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We describe the first case of Bartonella quintana endocarditis affecting a prosthetic valve in a person with no known risk factors for this infection. Bartonella should be considered as a cause of endocarditis in any clinical setting.
A man with AIDS presented with a deep soft-tissue mass involving the right thigh. Biopsy of a skin lesion on the back and culture of a specimen from this lesion showed bacillary angiomatosis due to Bartonella (formerly Rochalimaea) quintana. Magnetic resonance imaging revealed a large heterogeneous mass involving the vastus medialis and intermedius muscles. Therapy with erythromycin caused rapid resolution of both the cutaneous lesion and the muscle lesion. Bartonella infection is proposed as an additional cause of bacterial myositis and expands the spectrum of presentation of bacillary angiomatosis.
The purpose of this study was to understand the mechanisms of persistent infection with Bartonella henselae in cats. Blood samples were collected from three naturally infected cats for 24 months. These cats were confirmed to be persistently infected with B. henselae by serological and bacteriological examination. Relapsing bacteremia was found in all three cats with intervals of 3-19 months. Following the peaks of bacteremia, increases of specific antibody titer were observed in these cats. To examine the genetic differences among the isolates derived from the first and following bacteremia, the genome DNA patterns of the restriction enzyme fragment length polymorphism (RFLP) of the isolates were examined by pulsed field gel electrophoresis. The isolates derived from the first bacteremia showed an identical RFLP pattern in each of the three cats. The isolates derived from the following peaks, however, showed 1-3 of different RFLP patterns in these cats. Furthermore, the isolates showing different RFLP patterns from those of the first bacteremia were also detected at the following bacteremic peaks in all three cats examined. The 16S ribosomal RNA (rRNA) gene type of all isolates was found to be 16S rRNA type I. The emergence of genetically distinct organisms at various peaks of bacteremia may contribute to the establishment of persistent infection in the naturally infected cats.
The authors investigated bacteriologically the prevalence of Bartonella infection among 690 pet cats derived from 10 private animal hospitals in six cities (Sapporo, Hokkaido Prefecture; Sendai, Miyagi Prefecture; Joetsu, Niigata Prefecture; Fujisawa, Kanagawa Prefecutre; Kyoto, Kyoto Prefecture; Sanda, Hyogo Prefecutre) and 4 counties (Mishima, Osaka Prefecture; Hikawa, Shimane Prefecture; Aira, Kagoshima Prefecture; Shimajiri, Okinawa Prefecture) located from the north to the south of Japan. Bartonella species were isolated from 7.2% (50/690) of all the cats examined. No Bartonella species were isolated from the cats in Sapporo or Sendai. The isolation rate varied from 2% in Joetsu and Sanda to 20% in Shimajiri. Bartonella clarridgeiae was isolated from two of 50 cats in Kyoto, three of 50 in Mishima and one of 50 in Shimajiri, but not in cats from the other cities or counties. Though the cats of Joetsu, Fujisawa, Kyoto, Sanda, Aira and Shimajiri were infected with either B. henselae or B. clarridgeiae, one of eight infected cats in Mishima was harboring both Bartonella species. Type I of 16S rRNA gene was the predominant type among the isolates of B. henselae, but only one isolate derived from Shimajiri was found to be of type II. Prevalence of B. clarridgeiae and the 16S rRNA gene type of B. henselae among cats in Japan was demonstrated for the first time in this investigation.
The author investigated 4,853 specimens of wild living small mammals (43 species: Insectivora, Chiroptera, Lagomorpha, Rodentia, Carnivora) from Czechoslovakia for blood parasites. Trypanosomes were found in Talpa europaea, Sorex alpinus, Crocidura suaveolens, Myotis myotis, Apodemus sylvaticus, Apodemus flavicollis, Mus musculus, Rattus norvegicus, Clethrionomys glareolus and Microtus agrestis. Babesia was detected in Myotis emarginatus, Myotis myotis, Clethrionomys glareolus, Microtus arvalis and Microtus agrestis. Grahaemella was found in Talpa europaea, Sorex araneus, Neomys fodiens, Neomys anomalus, Myotis emarginatus, Myotis myotis, Apodemus sylvaticus, Apodemus flavicollis, Apodemus microps, Apodemus agrarius, Mus musculus, Clethrionomys glareolus, Arvicola terrestris, Pitymys subterraneus, Microtus arvalis, Microtus agrestis, and Microtus oeconomus. Spontaneous Bartonella-infection was ascertained in one Microtus arvalis and, in erythrocytes of one Sorex araneus, parasitic organisms very similar to Bartonella were found.
