Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea

Abstract

A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; a lower haemoglobin associated with malaria when compared with the placebo group and a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic.

Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6–36 month old Togolese children

“…For instance, the 2-month-old infants included in the later study (Oppenheimer et al, 1986) had probably not developed immunity to malaria, whereas our children had antimalarial antibodies before the iron supplementation. The form of iron supply in the study of Oppenheimer, intramuscular injection of iron, the de®cient nutritional status of their infants, or the high doses of oral iron supplements in other studies (Murray et al, 1978) may also account for the negative effect of iron on infections.…”

“…Other studies who concluded a negative impact of iron supplementation on infections (Oppenheimer et al, 1984;Murray et al, 1978), particularly on malaria (Murray et al, 1978;Oppenheimer et al, 1986) are subject to discussion. For instance, the 2-month-old infants included in the later study (Oppenheimer et al, 1986) had probably not developed immunity to malaria, whereas our children had antimalarial antibodies before the iron supplementation.…”

“…However, several studies have indicated that iron de®-ciency protects against infection and iron supplementation increases morbidity (Harvey et al, 1989;Oppenheimer et al, 1986). Other studies show the opposite, i.e.…”

Deferoxamine inhibition of malaria is independent of host iron status.

“…A number of clinical observations suggest that iron administration may aggravate the risk associated with malarial infection (3)(4)(5). The relative shortage of intracellular hemoglobin in iron-deficient RBC may be responsible for limiting parasite growth (16) .…”

Erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia

“…8 In humans, iron deficiency appears to protect against severe malaria, 9-11 while iron supplementation increases the risks of infection and disease. [12][13][14][15] Iron deficiency also provides protection against infection with Plasmodium berghei in mice. 16,17 M alaria, a major global health challenge worldwide, is accompanied by a severe anemia secondary to hemolysis and increased erythrophagocytosis.…”