Leishmaniasis Health Article

LEISHMANIASIS

Leishmaniasis is caused by protozoan parasites of the genus Leishmania that are spread by the bite of female phlebotomine sand flies of the genus Phlebotomus in the Old World and Lutzomyia in the New World.

Approximately 350 million people in eighty-eight countries are thought to be at risk for leishmania infection. The true number of infected individuals is unknown, as it is not considered a reportable disease in many of the affected countries. The World Health Organization (WHO) estimates that twelve million people are infected and that there are between 1.5 and 2 million new cases each year.

Leishmania infection occurs in a variety of mammalian hosts, including the domestic dog, rodents, and sloths. When a sand fly, a night-biting insect, takes a blood meal from an infected mammal, it will ingest leishmania parasites, called amastigotes, along with the blood. Over seven days leishmania multiply in the flight muscles and develop into infective, flagellated promastigote forms. When the sand fly next takes a blood meal, these promastigotes are injected into a new mammalian host, where they transform back into the amastigote form and begin to divide. Leishmania species are obligate intracellular parasites that infect and replicate in mononuclear phagocytic cells such as macrophages. Infection can also occur via blood transfusion, shared intravenous needles, or, rarely, direct contact with skin lesions. The incubation period in humans is usually from three to eight months, but can be as short as two weeks or as long as several decades.

The spectrum of clinical manifestations caused by leishmania is divided into three broad categories: cutaneous, mucocutaneous, and visceral leishmaniasis. Cutaneous leishmaniasis is found worldwide and results in skin lesions ranging from a single, discrete, self-healing ulcer to diffuse progressive induration. The spectrum of disease is determined by the species of the parasite and the ability of the host to mount a cell-mediated response. A hyper-immune response causes destructive changes such as those seen in mucocutaneous disease, and a hypo-immune response results in visceral and diffuse cutaneous leishmaniasis. In Old World cutaneous leishmaniasis, the usual causative species are L. major, L. tropica, or L. aethiopica. In the Americas, cutaneous lesions are usually the result of infection with L. braziliensis, L. mexicana, L. amazonensis, or L. panamensis.

In mucocutaneous leishmaniasis (also called espundia), the infection causes destruction of mucous membranes of the nose, mouth, and throat. This form of leishmania is found almost exclusively in the Americas and is seen predominantly in a subset of patients infected with L. braziliensis. Diffuse cutaneous leishmaniasisis, caused by L. aethiopica, is characterized by induration of skin without ulceration.

Visceral leishmaniasis, or kala-azar, is the most severe form of infection with parasites disseminated throughout the reticuloendothelial system. Patients experience fevers, night sweats, and weight loss. The spleen and liver become enlarged, sometimes massively. Blood work reveals anemia, leucopenia, thrombocytopenia, and a marked increase in gamma-globulin levels. If untreated, visceral leishmaniasis is virtually always fatal.

It used to be thought that each species of leishmania resulted in a particular clinical syndrome. However, it is now being recognized that there is considerable overlap in the clinical presentation of each species. Most people bitten by leishmania-infected sand flies will never manifest any evidence of the infection. After recovery from leishmaniasis, a person is immune for life from reinfection by that strain.

Conditions that impair cell-mediated immunity can result in more severe, disseminated leishmanial infections. This has been seen in organ transplant recipients and, most importantly, in persons infected with HIV (human immunodeficiency virus), in whom visceral leishmaniasis has become a frequent opportunistic infection in endemic regions.

Diagnosis is made by microscopic identification of the parasite in tissue samples, by growing the organisms in culture, or by polymerase chain reaction (PCR) of tissue. PCR is a test that will identify even trace amounts of leishmanial DNA in tissue. Samples are taken from the edge or base of a skin ulcer in cutaneous disease. Bone marrow or splenic aspirates are the best tissue samples in cases of visceral disease. Testing for serum antibodies against leishmania parasites may be helpful.

Cutaneous lesions often heal spontaneously. Treatment is undertaken when the lesions are in cosmetically disfiguring areas, when the infection is widespread, and for certain leishmania spp. that are less likely to heal (e.g., L. brasiliensis). Pentavalent antimony (sodium stibogluconate, Pentostam), given either systemically or intralesionally, is the drug of choice for cutaneous lesions. Mucocutaneous and visceral leishmaniasis always require intravenous treatment with a pentavalent antimonial. Other effective medications for some species include amphotericin B (HIV-infected individuals) and pentamidine (for L. panamensis).

As there are many animal reservoirs of infection, and as elimination of sand flies is unlikely, control of leishmaniasis depends on avoiding exposure to sand flies. This involves a combination of insect repellent, fine-meshed bed nets, and protective clothing, and avoiding areas known to harbor sand flies.

MARTHA FULFORD

JAY KEYSTONE

(SEE ALSO: Communicable Disease Control; Tropical Infectious Diseases)