Bartonellosis

Overview

The Gram-negative bacterial genus Bartonella currently comprises roughly fifteen different species, which cause Bartonellosis in humans. It is known to be transmitted by a vector, primarily fleas and also animal bites, scratches, or needle sticks. 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. B. henselae or "Cat scratch disease" is reported in approximately twenty thousand cases per year in the United States.

Bartonella henselae bacteria. Photo courtesy of Vulgaris-Medical.

Bartonella are intracellular parasites that generally show preference for red blood cells, macrophages, and endothelial cells. The evidence for ticks as vectors of Bartonella organisms is circumstantial but fairly strong. Laboratory studies have found that Ixodes ticks can be competent vectors of B. henselae in addition to Borrelia, Babesia and Anaplasma organisms (Cotte et al. 2008). Ixodes ricinus ticks have also been shown to be capable of acquiring Bartonella birtiesii infection from an infected mouse and transmitting this infection to an unifected mouse (Reis et al. 2011). However, the ability of Ixodes ticks to actually transmit B. henselae has not been specifically demonstrated.

Signs and Symptoms

Warthin Starry stain showing B. henselae in cardiac valve of a patient with endocarditis. The bacilli appear as black granulations. Photo courtesy of Pierre Houpikian and Didier Raoult, Unit des Rickettsies, Faculte de Medecine de Marseille, Marseille, France.

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, or infections of the liver, spleen, or bones. Some may also develop neurological involvment including encephalopathy, myelitis, and cranial neuritis/renitis. 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). Acute illnesses in healthy individuals will generally resolve on their own. However, recent case reports from a specific research group using PCR and DNA sequencing suggest that various species of Bartonella may lead to a chronic intravascular infection lasting months to years, possibly also causing a range of neuropsychiatric symptoms (Balakrishnan et al. 2016). 

Diagnosis

Diagnosis cannot be made purely on clinical grounds, requiring laboratory confirmation as clinical signs and symptoms may be nonspecific. Serological tests exist for Bartonella infections; most commonly employed are immunofluorescent fluorescent antibody (IFA) assays for both IgM and IgG antibodies. However, false negatives occur. In a study positive titers were found in only 30 percent of patients in whom Bartonella infection was confirmed by PCR and DNA sequencing. Cross reactions may occur with antibodies to Coxiella burnetti, chlamydia, and certain rickettsial infections. Western blot tests appear to have greater specificity.

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. Culture using standard medium is insensitive. Also important to note, animal studies reveal that Bartonella infection is not always pathogenetic, i.e. a high percentage of healthy individuals may test positive serologically but not recall a prior Bartonella-like infection. 

Treatment

Antibiotic treatment is usually not necessary for uncomplicated disease caused by B. henselae infection. It tends to resolve on its own and there is insufficient evidence to support that antibiotics shorten the duration of the disease. However, for complicated Bartonella infection, such as when it infects the central nervous system, there is a general agreement that antibiotic treatment is warrented. The optimal length for this treatment has yet to be determined, but guidelines suggest at least four to six weeks. The use of corticosteroids is not supported (Adelson et al. 2004; Eskow and Rao 2001; Reis et al. 2011; Rolain et al. 2004, Breitschwerdt 2014).