Why Iron Can Make Malaria Worse

Researchers have discovered having, or having a lack of, a certain hematologic protein can make a difference in malaria outcomes.


A National Institute of Health (NIH) research team that may have found the explanation for why iron supplements can sometimes worsen malaria infection. “Our study helps solve a long-standing mystery,” says Tracey Rouault, MD, a member of the team.

The researchers say the answer may lie with ferroportin, a protein that prevents iron from building to toxic levels in red blood cells and helps prevent malaria infection. Red blood cells use ferroportin to remove excess iron (a food source for malaria parasites). When the researchers fed mice a high-iron diet, they found that a hormone called hepcidin regulates ferroportin in erythroid cells. The hormone, which is more abundant in high-iron environments, not only lowered ferroportin levels in erythroblasts and red blood cells, but physically bound to ferroportin, preventing iron from being removed from cells.

Findings from 2 malaria studies suggest that Q248H, a ferroportin mutation often found in malaria-endemic regions, protects against malaria. In 1 study, nearly 20% of 66 children hospitalized for malaria in Zambia had the mutation; these children also tended to have fewer malarial parasites in the blood and tolerated their fevers for a longer period before coming to the hospital.

In the other study, of 290 pregnant women in Ghana, nearly 9% had the mutation. Those women were significantly less likely to have pregnancy-associated malaria.

Rouault says the findings may help explain why iron supplements can sometimes worsen malaria infection and why, conversely, iron deficiency can sometimes be protective. The findings also may help researchers develop strategies to prevent and treat malarial infections, which numbered nearly 216 million in 2016.

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