The blood-stage stage of malaria refers to when the clinical symptoms of the disease manifest.
Iron deficiency is the most common nutritional deficiency in the world and causes long-term adverse consequences in children.
Malaria is endemic to Africa and the concerns about the safety of iron supplements, particularly for children remains.
Previous studies have shown that having sickle-cell anemia offers protection against malaria.
Now, researchers at the University of North Carolina (UNC) at Chapel Hill have proven that treating anemia with iron supplementation removes the protective effect that anemia has to offer against malaria.
Life cycle of Plasmodium falciparum
Malaria parasites spread by successively infecting two types of hosts- female Anopheles mosquitoes and humans
When an infected mosquito bites a human, it injects sporozoites into the blood stream. These sporozoites are rapidly taken up by the liver cells in human where they multiply by asexually to form schizonts from which several merozoites develop.
The merozoites are released into the bloodstream when the liver cells rupture, where they rapidly invade the red blood cells.
These blood-stage parasites replicate asexually, multiply and destroy the red blood cells, leading to the clinical symptoms of malaria.
Malaria is a mosquito-borne illness that is entirely preventable and treatable.
In 2013, an estimated 3.4 billion people were at risk of malaria.
There were an estimated 207 million cases of malaria and an estimated 627 000 deaths in 2012. 90% of all malaria deaths occur in sub-Saharan Africa.
In 2012, malaria killed an estimated 482 000 children under five years of age, which equals 1300 children per day.
Between 2000 and 2012, malarial interventions saved an estimated 3.3 million lives.
Researchers recruited 135 children with anemia from The Gambia, a region endemic to malaria. They studied the red blood cells of the children.
Sickle-cell anemia was also common in that region.
As part of iron supplementation trial, the children received iron through micronutrient powder for 84 days.
Red blood cells (RBCs) from the children were analyzed at baseline, day 49 and day 84.
On a population-wide basis anemia reduced the blood-stage of malaria by 16% while the sickle-cell trait only reduced it by 4%.
"Our finding that anemia offers greater natural protection against blood-stage malaria infection than sickle-cell trait has led us to formulate the interesting hypothesis that the widespread prevalence of anemia in people of African descent is a genetic signature of malaria," said Morgan Goheen, Ph.D., the study's lead author and a graduate student in the UNC Department of Microbiology and Immunology.
On analysis of the RBCs of children on day 49 of iron supplementation, researchers found that deficits in invasion and growth for blood stage P. falciparum were reversed.
Iron supplementation produces more red blood cells. After iron supplementation, the increased invasion and growth rates by parasites are caused by their strong preference for young red blood cells.
"This study is elegant in its simplicity, yet remains one of the most substantial and systematic attempts to unveil the cellular-level relationship between anemia, iron supplementation and malaria risk," said Carla Cerami, M.D. Ph.D., lead scientist on the project at the MRC Unit in The Gambia.
This study was conducted by UNC researchers, along with colleagues from the Medical Research Council Unit in The Gambia, Africa, and the London School of Hygiene & Tropical Medicine and funded by the Bill and Melinda Gates Foundation.
The results were published in EBioMedicine
- Parasite lifecycle - (http://www.mmv.org/malaria-medicines/parasite-lifecycle)
- Factsheet on the World Malaria Report 2013 - (http://www.who.int/malaria/media/world_malaria_report_2013/en/)
- Morgan Goheen et al. Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation. EBioMedicine; (2016)