By increasing the stiffness of erythrocytes infected by the causal agent
of malaria, Viagra favors their elimination from the blood circulation
and may therefore reduce transmission of the parasite from humans to
mosquitoes. This astonishing discovery 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. Eradication
of this disease thus necessitates the development of new types of
treatments against sexual forms of the parasite in order to block
transmission and thus prevent dissemination of the disease within the
population.
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 (see the top of the image on page 2). 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 thus sought to stiffen the
infected erythrocytes. They showed that the deformability of
gametocyte-infected erythrocytes is regulated by a signaling 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 favor the elimination
of infected erythrocytes by the spleen.
This discovery could help find new ways to stop the spread of malaria
in a population. Modifying the active substance in Viagra to block its
erectile effect, or testing similar agents devoid of this adverse
effect, could indeed result in a treatment to prevent transmission of
the parasite from humans to mosquitoes.
This story is taken from Science Daily
