A wide spectrum of diseases results from infection with the four Bartonella bacterial species that infect humans. Although some of these diseases have been known since the early 1900s, they are increasing in incidence and expanding their range in human hosts. The most recently described illnesses associated with Bartonella infection were identified in 1987 and 1993. They may lead to serious illness in immunocompromised persons, especially those who are HIV-positive. The AIDS pandemic has contributed to the impact of these bacteria on the human race. Bartonella infection results in bartonellosis, cat-scratch disease, trench fever, bacillary angiomatosis, bacillary peliosis hepatis, and endocarditis.

Bartonellosis is a potentially severe disease resulting from infection with a small bacterium from the Bartonella genus that is transmitted by sand flies. These insect vectors have a very restricted range in the Andes mountain region; accordingly, bartonellosis is confined to a small area. The disease consists of two stages that were originally believed to be distinct illnesses. The first stage is characterized by fever and hemolytic anemia, which may be fatal. The second stage is a mild cutaneous infection. Cat-scratch disease results from infection by another Bartonella species. It is widespread and affects over 22,000 persons annually, costing over $12 million in the United States alone. It is a mild infection that causes enlarged lymph nodes that exude pus. Trench fever is also caused by a Bartonella bacterium. It is found among individuals living in crowded conditions with poor hygiene. This illness is characterized by fever, headache, and soreness and is usually not fatal but may be more serious among people with AIDS, the homeless, and alcoholics. Bacillary angiomatosis may develop following Bartonella infection of immunocompromised individuals, especially those who are HIV-positive.

Bartonellosis (also known as Carrión’s disease) was so designated in honor of Daniel Carrión, a Peruvian medical student in 1885 who investigated the initial stages of a cutaneous disease known as verruga peruana (Peruvian warts) by injecting himself with material taken from skin infected with Bartonella bacilliformis. Unfortunately, his experiment proved deadly, for he developed Oroya fever, a severe and often lethal hemolytic infection that was not then known to be the first stage of infection with Bartonella. Under appropriate conditions, epidemics of bartonellosis may occur within its narrow geographical confines. The building of the Central Railroad from Lima to Oroya in 1871 occasioned such an outbreak. Some 10,000 Chileans and Chinese with no prior immunity to Bartonella infection were brought into an endemic area of the Peruvian Andes. Approximately 7,000 workers were infected, and the mortality rate approached 40%. Another outbreak occurred in 1938 when B. bacilliformis spread into an adjacent region of Columbia where the population’s immunity to the bacterium was lower; 4,000 persons died in that epidemic. Archaeological evidence of verruga peruana suggests that it has afflicted persons in the Andes of Peru since pre-Columbian days.

The disease that was later designated cat-scratch disease was first recognized in the United States in the 1950 by Lee Foshay while he was studying tularemia. At approximately the same time, Robert Debré linked the occurrence of suppurative (pus-exuding) adenitis in children with multiple scratches from cats. He then studied ill persons who produced positive skin tests (Type IV hypersensitivity reaction) to Foshay’s antigen, leading to the clinical description of the illness. The causative agent was first visualized in lymph node samples in 1983 and identified in 1993.

Trench fever caused epidemics involving tens of thousands of troops and prisoners of war in Europe during World War I and again during World War II as a result of crowded, unsanitary living conditions that favor human infestation by lice, the disease vectors. Though not fatal, trench fever nevertheless led to prolonged periods of disability resulting from relapsing episodes of high fever and severe back and shin pain. Decreased use of trench warfare and improving hygienic conditions greatly reduced disease incidence in later wars. During the 1990s, a form of trench fever appeared among alcoholic, homeless individuals in Seattle, Washington, and also in France.

Bacillary angiomatosis was discovered in 1983, and in 1987 was found to be an opportunistic infection in individuals with AIDS. The lesions closely resembled those occurring during verruga peruana and those seen in Kaposi’s sarcoma (a skin cancer often found in AIDS patients; described in Chapter Seventeen). Kaposi’s sarcoma is caused by a viral infection, whereas the bacillary angiomatosis lesions contain bacilli and respond to antibiotics. The two Bartonella species that induce this condition were isolated from bacillary angiomatosis lesions beginning in 1992. One of these, Bartonella henselae, is also linked to cat-scratch disease; the link between the two diseases was suggested by the finding that individuals who developed bacillary angiomatosis had often done so following contact with cats. When serum samples were analyzed by the CDC, antibodies to B. henselae were found in patients with both conditions. Moreover, when the cats of several persons with bacillary angiomatosis were tested, the animals were found to be bacteremic for B. henselae.

Bartonellosis (Carrión’s Disease)

Bartonellosis is restricted to humans and other primates and shows no preference based on age, gender, or race. It manifests initially as a severe acute febrile illness (characterized by fever) with hemolytic anemia that is often fatal (Oroya fever). This stage usually persists for two to three months but may last as long as four months. Some persons may develop flulike prodromal symptoms, such as fever, muscle and joint aches (myalgia and arthralgia), and bone pain. These may be the only evidence of disease in persons with low-level infection. People with a higher level of infection rapidly progress to a toxic state characterized by high fever, chills, headache, and delirium. This is followed by hemolytic anemia resulting from destruction of large numbers of erythrocytes infected by the bacteria. This form of anemia (low number of erythrocytes in the blood) is due to the destruction of red blood cells rather than their loss by hemorrhage or decreased production. The hemolytic anemia induced by Bartonella bacilliformis is extremely rapid, second only to malaria in the rate of drop in hematocrit. Blood smears of infected persons contain large numbers of reticulocytes (immature red blood cells) that are rapidly produced by the bone marrow in an attempt to replace the mature erythrocytes that have been lost. The reticulocytes are polychromatic (stained blue-pink) and are slightly larger than mature cells. Erythrocyte inclusions, such as Howell-Jolly bodies (round remnants of the nucleus), Cabot rings, and basophilic stippling (punctuate, bluish inclusions composed of aggregated ribosomes) may also be present. The anemia leads to the development of jaundice, pallor (pale color), and apathy. Thrombocytopenia (low numbers of platelets) may occur. Nontender lymphadenopathy (swelling of the lymph nodes) and hepatomegaly (enlargement of the liver) may occur, as well as petechiae in some persons. Those who present meningeal symptoms or coma often die. Untreated, the mortality rate for Oroya fever averages 40% (range from 10% to 90%), and many of the fatal cases may be associated with malaria or secondary infection with Salmonella, Mycobacterium, or protozoa species due to immunosuppression following this stage of infection. If treated with antibiotics, mortality drops to 8%.