Some quick facts about malaria:
1. Malaria is a parasitic disease from the family Plasmodium and accounted for 241 million cases and 627,000 deaths worldwide in 2020.
2. 80% of all malaria cases are in children less than 5 years of age.
3. 98% of all malaria cases were caused by one species, Plasmodium falciparum which is highly relevant in parts of Africa.
Many things contribute to how potent an infection will be, including the genetic background of the host, age, environmental factors, and parasitic genetics. One host factor that has been well studied is the variability in red blood cells.
The most common variation in human RBCs (hemoglobinopathy) is sickle cell hemoglobin (HbS). Human red blood cells carry two α-globin and two β-globin proteins; the sickle cell mutation occurs in the β-globin. If both parents have this mutation, the child will be what is called homozygous for sickle cell. However, if only one parent is carrying the mutation, the child will be heterozygous.
Heterozygous HbS has been linked to protection from severe malaria since the pioneering work of Anthony Allison in the 1950s. However, there are still instances where severe infection occurs in this population of people.
There have been studies demonstrating the inside of the HbS cells are more challenging to survive in for the parasites compared to normal red blood cells.
Additionally, one research lab at Oxford discovered in late 2021 that the genome, or entire set of DNA within an organism, of the parasite varies and this variation plays a role in infectivity.
This leaves the question, has the malaria parasite evolved mechanisms to evade the HbS protective effect?
The researchers analyzed host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria due to P. falciparum infection. Three genetic regions, named Pfsa (Pf sickle-associated), had a strong correlation between host and parasite.
Public genetic databases were also used to compare relative frequencies of this genetic anomaly. It was found that Pfsa genes are much more common in Africa and their frequencies to be strongly correlated with the frequency of HbS. The researchers acquired evidence suggesting evolutionary pressure to be aiding in the selection of these Pfsa genes in the parasites.
The exact mechanism for how the Pfsa genes allow for malaria to take hold is unclear, but it can be said that the parasites containing these genes will need special attention to treat clinically.
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