Leishmaniasis

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Leishmaniasis

Leishmaniasis is a disease caused by parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sandfly, including flies in the genus Lutzomyia in the New World and Phlebotomus in the Old World. The disease was named in 1901 for the Scottish pathologist William Boog Leishman.This disease is also known as Leichmaniosis, Leishmaniose, leishmaniose, and formerly, Orient Boils, kala azar, black fever, sandfly disease, Dum-Dum fever or espundia.

Most forms of the disease are transmittable only from animals (zoonosis), but some can be spread between humans. Human infection is caused by about 21 of 30 species that infect mammals. These include the L. donovani complex with three species (L. donovani, L. infantum, and L. chagasi); the L. mexicana complex with 3 main species (L. mexicana, L. amazonensis, and L. venezuelensis); L. tropica; L. major; L. aethiopica; and the subgenus Viannia with four main species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana). The different species are morphologically indistinguishable, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies.

Geography and epidemiology

Leishmaniasis can be transmitted in many tropical and sub-tropical countries, and is found in parts of about 88 countries. Approximately 350 million people live in these areas. The settings in which leishmaniasis is found range from rainforests in Central and South America to deserts in West Asia. More than 90 percent of the world's cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil.

Leishmaniasis is also found in Mexico, Central America, and South America—from northern Argentina to southern Texas (not in Uruguay, Chile, or Canada), southern Europe (leishmaniasis is not common in travelers to southern Europe), Asia (not Southeast Asia), the Middle East, and Africa (particularly East and North Africa, with some cases elsewhere). The disease is not found in Australia or Oceania.

Leishmaniasis is present in Iraq and was contracted by a number of the troops involved in the 2003 invasion of that country and the subsequent occupation. The soldiers nicknamed the disease the Baghdad boil. It has been reported by Agence France-Presse that more than 650 U.S. soldiers may have experienced the disease between the start of the invasion in March 2003 and late 2004. ^* ^*

During 2004, it is calculated that some 3,400 troops from the Colombian army, operating in the jungles near the south of the country (in particular around the Meta and Guaviare departments), were infected with Leishmaniasis. Apparently, a contributing factor was that many of the affected soldiers did not use the officially provided insect repellent, because of its allegedly disturbing odor. It is estimated that nearly 13,000 cases of the disease were recorded in all of Colombia throughout 2004, and about 360 new instances of the disease among soldiers had been reported in February 2005. ^* ^* ^*

In September 2005 the disease was contracted by at least four Dutch marines who were stationed in Mazar-e-Sharif, Afghanistan and subsequently repatriated for treatment.

Life cycle

Leishmaniasis is transmitted by the bite of female phlebotomine sandflies. The sandflies inject the infective stage, metacyclic promastigotes, during blood meals (1). Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages (2) and transform into amastigotes (3). Amastigotes multiply in infected cells and affect different tissues, depending in part on which Leishmania species is involved (4). These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. Sandflies become infected during blood meals on an infected host when they ingest macrophages infected with amastigotes (5,6). In the sandfly's midgut, the parasites differentiate into promastigotes (7), which multiply, differentiate into metacyclic promastigotes and migrate to the proboscis (8).

Signs and symptoms

The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person affected is bitten by sand flies. Other consequences, which can become manifest anywhere from a few months to years after infection, include fever, damage to the spleen and liver, and anaemia.

In the medical field, leishmaniasis is one of the famous causes of a markedly enlarged spleen, which may become larger even than the liver. There are four main forms of leishmaniasis:

Visceral leishmaniasis - the most serious form and potentially fatal if untreated.
Cutaneous leishmaniasis - the most common form which causes numerous sores on the body, which heal within a few months leaving unpleasant looking scars.
Diffuse cutaneous leishmaniasis - this form produces widespread skin lesions which resemble leprosy and is particularly difficult to treat.
Mucocutaneous leishmaniasis - commences with skin ulcers which spread causing tissue damage to (particularly) nose and mouth

Treatment

There are two common therapies containing antimony, meglumine antimoniate (Glucantim®) and sodium stibogluconate (Pentostam®). It is not completely understood how these drugs act against the parasite; they may disrupt its energy production or trypanothione metabolism.

Several potential vaccines are being developed, under pressure from the World Health Organization, but as of 2006 none is available. The team at the Laboratory for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zurich are trying to design a carbohydrate-based vaccine ^*. The genome of the parasite has been sequenced (Ivens, et al., 2005), possibly allowing for identification of proteins that are used by the pathogen but not by humans; these proteins are potential targets for drug treatments.

Miltefosine (Impavido®), is a new drug for visceral (and probably also cutaneous) leishmaniasis. The cure rate of miltefosine in phase III clinical trials is 95%; but the results of trials outside of India have been disappointing. Miltefosine has received approval by the Indian and German regulatory authorities (2003) and is the first orally administered breakthrough therapy for visceral leismaniasis.(More, et al, 2003) There are problems with toxicity (gastrointestinal and renal) as well as the rapid development of resistance. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it an attractive alternative.

The Institute for OneWorld Health has developed paromomycin, results with which led to its approval as an orphan drug.

References

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