LEISHMANIASIS

Leishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species ofsand fly . Elsewhere in the world, the genus Phlebotomus is considered the vector of leishmaniasis.

Most forms of the disease are transmissible only from animals (zoonosis), but some can be spread between humans. Human infection is caused by about 21 of 30 species that infect mammals, the different species are morphologically indistinguishable, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies.

Cutaneous leishmaniasis is the most common form of leishmaniasis. Visceral leishmaniasis is a severe form in which the parasites migrate to the vital organs. Leishmaniasis is a parasitic disease that is found in parts of the tropics, subtropics, and southern Europe. It is classified as a Neglected Tropical Disease (NTD). Leishmaniasis is caused by infection with Leishmania parasites, which are spread by the bite of phlebotomine sand flies.

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 manifest anywhere from a few months to years after infection, include fever, damage to the spleen and liver, and anemia.

In clinical medicine, leishmaniasis is considered one of the classic causes of a markedly enlarged (and therefore palpable) spleen; the organ, which is not normally felt during examination of the abdomen, may become larger even than the liver in severe cases.

Leishmaniasis may be divided into the following types.

·         Visceral leishmaniasis is the most serious form, and is potentially fatal if untreated.

·         Cutaneous leishmaniasis is the most common form, which causes a sore at the bite site, which heals in a few months to a year, leaving an unpleasant-looking scar. This form can progress to any of the other three forms.

·         Diffuse cutaneous leishmaniasis 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, the nose and mouth.

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 whichLeishmania 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 infected hosts 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).

Leishmaniasis is caused by infection with the pathogen Leishmania. The genomes of three Leishmaniaspecies (L. major, L. infantum, and L. braziliensis) have been sequenced and this has provided much information about the biology of the parasite. For example, in Leishmania, protein-coding genes are understood to be organized as large polycistronic units in a head-to-head or tail-to-tail manner; RNA polymerase II transcribes long polycistronic messages in the absence of defined RNA pol II promoters, and Leishmania has unique features with respect to the regulation of gene expression in response to changes in the environment. The new knowledge from these studies may help identify new targets for urgently needed drugs and aid the development of vaccines.^[1]

The sand flies that transmit the parasite are only about one third the size of typical mosquitoes or even smaller. On the left, an example of a vector sand fly (Phlebotomus papatasi) is shown; its blood meal is visible in its distended transparent abdomen. On the right, Leishmaniapromastigotes from a culture are shown. The flagellated promastigote stage of the parasite is found in sand flies and in cultures.

Currently, no vaccines are in routine use. However, the genomic sequence of Leishmania has provided a rich source of vaccine candidates. Genome-based approaches have been used to screen for novel vaccine candidates. One study screened 100 randomly selected genes as DNA vaccines againstL. major infection in mice. Fourteen reproducibly protective, novel vaccine candidates were identified. A separate study used a two-step procedure to identify T cell antigens. Six unique clones were identified: glutamine synthetase, a transitional endoplasmic reticulum ATPase, elongation factor 1gamma, kinesin K-39, repetitive protein A2, and a hypothetical conserved protein. The 20 antigens identified in these two studies are being further evaluated for vaccine development.^[4]