PTI
LONDON, MAY 10
The anti-impotence drug Viagra helps eliminate malaria from the blood circulation which may reduce transmission of the deadly parasite from humans to mosquitoes, a new study has found.It does so by increasing the stiffness of erythrocytes infected by the causal agent of malaria, researchers said.
This astonishing discovery, made by scientists at the Institut Cochin in Paris and the Institut Pasteur, working in collaboration with a team from the London School of Hygiene and Tropical Medicine, could lead to a treatment to reduce the spread of malaria within a population.
Plasmodium falciparum, the parasite that causes malaria, has a complex developmental cycle that is partially completed in humans and partially in the anopheline mosquito.
Treatments for malaria target the asexual forms of this parasite that cause symptoms, but not the sexual forms transmitted from a human to a mosquito when it bites.
The sexual forms of the parasite develop in human erythrocytes sequestered in the bone marrow before they are released into the blood. They are then accessible to mosquitoes, which can ingest them when they bite.
But circulating erythrocytes - whether they are gametocyte-infected or not - are deformable, thus preventing their clearance via the spleen, which constantly filters the blood and only retains stiff, old or abnormal erythrocytes.
However, gametocyte-infected erythrocytes can easily pass through the spleen and persist for several days in the blood circulation.
During a new study, the scientists showed that the deformability of gametocyte-infected erythrocytes is regulated by a signalling pathway that involves cAMP.
When the cAMP molecules accumulate, the erythrocyte becomes stiffer. CAMP is degraded by the enzyme phosphodiesterase, whose action thus promotes erythrocyte deformability.
Using an in vitro model reproducing filtration by the spleen, the scientists were able to identify several pharmacological agents that inhibit phosophodiesterases and can therefore increase the stiffness of infected erythrocytes.
One of these agents is sildenafil citrate, better known under its brand name of Viagra.
The authors showed that this agent, used at a standard dose, had the potential to increase the stiffness of sexual forms of the parasite and thus favour the elimination of infected erythrocytes by the spleen.
This discovery could help find new ways to stop the spread of malaria in a population, researchers said.
Modifying the active substance in Viagra to block its erectile effect, or testing similar agents devoid of this adverse effect, could result in a treatment to prevent transmission of the parasite from humans to mosquitoes.
The research was published in the journal PLOS Pathogens.
