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Could Viagra Help Reduce Transmission of Malarial Parasites?

Last updated May 13, 2015

Approved by: Maulik P. Purohit MD MPH

The life cycle of malaria


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:

  • When the female Anopheles mosquito carrying malarial parasites feeds on a human’s blood, it injects the parasites into the bloodstream.
  • The parasites invade the liver cells, multiply, and get back in the bloodstream in red blood cells.
  • Some of the parasites form gametocytes (male and female sexual forms) and such erythrocytes are called the gametocyte-infected erythrocytes or GIEs.
  • In the immature form, GIEs are stiff; however, as they mature, they become more flexible.
  • The deformability of the mature GIEs allows them to circulate freely in the spleen and the bloodstream.
  • It is the mature GIEs that are ingested by a mosquito feeding on the human blood.

 

The research being discussed here targeted the stiffness of the immature GIEs. The study shows that:

  • The stiffness of immature GIEs in malaria depend on phosphorylation events in the parasite
  • The deformability of the GIEs is regulated by a pathway involving cyclic Adenosine Monophosphate (cAMP) in the parasite
  • Accumulation of cAMP renders the immature GIEs stiff
  • Since cAMP accumulation could be achieved by deactivating an enzyme (Phosphhodiesterase) that blocks its degradation, Forskolin, Zaprinast, and Sildenafil could accomplish this task
  • Indeed, as proof of concept, the scientists were able to mimic splenic filtration by using a microsphere matrix and show retention of immature GIEs following treatment with Phosphodiesterase inhibitors.

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/

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 13, 2015
Last updated: May 13, 2015