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Bartonella species are emerging pathogens. Renewed interest in this group of bacteria has been highlighted by the recent description of new species, which are pathogenic for humans (Bartonella elizabethae and Bartonella clarridgeae), and their association with an increasing number of clinical manifestations, the more prevalent being cat scratch disease, bacillary angiomatosis, and culture-negative endocarditis.
Bartonella are vector-borne, fastidious Gram-negative bacteria causing persistent bacteremia in their reservoir hosts. Felids represent a major reservoir for several Bartonella species. Domestic cats are the main reservoir of B. henselae, the agent of cat-scratch disease. Prevalence of infection is highest in warm and humid climates that are optimal for the survival of cat fleas, as fleas are essential for the transmission of the infection. Flea feces are the likely infectious substrate. Prevalence of B. henselae genotypes among cat populations varies worldwide. Genotype Houston I is more prevalent in the Far East and genotype Marseille is dominant in western Europe, Australia, and the western United States. Cats are usually asymptomatic, but uveitis, endocarditis, neurological signs, fever, necrotic lesions at the inoculation site, lymphadenopathy, and reproductive disorders have been reported in naturally or experimentally infected cats. Domestic cats are also the reservoir of B. clarridgeiae and co-infection has been demonstrated. B. koehlerae has been isolated from domestic cats, and was identified in cat fleas and associated with a human endocarditis case. B. bovis was isolated from a few cats in the United States and B. quintana DNA was recently identified in a cat tooth. Bartonella spp. have also been isolated from free-ranging and captive wild felids from North America and Africa. Whereas, B. henselae was identified in African lions and a cheetah, some strains specific to these wild cats have also been identified, leading to the concept of a B. henselae group including various subspecies, as previously described for B. vinsonii.
Recent observations have begun to support a role for Bartonella spp. as animal as well as human pathogens. Bartonella spp. are vector-transmitted, blood-borne, intracellular, gram-negative bacteria that can induce prolonged infection in the host. Persistent infections in domestic and wild animals result in a substantial reservoir of Bartonella organisms in nature that can serve as a source for inadvertent human infection. The prevalence of bacteremia can range from 50 to 95% in selected rodent, cat, deer, and cattle populations. Dogs infected with Bartonella spp. can develop lameness, endocarditis, granulomatous lymphadenitis, and peliosis hepatis, lesions that have also been reported in association with human infection. Understanding the role of Bartonella spp. as pathogens in cats and other wild or domestic animals awaits the results of additional studies. Considering the extensive animal reservoirs and the large number of insects that have been implicated in the transmission of Bartonella spp., both animal and human exposure to these organisms may be more substantial than is currently believed.
We evaluated the usefulness of a serological diagnostic kit (Bartonella IFA IgG, IgM; MRL Diagnostics) for Bartonella henselae infection. Of the 110 healthy individuals, 107 (97.3%) were with titers being less than 1:64 for IgG antibody to B. henselae, 2 were with titers being 1:64 and 1 with 1:128, IgM antibody to B. henselae was negative in all individuals. Serological diagnosis of cat scratch disease (CSD) using indirect fluorescence antibody (IFA) methods (in-house and diagnostic kit) was made in either elevated titers of IgM (> or = 1:20) or IgG (> or = 1:256) antibodies, or a four-fold rise in IgG titer between acute and convalescent sera. Of the 18 individuals with serological diagnosis of CSD by in-house IFA method in 26 CSD clinical diagnosed patients, 15 (83%) were compatible with the results of the diagnostic kit, whereas 3 (17%) were not compatible. Of the 8 without serological diagnosis, 1 (13%) was serologically diagnosed as CSD, and the others were negative. Overall, the serological diagnosis was made in 16 of 26 (62%). The specificity and sensitivity of this kit were 100% and 62%, respectively. The cross-reaction between B. henselae and Bartonella quintana was observed in sera from controls and patients. Our results show that the diagnostic kit as well as in-house method is an useful tool for the serological diagnosis of cat scratch disease.
