The Gram-negative bacterial genus Bartonella currently comprises roughly two dozen identified species, about half of which are known to infect humans. However, the clinical implications of many of these human infections are poorly understood, and it is possible that some of the species are non-pathogenic, at least in immunocompetent people. Until around 15 years ago, only three human diseases were recognized as clearly attributable to Bartonella organisms: cat scratch disease (CSD, also sometimes referred to as cat scratch fever), caused by B. henselae; Carrion's disease, caused by B. bacilliformus (and limited to South America); and trench fever, caused by B. quintana. More recently, however, additional pathogenic Bartonella species have been discovered. The full clinical spectrum of all Bartonella infections remains to be elucidated, but includes conditions as diverse as hepatitis, endocarditis, encephalopathy and meningoencephalitis.
Bartonella are intracellular parasites that generally show preference for erythrocytes and endothelial cells in humans. The organisms are found in a wide range of both wild and domestic mammals, including cattle, rodents, dogs and cats. The various Bartonella species appear to be adapted to specific hosts. Cats are the main reservoir for B. henselae, which causes approximately 20,000 reported cases of cat scratch disease per year in the United States. (As with many reportable diseases, however, the true incidence of CSD is underreported and generally believed to be considerably higher.) Bartonella are also found in numerous arthropods, including fleas (a known vector of CSD), biting flies, lice and ticks.
The evidence for ticks as vectors of Bartonella organisms is circumstantial but fairly strong. Recent studies in both the United States and Europe have found that Ixodes ticks harbor B. henselae in addition to Borrelia, Babesia and Anaplasma organisms; in fact, a 2004 PCR analysis of I. Scapularis ticks in New Jersey discovered that a higher percentage of ticks were infected with B. henselae than any of these other pathogens. In addition, B. henselae has been detected in the spinal fluid of patients co-infected with Borrelia burgdorferi, the agent of Lyme disease. However, the ability of Ixodes ticks to actually transmit B. henselae has not been specifically demonstrated.
Signs and Symptoms
Cat scratch disease is caused by the transmission of B. henselae to humans by a flea bite or the scratch of a cat. Cat bites may be implicated as well. A week or so after exposure, a papule forms at the transmission site and then usually develops into a pustule. In immunocompetent people, the systemic symptoms of cat scratch disease are usually limited to regional adenopathy, though it can also cause fever and, more rarely, eye disorders, hepatosplenic infection, osteomyelitis, and encephalopathy. Immunocompromised patients, such as those with HIV, can develop more serious manifestations such as endocarditis and bacillary angiomatosis (tumor-like masses caused by the pathological proliferation of blood vessels).
Given the uncertainties surrounding the presentation and incidence of tick-transmitted bartonellosis, diagnosis cannot be made purely on clinical grounds. Thus, laboratory confirmation of infection assumes increased importance. Serological tests exist for Bartonella infections; most commonly employed are immunofluorescent fluorescent antibody (IFA) assays for both IgM and IgG antibodies. However, cross reactions may occur with antibodies to Q fever, Chlamydia, and certain rickettsial infections. Western blot tests appear to have greater specificity.
False negative serological results can occur in immunocompromised patients.
Bartonella organisms can sometimes be visualized by immunohistochemical staining, although this method of diagnosis is usually reserved for patients with angiomatosis. The DNA of various Bartonella species can also be amplified by PCR in blood, spinal fluid and tissue; given the cross-reactivity of the Bartonella antibody tests, PCR may be the most reliable and useful test for Bartonella infection.
Culture of Bartonella organisms is possible, but the bacteria are generally slow-growing in the laboratory. Thus, this method of diagnosis is of limited usefulness, and is employed mostly in patients with serious and otherwise unexplained disease presentations, such as endocarditis. Studies are currently underway to determine the optimal culture media and methods for Bartonella.
Bartonella is sensitive to many different antibiotics in vitro, but the in vivo performance of these antibiotics in humans and domestic pets does not correlate well with in vitro laboratory studies. Most likely, this stems from two factors: 1) almost all antibiotics are bacteriostatic against Bartonella, rather than bactericidal; and 2) the pathogen is often sequestered in erythrocytes.
Cat scratch disease usually resolves even without treatment, and there is little evidence that antibiotics shorten the duration of the disease. Thus, there is disagreement over whether or not antibiotic treatment is even necessary for uncomplicated CSD. Tick-transmitted Bartonella may be a more serious matter, however, since the possibility of co-infection is always present. In addition, there is general agreement that the presence of B. henselae in cerebrospinal fluid, whatever its origin, warrants treatment.
CSD is most often treated with tetracyclines, macrolides or aminoglycosides. For CNS infection, antibiotics that cross the blood brain barrier are necessary, and combination therapy is usually recommended, as it may have more efficacy. Among the recommended regimens are azithromycin or doxycycline in combination with rifampin, clarithromycin or a fluoroquinolone. The optimal length of therapy has yet to be determined, but most guidelines suggest that treatment should last for at least 4-6 weeks.
No data exist to support the use of corticosteroids in CNS Bartonella infections.
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