Uninfected sand flies cut risk against infected ones

THURSDAY, Nov. 16 (HealthScout) -- Researchers have found a surprising way to protect against leishmaniasis, a disfiguring tropical disease spread by the bites of tiny flies infected with the parasite that causes the disease.

Immunity against the disease can be bolstered by bites from flies that aren't infected by the parasite, says a group headed by David L. Sacks, a senior investigator at the National Institute of Allergy and Infectious Diseases. That finding could help create a new kind of vaccine against leishmaniasis, the researchers report in the Nov. 17 issue of the journal Science. Leishmaniasis isn't a concern for most Americans, because it occurs primarily in countries such as Brazil and Sudan. But it is a major health problem in those countries and for those who visit them. About 600,000 new cases are reported yearly, but the World Health Organization says the real annual incidence may be as high as 1.5 million cases.

Leishmaniasis is a family of diseases caused by single-cell parasites called Leishmania, which are transmitted to humans by the bites of sand flies. Cutaneous leishmaniasis, the kind investigated by the American researchers, causes a disfiguring ulcer at the site where the fly bites.

"The initial objective of our research was to succeed in transmitting the infection in the laboratory, which had not been accomplished to date," Sacks says. "No one ever really had a model of infection that reproduces what is done in nature, because sand flies are much more difficult than mosquitoes to rear in the laboratory."

So Sacks turned to the Walter Reed Army Institute of Research, which maintains sand fly colonies because American soldiers can be sent to leishmaniasis-prone regions. The joint effort did succeed in infecting laboratory mice, and then moved on to another question, Sacks says: "What happens if we try to transmit leishmaniasis to animals that were bitten by an uninfected sand fly?"

Reacting to fly's saliva

What they found was that the bite of an uninfected insect produces a powerful and severe inflammatory response in the skin, a reaction to something in the fly's saliva. That response to saliva is harmful to any parasites transmitted by a future sand fly bite, Sacks says.

"The immediate implication is that this might explain why there is such a range of outcomes in endemic regions after exposure to the parasite," he says. "Some people are severely affected, others develop little or no disease. It was previously thought this was because people have different levels of immune response to the parasites."

Now it appears that there are different levels of response to the fly that transmits the parasite, "so we might consider vaccinating people using components of the saliva of the flies," Sacks says.

The researchers have isolated components of fly saliva that produce the immune response and are testing them, first in mice and then in monkeys. The goal is to use them in a vaccine against leishmaniasis, a long-sought goal where progress has been "painfully slow," Sacks says.

Researchers have been working on a leishmaniasis vaccine based on producing immunity against the parasite for a decade, he says. Human trials sponsored by the World Health Organization began in the Middle East and Africa about five years ago, and the results are still being assessed.

The new idea would be a two-component vaccine designed to get an immune system response against both the parasite and the fly saliva, Sacks says.

Leishmaniasis vaccination and the disease itself are barely a concern for Americans who travel abroad, says Dr. David C. Helfgott of the Travelers Medical Center in New York. "It's important for residents of the area, but it is very, very unusual in a traveler," he says.

The disease has received more attention in the United States and Europe recently because two or three cases have been reported among travelers, Helfgott says, but those have been just "a little blip on the screen" and he detects no signs of concern in his practice.

(From HealthScout)