OBJECTIVE: To correlate the presence of different Bartonella species in the blood of a stray cat population trapped on a French military base with specific antibodies and species detected in cat fleas. METHODS: The prevalence of Bartonella bacteremia was investigated in 61 cats by plating frozen whole blood on blood agar plates. Identification of isolates and detection of Bartonella DNA from cat flea batches from ten cats was achieved by PCR amplification and sequencing. Antibody detection was performed by microimmunofluorescence. RESULTS: We obtained 38 isolates of Bartonella from blood. Sixteen were identified as B. clarridgeiae, 15 as B. henselae genotype/serotype Houston 1 (type I), and seven as B. henselae genotype/serotype Marseille (type II). B. henselae was detected in five fleas, and B. clarridgeiae in one flea. Sixty-one per cent of the cats had detectable antibodies against at least one species or serotype. Sixteen cats had antibodies against only one antigen. For each species, the distribution of bacteremia among the cats could not be correlated with either the distribution of infected fleas or the distribution of specific antibodies. CONCLUSIONS: The lack of correlation between Bartonella DNA detection within fleas, serological results, and results of blood culture is probably due to a lack of natural heterologous protection between species or serotypes. Cats suffer bacteremia with three Bartonella species and should therefore be considered the reservoirs of at least three human pathogens.
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Erythrocyte parasitism, or hemotrophy, is not a common strategy for bacteria. However, Bartonella species are elegantly adapted to parasitize a variety of cell types including red blood cells. Bartonella bacilliformis, a useful model organism for the genus, has been used to study virulence determinants involved in colonization, attachment and invasion of host cells.
Bartonella henselae can cause cat scratch disease and bacillary angiomatosis, a multisystem disorder seen primarily in patients with the acquired immunodeficiency syndrome. Both of these diseases are associated with neurologic complications, particularly encephalopathy. B. henselae may also cause bacteremia and endocarditis, and has been associated with aseptic meningitis and with dementia in patients also infected with the human immunodeficiency virus. Recent advances in identification of this difficult-to-culture organism will lead to recognition of more neurologic complications.
Bartonella henselae is the main agent of cat scratch disease in humans and domestic cats are the main reservoir of this bacterium. We conducted a serosurvey to investigate the role of American wild felids as a potential reservoir of Bartonella species. A total of 479 samples (439 serum samples and 40 Nobuto strips) collected between 1984 and 1999 from pumas (Felis concolor) and 91 samples (58 serum samples and 33 Nobuto strips) collected from bobcats (Lynx rufus) in North America, Central America and South America were screened for B. henselae antibodies. The overall prevalence of B. henselae antibodies was respectively 19.4% in pumas and 23.1% in bobcats, with regional variations. In the USA, pumas from the southwestern states were more likely to be seropositive for B. henselae (prevalence ratio (PR) = 2.82, 95% confidence interval (CI) = 1.55, 5.11) than pumas from the Northwest and Mountain states. Similarly, adults were more likely to be B. henselae seropositive than juveniles and kittens (PR = 1.77, 95% CI = 1.07, 2.93). Adult pumas were more likely to have higher B. henselae antibody titers than juveniles and kittens (p = 0.026). B. henselae antibody prevalence was 22.4% (19/85) in bobcats from the USA and 33.3% (2/6) in the Mexican bobcats. In the USA, antibody prevalence varied depending on the geographical origin of the bobcats. In California, the highest prevalence was in bobcats from the coastal range (37.5%). These results suggest a potential role of wild felids in the epidemiological cycle of Bartonella henselae or closely related Bartonella species.
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Bartonella henselae is responsible for various disease syndromes that loosely correlate with the immune status of the host. In the immunocompromised individual, B. henselae-induced angiogenesis, or bacillary angiomatosis, is characterized by vascular proliferative lesions similar to those in Kaposi's sarcoma. We hypothesize that B. henselae-mediated interaction with immune cells, namely, macrophages, induces potential angiogenic growth factors and cytokines which contribute in a paracrine manner to the proliferation of endothelial cells. Vascular endothelial growth factor (VEGF), a direct inducer of angiogenesis, and interleukin-1beta (IL-1beta), a potentiator of VEGF, were detected within 12 and 6 h, respectively, in supernatants from phorbol 12-myristate 13-acetate-differentiated human THP-1 macrophages exposed to live B. henselae. Pretreatment of macrophages with cytochalasin D, a phagocytosis inhibitor, yielded comparable results, suggesting that bacterium-cell attachment is sufficient for VEGF and IL-1beta induction. IL-8, an angiogenic cytokine with chemotactic properties, was induced in human microvascular endothelial cells (HMEC-1) within 6 h of infection, whereas no IL-8 induction was observed in infected THP-1 cells. In addition, conditioned medium from infected macrophages induced the proliferation of HMEC-1, thus demonstrating angiogenic potential. These data suggest that Bartonella modulation of host or target cell cytokines and growth factors, rather than a direct role of the bacterium as an endothelial cell mitogen, is the predominant mechanism responsible for angiogenesis. B. henselae induction of VEGF, IL-1beta, and IL-8 outlines a broader potential paracrine angiogenic loop whereby macrophages play the predominant role as the effector cell and endothelial cells are the final target cell, resulting in their proliferation.
