Background
Bartonellosis comprises infections caused by pathogens in the genus Bartonella. [1] In 1909, AL Barton described organisms that adhered to RBCs. The name Bartonia, later Bartonella bacilliformis, was used for the only member of the group identified before 1993. Rochalimaea (named for Rocha-Lima), a similar group, were recently combined with Bartonella. Although these organisms were originally thought to be rickettsiae, Bartonella bacteria can be grown on artificial media, unlike rickettsiae.
Almost 20 species belong to the genus Bartonella. [1] Three Bartonella species are currently considered important causes of human disease, but other significant human pathogens in this genus were found to causes disease in humans occasionally. In one study, serum specimens from 114 patients hospitalized with a febrile illness were tested with an indirect immunofluorescence assay (IFA) using rodent and human Bartonella pathogens; five patients had high-titer seroconversion to rodent-associated Bartonella. [2]
B bacilliformis causes Oroya fever and verruga peruana. Bartonella henselae causes cat scratch disease (CSD) and peliosis of the liver (often called bacillary peliosis). Bartonella quintana causes trench fever. [3] Both B henselae and B quintana may cause bacillary angiomatosis, infections in homeless populations, and infections in patients with HIV. [1]
New Bartonella species that may cause human disease include Bartonella vinsonii subspecies berkhoffii, Bartonella clarridgeiae, Bartonella tamiae, Bartonella rochalimae,Bartonella elizabethae, Bartonellakoehlerae, Bartonella grahamii, and Bartonellaalsatica. [1] Candidatus Bartonella mayotimonensis and Candidatus Bartonella melophagi were respectively isolated from the aortic valve of a patient with culture-negative endocarditis and the blood of two patients with symptoms consistent with bartonellosis. [4, 5] Several of these other species are found in animals. Candidatus Bartonella ancashi was isolated from the blood of a patient with verruga peruana in Peru. [6] Numerous other Bartonella species that can potentially cause human disease have been discovered in ticks.
For additional information on emerging and reemerging infectious diseases, see Medscape’s Emerging and Reemerging Infectious Diseases Resource Center.
Pathophysiology
The transmission of Bartonella species occurs by traumatic contact with infected animals or by vectors like cat fleas or other blood-sucking arthropods (eg, sand fly, Phlebotomus for B bacilliformis). [1]
B bacilliformis, which uses a polar flagellum for motility, adheres to and invades RBCs. After entry, the organism replicates in vacuoles. This species also makes an endothelial cell–stimulating factor that causes proliferation of both endothelial cells and blood vessels.
B henselae and B quintana do not bind to intact human erythrocytes in the same way that B bacilliformis does; however, these organisms make a protein binder that adheres to feline RBC membranes, and they penetrate into endothelial cells. Both species also initiate production of an endothelial cell–stimulating factor. Because lysis-centrifugation blood cultures show enhanced isolation of B henselae and B quintana, intracellular forms are most likely present in humans. Erythrocytes may serve as a reservoir for Bartonella species.
B quintana also invades endothelial cells and forms bacterial aggregates that are taken internally by the invasome, a unique phagosomal structure. [7] These proliferate and make intracellular blebs.
Epidemiology
Frequency
United States
Cat scratch disease caused by B henselae infection occurs in approximately 1 per 10,000 persons.
B quintana is found worldwide and causes febrile outbreaks. Poor sanitation and lack of personal hygiene strongly correlate with transmission by the body louse Pediculus humanus. B quintana is emerging as a recognized cause of disease among homeless persons and persons with AIDS. Trench fever syndrome is found among people with alcoholism and those who are homeless. Persons who are indigent in inner-city Seattle were evaluated for antibodies to B quintana. Approximately 20% of these people had antibody titers of 1:64 or greater; in comparison, this titer was found in only 2% of blood donors. [8]
International
B bacilliformis transmission is limited to the Andes Mountains at elevations of 1000-3000 meters because of the habitat of the sand fly Phlebotomus, now called Lutzomyia. Outbreaks of B bacilliformis infection occur only in the Andes. Cases elsewhere in the world are found in travelers.
B henselae is found throughout the world in association with both domestic and feral cats. The cat flea Ctenocephalides felis is an arthropod vector. B henselae and other Bartonella species have been isolated from ticks, but their competence in disease transmission is unclear. [9, 10]
One study from Eastern China done on rabies clinic and blood donors (557 patients) found a seroprevalence of about 20%. Patients bitten by a dog had a higher seroprevalence compared with blood donors (27% vs 14%). [11]
B quintana infection has been reported in 16% of homeless hospitalized patients in France.
Other species, such as B clarridgeiae, may be a cause of asymptomatic infection in cats.
Review of studies from the United States, Japan, and France showed a seasonality in cat scratch disease. In the United States, most cases are diagnosed during the last 6 months of the year, in Japan most of the transmission occurs from September to December with a peak in November, and in France most cases were found between September and April with a peak in December. This is likely related to the weather, reproductive behavior of cats, their contact frequency with humans, and flea activity. [12]
Mortality/Morbidity
Cat scratch disease usually causes self-limited regional adenopathy. Acute hemiplegia has been reported in an 11-year-old boy. [13] Encephalopathy is the most common neurologic complication but is rare.
B henselae is a common cause of culture-negative endocarditis. Valve replacement is required in approximately 80% of cases, but overall prognosis is good, with survival rates in excess of 80%. [14] In a 2003 article in Medicine by Houpikian and Raoult, Bartonellaendocarditis was associated with B quintana in 75% of cases and with B henselae in 25% of cases. They reported a mortality rate of 7% among 99 patients with Bartonella endocarditis. [15]
Trench fever is a self-limited relapsing febrile illness. Affected persons regularly recover, even without treatment. Liver abscesses and spleen abscesses in the absence of endocarditis in an immunocompetent host have been described. [16, 3]
Disseminated forms of bartonellosis develop in patients infected with HIV, solid organ transplants and other immunocompromised patients. [17] Bacillary angiomatosis and culture-negative endocarditis are caused by B henselae and B quintana. Peliosis hepatis is caused by B henselae. Mortality is low but morbidity is caused by direct organ involvement of bacillary angiomatosis; relapses are common, especially with short courses of treatment.
Carrión disease commonly affects the pediatric population in Peru and Ecuador. Mortality and morbidity of the acute phase vary because of superimposed infections and other complications. Mortality rates associated with the eruptive phase, known as Peruvian wart, are extremely low. [18]
Sex
Manifestations of cat scratch disease in pregnant women are the same as in immunocompetent patients. An article by Bilavsky et al reviewed 19 women with the disease. There was no major adverse effect on the pregnancy in all of them except one abortion during the first trimester. Causality to cat scratch disease could not be established. There was no deleterious effects on the newborns or long-term sequelae in patients. [19]
Prognosis
Cat scratch disease rarely results in neurologic sequelae. Adenopathy persists for 6-24 months in 20% of patients. After several months, the lesions of visceral organs calcify or resolve.
Trench fever is a nonlethal and self-limiting disease, although relapses and chronic bacteremic states are well known. [3]
Bartonella endocarditis has caused fatalities and usually requires surgical repair. Of 22 cases reported by Raoult and colleagues in 1996, 19 patients underwent valvular surgery, and 6 patients died. [20]
Immunocompromised patients with bacillary angiomatosis or peliosis hepatis respond well to antibiotics. Relapse may occur.
