Breakthrough discovery on Leishmaniasis, world's most deadly tropical diseases

Jul 29 2004

Scientists at the Liverpool School of Tropical Medicine, working with colleagues at the University of Dundee, have discovered how the tiny sand fly spreads one of the world's most deadly tropical diseases - Leishmaniasis.

Their discovery, which has been published in the magazine Nature, has been welcomed as the sort of fundamental breakthrough which could eventually lead to a vaccine being developed against the parasitic disease which can cause severe illness and even death.

Leishmaniasis affects about 12 million people worldwide at any one time, with about 2 million new cases every year. Humans catch it when bitten by sand flies carrying the single-celled organism Leishmania. However, many things about the transmission of Leishmaniasis have remained a mystery such as the dosage of parasite in each sand-fly bite required to cause disease, and the identity of shadowy 'virulence factors' thought to enhance the infection.

Working with colleagues at the University of Dundee, Liverpool researchers Dr Paul Bates and Matt Rogers have worked out how the Leishmania parasite has manipulated the sand fly as the perfect transmission system for itself.

Their research reveals the size of the infectious dose, the underlying mechanism of parasite delivery by regurgitation, and the novel contribution made to infection by filamentous proteophosphoglycan (fPPG), a component of a parasite-secreted gel that is co-injected with the parasite when the sand-fly bites its victim. Their findings - the result of four years research - shows that this gel greatly enhances the infectivity of the parasite.

As Dr Bates points out: “Scientists have known for many years that if you get bitten by a sand-fly you may catch Leischmaniasis. But what we didn’t understand was the actual mechanics of it.

"There are three players - the person or animal affected, the sand fly itself and the parasite living in the sand-fly and then in the human/animal that gets bitten. To understand the transmission of the disease we have had to look at the three players together and in doing so have discovered something completely new about the transmission - namely that the gel that the parasite manufactures itself and which the sand-fly carries actually causes more disease. This is because the gel is sticky and stops the sand fly being able to feed properly on its victim’s blood. This means that it gets more and more frustrated, causing it to bite again and again, which means more likelihood of infection.

" But the gel also helps the parasite to pass more easily into the victim, again making disease more likely. The practical implications of this are that if we can target the gel with a vaccine, we can reduce the severity of the disease or prevent it happening at all. If you don¹t understand the mechanics of something like this you are stumbling about in the dark, trying things at random.”

The contributions of Andrei Nikolaev and Mike Ferguson, at the University of Dundee, revolved around the chemical analysis and the chemical sythesis of this gel material (a complex phosphoglycan) which allowed Bates and Rogers to test their hypothesis with completely defined material.

Said Professor Ferguson: “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.”

The sand fly, a hairy little creature about half the size of a mosquito, has caused major epidemics in countries such as India and Bangladesh and is likely to affect people who have been forced to migrate through civil war, as in Sudan at present. It is a huge problem among the urban poor and tends to affect the vulnerable and malnourished most severely.