Bartonella (formerly Rochalimaea) quintana is the etiological agent of trench fever, a disease extensively reported during the World Wars. Recent molecular biology approaches have allowed dramatic extension of the spectrum of Bartonella infections. B. quintana is now also recognized as an etiological agent of fever and bacteremia, endocarditis, bacillary angiomatosis, and chronic lymphadenopathy. Human immunodeficiency virus-infected patients and/or homeless people are the most vulnerable to infection. Poverty and louse infestation were the main epidemiological factors associated with B. quintana infections during wartime. Although poverty and chronic alcoholism have been associated with modern cases of trench fever and bacteremia due to B. quintana in Europe and the United States, vectors for B. quintana have not been clearly identified and B. quintana has not been isolated from modern-day lice. Microscopic bacillary angiomatosis lesions are characterized by tumor-like capillary lobules, with proliferating endothelial cells. In vitro experiments have shown that B. quintana survives within endothelial cells and stimulates cell proliferation. These observations, together with the finding that lesions may regress when antibiotic therapy is administered, strongly suggest that B. quintana itself stimulates angiogenesis. Bartonella infections are characterized by a high frequency of relapses after brief courses of antibiotic therapy. It is to be noted that in vitro, although Bartonella species are highly susceptible to antibiotics, only the aminoglycosides have proved to be bactericidal. However, the most effective antibiotic regimen for Bartonella infections remains to be established.
Within the last 15 years, several bacteria of the genus Bartonella were recognized as zoonotic agents in humans and isolated from various mammalian reservoirs. Based on either isolation of the bacterium or PCR testing, eight Bartonella species or subspecies have been recognized as zoonotic agents, including B. henselae, B. elizabethae, B. grahamii, B. vinsonii subsp. arupensis, B. vinsonii subsp. berkhoffii, B. grahamii, B. washoensis and more recently B. koehlerae. The present manuscript reviews the factors associated with the emergence of these zoonotic pathogens, including better diagnostic tools and methods to identify these fastidious bacteria, host immunosuppression (caused by infectious agents, cancer, aging or induced by immunosuppressive drugs), the interaction of co-infection by several infectious agents that may enhanced the pathogenecity of these bacteria, increased outdoor activity leading to exposure to wildlife reservoirs or vectors, poverty and low income associated with infestation by various ectoparasites, such as body lice and finally the dispersal of Bartonellae around the world. Furthermore, a description of the main epidemiological and clinical features of zoonotic Bartonellae is given. Finally, the main means for diagnosis, treatment and prevention of these diseases are presented.
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OBJECTIVE: To establish polymerase chain reaction (PCR) technique for the detection of specific genes related to species of genus Bartonella, and for diagnosing clinically suspected cat-scratch disease (CSD) case complicated with pneumonia on both lungs. The appearance of Bartonella infectious diseases calls for genus and species detection and tools for identification in order to make clinical diagnosis and carry on epidemiological studies. METHODS: One pair of primer TIle.455p-TAla.885n was designed based on the fact that tRNA(Ile)-tRNA(Ala) intergenic spacer region in 16S-23S rRNA intergenic spacer (ITS) of genus Bartonella were high variable sequences flanked by completely conserved tRNA-encoding genes. 16S-23S rRNA was longer than that which had been described in other bacteria. Two published pairs of primers were used to directly detect the specific gene fragments of Bartonella species DNA extracts from human blood, followed by PCR product Sequencing and nucleotide base sequence analysis. RESULTS: Amplification products of the three pairs of primers had the same predicted size of those in Bartonella spp. According to the different length of electrophoresis bank, the sample was identified as a species of genus Bartonella other than the positive control. Sequence analysis showed that the nuleotide sequence from the PCR product of primer TIle.455p-TAla.885n was identical to the Bartonella isolated from Yunnan in China. CONCLUSIONS: PCR-based assay provided a simple and rapid means to detect pathogenic Bartonella species in humans and mammalian hosts as well as in arthropod vecters. This study suggested that this pathogenic Bartonella species existed in patients in northern and southern parts of China.