Comprehensive, up-to-date information on HIV/AIDS treatment, prevention, and policy from the University of California San Francisco

Bartonella is a genus of facultative intracellular bacteria including 21 species, only a few of which have been implicated as human pathogens (104Rolain JM, Brouqui P, Koehler JE, et al. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother 2004;48:1921-33., 105Wormser GP. Discovery of new infectious diseases-Bartonella species. N Engl J Med 2007;356:2346-7., 106Slater LN, Welch DF. Bartonella, including cat-scratch disease. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone; 2005.). Of these, Bartonella henselae and Bartonella quintana cause a spectrum of diseases specifically in immunocompromisedvhosts, such as those infected with HIV (107Koehler JE, Quinn FD, Berger TG, et al. Isolation of Rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis. N Engl J Med 1992;327:1625-31., 108Spach DH, Koehler JE. Bartonella-associated infections. Infect Dis Clin North Am 1998;12:137-55.). These diseases include bacillary angiomatosis and bacillary peliosis. Immunocompromised persons also are susceptible to Bartonella-associated bacteremia and dissemination to other organ systems. Complications of Bartonella infection are relatively uncommon in the pediatric HIV-infected population (4Nesheim SR, Kapogiannis BG, Soe MM, et al. Trends in opportunistic infections in the pre- and post-highly active antiretroviral therapy eras among HIV-infected children in the Perinatal AIDS Collaborative Transmission Study, 1986-2004. Pediatrics 2007;120:00 100–9.), although complications in adult immunocompromised hosts also can occur in immunocompromised children with AIDS. Bartonella infections involve an intraerythrocytic phase that appears to provide a protective niche for the bartonellae leading to persistent and often relapsing infection, particularly in immunocompromised persons (104Rolain JM, Brouqui P, Koehler JE, et al. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother 2004;48:1921-33.). A feature of infections with the genus Bartonella is the ability of the bacteria to cause either acute or chronic infection with either vascular proliferative or suppurative manifestations, depending on the immune status of the patient (104Rolain JM, Brouqui P, Koehler JE, et al. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother 2004;48:1921-33.).

In the general population, B. henselae typically is associated with cat-scratch disease. Most cases of cat-scratch disease occur in patients aged < 20 years (109American Academy of Pediatrics. Cat-scratch disease. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red book: 2006 report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.). A study examining the epidemiology of cat-scratch disease in the United States estimated that 437 pediatric hospitalizations associated with cat-scratch disease occurred among children aged <18 years during 2000, giving a national hospitalization rate of 0.6 per 100,000 children aged <18 years and 0.86 per 100,000 children aged <5 years (110Reynolds MG, Holman RC, Curns AT, et al. Epidemiology of catscratch disease hospitalizations among children in the United States. Pediatr Infect Dis J 2005;24:700-4.). Data are lacking on the epidemiology of infection with Bartonella spp. in HIV-infected children.

The household cat is a major vector for transmission of B. henselae to humans. Transmission of B. henselae from cat to cat appears to be facilitated by cat fleas, but data do not suggest that B. henselae is efficiently transmitted from cats to humans by fleas (111Chomel BB, Kasten RW, Floyd-Hawkins K, et al. Experimental transmission of Bartonella henselae by the cat flea. J Clin Microbiol 1996;34:1952-6.). More than 90% of patients with cat-scratch disease have a history of recent contact with cats, often kittens (109American Academy of Pediatrics. Cat-scratch disease. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red book: 2006 report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.), and a cat scratch or bite (112Zangwill KM, Hamilton DH, Perkins BA, et al. Cat scratch disease in Connecticut. Epidemiology, risk factors, and evaluation of a new diagnostic test. N Engl J Med 1993;329:8-13.) has been implicated as the principal mode of cat-to-human transmission. Compared with adult cats, kittens (<1 year of age) are more likely to have B. henselae bacteremia and to have high levels of bacteremia, and more likely to scratch. Despite the evidence against fleaborne cat-to-human transmission, researchers acknowledge the potential for such transmission and the need for further investigation (111Chomel BB, Kasten RW, Floyd-Hawkins K, et al. Experimental transmission of Bartonella henselae by the cat flea. J Clin Microbiol 1996;34:1952-6.). Elimination of flea infestation is important in preventing transmission because contamination of cat claws or of a scratch wound with infected flea feces is a possible mechanism for infecting humans (111Chomel BB, Kasten RW, Floyd-Hawkins K, et al. Experimental transmission of Bartonella henselae by the cat flea. J Clin Microbiol 1996;34:1952-6.). Infection occurs more often during the autumn and winter (109American Academy of Pediatrics. Cat-scratch disease. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red book: 2006 report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006., 112Zangwill KM, Hamilton DH, Perkins BA, et al. Cat scratch disease in Connecticut. Epidemiology, risk factors, and evaluation of a new diagnostic test. N Engl J Med 1993;329:8-13., 113Carithers HA. Cat-scratch disease. An overview based on a study of 1,200 patients. Am J Dis Child 1985;139:1124-33., 114Jackson LA, Perkins BA, Wenger JD. Cat scratch disease in the United States: an analysis of three national databases. Am J Public Health 1993;83:1707-11.).

