London School of Hygiene & Tropical Medicine

The findings, published in PLOS Pathogens, reveal how the drug could cause the malaria parasite Plasmodium falciparum to be trapped in the spleen by changing its shape.

The research was conducted by CNRS, INSERM, Université Paris Descartes at the Institut Cochin and the Institut Pasteur in partnership with the London School of Hygiene & Tropical Medicine.

Plasmodium falciparum has a complex developmental cycle that is partially completed in humans and partially in the mosquito. When in humans, the parasite inhabits red blood cells (erythrocytes) in an asexual form.

These blood cells burst and some of the parasites continue infecting and bursting more cells (causing the symptoms of malaria), while others re-enter red blood cells to develop in to male and female forms known as gametocytes. These gametocytes deform the blood cell into a crescent shape which slips undetected past the spleen's blood filter. When they mature they are then free to circulate in the blood and can pass back to the mosquito when it bites an infected human to take a blood meal.

Current treatments for malaria target the asexual forms of the parasite which cause the symptoms of malaria, but have little or no effect on the sexual forms that are responsible for transmission to mosquitoes.

To tackle this problem, the researchers looked for a way to change the shape of the deformed gametocyte-infected blood cells so they were captured in the spleen. They found that by using sildenafil citrate - better known as Viagra - they were able to affect a molecular signal which stiffened the shape of the parasite so that the rigid infected blood cells would be detected and trapped in the spleen.

Study co-author David Baker, Professor of Malaria Parasite Biology at the London School of Hygiene & Tropical Medicine, said: "We know from previous work in my lab that inhibiting malaria phosphodiesterase enzymes, or deleting the genes that encode them, can disrupt malaria parasite growth. In this new study we show that Viagra, a drug shown to be safe in humans, can make the sexual forms of the malaria parasite stiff. This causes them to be inactivated in the spleen and so prevents transmission of the sexual malaria parasites to mosquitoes. This is an interesting proof of concept which gives us hope that new drugs could be developed that specifically target the malaria parasite phosphodiesterase enzymes and block malaria transmission."

• Ramdani G, Naissant B, Thompson E, Breil F, Lorthiois A, Dupuy F, et al. cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission. PLOS Pathogens. DOI: 10.1371/journal.ppat.1004815