Breakthrough claimed in research on leishmaniasis

Scientists are claiming to have achieved a major step in in the battle against leishmaniasis, a potentially fatal disease affecting about 12 million people, largely in the tropics and subtropics.

The researchers say they have discovered the mechanism by which parasites are transmitted when a sand fly bites. Their results also reveal the number of parasites transmitted, and the role of a chemical that accompanies the parasites when they are transmitted.

Leishmaniasis is caused by a microscopic parasite similar to the one that causes malaria and is transmitted to humans by bites from sand flies. Three forms the disease occur, one affecting internal organs, one causing skin ulcers, and one causing the membranes of the nose and mouth to erode away.

Describing their findings as “a new picture” of the way the disease is transmitted, the researchers say that their work has important implications for understanding the pathology of the disease, and for the development of drugs and vaccines against the parasite.

The study, published in this week’s Nature, reveals that the average sand fly bite can deliver more than 1,000 parasites, the majority of which are at the stage in their life cycle when they are capable of causing infection.

By counting parasites in different parts of the sand flies’ digestive tract, the researchers have shown that the flies “actively regurgitate” the parasite when they bite. But the researchers also showed that the sand fly does more than just inject the parasite.

Mice receiving a single infectious sand fly bite developed more severe skin lesions faster than those injected with 1,000 infective parasites from a syringe. This suggested that something else — dubbed an ‘exacerbation factor’ — was transmitted along with the parasites.

The exacerbation factor is in fact the main component of a gel released by the parasites while they are inside sand flies. The gel is known to block the sand fly gut, causing it to feed more often and for longer, which increases the chance of parasite transmission. Its additional role in enhancing infectivity, however, was unknown until now.

“This is an excellent example of collaborative research bringing together biology and chemistry to unravel key questions, in this case the mechanism of disease transmission in Leishmaniasis,” says Mike Ferguson, one of the authors of the study.

The research shows how the parasite has evolved the production of a chemical that functions both in the insect that transmits it and in its mammalian host. This, say the researchers, highlights the importance of studying all three organisms simultaneously.

The study was carried out by a collaborative team from the Liverpool School of Tropical Medicine in the United Kingdom, the Max-Planck-Institut fϋr Biologie in Germany, and the Wellcome Trust Biocentre at the University of Dundee.

Link to full paper by Rogers et al in Nature

Reference: Nature 430, 463, (2004)