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Indian researchers have identified a key protein that plays an important role in regulating the survival, infectivity and drug response of the parasite that causes visceral leishmaniasis, also known as 'kala-azar'.

The study was published in the April issue of Molecular Microbiology.  

Kala-azar is the most severe form of leishmaniasis, and is caused by a parasite called Leishmania donovani, which spreads to people through the bite of an infected female sandfly.

Jitesh P. Iyer and co-workers from the National Institute of Immunology, New Delhi, India, found that higher levels of an enzyme, cytosolic tryparedoxin peroxidase (cTXNPx), at a certain stage of the L. donovani life cycle made the parasite more virulent. Laboratory tests also showed a higher parasite burden in immune cells.

cTXNPx belongs to the group of enzymes that detoxify peroxides, chemicals that are toxic to L. donovani. When humans are infected by L. donovani, their immune cells release hydrogen peroxide to destroy the parasite.

Parasites with higher levels of cTXNPx were more able to withstand high levels of hydrogren peroxide, and were also resistant to an antileishmanial drug.

"This study provides a link between cTXNPx expression to survival, virulence and drug response in L. donovani," the researchers write.

"This study invites further studies to explore the plausibility of any new drug molecule targeting this enzyme," says Swapan Jana, secretary of Indian nongovernmental organisation Society for Social Pharmacology. "The study is impressive — given the emerging drug resistance of Leishmania donovani, it's important to work on the ways to combat the parasite through newer drugs."

Drug-resistance of L. donovani is a major issue in developing countries like India, says Jana.

"Even though different centres have reported different findings, it is a fact that resistance [of Leishmania donovani] to the first line drug sodium antimony gluconate has been increasing since the late seventies," says Sarman Singh, head of the division of Clinical Microbiology at the All India Institute of Medical Sciences.

Kala-azar is endemic in four Indian states, the worst affected being the eastern state of Bihar. The disease infects about 300,000 people and kills 20,000 in India each year.

"In some areas of Bihar [drug] resistance is reported in up to 70 per cent of cases," adds Singh.

Link to abstract in Molecular Microbiology


Molecular Microbiology 68, 372 (2008)

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