In a landmark discovery, scientists have found that the parasites responsible for leishmaniasis does reproduce sexually, and that they do it inside sand flies - a natural vector of Leishmania.
Leishmania parasites cause widely differing forms of the disease, some of which horrific skin infections, and others affect the internal organs and can cause death.
The new finding may open up new opportunities for fighting the deadly disease.
Although Leishmania parasites reproduce clonally, there has been no proof that they can exchange genes through sex and form hybrids.
"We could say circumstantial evidence is strong because we see apparent hybrids in nature, but that's not the same as saying one has or can attain a population-genetics proof. Formal experimental proof has been lacking," Nature magazine quoted Michael Miles, a Leishmania expert at the London School of Hygiene and Tropical Medicine, as saying.
But, a research team led by David Sacks, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, have now established that the parasites reproduce in sand flies.
The researchers infected flies with two different strains of Leishmania that are resistant to two different drugs.
Hybrid parasites resistant to both drugs were later isolated from the flies, showing that the parasites had reproduced sexually.
Overall, 18 hybrids were eventually recovered, each showing a full set of chromosomes from each parent plus additional genetic material called kinetoplast DNA from one parent.
And one reason why sexual reproduction in Leishmania parasites has not been before might be due to practical difficulties of studying its sand-fly vector in the lab.
"It is likely [gene exchange] only occurs in the insect vector, and very few researchers have sand-fly colonies. If sex only occurs in the flies, you have to have flies to investigate the problem," said Sacks.
He added: "We were convinced it had to occur because of all of those examples of hybrid genotypes from field samples."
However, he said that parasite sex is not the major method by which Leishmania reproduce.
"Sex is rare. When it occurs, if it confers a powerful sexual advantage, then these lines will propagate clonally," he said.
And as Leishmania hybrids have now been created in the lab, researchers can bring traditional genetic approaches to bear on the parasite and track down the reasons behind some of the differences between strains, improving our understanding of disease virulence and drug resistance.
The study has been published in the journal Science.