10. The sequence of the noncoding RNA strand is shown. The numbers correspond to the Escherichia coli numbering scheme. Unless noted in boldface type in the table, all intervening sequences between no. 45 and 207 for all isolates were identical. Dashes (a) indicate the lack of comparable sequence. aP, alpha proteobacterium.

Historically, the duration and severity of disease presentation varied considerably among these dogs. An acute onset of illness characterized by fever, lethargy, anorexia, weight loss, and collapse was identified in eight dogs. In contrast, cardiac disease was diagnosed in four dogs following a protracted illness of at least 6 months' duration. When the historical duration of illness was compared to theBartonella-reactive antibody titer, there was a poor correlation. Of the five dogs with reciprocal antibody titers of 4,096 or higher, three had an acute onset of illness whereas two dogs were ill for at least 6 months prior to the diagnosis of endocarditis. These serologic observations appear to support a more chronic course of infection with acute cardiac decompensation. On an evolutionary basis,Bartonella species appear to be well adapted to facilitate intracellular persistence within most host species (21, 26, 27, 29). Although persistent infection of 16 months' duration withB. vinsonii has been documented in a healthy dog (26), similar data based on culturing the organism from the blood of sick dogs is lacking. Persistent infection with B. henselae or B. clarridgeiae spanning years in duration has been documented in both naturally and experimentally infected cats (21, 27). Although the duration of Bartonellainfection in various domestic and wild animal species requires additional clarification, documentation of endocarditis presumably represents a manifestation of chronic Bartonella infection with eventual bacterial localization in the heart valve.

Comparatively low Bartonella-specific serum antibody titers were found in several dogs; dogs 2 and 12 had low antibody titers, despite a prolonged duration of illness. Similar to findings in experimentally infected cats (23), wild animal species such as deer (8), and a recently described human case of B. quintana bacteremia (11), this observation may relate to failure of selected individuals to develop a strong humoral immune response when chronically infected with Bartonella (cases 1 to 3) (34). Specifically, low or undetectable levels ofBartonella-specific antibodies have been observed in culture-positive animals or human patients, even when the homologous organism is used as the test antigen. A similar observation was made in the case of a Swedish patient infected with the Rasbo bacterium, who failed to develop a detectable IgG antibody response to the organism despite a chronic course of infection (5). Alternatively, failure to detect an IgG-specific immune response to these organisms may reflect differences in culture- or tissue culture-grown organisms compared to the antigenic properties of the organisms in vivo.

In contrast to the low Bartonella-reactive titers, four of the highest reciprocal antibody titers to B. vinsoniiantigens (4,096 to 8,192) were in dogs with PCR evidence of infection with a species of proteobacteria other than Bartonella. Presumably, this organism(s) cross-reacts serologically with B. vinsonii antigens, or some of these dogs may have been coinfected with more than one alpha-proteobacteria species. Our results indicate that B. vinsonii-reactive serum does not cross-react with Brucella canis, E. canis, orR. rickettsii antigens (31). Until less technically demanding procedures are developed, detection ofBartonella-reactive antibodies, in conjunction with PCR amplification and sequencing of DNA from blood or tissue specimens, would seem the most beneficial approach for detecting B. vinsonii or alpha-Proteobacteria spp. in dogs with endocarditis or arrhythmias.

Based on the results of this study, endocarditis associated withBartonella and other alpha proteobacteria occurs in large-breed dogs. There also appears to be a strong predisposition for these organisms to infect the aortic valve (70%), in contrast to a review of five studies of bacterial endocarditis, involving 187 dogs, in which the mitral valve was affected nearly three times as often as the aortic valve (67% versus 23%) (20). Preexisting valvular disease, such as subaortic stenosis, might explain the increased predilection for aortic valve involvement, particularly in boxers, a breed predisposed to congenital aortic stenosis. AlthoughB. henselae was the third most frequent infectious agent identified in 146 children with fever of unknown origin (18), fever was not found in over half of the dogs in this study. Hematologic abnormalities such as neutrophilia, band neutrophils, and neutrophil toxic change are frequently not detected. Hemoglobinuria and proteinuria, potentially a reflection of glomerulonephritis or renal microinfarction due to bacteremia, were identified in most of the dogs in this series. Despite the severity of illness documented in most of these dogs, neither conventional blood culture nor lysis centrifugation blood culture was of value for the isolation of alpha proteobacteria from blood.

