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Study: Iron Supplements Can Make Children with Malaria Sicker

A new study says United Nations health guidelines recommending iron supplements for anemic children could be dangerous in certain circumstances. Researchers from the United States and Zanzibar say that in areas where malaria is intense, iron supplements can increase the risk of severe illness and death.

U.N. data show that about 75 percent of East African children under five suffer anemia caused by iron deficiency. In areas where anemia is common, international guidelines call for iron and folic acid supplements for all children under two.

But a study in the medical journal Lancet shows that in places where anemia and malaria coincide, the iron supplements result in increased hospitalizations and death.

Johns Hopkins University physician Robert Black led the study of more than 24,000 children aged one month to three years in Pemba, Zanzibar, an area of high malaria transmission.

"For a number of years, there has been a concern about giving iron to populations, particularly children, that have malaria, and this seems to have been borne out in this study," said Mr. Black.

Black's team assigned the children to randomly receive various combinations of iron, folic acid, and zinc, or no supplements at all. They stopped the study early for groups getting the iron and folic acid combination because it made some children's malaria worse. Overall, children getting those minerals had a 12 percent higher risk of hospitalization for severe disease or death than those receiving no supplements.

In contrast, a companion study by Black and his colleagues in Nepal, where malaria transmission is low, shows that the supplements did not increase death and sickness among children.

The Johns Hopkins University doctor says the Zanzibar research shows that the problem seems to be with iron, not folic acid, but the biological explanation is unclear.

"It appears that there is an adverse affect of giving iron in this setting, perhaps related to the stimulation of the bone marrow to produce red blood cells that are then more readily infected with the malaria parasite," he said. "Or perhaps there is a direct toxic effect of the iron that has been hypothesized, but the exact mechanism has not been worked out."

The Zanzibar study shows that iron supplements did help some children, but only those who were anemic in the first place. As a result, the researchers recommend revising international guidelines to avoid blanket iron supplementation in places where malaria is endemic.

"One possibility is to provide iron only when there is adequate malaria control or possibly iron and antimalarial drugs simultaneously so that the malaria is controlled when iron is presented to the child," he noted. "A second possibility is that there could be screening for anemia so that only children with iron deficiency anemia would be given iron."

A Lancet commentary accompanying the Zanzibar and Nepal studies calls them a significant advance. But its authors say they represent only the extreme ends of the malaria spectrum and do not yet provide adequate evidence for global policy. The authors, from the Kenya Medical Research Institute in Nairobi, are calling for more large iron supplementation trials in areas of different levels of malaria transmission.