B. quintana is globally distributed. The vector for B. quintana is the human body louse. Outbreaks of trench fever have been associated with poor sanitation and personal hygiene, which may predispose individuals to the human body louse (106Slater LN, Welch DF. Bartonella, including cat-scratch disease. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone; 2005.).

The clinical manifestations of B. henselae infection are largely determined by the host's immune response. Localized disease (e.g., focal suppurative regional lymphadenopathy such as in typical cat-scratch disease) appears most common in patients with an intact immune system; systemic infection appears more commonly in immunocompromised patients, although systemic disease has also been reported among otherwise normal children (115Massei F, Gori L, Macchia P, et al. The expanded spectrum of bartonellosis in children. Infect Dis Clin North Am 2005;19:691-711., 116Resto-Ruiz S, Burgess A, Anderson BE. The role of the host immune response in pathogenesis of Bartonella henselae. DNA Cell Biol 2003;22:431-40.). Clinical manifestations of B. henselae and B. quintana specific to HIV-infected and other immunocompromised patients include bacillary angiomatosis and bacillary peliosis.

Bacillary angiomatosis is a rare disorder that occurs almost entirely in severely immunocompromised hosts (117Myers SA, Prose NS, Garcia JA, et al. Bacillary angiomatosis in a child undergoing chemotherapy. J Pediatr 1992;121:574-8., 118Tappero JW, Koehler JE, Berger TG, et al. Bacillary angiomatosis and bacillary splenitis in immunocompetent adults. Ann Intern Med 1993;118:363-5.). It is a vascular proliferative disease that has been reported most often in HIV-infected adults who have severe immunosuppression with a median CD4 count of <50 cells/mm³ in a majority of case studies of HIV-infected adults (108Spach DH, Koehler JE. Bartonella-associated infections. Infect Dis Clin North Am 1998;12:137-55., 119Koehler JE, Glaser CA, Tappero JW. Rochalimaea henselae infection. A new zoonosis with the domestic cat as reservoir. JAMA 1994;271:531-5.). The disease is characterized by cutaneous and subcutaneous angiomatous papules; the lesions of this disease can be confused with KS. Lesions are often papular and red with smooth or eroded surfaces; they are vascular and bleed if traumatized. Nodules may be observed in the subcutaneous tissue and can erode through the skin. Less frequently, it may involve organs other than the skin.

Bacillary peliosis is characterized by angiomatous masses in visceral organs; it mainly occurs in severely immunocompromised patients with HIV infection. It is a vasoproliferative condition that contains blood-filled cystic spaces. The organ most commonly affected is the liver (i.e., peliosis hepatis), but the disease also can involve bone marrow, lymph nodes, lungs, and CNS (120Koehler JE. Bartonellosis. In: Dolin R, Masur H, Saag MS, eds. AIDS therapy. 2nd ed. New York, NY: Churchill Livingstone; 2003: 491-7., 121Koehler JE, Sanchez MA, Tye S, et al. Prevalence of Bartonella infection among human immunodeficiency virus-infected patients with fever. Clin Infect Dis 2003;27:559-66. Vol. 58 / RR-11 Recommendations and Reports 103, 122Regnery RL, Childs JE, Koehler JE. Infections associated with Bartonella species in persons infected with human immunodeficiency virus. Clin Infect Dis 1995;21(Suppl 1):S94-8.).

Immunocompromised patients infected with B. henselae or B. quintana can also present with persisting or relapsing fever with bacteremia, and these bacteria should be considered in the differential diagnosis of fever of unknown origin in immunocompromised children with late-stage AIDS (123Gerber MA. Bartonella species (cat-scratch disease, bacillary angiomatosis, bacillary peliosis). In: Long SS, Pickering LK, Prober CG, eds. Principles and practice of pediatric infectious diseases. 2nd ed. Orlando, FL: Churchill Livingstone; 2003.). Dissemination to almost all organ systems has been described, including bone (e.g., osteomyelitis), heart (e.g., subacute endocarditis), and CNS (e.g., encephalopathy, seizures, neuroretinitis, transverse myelitis) (124Bass JW, Vincent J, Person DA. The expanding spectrum of Bartonella/i> infections: II. Cat-scratch disease. Pediatr Infect Dis J 1997;16:163-79.). Most patients with visceral involvement have nonspecific systemic symptoms, including fever, chills, night sweats, anorexia and weight loss, abdominal pain, nausea, vomiting, and diarrhea.