Concurrent isolation of other bacterial organisms from three dogs was an unexpected finding. These isolates may represent infection, isolation contaminants, catheter-acquired infections associated with intensive care management, or postmortem contamination. In dog 7,Serratia marcescens was isolated at necropsy from an aortic cusp mass and gram-negative bacteria were visualized in the tissues. However, this dog had a reciprocal B. vinsonii titer of 8,192, and alpha-proteobacterial DNA was amplified from EDTA-treated blood and valve tissue on two independent occasions. In this instance,S. marcescens may have been a postmortem contaminant, orS. marcescens bacteremia may have developed secondary to chronic alpha-proteobacterial infection. In human endocarditis patients, isolation of multiple bacterial organisms generally occurs in association with severe immunosuppression or intravenous drug use (3). Additional efforts to establish whether these organisms can contribute to immunosuppression in dogs appear justified. Clinical observations related to human infection with Bartonella bacilliformis in South America support an immunosuppressive role for the organism, potentially leading to death from concurrent bacterial infections (12). Concurrent viral infections, including those caused by Epstein-Barr virus or the human immunodeficiency virus, can markedly influence the severity and clinical course of B. henselae or B. quintanainfection in humans (20, 22, 39). Similarly, cats coinfected with B. henselae and the feline immunodeficiency virus were more likely to exhibit lymphadenopathy and gingivitis than cats infected with only one of these organisms (38). Previously, we documented severe suppression of circulating CD8 lymphocytes in dogs experimentally infected with B. vinsonii (31). Although these and other, uncited observations support a potentially important role for the immune system in determining the clinical outcome of Bartonella infections, the immunopathogenesis associated with human or canine infection remains incompletely understood (29, 34).

The spectrum of histologic changes observed in the four dogs with endocardial lesions may provide some insight into possible pathogenic mechanisms associated with alpha-proteobacterial infections. Dog 4 had mitral valvular endocardiosis; however, the myocardium contained mild inflammatory foci, and DNA sequencing of amplicons from both the blood and the valvular region were identical and indicative of an undetermined alpha-Proteobacteria species. In dogs 2 (infected with B. vinsonii), 7, and 10 (both infected with alpha proteobacteria), the valvular lesions were inflammatory and more severe. Additionally, the myocardium of dogs 2 and 7 contained multifocal areas of inflammation. Alpha proteobacteria may preferentially colonize damaged tissue sites, such as degenerative heart valve leaflets. Once valvular colonization is established, the inflammatory response to the organism results in a progressive valvular inflammatory lesion that may serve as a source of inflammatory debris, spreading the organism to other areas of the heart or to more distal sites.

Based on review of our cases, the prognosis for alpha-proteobacterial endocarditis is generally poor, as is described for other causes of bacterial endocarditis in dogs (1). However, based on comparative medical data, therapeutic elimination of alpha-proteobacterial infection, particularly in dogs or human patients with endocarditis or myocarditis, may be difficult to attain. Although enrofloxacin was more efficacious than doxycycline for the treatment ofB. henselae or B. clarridgeiae infection in experimentally or naturally infected cats, neither drug eliminated the infection in all animals, even when administered for a duration of 4 weeks (24). Similarly, despite prolonged treatment with numerous antibiotics, including doxycycline and imipenem, the Swedish patient infected with the Rasbo bacterium experienced at least three relapses during a 1-year period (5). In the present study, dog 6 is notable in that it has lived 3 years beyond the initial diagnosis of endocarditis while being maintained on continuous therapy with enrofloxacin by the referring veterinarian. Despite a seemingly favorable therapeutic response and a gradual decline in serum antibody titers, this dog has remained seroreactive to B. vinsoniiantigens, alpha-proteobacteria DNA has been amplified from pretreatment and early posttreatment blood samples, and cardiac performance has deteriorated to the point of congestive heart failure. Since a recent prospective randomized double-blind placebo-controlled study indicated that azithromycin was of clinical benefit to patients with typical cat scratch disease, macrolide antibiotics may hold additional promise for the treatment of chronic Bartonella or alpha-proteobacterial infections (2).

