Information on the following diseases can be found in the Related Disorders section of this report:

• Cat-Scratch Disease
• Trench Fever
• Associated Infectious Diseases (General

In most affected individuals, bartonellosis is characterized by two well-defined stages. The first stage, known as Oroya fever, usually develops about three to 12 weeks following exposure to the B. bacilliformis bacterium. This period between exposure to the bacterium and the onset of symptoms is known as the "incubation period."

Oroya fever may be characterized by a sudden (acute) onset of high fever, profuse sweating (diaphoresis), severe headache, chills, weakness, and paleness of the skin (pallor). In addition, in many cases, mental changes may develop, including confusion and disorientation (delirium) or a state of unconsciousness and unresponsiveness (coma). Such abnormalities occur in association with rapidly developing, severe hemolytic anemia or markedly reduced levels of red blood cells (erythrocytes) due to bacterial invasion and destruction of these cells. (For more, see "Causes" below.)

Additional associated findings may include abdominal pain; severe muscle aches (myalgia) and joint pain (arthralgia); enlarged lymph nodes (lymphadenopathy); inflammation of the brain and its protective membranes (meningoencephalitis); episodes of uncontrolled electrical activity in the brain (seizures); and/or other abnormalities. In addition, some affected individuals may develop chest pain due to insufficient oxygen supply to heart muscle (angina); abnormally low levels of platelets essential in blood clotting (thrombocytopenia); labored breathing (dyspnea); impaired digestive and liver function; and/or other abnormalities. Such findings are thought to result from severe hemolytic anemia and the abnormal formation of blood clots within small blood vessels (microvascular thrombosis), leading to an insufficient supply of oxygen to tissues (ischemia), impaired functioning of organs, and potentially life-threatening complications.

In addition, in some cases, the acute stage of bartonellosis may be complicated by, and increased in severity due to, the presence of other infections, such as salmonellosis or malaria (i.e., intercurrent infections). (For more on salmonellosis, see below. For further information on malaria, please choose "malaria" as your search term in the Rare Disease Database.)

In its mildest form, bartonellosis may not be noted until the development of characteristic skin (cutaneous) lesions (see below). In such instances, bartonellosis may have a gradual (insidious) onset and initially be characterized by a febrile illness. Febrile refers to elevated body temperature or fever. The febrile illness may be present for less than a week and remain unrecognized as a manifestation of bartonellosis.

In those affected by Oroya fever, the period of recovery (convalescence) is typically associated with gradually reduced fever and disappearance of the bacterium as seen on microscopic examination of small blood specimens (blood smears). (For more, see "Standard Therapies: Diagnosis" below). However, some affected individuals may temporarily have an increased susceptibility to certain, subsequent infections, such as with Salmonella bacteria (salmonellosis). (Infection with certain strains of Salmonella bacteria may cause high fever, abdominal pain, bloody diarrhea, nausea, vomiting, rash, and/or other symptoms and findings.) In addition, in some cases, without appropriate antibacterial therapy, B. bacilliformis bacterium may remain present in the blood (bacteremia) for months to years without apparent symptoms (asymptomatic), potentially resulting in continued spread of the disease to others (i.e., as a "reservoir" or an ongoing source of infectious disease). Reports suggest that relapses or recurrences of Oroya fever are rare. According to experts, recurrence of fever after initial improvement of symptoms is considered suggestive of a secondary infection.

Following resolution of the acute stage of infection (Oroya fever), untreated individuals typically develop distinctive skin lesions within weeks or months. This second stage of bartonellosis is known as verruga peruana. As noted above, verruga peruana may develop in individuals who have or have not had previous symptoms of Oroya fever.

Verruga peruana is typically characterized by reddish, purple skin lesions occurring in a series of crops that may develop in one area as they heal in another and recur in certain sites. The lesions may initially be minute, eventually become nodular and range from about 0.2 to 4 centimeters in diameter, and potentially bleed, ulcerate, or become pus-containing blisters (pustules). Although they typically erupt on exposed skin, such as on the face, arms, and legs, they may also sometimes develop within mucous membranes and internal organs. In untreated individuals, verruga peruana may persist over a period of months to years.
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Bartonellosis is caused by a parasitic bacterium known as Bartonella bacilliformis (B. bacilliformis). The bacterium is primarily carried and transmitted by the night-biting sandfly (vector) known as Lutzomyia (formerly Phlebotomus). A vector is any organism that may transmit a particular infectious agent, such as a bacterium or virus.

The B. bacilliformis bacterium is "injected" into the bloodstream via the bite of the sandfly, enabling the bacterium to attach to the surface of red blood cells (erythrocytes). Bacterial invasion and reproduction leads to abnormal fragility and premature destruction of many erythrocytes in the bloodstream (hemolysis). This results in abnormally decreased red blood cell levels and reduced concentrations of hemoglobin, the oxygen-carrying component of the blood (hemolytic anemia). In addition, the bacterium may invade cells lining small blood vessels (capillary endothelial cells), potentially leading to blockage of normal blood flow (vascular occlusion). As mentioned above, severe hemolytic anemia and the abnormal formation of blood clots within small blood vessels may potentially lead to life-threatening complications without prompt appropriate treatment.

With developing immunity, levels of the bacterium markedly decrease in the blood. However, as mentioned above (see "Symptoms), without appropriate antibiotic therapy, asymptomatic low-grade bacteremia may persist for months or years in some cases.

