On Line Learning Center

On Line Learning Center

Chapters 22 and 28 LEISHMANIASIS

Leishmaniasis (pronounced leesh-mah-NYE-a-sis) is a protozoan disease transmitted by sandflies that occurs in 88 countries around the world, including parts of the Middle East and Northern Africa, and areas of the Western Hemisphere from Texas to Argentina. Many cases have occurred in United States civilians and military personnel involved with war in Iraq. There aretwo main forms of the disease, cutaneous (involving the skin), also known by names such as oriental sore, Jericho boil or Dehli boil, and visceral (involving the internal organs), also known as kala-azar or Dum-Dum fever.

Symptoms

After an incubation period of 2 to 8 weeks (occasionally months) a small red papule develops at the site of a sandfly bite. The papule enlarges to become a nodule, which then ulcerates to produce an enlarging painless sore with a raised edge. Secondary infection can cause the sores to become painful. In most cases the lesions heal without treatment in a matter of months, or years in a few cases. Healing leaves a depressed scar. There can be multiple lesions if the victim encounters a swarm of sandflies. Especially in parts of Central and South America, the disease can spread to the mucous membranes of the nose and mouth, causing disfigurement. In visceral leishmaniasis, the incubation is usually longer, typically several months, the main symptoms being weight loss and fever. The spleen becomes massively enlarged. Without treatment, visceral leishmaniasis is often fatal.

Causative Agent

The disease can be caused by at least 20 different species of Leishmania, a tiny protozoan whose life cycle involves sand flies and an animal such as a dog or rodent. In the sandfly, the organism exists as a promastigote form, elongated with pointed ends, and having a single anterior flagellum. It multiplies in the insect intestine, and after about 10 days becomes infectious for the mammalian host. Introduced into host tissues by the sandfly bite, Leishmania sp. develops into a tiny (2.5-7 micrometer diameter), non-motile, obligately intracellular form called an amastigote. This form has a characteristic microscopic appearance (“dot and dash”), each organism showing a tiny nucleus and a short rod-shaped mitochondrium called a kinetoplast. The amastigote is the form that causes disease in humans, and is the form infectious for sand flies to complete the life cycle. Some Leishmania species are prone to cause visceral leishmaniasis, and others, cutaneous or mucosal disease.

Pathogenesis

Introduced into human tissue, the promastigotes activate complement, are opsonized by C3 and taken up by macrophages. They resist digestion in the phagolysosme, multiply as amastigotes, and are released to infect other cells upon death of the host cell. In most cases of cutaneous leishmaniasis, lymphocytes eventually congregate, interferon is released from TH cells, macrophages are activated and the organisms are killed. By contrast, in visceral leishmaniasis, the organisms appear to suppress the T cell response and spread throughout the body.

Epidemiology

There are over one million new cases of cutaneous, and 500,000 of visceral leishmaniasis each year, with a population of 350 million people at risk for the disease. Most cases of cutaneous leishmaniasis cases occur in Brazil, Peru, Algeria, Afghanistan, Iran, Saudi Arabia and Syria, whereas most cases of visceral leishmaniasis occur in India, Bangladesh, Nepal, Sudan and Brazil. There has been an increased incidence of the disease in a number of regions such as in Brazil, Syria and Afghanistan, probably because of new human settlements in sandfly-infested areas. Sandflies breed in rodent burrows, dung and other decaying organic material. They tend to bite between dusk and dawn.

Prevention and Treatment

No vaccines or preventive medications are available so far. The best prevention is to avoid sandfly bites by using protective clothing, insecticides, and insect repellants such as DEET. Bed nets impregnated with permethrin give good protection, but ordinary screening my not keep out sandflies because of their small size (about 2 mm). Outdoor activities between dusk and dawn should be avoided when possible.

Selected cases of cutaneous leishmaniasis can be followed carefully without treatment as long as the infected individuals are healthy and have small stable lesions. For others, currently, pentavalent antimony compounds such as stibugluconate (Pentostam) represent the treatment of choice. They are given by injection over a three or four week period for cutaneous leishmaniasis, much longer for visceral disease. Anti-fungal medications such as amphotericin B and ketoconazole, and the aminoglycoside, paromomycin are also used in some cases. An oral medicine, miltefosine, has been approved for use in India.