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Gene Study Throws Up New Targets for Leishmaniasis

Gene sleuths believe they may have identified potential chinks in the parasite that causes leishmaniasis, a disfiguring and sometimes fatal disease that afflicts some 12 million people around the world . Their comparison of three species of protozoa that cause most cases of leishmaniasis could be a boon for drug engineers, whose budgets for tackling this neglected disease are already slender.

British-led scientists compared the genetic code of Leishmania major, which causes the cutaneous form of leishmaniasis, with those of L. infantum and L. braziliensis, which cause the more dangerous, visceral form of the disease, also called kala-azar. What struck the researchers was that these parasites were very similar genetically, even though they cause very different types of disease.

Each genome has more than 8,000 genes, but only 200 of them differ across the three species. "The degree of similarity between these species was unexpected," said Deborah Smith, a professor at the University of York, northern England. "Perhaps only a few parasite genes are important in determining which type of disease develops after infection, and the host genome plays a major role in clinical outcome."

Another surprise was to find a small number of genes that have never been spotted before. Fellow investigator Chris Peacock described these novel genes as a "short cut" that could help the pharmaceutical quest. "Given their lack of similarity to human genes, they present a limited repertoire of potential targets for drug and vaccine development, allowing researchers to optimise the use of limited resources."

The Leishmania parasite is transmitted in the saliva of sandflies, who tuck in to a blood meal on humans, wild animals and dogs. Around 350 million people in 88 countries are "at risk" of the disease, whose incidence has risen sharply over the past decade, according to the Wellcome Trust Sanger Institute, a British medical research ch arity that led the genome comparison.

The frontline affordable drug, sodium stiboglucomate, marketed as Pentostam, is running into bad resistance problems, leaving many doctors with the option of more expensive treatment that, in the case of visceral leishmaniasis, can cost up to 150 dollars for a four-week course. Cutaneous and mucosal leishmaniasis results in painful, crater-like lesions on the skin.

Visceral leishmaniasis, which affects the spleen and liver, causing fever and weight loss, is fast becoming an opportunistic disease among people whose immune systems have been compromised by the AIDS virus. The study appears on Sunday in the journal Nature Genetics.


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