BACKGROUND: Bartonella species are the only known bacterial pathogens causing vasculoproliferative disorders in humans (bacillary angiomatosis [BA]). Cellular and bacterial pathogenetic mechanisms underlying the induction of BA are largely unknown. METHODS AND RESULTS: Activation of hypoxia-inducible factor-1 (HIF-1), the key transcription factor involved in angiogenesis, was detected in Bartonella henselae-infected host cells in vitro by immunofluorescence, Western blotting, electrophoretic mobility shift, and reporter gene assays and by immunohistochemistry in BA tissue lesions in vivo. Gene microarray analysis revealed that a B henselae infection resulted in the activation of genes typical for the cellular response to hypoxia. HIF-1 was essential for B henselae-induced expression of vascular endothelial growth factor as shown by inhibition with the use of HIF-1-specific short-interfering RNA. Moreover, infection with B henselae resulted in increased oxygen consumption, cellular hypoxia, and decreased ATP levels in host cells. Infection with a pilus-negative variant of B henselae did not lead to cellular hypoxia or activation of HIF-1 or vascular endothelial growth factor secretion, suggesting a crucial role of this bacterial surface protein in the angiogenic reprogramming of the host cells. CONCLUSIONS: B henselae induces a proangiogenic host cell response via HIF-1. Our data provide for the first time evidence that HIF-1 may play a role in bacterial infections.
The genus Bartonella includes important human-specific and zoonotic pathogens which cause intraerythrocytic bacteremia in their mammalian reservoir host(s). It is accepted that cellular immunity plays a decisive role in the host's defense against most intracellular bacteria. Bartonella sp. infection in the immunocompetent host typically leads to immunity against homologous challenge. The basis of this immunity, be it cellular or humoral, is unclear. In this study, the course of Bartonella grahamii bacteremia in immunocompetent and immunocompromised mice was compared. In immunocompetent hosts, the bacteremia is transient and induces a strong humoral immune response. In contrast, bacteremia persists in immunocompromised B and T cell-deficient mice. Immune serum transfer beginning with day 6 postinfection to B cell-deficient mice unable to produce Igs converted the persistent bacteremia to a transient course indistinguishable from that of immunocompetent animals. These data demonstrate an essential role for specific Abs in abrogating the intraerythrocytic bacteremia of B. grahamii in mice.
The prevalence of Bartonella infection in a pet cat population from France was found to be 8.1% (8 of 99 cats). The intraerythrocytic location of Bartonella clarridgeiae is shown for the first time, and we show that immunofluorescence detection of the organism in erythrocytes correlates with the number of bacteria in blood.
Bartonella (Rochalimaea) henselae causes a variety of diseases, including bacillary angiomatosis, peliosis hepatis, lymphadenitis, aseptic meningitis with bacteremia, and cat-scratch disease (CSD). Cases of B. henselae-related disease were collected from September 1991 through November 1993. Patients with suspected CSD, unexplained fever and lymphadenitis, or suspected B. henselae infection who were seen in the Infectious Diseases Clinic at Wilford Hall Medical Center (Lackland Air Force Base, TX) underwent physical and laboratory examinations. In addition to three previously described cases, 23 patients with R. henselae-related infection were identified. The patients included 19 immunocompetent individuals presenting with lymphadenitis (11), stellate neuroretinitis (5), Parinaud's oculoglandular syndrome with retinitis (1), chronic fatigue syndrome-like disease (1), and microbiologically proven adenitis without the presence of immunofluorescent antibodies to B. henselae (1) and four patients infected with human immunodeficiency virus type 1 presenting with isolated lymphadenitis (1), diffuse upper-extremity adenitis (1), neuroretinitis (1), and aseptic meningitis (1). A couple with neuroretinitis and their pet cat, a persistently fatigued patient, and a patient with Parinaud's oculoglandular syndrome were shown to have bacteremia. Tissue cultures were positive for B. henselae in three recent cases of adenitis. Twenty-two patients were exposed to cats. This series further demonstrates the similarities between B. henselae-related diseases and CSD and identifies several new syndromes due to B. henselae.
Transmission of Bartonella species from ectoparasites to the mammalian host involves adaptation to thermal and other forms of stress. In order to better understand this process, the heat shock response of Bartonella henselae and Bartonella quintana was studied. Cellular proteins synthesized after shift to higher temperatures were intrinsically labelled with [25S]methionine and analysed by gel electrophoresis and fluorography. The apparent molecular masses of three of the major heat shock proteins produced by the two Bartonella species were virtually identical, migrating at 70, 60 and 10 kDa. A fourth major heat shock protein was larger in B. quintana (20 kDa) than in B. henselae (17 kDa). The maximum heat shock response in B. quintana and B. henselae was observed at 39 degrees C and 42 degrees C, respectively. The groEL genes of both Bartonella species were amplified, sequenced and compared to other known groEL genes. The phylogenetic tree based on the groEL alignment places B. quintana and B. henselae in a monophyletic group with Bartonella bacilliformis. The deduced amino acid sequences of Bartonella GroEL homologues contain signature sequences that are uniquely shared by members of the Gram-negative alpha-purple subdivision of bacteria, which live within eukaryotic cells. Recombinant His6-GroEL fusion proteins were expressed in Escherichia coli to generate specific rabbit antisera. The GroEL antisera were used to confirm the identity of the 60 kDa Bartonella heat shock protein. These studies provide a foundation for evaluating the role of the heat shock response in the pathogenesis of Bartonella infection.