Although myocarditis was documented histologically in only two dogs, the potential of alpha-Proteobacteria spp. contributing to myocardial involvement in these dogs was supported by clinical findings such as syncope, acute collapse, or sudden death and by the documentation of conduction abnormalities, ventricular arrhythmias, or decreased myocardial contractility. Myocarditis was identified in a 60-year-old male who died suddenly during a running competition (17). Similar to the dogs in this report, serologic and molecular evidence implicated infection with Bartonella or a closely related species of bacteria. Recently, focal myocardial inflammation, consisting predominantly of mononuclear cells, has been observed in cats experimentally infected with B. henselae(14, 27).

Complete atrioventricular block has been associated with Borrelia burgdorferi infection in dogs and human patients in regions with endemic Lyme Disease (28). Recently, it has been determined that Ixodes scapularis ticks in these regions can cotransmit multiple tickborne pathogens, including B. burgdorferi,Babesia microti, a granulocytic Ehrlichia species (presumably E. equi), and an as-yet-uncharacterizedBartonella species (16). In this study, complete atrioventricular block required pacemaker implantation in dog 5 (alpha-proteobacterium infected), which was seroreactive to B. vinsonii, E. canis, and R. rickettsiiantigens. Collectively, these observations serve to illustrate the potential difficulty in establishing causation in dogs or people coinfected with multiple tick-transmitted pathogens. Since certainBorrelia, Ehrlichia, Babesia, andBartonella species can induce chronic, insidious infection in dogs (7), the relative role of each of these organisms in the pathogenesis of a specific disease manifestation in a sick dog will be difficult to establish in nature.

Findings generated through this study indicate that B. vinsonii and other closely related alpha-Proteobacteriaspp. can be detected in dogs with cardiac arrhythmias, endocarditis, or myocarditis. Importantly, infection with these organisms may contribute to syncope, collapse, conduction defects, arrhythmias, or sudden death. Since the initial intent of this study was to identify dogs with serologic evidence of Bartonella endocarditis, case selection was biased toward Bartonella-seroreactive dogs with clinical, echocardiographic, or necropsy evidence of endocarditis. Therefore, the role of alpha proteobacteria as a cause of cardiac arrhythmias or myocarditis might well be expanded through additional studies that target different patient populations.

ACKNOWLEDGMENTS

This work was supported by the state of North Carolina, by a grant from Intervet Inc., and through a donation from Heska Corporation.

We acknowledge the technical support of KwangOk Shin, Brandee Pappalardo, Barbara Hegarty, Susan Hancock, Robin Gager, and Julie Bradley.

FOOTNOTES

    • Received 4 January 1999.
    • Returned for modification 10 May 1999.
    • Accepted 4 August 1999.
  • Copyright © 1999 American Society for Microbiology

