Bartonella Infection: Treatment and Drug Resistance

Silpak Biswas; Jean-Marc Rolain


Future Microbiol. 2010;5(11):1719-1731. 

In This Article

Human Bartonellosis

In humans, different Bartonella species are responsible for a wide range of symptoms.[1,2,4,16] The laboratory diagnosis of Bartonella infection is not described here, as it is beyond the scope of this article.

Bartonella bacilliformis is the etiological agent of Carrion's disease, which has been recognized since pre-Columbian times in populations living in the Andes. However, the suspected link between the acute form (Oroya fever) and the chronic form (verruga peruana) was only confirmed in 1885 when Carrion, a medical student, died of Oroya fever after inoculating himself with material from a wart.[1,2,4,50,51]B. bacilliformis is a sandfly-transmitted Bartonella species.[52,53] Oroya fever, is characterized by severe, life-threatening hemolytic anemia. Verruga peruana results in the appearance of unique vascular proliferative lesions of the skin.[1,4] In some patients, Oroya fever occurs when the bacteria enter erythrocytes, and hemolysis occurs due to erythrophagocytosis by histiocytes and macrophages.[4] Prior to the development of antibiotics, Oroya fever-associated mortality was reported to be as high as 40%.[54–56] The majority of the infected individuals are children or young adults.[54] The second stage of infection (verruga peruana) leads to the eruption of nodular angioproliferative cutaneous lesions weeks to months after infection.[57] The disease has a very limited geographical distribution, with most cases reported in arid areas that are 500–3000 m above sea level in the Peruvian Andes between southwestern Colombia and central Peru.[4,54,58]

Bartonella quintana, which is transmitted by P. humanus, is the etiological agent of trench fever.[4,59] Trench fever is characterized by the infection of human red blood cells. The disease was initially characterized in infected troops during World War I.[59] Trench fever can range from an asymptomatic infection to a severe illness.[59] B. quintana has also been linked to a chronic bacteremia in homeless individuals in both the USA and Europe and patients with chronic alcoholism.[60–62]

Bartonella henselae isolates from the humans and animals they had come in contact with have been shown to be related, thereby implicating the animals as the source of the human infection.[4,63,64] Different B. henselae types may induce various pathological features in infected individuals, and certain types have been proposed to be more likely associated with human disease than others.[63,65,66] Cats are the primary reservoir and vector for transmission of B. henselae.[14,18,67]B. henselae is the primary etiologic agent of CSD, even if Bartonella alsatica has been recently reported in a patient with lymphadenopathy.[68] CSD has been reported worldwide and seems to be the most common Bartonella infection in people today.[4,67,69,70] CSD presents as a gradual regional lymph node enlargement, usually accompanied by a distal scratch and/or red-brown skin papule. While the enlarged lymph node is often painful and tender, the infection is usually self-limiting, with the frequent development of extensive regional lymph node enlargement that typically lasts 2–3 months and occasionally longer.[67,71,72] Usually, CSD is not severe in healthy persons but complications may occur especially in immunocompromised patients including osteomyelitis, neuroretinitis or encephalopathy.

Bartonella henselae is also known to cause PH in humans. PH is defined as a vascular proliferation of the sinusoidal hepatic capillaries, resulting in blood-filled spaces in the liver. This disease was first described in patients with TB and advanced cancer, and is associated with the use of drugs such as anabolic steroids. B. henselae is now recognized as an infectious cause of PH in HIV-infected patients.[2,73,74]

Among all Bartonella species, B. quintana, followed by B. henselae, most frequently causes endocarditis. The probability of B. quintana-mediated endocarditis is higher (~9.8%) in North Africa, which is probably due to differences in living conditions or higher temperature, and the probability of endocarditis is lower in European countries especially in the northern European countries (0.5% in Sweden, 1% in both UK and Germany, and 3% in France).[75,76]B. quintana endocarditis is most often observed in homeless people with chronic alcoholism and exposure to body lice. B. henselae endocarditis occurs in patients with known valvulopathy and contact with cats.[77]B. vinsonii subsp. berkhoffii, which was originally isolated from a dog with endocarditis, was subsequently isolated from a human endocarditis patient.[12,78]B. quintana, B. henselae, B. elizabethae, B. vinsonii subsp. berkhoffii, B. vinsonii subsp. arupensis, B. koehlerae and B. alsatica have been associated with endocarditis in patients with existing valvulopathies.[77–86] Finally, Lin et al. described a new Bartonella species, 'candidatus Bartonella mayotimonensis', which was identified from the aortic valve of a patient with infectious endocarditis in the USA.[87] Other Bartonella species, such as Bartonella tamiae were isolated from human patients with febrile illness from Thailand[88] and B. rochalimae was isolated from a woman with bacteremia, fever and splenomegaly.[89]