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. 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. Visceral leishmaniasis is a severe form in which the parasites have migrated to the vital organs.
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 found through much of the Americas from northern Argentina to southern Texas, though not in Uruguay or Chile, and has recently been shown to be spreading to North Texas. 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.
The disease in found across much of Asia, though not Southeast Asia, and the Middle East. Within Afghanistan, in particular Kabul is a town where leishmaniasis occurs commonly - partly to do with bad sanitation and waste left uncollected in streets, allowing parasite-spreading sand flies an environment they find favorable.. In Kabul the number of people infected is estimated at at least 200,000, and in three other towns (Herat, Kandahar and Mazar-i-Sharif) there may be about 70,000 more, according to WHO figures from 2002.
Leishmaniasis is mostly a disease of the Developing World, and is rarely known in the developed world outside a small number of cases, mostly in instances where troops are stationed away from their home countries. Leishmaniasis has been reported by U.S. troops stationed in Saudi Arabia and Iraq since the Gulf War of 1990, including visceral leishmaniasis. In September 2005 the disease was contracted by at least four Dutch marines who were stationed in Mazari Sharif, Afghanistan, and subsequently repatriated for treatment.
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)
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:
Miltefosine (Impavido), is a new drug for visceral and cutaneous leishmaniasis. The cure rate of miltefosine in phase III clinical trials is 95%; Studies in Ethiopia show that it is also effective in Africa. In HIV immunosuppressed people who are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment. Clinical trials in Colombia showed a high efficacy for cutaneous leishmaniasis. In mucocutaneous cases caused by L.brasiliensis it has shown to be more effective than other drugs. Miltefosine received approval by the Indian regulatory authorities in 2002 and in Germany in 2004. In 2005 it received the first approval for cutaneous leishmaniasis in Colombia. Miltefosine is also currently being investigated as treatment for mucocutaneous leishmaniasis caused by L. braziliensis in Colombia, and preliminary results are very promising. It is now registered in many countries and is the first orally administered breakthrough therapy for visceral and cutaneous leishmaniasis.(More, et al, 2003). In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated than other drugs. Main side effects are gastrointetinal disturbance in the 1-2 days of treatment which does not affect the efficacy. 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. The Drugs for Neglected Diseases Initiative is also actively facilitating the search for novel therapeutics.
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 Zürich are trying to design a carbohydrate-based vaccine The genome of the parasite Leishmania major has been sequenced, possibly allowing for identification of proteins that are used by the pathogen but not by humans; these proteins are potential targets for drug treatments.
Leishmaniasis is caused by infection with the pathogen Leishmania. The genomes of three Leishmania species (L. major, L. infantum and L. braziliensis) have been sequenced and this has provided much information about the biology of the parasite. For example it is now understood that in Leishmania protein-coding genes are 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.
Who first discovered the organism is somewhat disputed. It is possible that Surgeon major Cunningham of the British Indian army saw it first in 1885 without being able to relate it to the disease. In 1901, Leishman identified certain organisms in smears taken from the spleen of a patient who had died from "dum-dum fever" (Dhum dhum is an area close to Calcutta) and in 1903 Captain Charles Donovan (1863-1951) described them as being new organisms. Eventually Ronald Ross established the link with the disease and named the organism Leishmania donovani.
CVBD stands for Canine Vector-borne diseases, which are diseases transmitted through Ectoparasites.