REFERENCES

  1. 1.↵
    1. Atkins C. E.
    Bacterial endocarditis Small animal medicine. J. B. Allen D. G. 1991 299 308 Lippincott Company Philadelphia, Pa
  2. 2.↵
    1. Bass J. W.,
    2. Freitas B. C.,
    3. Freitas A. D.,
    4. Sisler C. L.,
    5. Chan D. S.,
    6. Vincent J. M.,
    7. Person D. A.,
    8. Claybaugh J. R.,
    9. Wittler R. R.,
    10. Weisse M. E.,
    11. Regnery R. L.,
    12. Slater L. N.
    Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat scratch disease.Pediatr. Infect. Dis. J.171998447452
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Berbari E. F.,
    2. Cockerill F. R.,
    3. Steckelberg J. M.
    Infective endocarditis due to unusual or fastidious microorganisms.Mayo Clin. Proc.721997532542
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    1. Bergmans A. M. C.,
    2. Groothedde J. W.,
    3. Schellekens J. F. P.,
    4. van Embden J. D.,
    5. Ossewaarde J. M.,
    6. Schouls L. M.
    Etiology of cat scratch disease: comparison of polymerase chain reaction detection of Bartonella (formerly Rochalimaea) and Afipia felis DNA with serology and skin tests.J. Infect. Dis.1711995916923
    OpenUrlCrossRefPubMedWeb of Science
  5. 5.↵
    1. Blomqvist G.,
    2. Wesslén L.,
    3. Påhlson C.,
    4. Hjelm E.,
    5. Pettersson B.,
    6. Nikkilä T.,
    7. Allard U.,
    8. Svensson O.,
    9. Uhlén M.,
    10. Morein B.,
    11. Friman G.
    Phylogenetic placement and characterization of a new alpha-2 proteobacterium isolated from a patient with sepsis.J. Clin. Microbiol.35199719881995
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Breitschwerdt E. B.,
    2. Kordick D. L.,
    3. Malarkey D. E.,
    4. Keene B.,
    5. Hadfield T. L.,
    6. Wilson K.
    Endocarditis in a dog due to infection with a novel Bartonella subspecies.J. Clin. Microbiol.331995154160
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Breitschwerdt E. B.,
    2. Hegarty B. C.,
    3. Hancock S. I.
    Sequential evaluation of dogs naturally infected with Ehrlichia canis, Ehrlichia chaffeensis, Ehrlichia equi, Ehrlichia ewingii, or Bartonella vinsonii.J. Clin. Microbiol.36199826452651
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Chomel B. B.,
    2. Kasten R. W.,
    3. Chang C. C.,
    4. Yamamoto K.,
    5. Heller R.,
    6. Maruyama S.,
    7. Ueno H.,
    8. Simpson D.,
    9. Swift P. A.,
    10. Jang S. S.,
    11. Piemont Y.,
    12. Pedersen N. C.
    Isolation of Bartonella spp. from California wildlife, abstr. P-21-10.In Proceedings of the International Conference on Emerging Infectious Diseases, Atlanta, Ga.1998
  9. 9.↵
    1. Daly J. S.,
    2. Worthington M. G.,
    3. Brenner D. J.,
    4. Moss C. W.,
    5. Hollis D. G.,
    6. Weyant R. S.,
    7. Steigerwalt A. G.,
    8. Weaver R. E.,
    9. Daneshvar M. I.,
    10. O'Connor S. P.
    Rochalimaea elizabethae sp. nov. isolated from a patient with endocarditis.J. Clin. Microbiol.311993872881
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Drancourt M.,
    2. Mainardi J. L.,
    3. Brouqui P.,
    4. Vandenesch F.,
    5. Carta A.,
    6. Lehnert F.,
    7. Etienne J.,
    8. Goldstein F.,
    9. Acar J.,
    10. Raoult D.
    Bartonella (Rochalimaea) quintana endocarditis in three homeless men.N. Engl. J. Med.3321995419423
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    1. Drancourt M.,
    2. Maol V.,
    3. Brunet P.,
    4. Dussol B.,
    5. Berland Y.,
    6. Raoult D.
    Bartonella (Rochalimaea) quintana infection in a seronegative hemodialyzed patient.J. Clin. Microbiol.34199611581160
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Garcia-Caceres U.,
    2. Garcia F. U.
    Bartonellosis: an immunodepressive disease and the life of Daniel Carrion.Am. J. Clin. Pathol.95 (Suppl. I)1991S58S66
    OpenUrlPubMed
  13. 13.↵
    1. Goldenberger D.,
    2. Künzli A.,
    3. Vogt P.,
    4. Zbinden R.,
    5. Altwegg M.
    Molecular diagnosis of bacterial endocarditis by broad-range PCR amplification and direct sequencing.J. Clin. Microbiol.35199727332739
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Guptill L.,