Bartonella spp. are small, gram-negative bacilli. In cases of bacillary angiomatosis and bacillary peliosis, diagnosis is usually made through biopsy with a characteristic histologic picture: clusters of organisms can be demonstrated with Warthin-Starry silver stain of affected tissue. The organisms can be isolated with difficulty from blood or tissue culture using enriched agar; they have been isolated more successfully from specimens from patients with bacillary angiomatosis and peliosis than from patients with typical cat-scratch disease (107Koehler JE, Quinn FD, Berger TG, et al. Isolation of Rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis. N Engl J Med 1992;327:1625-31.). B. henselae, similar to other Bartonella spp., is a fastidious, slow-growing organism; in most cases, colonies first appear after 9-40 days; therefore incubation for up to 6 weeks is recommended (124Bass JW, Vincent J, Person DA. The expanding spectrum of Bartonella/i> infections: II. Cat-scratch disease. Pediatr Infect Dis J 1997;16:163-79.).

Serologic tests such as indirect fluorescent antibody (IFA) test and enzyme immunoassay (EIA) are also available. The IFA is available at many commercial laboratories and state public health laboratories and through CDC (109American Academy of Pediatrics. Cat-scratch disease. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red book: 2006 report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.). Unfortunately, cross-reactivity among Bartonella spp. and other bacteria, such as Chlamydia psittaci (115Massei F, Gori L, Macchia P, et al. The expanded spectrum of bartonellosis in children. Infect Dis Clin North Am 2005;19:691-711.), is common, and serologic tests do not accurately distinguish among them. Additionally, the sensitivity of the currently available IFA is lower in immunocompromised than immune-competent patients; 25% of HIV-infected Bartonella culture-positive patients never develop anti-Bartonella (121Koehler JE, Sanchez MA, Tye S, et al. Prevalence of Bartonella infection among human immunodeficiency virus-infected patients with fever. Clin Infect Dis 2003;27:559-66. Vol. 58 / RR-11 Recommendations and Reports 103).

The most sensitive method of diagnosis is with PCR testing of clinical specimens; different procedures have been developed that can discriminate among different Bartonella spp. (125Sander A, Penno S. Semiquantitative species-specific detection of Bartonella henselae and Bartonella quintana by PCR-enzyme immunoassay. J Clin Microbiol 1999;37:3097-101., 126Matar GM, Koehler JE, Malcolm G, et al. Identification of Bartonella species directly in clinical specimens by PCR-restriction fragment length polymorphism analysis of a 16S rRNA gene fragment. J Clin Microbiol 1999;37:4045-7.). PCR assays are available in some commercial and research laboratories.

No evidence exists that supports the use of chemoprophylaxis for bartonellosis, such as after a cat scratch. (CIII)

Not applicable.

Response to treatment can be dramatic in immunocompromised patients. Cutaneous bacillary angiomatosis skin lesions usually improve and resolve after a month of treatment. Bacillary peliosis responds more slowly than cutaneous angiomatosis, but hepatic lesions should improve after several months of therapy.

Some immunocompromised patients develop a potentially life-threatening Jarisch-Herxheimer-like reaction within hours after institution of antibiotic therapy, and immunocompromised patients with severe respiratory or cardiovascular compromise should be monitored carefully after institution of therapy (104Rolain JM, Brouqui P, Koehler JE, et al. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother 2004;48:1921-33., 107Koehler JE, Quinn FD, Berger TG, et al. Isolation of Rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis. N Engl J Med 1992;327:1625-31.).

No cases of Bartonella-associated IRIS have been reported.

In immunocompromised patients with relapse, retreatment should be continued for 4-6 months; repeated relapses should be treated indefinitely (AIII) (128Bass JW, Freitas BC, Freitas AD, et al. Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease. Pediatr Infect Dis J 1998;17:447-52.). Among patients whose Bartonella infections fail to respond to initial treatment, one or more of the second-line regimens should be considered (AIII).

Relapses in bone and skin have been reported and are more common when antibiotics are administered for a shorter time (<3 months), especially in severely immunocompromised patients. For an immunocompromised HIV-infected adult experiencing relapse, long-term suppression of infection with doxycycline or a macrolide is recommended as long as the CD4 cell count is <200 cells/mm³ (AIII). Although no data exist for HIV-infected children, it seems reasonable that similar recommendations should be followed (AIII).

No specific data are available regarding the discontinuation of secondary prophylaxis.