Members of the genus Bartonella (formerly Rochalimaea) were virtually unknown to modern-day clinicians and microbiologists until they were associated with opportunistic infections in AIDS patients about 6 years ago. Since that time, Bartonella species have been associated with cat scratch disease, bacillary angiomatosis, and a variety of other disease syndromes. Clinical presentation of infection with Bartonella ranges from a relatively mild lymphadenopathy with few other symptoms, seen in cat scratch disease, to life-threatening systemic disease in the immunocompromised patient. In some individuals, infection manifests as lesions that exhibit proliferation of endothelial cells and neovascularization, a pathogenic process unique to this genus of bacteria. As the spectrum of disease attributed to Bartonella is further defined, the need for reliable laboratory methods to diagnose infections caused by these unique organisms also increases. A brief summary of the clinical presentations associated with Bartonella infections is presented, and the current status of laboratory diagnosis and identification of these organisms is reviewed.

Bartonella spp. as emerging human pathogens.

Members of the genus Bartonella are facultative intracellular bacteria belonging to the alpha 2 subgroup of the class Proteobacteria and are phylogenetically closely related to Brucella species (15, 73). Until 1993, only three diseases were known to be caused by Bartonella species: Carrion's disease (Bartonella bacilliformis), trench fever (Bartonella quintana), and cat scratch disease (CSD; Bartonella henselae). The genus now comprises B. bacilliformis, species of the former genera Rochalimea and Grahamella (14, 18), and additional, recently described species (Table ​(Table1).1). In mammals, each Bartonella species is highly adapted to its reservoir host; the bacteria can persist in the bloodstream of the host as the result of intraerythrocytic parasitism (49). Intraerythrocytic localization of B. henselae has been demonstrated in cat erythrocytes (88), and B. bacilliformis bacilli have been observed within erythrocytes during the acute phase of Carrion's disease (Oroya fever) (88). Bartonellae also have a tropism for endothelial cells, and intracellular B. henselae can be identified in endothelial cells infected in vitro (28), although intraendothelial cell bacilli have not been identified in vivo.



TABLE 1.

Epidemiological and clinical data for species of the genus Bartonella



Bartonella species cause long-recognized diseases, such as Carrion's disease, trench fever, and CSD, and more recently recognized diseases, such as bacillary angiomatosis (BA), peliosis hepatis (PH), chronic bacteremia, endocarditis, chronic lymphadenopathy, and neurological disorders (Table ​(Table2)2) (73). A remarkable feature of the genus Bartonella is the ability of a single species to cause either acute or chronic infection and either vascular proliferative or suppurative manifestations.



TABLE 2.

Human diseases caused by Bartonella spp.



The pathological response to infection with Bartonella spp. varies substantially with the status of the host immune system. Indeed, infection with the same Bartonella species (e.g., B. henselae) can result in a focal suppurative reaction (CSD in immunocompetent patients), a multifocal angioproliferative response (BA in immunocompromised patients), endovascular multiplication of the bacteria (endocarditis), or an exaggerated inflammatory response without evidence of bacteria in patient tissues (meningoencephalitis) (86).

Some of the diseases due to Bartonella species can resolve spontaneously without treatment, but in other cases, the disease is fatal without antibiotic treatment and/or surgery. The clinical situations are so different that a single treatment for all Bartonella-related diseases has not been identified, and the approach to treatment must be adapted to each species and clinical situation (49). Moreover, the database of clinical studies with a standard case definition, culture confirmation, rigidly defined disease outcomes, and patients with similar host defenses is very limited. Thus, case reports with a very limited number of subjects often serve to dictate therapy. The objective of this minireview is to summarize the antibiotic treatment recommendations for the different infections caused by Bartonella species. We have compiled the in vitro antibiotic susceptibility data and our knowledge of the in vivo efficacies of antibiotics for each clinical manifestation, and finally, we have summarized and ranked our treatment recommendations according to the Infectious Diseases Society of America (IDSA) practice guidelines (see Table ​Table5)5) (51).



TABLE 5.

System for ranking recommendations in clinical guidelines recommended by IDSAa

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Recommendations for Treatment of Human Infections Caused by Bartonella Species

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.

Bartonella Infection in Animals: Carriership, Reservoir Potential, Pathogenicity, and Zoonotic Potential for Human Infection

Among the many mammals infected with Bartonella spp., pets represent a large reservoir for human infection because most Bartonella spp. infecting them are zoonotic. Cats are the main reservoir for Bartonella henselae, B. clarridgeiae, and B. koehlerae. Dogs can be infected with B. vinsonii subsp. berkhoffii, B. henselae, B. clarridgeiae, B. washoensis, B. elizabethae, and B. quintana. The role of dogs as an important reservoir of Bartonella spp. is less clear than for cats because domestic dogs are more likely to be accidental hosts, at least in nontropical regions. Nevertheless, dogs are excellent sentinels for human infections because a similar disease spectrum develops in dogs. Transmission of B. henselae by cat fleas is better understood, although new potential vectors (ticks and biting flies) have been identified. We review current knowledge on the etiologic agents, clinical features, and epidemiologic characteristics of these emerging zoonoses.

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Bartonella Spp. in Pets and Effect on Human Health

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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Factors associated with the rapid emergence of zoonotic Bartonella infections.

Bartonella henselae is an emerging bacterial pathogen, causing cat scratch disease and bacillary angiomatosis. Cats bacteremic with B. henselae constitute a large reservoir from which humans become infected. Prevention of human infection depends on elucidation of the natural history and means of feline infection. We studied 47 cattery cats in a private home for 12 months to determine the longitudinal prevalence of B. henselae bacteremia, the prevalence of B. henselae in the fleas infesting these cats, and whether B. henselae is transmitted experimentally to cats via fleas. Vector-mediated transmission of B.henselae isolates was evaluated by removing fleas from the naturally bacteremic, flea-infested cattery cats and transferring these fleas to specific-pathogen-free (SPF) kittens housed in a controlled, arthropod-free University Animal Facility. B. henselae bacteremia was detected in 89% of the 47 naturally infected cattery cats. A total of 132 fleas were removed from cats whose blood was simultaneously cultured during different seasons and were tested individually for the presence of B. henselae DNA by PCR. B. henselae DNA was detected in 34% of 132 fleas, with seasonal variation, but without an association between the presence or the level of bacteremia in the corresponding cat. Cat fleas removed from bacteremic cattery cats transmitted B. henselae to five SPF kittens in two separate experiments; however, control SPF kittens housed with highly bacteremic kittens in the absence of fleas did not become infected. These data demonstrate that the cat flea readily transmits B. henselae to cats. Control of feline infestation with this arthropod vector may provide an important strategy for the prevention of infection of both humans and cats.

B Chi

Papers

Experimental transmission of Bartonella henselae by the cat flea.