    2. Slater L.,
    3. Wu C.,
    4. Lin T.,
    5. Glickman L.,
    6. Welch D.,
    7. HogenEsch H.
    Experimental infection of young specific pathogen-free cats with Bartonella henselae.J. Infect. Dis.1761997206216
    OpenUrlCrossRef
  15. 15.↵
    1. Hadfield T. L.,
    2. Warren R.,
    3. Kass M.,
    4. Brun E.,
    5. Levy C.
    Endocarditis caused by Rochalimaea henselae.Hum. Pathol.24199311401141
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Hofmeister E. K.,
    2. Kolbert C. P.,
    3. Abdulkarim A. S.
    Cosegregation of a novel Bartonella species with Borrelia burgdorferi and Babesia microti in Peromyscus leucopus.J. Infect. Dis.1771998409416
    OpenUrlCrossRefPubMedWeb of Science
  17. 17.↵
    1. Holmberg M.,
    2. Wesslen L.,
    3. Hjelm E.,
    4. Pahlson C.,
    5. Lindquist O.,
    6. Friman G.,
    7. Regnery R.
    Bartonella spp. in a 60 year-old Swedish male with myocarditis who succumbed to sudden death, abstr. 1.In Proceedings of the 13th Sesquiannual Meeting of the American Society for Rickettsiology, Champion, Pa.1997
  18. 18.↵
    1. Jacobs R. F.,
    2. Schutze G. E.
    Bartonella henselae as a cause of prolonged fever and fever of unknown origin in children.Clin. Infect. Dis.2619978084
    OpenUrlCrossRef
  19. 19.↵
    1. Jalava J.,
    2. Kotilainen P.,
    3. Nikkari S.,
    4. Skurnik M.,
    5. Vanttinen E.,
    6. Lehtonen O.,
    7. Eerola E.,
    8. Toivanen P.
    Use of the polymerase chain reaction and DNA sequencing for detection of Bartonella quintana in the aortic valve of a patient with culture-negative infective endocarditis.Clin. Infect. Dis.211995891896
    OpenUrlCrossRefPubMedWeb of Science
  20. 20.↵
    1. Koehler J. E.,
    2. Sanchez M. A.,
    3. Garrido C. S.,
    4. Whitfeld M. J.,
    5. Chen F. M.,
    6. Berger T. G.,
    7. Rodriguez-Barradas M. C.,
    8. LeBoit P. E.,
    9. Tappero J. W.
    Molecular epidemiology of Bartonella infections in patients with bacillary angiomatosis-peliosis.N. Engl. J. Med.337199718761883
    OpenUrlCrossRefPubMedWeb of Science
  21. 21.↵
    1. Kordick D. L.,
    2. Wilson K. H.,
    3. Sexton D. J.,
    4. Hadfield T. L.,
    5. Berkhoff H. A.,
    6. Breitschwerdt E. B.
    Prolonged Bartonella bacteremia in cats associated with cat-scratch disease patients.J. Clin. Microbiol.33199532453251
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Kordick D. L.,
    2. Swaminathan B.,
    3. Greene C. E.,
    4. Wilson K. H.,
    5. Whitney A. M.,
    6. O'Connor S.,
    7. Hollis D. G.,
    8. Matar G. M.,
    9. Steigerwalt A. G.,
    10. Malcolm G. B.,
    11. Hayes P. S.,
    12. Hadfield T. L.,
    13. Breitschwerdt E. B.,
    14. Brenner D. J.
    Bartonella vinsonii subsp. berkhoffii subsp. nov., isolated from dogs; Bartonella vinsonii subsp. vinsonii; and emended description of Bartonella vinsonii.Int. J. Syst. Bacteriol.461996704709
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Kordick D. L.,
    2. Breitschwerdt E. B.
    Relapsing bacteremia following blood transmission of Bartonella henselae in cats.Am. J. Vet. Res.581997492497
    OpenUrlPubMedWeb of Science
  24. 24.↵
    1. Kordick D. L.,
    2. Papich M. G.,
    3. Breitschwerdt E. B.
    Efficacy of enrofloxacin or doxycycline for treatment of Bartonella henselae or Bartonella clarridgeiae infection in cats.Antimicrob. Agents Chemother.41199724482455
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Kordick D. L.,
    2. Hilyard E. J.,
    3. Hadfield T. L.,
    4. Wilson K. H.,
    5. Steigerwalt A. G.,
    6. Brenner D. J.,
    7. Breitschwerdt E. B.
    Bartonella clarridgeiae, a newly recognized zoonotic pathogen causing inoculation papules, fever, and lymphadenopathy (cat scratch disease).J. Clin. Microbiol.35199718131818
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Kordick D. L.,
    2. Breitschwerdt E. B.
    Persistent infection of pets within a household with three Bartonella species.Emerg. Infect. Dis.41998325328
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Kordick D. L.,
    2. Brown T. T.,
    3. Shin K.,