Bartonella henselae uveitis was diagnosed in a 40-year-old woman with underlying HLA-B27 uveitis on the basis of immunodetection and molecular detection of the organism, a Marseilles genogroup and a CAL-1 genotype strain, in the vitreous fluid. This case illustrates that B. henselae should be included in the differential diagnosis of uveitis and the usefulness of immunodetection for rapid and specific diagnosis.
PURPOSE: To report a case of bacillary angiomatosis of the lower eyelid, conjunctiva, and anterior orbit. DESIGN: Interventional case report. METHODS: A 76-year-old immunocompromised male patient developed a firm vascularized nodule in his left lower eyelid and anterior orbit. RESULTS: An excisional biopsy was performed. Histopathologic examination revealed an abnormal vascular proliferation and a mixed inflammatory infiltrate. A Warthin-Starry stain showed numerous bacilli. These findings are characteristic of bacillary angiomatosis. A serologic specimen was positive for antibodies to Bartonella Quintana. CONCLUSION: The lower lid and anterior orbit are rare locations for bacillary angiomatosis. Our case brings to attention the increasing importance of Bartonella infection as a causative agent of ophthalmic diseases.
Among the species that compose the expanding genus Bartonella, thus far only B. henselae and B. quintana have reportedly been isolated from humans in Europe. To evaluate the prevalence of Bartonella infection in Sweden, we conducted a retrospective serological examination of 126 human serum samples. These samples were analyzed for antibodies to B. henselae, B. quintana, and B. elizabethae. Serum samples from 100 blood donors, who spanned the ages of 20 to 60 and had no apparent clinical signs of illness, were also studied as a control group. An immunoglobulin G indirect fluorescence antibody assay revealed 4 and 8.3% Bartonella positivity rates for the blood donor and patient group, respectively, when a cutoff titer of >/=64 was chosen. Among the blood donors, four were seropositive to B. elizabethae; one of these also had concordant positive titer to B. henselae. In the patient group, 14 serum samples were positive against Bartonella spp. These serum specimens represented nine patients. In three of these seropositive patients, paired serum samples displayed a fourfold increase in antibody titer to at least one of the three antigens. These three patients are discussed. In this report we also present a case study of a 60-year-old Swedish male with fatal myocarditis. Postmortem serological analysis revealed a high titer against B. elizabethae. PCR and nucleotide sequencing of the myocardial tissue from this patient, and of liver tissue from one of the other three patients, showed sequences similar to B. quintana. The age, geographical origin, animal contacts, and serological response pattern to the different Bartonella antigens differed among the four patients. This study substantiates the presence of Bartonella spp. in Sweden, documents the seroreactivity to three Bartonella antigens in Swedish patients, and reports the first two cases of B. quintana-like infections in Sweden.
We describe a patient who presented with a massive chest-wall abscess after a severe debilitating illness that lasted 3 months. Steroid therapy, administered for 4 weeks, masked the slow development of an extensive axillary and chest-wall abscess. After multiple negative tests, the patient's prolonged illness was diagnosed as cat-scratch disease (CSD). An indirect fluorescent antibody test revealed that two convalescent serum samples were positive for IgG to Bartonella clarridgeiae, but no other Bartonella species. We also review 12 cases of severe chest and pulmonary disease due to CSD that were reported in the English-language literature. Thoracopulmonary findings associated with CSD, pathogenic mechanisms of bartonella infections, diagnostic criteria, and management of CSD are presented.