Following the symptom-free (latent) period, most untreated individuals develop the distinctive skin lesions characteristic of verruga peruana. The nodular lesions consist of newly formed blood vessels (neovascular proliferation) infiltrated by certain white blood cells that play an important role in fighting and destroying invading microorganisms (e.g., lymphocytes, macrophages).
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Bartonellosis is a rare infectious disease that is found only at certain altitudes (e.g., elevations of 1 to 3 kilometers) in the Andes mountain regions of the South American countries, Columbia, Peru, and Ecuador. Oroya fever was first recognized in the nineteenth century as the cause of acute fever and hemolytic anemia in railroad workers in Peru. Reports suggest that the chronic skin (cutaneous) stage was described earlier.

The common bacterial cause of Oroya fever and verruga peruana was confirmed by a Peruvian medical student, Daniel Carrion, in 1885, when he succumbed to acute hemolytic anemia after injecting himself with blood from a verruga peruana skin lesion. The spectrum of B. bacilliformis infection (i.e., Oroya fever and verruga peruana) has since been named "Carrion's Disease" (eponym). (An eponym is a name for a disease derived from the name of a physician, investigator, or other individual who first identified the condition in question.)

The bacterium responsible for bartonellosis was originally described in 1909 (Barton AL). Although the term bartonellosis is usually used to refer to infectious disease caused by the B. bacilliformis bacterium, the "Bartonella" bacterial family includes several other bacteria, some of which may cause other human infectious diseases. These include cat-scratch disease and trench fever. (For further information, please see the "Related Disorders" section below.)
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Certain features of the following disorders may be similar to those of bartonellosis:

Cat-scratch disease is an infection occurring at the site of a cat scratch or bite caused by the bacterium Bartonella henselae. This microorganism, which belongs to the same bacterial family as the agent responsible for bartonellosis, is primarily carried and transmitted by cats, particularly domestic kittens or wild (feral) cats. Within about three to 10 days following a cat scratch or bite, an affected individual may develop a reddish, crusted blister. Lymph nodes in the region may begin to swell, become firm and tender, and, in some cases, eventually drain pus through the skin. Additional symptoms may include fever, a general feeling of ill health (malaise), fatigue, headache, sore throat, and/or lack of appetite (anorexia). In some rare cases, affected individuals may also develop other symptoms and findings. In addition, a severe form of the disease has been reported in individuals with deficient immune responses (immunocompromised), most often those with acquired immune deficiency syndrome (AIDS). (For further information, please choose "cat scratch" as your search term in the Rare Disease Database.)

Trench fever is a rare infectious disease caused by Bartonella quintana, a bacterium belonging to the same family as the agents responsible for bartonellosis and cat-scratch disease. B. quintana is carried and transmitted by lice. Trench fever was first recognized in military personnel during World Wars I and II, and is primarily found in eastern Europe, Mexico, North Africa, and certain parts of Asia. Within a few days up to five weeks following exposure to the bacterium, affected individuals may develop sudden fever, chills, weakness, headache, dizziness, leg and back pain, and/or other abnormalities. Initial fever may last about four to five days and may recur one or several times, with each episode lasting about five days. Additional findings may include a temporary skin rash consisting of flat (macular) or raised (papular) lesions, enlargement of the spleen (splenomegaly), and/or enlargement of the liver (hepatomegaly). A severe form of B. quintana infection has also been reported in immunocompromised individuals, such as in association with AIDS.

Various infectious diseases may cause symptoms and findings similar to those associated with the acute and/or chronic stage of bartonellosis (i.e., Oroya fever and/or verruga peruana). (For further information, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Diagnosis
Bartonellosis may be diagnosed based upon thorough clinical evaluation; detection of characteristic symptoms and physical findings; a complete patient history, including information concerning recent travel to regions where bartonellosis is known to occur; and specialized laboratory tests. For example, during the acute stage, the bacterium may easily be seen within red blood cells on blood smears. With this diagnostic test, a drop of blood is smeared on a slide, stained with special dyes to make blood cells more visible, and examined under a microscope. During the chronic, skin (cutaneous) stage, the bacterium may be isolated from skin lesions. Blood smears are typically negative during this second stage. However, the bacterium may be cultured from the blood and grown under controlled conditions in the laboratory, enabling identification of the causative microorganism. In some cases, other laboratory studies may be used to help diagnose bartonellosis.

Treatment
The treatment of choice for bartonellosis is administration of the antibiotic medication chloramphenicol (due to frequent, intercurrent infection with Salmonella). In some cases, appropriate alternatives may include doxycycline, other tetracyclines, or ampicillin. Antibiotic therapy may rapidly treat acute febrile illness associated with bartonellosis and speed healing of chronic skin lesions. Blood transfusions may be required to treat severe anemia. Other treatment for this disorder is symptomatic and supportive.

Bartonellosis may be prevented by avoiding the sandflies that transmit the bacterium to humans. Insect repellents, bed nets, and long-acting insecticides can help prevent exposure to these insects.
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Research on tropical diseases is ongoing. The development of vaccines is also being investigated. For more information, contact the World Health Organization (WHO) listed in the Resources section below.

Mandell GL, et al., eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, PA: Churchill Livingstone; 2000:2444-56.

Beers MH, et al., eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:1233-37.

Wyngaarden JB, et al., eds. Cecil Textbook of Medicine. 19th ed. Philadelphia, PA: W.B. Saunders Company; 1992:1729, 1732.

JOURNAL ARTICLES
Amano Y, et al. Bartonellosis in Ecuador: serosurvey and current status of cutaneous verrucuous disease. Am J Trop Med Hyg. 1997;57:174-79.

Arrese Estrada J, et al. Dendrocytes in verruga peruana and bacillary angiomatosis. Dermatology. 1992;184:22-25.

Garcia U, et al. Bartonellosis. An immunodepressive disease and the life of Daniel Alcides Carrion. Am J Clin Pathol. 1991;95:S58-66.

Gray GC, et al. An epidemic of Oroya fever in the Peruvian Andes. Am J Trop Med Hyg. 1990;42:215-21.