    4. Breitschwerdt E. B.
    Clinical and pathologic evaluation of chronic Bartonella henselae or Bartonella clarridgeiae infection in cats.J. Clin. Microbiol.37199915361547
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Levy S. A.,
    2. Duray P. H.
    Complete heart block in a dog seropositive for Borrelia burgdorferi.J. Vet. Intern. Med.21988138144
    OpenUrlCrossRefPubMedWeb of Science
  29. 29.↵
    1. Minnick M. F.,
    2. Mitchell S. J.,
    3. McAllister S. J.
    Cell entry and the pathogenesis of Bartonella infections.Trends Microbiol.41996343347
    OpenUrlCrossRefPubMedWeb of Science
  30. 30.↵
    1. Pappalardo B. L.,
    2. Correa M. T.,
    3. York C. C.,
    4. Peat C. Y.,
    5. Breitschwerdt E. B.
    Epidemiologic evaluation of the risk factors associated with exposure and seroreactivity to Bartonella vinsonii in dogs.Am. J. Vet. Res.581997467471
    OpenUrlPubMedWeb of Science
  31. 31.↵
    1. Pappalardo B. L.,
    2. Gebhard D. H.,
    3. Breitschwerdt E. B.
    Cyclic CD8 lymphopenia associated with dogs experimentally infected with Bartonella vinsonii subspecies berkhoffii, abstr. 19.In Proceedings of the 13th Sesquiannual Meeting of the American Society for Rickettsiology, Champion, Pa.1997
  32. 32.↵
    Pappalardo, B. L., T. T. Brown, J. L. Gookin, C. L. Morrill, and E. B. Breitschwerdt. Bartonella induced granulomatous disease in two dogs. J. Vet. Intern. Med., in press.
  33. 33.↵
    1. Raoult D.,
    2. Fournier P. E.,
    3. Drancourt M.,
    4. Marrie T. J.,
    5. Etienne J.,
    6. Cosserat J.,
    7. Cacoub P.,
    8. Poinsignon Y.,
    9. Leclercq P.,
    10. Sefton A. M.
    Diagnosis of 22 new cases of Bartonella endocarditis.Ann. Intern. Med.1251996646652
    OpenUrlCrossRefPubMedWeb of Science
  34. 34.↵
    1. Rodriguez-Barradas M. C.,
    2. Bandres J. C.,
    3. Hammill R. J.,
    4. Trial J.,
    5. Clarridge J. E. III,
    6. Baughn R. E.,
    7. Rossen R. D.
    In vitro evaluation of the role of humoral immunity against Bartonella henselae.Infect. Immun.63199523672370
    OpenUrlAbstract/FREE Full Text
  35. 35.↵
    1. Spach D. H.,
    2. Callis K. P.,
    3. Paauw D. S.,
    4. Houze Y. B.,
    5. Schoenknecht F. D.,
    6. Welch D. F.,
    7. Rosen H.,
    8. Brenner D. J.
    Endocarditis caused by Rochalimaea quintana in a patient infected with human immunodeficiency virus.J. Clin. Microbiol.311993692694
    OpenUrlAbstract/FREE Full Text
  36. 36.↵
    1. Spach D. H.,
    2. Kanter A. S.,
    3. Daniels N. A.,
    4. Nowowiejski D. J.,
    5. Larson A. M.,
    6. Schmidt R. A.,
    7. Swaminathan B.,
    8. Brenner D. J.
    Bartonella (Rochalimaea) species as a cause of apparent “culture-negative” endocarditis.Clin. Infect. Dis.20199510441047
    OpenUrlCrossRefPubMedWeb of Science
  37. 37.↵
    1. Spach D. H.,
    2. Kanter A. S.,
    3. Dougherty M. J.,
    4. Larson A. M.,
    5. Coyle M. B.,
    6. Brenner D. J.,
    7. Swaminathan B.,
    8. Matar G. M.,
    9. Welch D. F.,
    10. Root R. K.,
    11. Stamm W. E.
    Bartonella (Rochalimaea) quintana bacteremia in inner-city patients with chronic alcoholism.N. Engl. J. Med.3321995424428
    OpenUrlCrossRefPubMedWeb of Science
  38. 38.↵
    1. Ueno H.,
    2. Hohdatsu T.,
    3. Muramatsu Y.,
    4. Koyama H.,
    5. Morita C.
    Does coinfection of Bartonella henselae and FIV induce clinical disorders in cats? Microbiol. Immunol. 40 1996 617 620
    OpenUrlPubMed
  39. 39.↵
    1. Zbinden R.,
    2. Kurer S. B.,
    3. Altwegg M.,
    4. Weber R.
    Generalized infection with Bartonella henselae following infection due to Epstein-Barr virus.Clin. Infect. Dis.23199611841185
    OpenUrlCrossRefPubMed
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Bartonella vinsonii subsp.berkhoffii and Related Members of the Alpha Subdivision of the Proteobacteria in Dogs with Cardiac Arrhythmias, Endocarditis, or Myocarditis
Edward B. Breitschwerdt, Clarke E. Atkins, Talmage T. Brown, Dorsey L. Kordick, Patti S. Snyder
Journal of Clinical Microbiology Nov 1999, 37 (11) 3618-3626; DOI: 10.1128/JCM.37.11.3618-3626.1999

