Abstract & Commentary

Iron Deficiency Protects against Severe Malaria,

By Dean L. Winslow, MD, FACP, FIDSA, Chairman, Department of Medicine, Santa Clara Valley, Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.

Chairman, Department of Medicine, Santa Clara Valley, Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.

Dr. Winslow is a consultant for Siemens Diagnostic.

Synopsis: 785 Tanzanian children living in an area of intense malaria transmission were enrolled at birth and monitored for malaria parasitemia until age 3. Iron deficiency (ID) at routine visits decreased the odds of parasitemia and severe malaria as well as all-cause mortality.

Source: Gwamaka M, et al. Iron deficiency protects against severe Plasmodium falciparum malaria and death in young children. CID 2012; 54: 1137-44.

785 Tanzanian children living in an area of high malaria endemicity were intensely monitored for parasitemia and other illness from birth to 3 years of age. The degree of parasitemia was determined by number of parasites/200 WBC's on thick smear. Severe malaria was defined by WHO criteria. Iron deficiency was defined as ferritin concentration < 30 ng/mL when CRP was < 8.2 ug/mL or ferritin < 70 ng/mL when CRP was > 8.2 ug/mL. Iron deficiency at well-child visits decreased the odds of subsequent parasitemia (23% decrease) and severe malaria (38% decrease). When sick visits were also included in the analysis, iron deficiency was associated with a reduced prevalence of parasitemia, hyperparasitemia and severe malaria.

Commentary

Both malaria and iron deficiency are common in sub-Saharan Africa. While malaria and diarrheal disease are the leading causes of mortality in young children in sub-Saharan Africa, iron deficiency in children is associated with impaired cognition, motor development, growth velocity and anorexia in addition to anemia. International guidelines currently recommend iron and folic acid supplementation in children < 2 years of age. However, children in a malaria-endemic region of Tanzania randomized to receive iron supplementation suffered from 15% increased all-cause mortality.1

This study is of great interest since it specifically addresses malaria outcomes in a population of children from a malaria-endemic region who did not generally receive iron supplementation. From the standpoint of pathogenesis the results of this study are intriguing, yet it is unclear whether iron deficiency limits parasite density due to parasite or host-specific effects. Malaria parasites acquire iron through a transferrin-independent pathway and iron chelation reduces parasite growth.2,3 In the host, iron chelation increases cellular nitric oxide (NO) production and parasite killing in cell culture.4 Iron has also been shown to inhibit NO synthase (iNOS), therefore iron supplementation may impair iNOS-mediated macrophage-mediated cytotoxicity against malaria parasites.

These data show that interventional studies are needed which are designed to ascertain the benefits and risks of iron supplementation in children in malaria-endemic regions, but only in conjunction with effective malaria control measures.

References

  1. Sazawal S, et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomized, placebo-controlled trial. Lancet 2006;367:133-43.
  2. Sanchez-Lopez R, et al. A transferrin-independent iron uptake activity in Plasmodium falciparum-infected and uninfected erythrocytes. Mol Biochem Parasitol 1992;55:9-20.
  3. Hershko C, et al. Deferoxamine inhibition of malaria is independent of host iron status. J Exp Med 1988;168:375-87.
  4. Fritsche G, et al. Regulatory interaction between iron and nitric oxide metabolism for immune defense against Plasmodium falciparum infection. J Infect Dis 2001;183:1388-94.