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).
The clinical manifestations of tick-transmitted bartonellosis are essentially unknown. They may resemble cat scratch disease, take other clinical forms, or be benign. It is also unclear if Bartonella co-infection with other tick-transmitted organisms can result in more serious illness; some of the few reported cases of concurrent B. burgdorferi and B. henselae infection in the medical literature appear to suggest this could be the case. Thus, it may be prudent to consider the possibility of Bartonella co-infection in cases of poorly resolving or apparent relapsing Lyme disease.
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 polymerase chain reaction (PCR) in blood, spinal fluid, and tissue; given the cross-reactivity of the Bartonellaantibody 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.