Infection with Bartonella, an emerging bacterial pathogen which often affects immunodeficient patients, has been reported in Sweden over the past few years, with a high seroprevalence of B. elizabethae. A high prevalence of antibodies against B. elizabethae has also been found in urban intravenous drug users in the USA. Using immunofluorescence, we retrospectively examined serum samples taken at autopsy from 59 Swedish intravenous drug addicts from the Stockholm area for evidence of antibodies against 6 pathogenic strains of Bartonella. The 59 addicts died following heroin injection during the years 1987-1992 and include 24 individuals (41%) who were additionally HIV-positive. An overall seropositivity rate for Bartonella spp. of 39% (23/59) was found with the following antigenic reactivities: B. elizabethae, 39% (23/59); B. grahamii, 3% (2/59); B. henselae (Houston-1), 14% (8/59); and B. quintana, 3% (2/59). There were no positive reactions for B. henselae (Marseille) or B. vinsonii subsp. vinsonii. The Bartonella-seropositive cases included 11/23 (48%) individuals who were HIV-positive. Subacute to chronic myocarditis was seen in 2/11 microscopically investigated Bartonella-seropositive cases that were HIV-negative and in 1/14 seronegative cases. No cases of endocarditis or other common manifestations of Bartonella infection were found. An overall Bartonella seropositivity of 21% (9/44) was observed in control forensic autopsy samples.
Currently, 19 species are recognized in the genus Bartonella, 7 of which are involved in an increasing variety of human diseases. Development of molecular tools for detection, identification, and subtyping of strains and isolates has promoted research on Bartonella spp. We amplified and sequenced the portion of the ftsZ gene encoding the N-terminal region of the cell division protein for 13 Bartonella species: Bartonella alsatica, B. birtlesii, B. doshiae, B. elizabethae, B. grahami, B. koehlerae, B. schoenbuchensis, B. taylorii, B. tribocorum, Bartonella vinsonii subsp. arupensis, Bartonella vinsonii subsp. berkhoffii, Bartonella vinsonii subsp. vinsonii, and B. bovis Bermond et al.("B. weissii"). Phylogenetically derived trees revealed four statistically supported groups, indicating that sequencing of the ftsZ gene is a useful tool for identifying evolutionary relationships among Bartonella species. Furthermore, we amplified and sequenced the portion of the ftsZ gene encoding the C-terminal region of the protein for 4 B. bacilliformis isolates, 14 B. clarridgeiae isolates, 14 B. quintana isolates, and 30 B. henselae isolates that were obtained from different geographic regions, hosts, and clinical specimens. B. clarridgeiae and B. quintana sequences were highly conserved, while those of the four B. bacilliformis isolates differed from the type strain at 5 positions. Among B. henselae strains isolated from cats and patients, only two genotypes were detected: Houston and Marseille. Among 80 clinical samples we detected Bartonella spp. in 35 (43.75%) and found the assay to be comparable to that of a combined intergenic-spacer-region- and pap31-based PCR assay. Our results show the usefulness of the portion of the ftsZ gene encoding the C-terminal region for diagnosis of Bartonella infections. More samples should be tested to study its usefulness for epidemiological investigations.
In a search for methods for subtyping of Bartonella henselae in clinical samples, we amplified and sequenced a 701-bp region in the 3' end of the ftsZ gene in 15 B. henselae isolates derived from cats and humans in the United States and Europe. The ftsZ sequence variants that were discovered were designated variants Bh ftsZ 1, 2, and 3 and were compared with 16S rRNA genotypes I and II of the same isolates. There was no ftsZ gene variation in the strains of 16S rRNA type I, all of which were Bh ftsZ 1. The type II strains constituted two groups, with nucleotide sequence variation in the ftsZ gene resulting in amino acid substitutions at three positions, one of which was shared by the two groups. One 16S rRNA type II isolate had an ftsZ gene sequence identical to those of the type I strains. Variants Bh ftsZ 1 and 2 were detected in tissue specimens from seven Swedish patients with diagnoses such as chronic multifocal osteomyelitis, cardiomyopathy, and lymphadenopathy. Patients with similar clinical entities displayed either Bh ftsZ variant. The etiological role of B. henselae in these patients was supported by positive Bartonella antibody titers and/or amplification and sequencing of a part of the B. henselae gltA gene. B. henselae ftsZ gene sequence variation may be useful in providing knowledge about the epidemiology of various B. henselae strains in clinical samples, especially when isolation attempts have failed. This report also describes manifestations of atypical Bartonella infections in Sweden.
In spite of the very significant advances made during the 20 th century in the prevention and the treatment of communicable diseases, infections are still today, even in developed countries, a major cause of morbidity and mortality. New infectious diseases have emerged (AIDS, legionellosis, exterotoxigenic E. coli, Ebola fever), others have significantly reemerged (tuberculosis, diphtheria, Bartonella infections) or have seen their geographic distribution widen considerably (dengue, Hantavirus, West Nile Virus, Lyme disease). New and widespread hepatotropic viruses (mainly hepatitis C) have been identified, while the bacterial cause (Helicobacter pylori) of gastric ulcer was demonstrated. The second part of this review will deal with other examples of emerging or reemerging infections and with the problem of the increasing resistance of pathogens to antimicrobial agents. It will analyse the multiple causes of these various phenomena and describe the diverse strategies which should become available for the prevention and/or treatment of these numerous infectious diseases.