Iron deficiency may protect against malaria infection and mortality, reports a new study published Sunday (April 15) in Clinical Infectious Diseases. The data, gathered from nearly 800 Tanzanian children followed from birth to age three, support growing doubt regarding iron supplementation in children and pregnant women living in malaria-endemic areas.
“This study provides new data indicating that naturally occurring iron deficiency is actually protective against malaria,” Philip Fischer, a Mayo Clinic pediatrician who was not involved in the research, wrote in an email. The project expands upon previous studies that had suggested that iron supplementation increased risk of malaria infection, Fischer explained.
Understanding the interaction between malaria infection and iron is of paramount importance in areas where malaria kills many children, said Patrick Duffy, study author and chief of the Laboratory of Malaria Immunology and Vaccinology at the National Institute of Allergy and Infectious Diseases. Iron deficiency can cause its own problems in children, including delayed development and poor growth, but a supplementation program that may increase malaria risk cannot be undertaken lightly, Duffy said.
His group’s study was designed to address the controversial issue of whether iron supplementation increased malaria risk, as previous studies of the phenomenon were contradictory. “We wanted to follow these children over time and see whether iron deficiency could predict malaria risk,” rather than take a snapshot and try to correlate iron deficiency with malaria infection, explained Duffy.
In order to determine whether iron deficiency might have a protective effect, Duffy’s group followed 785 children from birth to age three. Doctors assessed the children’s overall health at routine well child visits (conducted every two weeks for the first year and monthly thereafter) and analyzed blood smears for evidence of parasite infection and iron levels. The study focused on children at the greatest risk of contracting malaria, Duffy explained.
Duffy’s group found that iron deficiency appears to protect against both malaria infection and mortality, as well as all causes of mortality in the young children they followed.
Children with iron deficiencies were approximately 7 times less likely to contract malaria, and their blood parasite count when they did contract the disease was about 4-fold lower. Children with normal iron levels were 4 times more likely to acquire severe malaria infection and 24 times more likely to have elevated parasite levels in their blood.
The results are “very likely to be true,” and the number of children involved, close monitoring, and “outstanding” rate of follow-up in the study strengthened the results, said Chandy John, a pediatric infectious disease specialist at the University of Minnesota Medical School who did not participate in the study. Although causation is not yet proved, John said, the data is very unlikely to be mere correlation.
How, exactly, iron deficiency may be working to protect against malaria remains to be seen, said Duffy. Organisms in general need iron, he explained, so it may be that malaria parasites cannot grow as well without access to abundant iron. Severe malaria is associated with parasite infection creating sticky red blood cells, and it may be that without iron, infected red blood cells become less sticky. Another hypothesis, he said, is that iron may alter the protective immune response against the parasite.
Duffy also highlighted the reduction in mortality from all causes in iron-deficient children as an important finding. Again, he noted, more work needs to examine the mechanism—does iron deficiency directly protect against many infectious diseases, or do malaria infections predispose children to other health problems?
Better tools for accurately measuring iron deficiency are needed, said Duffy, whose lab is looking at how red blood cells incorporate zinc, to which developing cells turn when iron is scarce.
It’s also vital to understand more about how the severity of iron deficiency may affect protection against infection, Duffy said, so health officials can help children avoid the detrimental effects of malaria and iron deficiency. Fischer pointed out that the results argue for a more holistic approach to children’s healthcare, rather than concentrating on only one facet, writing, “Sometimes, helping part of a child can be worse than doing nothing.”
M. Gwamaka, et al., “Iron Deficiency Protects Against Severe Plasmodium falciparum Malaria and Death in Young Children,” CID, 54:1137-44, 2012.