Sickle Cell Against Malaria

Sickle Cell is a recessive inherited trait caused by a mutation in the hemoglobin-beta gene on chromosome 11. The disease causes red blood cells, to be abnormal (crescent shaped). 

Normal and Sickle red blood cells

An article published by ScienceDirect notes that Sickle human hemoglobin (Hb) can actually protect against malaria. The article notes that people that are heterozygous for the sickle cell gene, show a survival advantage in areas where malaria is prevalent. The disease in fact does not prevent the host from developing the parasite, but makes it tolerant to it. Individuals with sickle cell accumulate cell free hb and heme (non-protein part of hb) in the plasma which induces the expression of heme oxygenase-1. This enzyme catalyzes heme into other molecules including carbon monoxide, which binds to sickle hb and prevents it from releasing more heme and hence the pathogenesis of experimental malaria. 

Specialists think that the mechanism involving sickle hb is similar to other genetic blood diseases that also seem to provide  a type of protection to the host. These findings provide a great advantage and open ways to new therapeutic inventions against malaria.

Resistance To Antimalarial Drugs Is Not Passed On To Parasite Offspring

The parasites that cause malaria often develop resistance to antimalarial drugs, but according to a new study, parasites with mutations that make them resistant to an antimalarial called atovaquone can’t pass their resistance on to their offspring. The drug disrupts the lifecycles of the parasites while they’re living within their mosquito hosts. Atovaquone, is a component of the antimalarial medication Malarone. It kills both the blood and liver stages of malaria, however researchers believed that it’s prone to resistance like so many other antimalarial medications. To investigate, a team of scientists examined three atovaquone resistant strains of Plasmodium Bergheim, a malarial parasite. Each strain contains a different mutation in their cytB gene, which is encoded in their mitochondrial DNA. The team let mosquitoes infected with the Plasmodium feed on mice infected with the resistant Plasmodium strains, and then they followed the parasites over the course of their entire lifecycle.

While resistance mutations protected the parasites from the drug, it was lethal later on in the mosquito phase. "Two of the mutations resulted in developmental defects in the parasites’ fertilized embryos, and the third mutation led to complete infertility. The team describes cytB mutations as genetic time bombs. Because maternally-inherited mitochondrial DNA is critical for a molecular process that Plasmodium rely on when they’re living inside of mosquitoes, the resistant parasites weren’t able to respire efficiently. Since this severely impairs their reproductive cells, atovaquone-resistant mutations can’t be passed on to the next generation of parasites. " (Goodman)

In a total of 44 separate transmission attempts which involved over 750 mosquito bites, the transmission of atovaquone resistance was observed just once. And this mutation couldn’t be transmitted further despite seven attempts. Cross breeding parasites with and without these mutations didn’t work either, which means we could be one step closer to being able to stop malaria from spreading across the world.

Original source: http://science.sciencemag.org/content/352/6283/349.full
Related source : http://www.eurekalert.org/pub_releases/2016-04/uom-nhf041316.php