The saliva of a sand fly may help to prevent a horrific skin infection that now affects millions of people in the tropics, subtropics and southern Europe.
Ironically, the infection, cutaneous leishmaniasis, develops when a sand fly infected with Leishmania parasites bites a person. The bite can turn into a raised red lesion that, in some cases, may form an open ulcer that can then become infected with bacteria. Sores in the nose and mouth may cause further complications.
"People get this disease if they visit areas where the sand fly occurs, like parts of Brazil, India and Iran," Camil de Oliveira of the Instituto Gonçalo Moniz, Fundação Oswaldo Cruz in Brazil told Seeker. "The name sand fly is not related to the insect being found on the beach."
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In Brazil, one of 10 countries where 75 percent of cutaneous leishmaniasis cases are concentrated, the infection is generally caused by the parasite Leishmania braziliesis, and is transmitted in the spit of the biting sand flies Lutzomyia intermedia and Lutzomyia whitmani. Prior research found that immunity to proteins in Lutzomyia intermedia's saliva exacerbated leishmaniasis, resulting in an increased immune response to the bites of infected sand flies.
For the new study, published in the journal PLOS Neglected Tropical Diseases, de Oliveira, Aldina Barral and their team tested the effect of immunity to the other major sand fly, Lutzomyia whitmani, on leishmaniasis. As you might imagine, the small insects produce a tiny amount of spit, making the research quite a challenge.
The flies "produce very little of it, and we need to obtain the flies, separate the females - the ones that have the salivary molecules we are interested in - and then dissect the salivary glands," de Oliveira said. "It is all very small and we need the use of lab equipment to do the dissection."
The scientists next immunized mice with the fly spit. They then injected the mice with some of the infection-causing parasites. The mice that were previously immunized with the fly saliva did not develop lesions, but other mice that had no such treatment did. The researchers also noted that the immunized mice had lower levels of parasites at the injection sites and higher levels of certain immune molecules.
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The scientists next tested 300 people from Corte de Pedra, Brazil. Some of them had the infection, others had a lesser version of it without the lesions, and still others had no history of the disease. De Oliveira and colleagues detected the antibodies in all three groups of people, but patients with lesions had the lowest levels.
Together, the experiments strongly suggest that immunity against the infection is possible, and that the fly saliva helps to boost an individual's ability to fight off leishmaniasis. Why this happens remains a mystery, since insects do not even have antibodies.
"Nevertheless," de Oliveira said, "they can recognize invaders and trigger different mechanisms of defense ... For sand flies, little is known about how they may fight off Leishmania parasites, however, they can survive Leishmania presence and thrive."
The next phase of the research is a bit blood curdling: the researchers plan to replicate their findings using live sand fly bites. They say this is a critical next step since injected compounds don't fully mirror what happens to a victim after a natural bite.
De Oliveira said this can be done on rodents and possibly primates in labs, but it will demand "vast amounts of sand flies that can be experimentally infected with Leishmania parasites."
Ideally, the scientists will be able to pinpoint the components in the sand fly saliva that induce protection against the infection. If so, then they can chemically recreate them, foregoing the incredible challenge of obtaining spit from countless little flies.