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Journal of Clinical Microbiology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Bartonella vinsonii subsp.berkhoffii and Related Members of the Alpha Subdivision of the Proteobacteria in Dogs with Cardiac Arrhythmias, Endocarditis, or Myocarditis
(Your Name) has forwarded a page to you from Journal of Clinical Microbiology
(Your Name) thought you would be interested in this article in Journal of Clinical Microbiology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Bartonella vinsonii subsp.berkhoffii and Related Members of the Alpha Subdivision of the Proteobacteria in Dogs with Cardiac Arrhythmias, Endocarditis, or Myocarditis
Edward B. Breitschwerdt, Clarke E. Atkins, Talmage T. Brown, Dorsey L. Kordick, Patti S. Snyder
Journal of Clinical Microbiology Nov 1999, 37 (11) 3618-3626; DOI: 10.1128/JCM.37.11.3618-3626.1999
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Alphaproteobacteria
Arrhythmias, Cardiac
Bartonella
Bartonella Infections
Dog Diseases
Endocarditis, Bacterial
Myocarditis

Related Articles

Cited By...

About

  • About JCM
  • Editor in Chief
  • Board of Editors
  • Editor Conflicts of Interest
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Resources for Clinical Microbiologists
  • Ethics
  • Contact Us

Follow #JClinMicro

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

 

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0095-1137; Online ISSN: 1098-660X