A study published in PLOS Pathogens by Dr. Ramdani and fellow scientists reports that Phosphodiesterase inhibitors like Forskolin, Sildenafil (Viagra), and Zaprinast are able to increase the rigidity of red blood cells (erythrocytes) carrying malarial parasites, which get retained in the spleen instead of circulating in the peripheral blood. This could potentially lead to a decrease in transmission of the parasite from an infected human to a mosquito and thus, lessen the spread of malaria.
Red blood cells have the ability to be flexible without breaking/rupturing. The spleen usually filters the blood cells in such a way that the elastic or normal blood cells are free to circulate, while the stiff cells are retained. The ability of the erythrocytes to be flexible is called their “deformability.”
It is this deformability of the erythrocytes that have been targeted for the current study.
Some important facts about the malarial infection process:
The research being discussed here targeted the stiffness of the immature GIEs. The study shows that:
In the authors’ words, “Our observations provide an opportunistic approach towards the discovery of new malaria transmission-blocking drugs, by taking advantage of the wealth of clinical data available for sildenafil, which (has) been approved by the Food and Drugs Administration and is widely used in humans with little side effects to treat erectile dysfunction.”
Similar to Sildenafil, there are other Phosphodiesterase inhibitors on the market such as Tadalafil, Vardenafil, Udenafil, etc.
According to the Word Health Organization, about 584,000 deaths were attributed to malarial infections around the world in 2013, the majority of them being children in Africa. Since malaria is a preventable disease, it would be interesting to see if drugs already approved by the US Food and Drugs Administration for one indication could be repurposed for preventing malarial parasite transmission and thus decrease the spread of malaria. As the authors conclude, the findings “open new avenues towards the design of novel interventions to halt the spread of malaria to humans.”
Written by Mangala Sarkar Ph.D.
Primary Reference:
Ramdani, G., Naissant, B., Thompson, E., Breil, F., Lorthiois, A., Dupuy, F., . . . Lavazec, C. (2015). CAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission. PLOS Pathogens. Retrieved May 9, 2015, from http://www.plospathogens.org/article/related/info:doi/10.1371/journal.ppat.1004815
Additional References:
Malaria. (n.d.). Retrieved May 12, 2015, from http://www.niaid.nih.gov/topics/malaria/pages/lifecycle.aspx
Malaria. (n.d.). Retrieved May 12, 2015, from http://www.who.int/mediacentre/factsheets/fs094/en/
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