Delaying the start of iron until 28 days after antimalarial treatment is associated with lower incidence of subsequent illness in children with malaria and iron deficiency

We evaluated the incidence of all-cause and malaria-specific clinic visits during follow-up of a recent trial of iron therapy. In the main trial, Ugandan children 6-59 months with smear-confirmed malaria and iron deficiency [zinc protoporphyrin (ZPP > = 80 μmol/mol heme)] were treated for malaria and randomized to start a 27-day course of oral iron concurrently with (immediate group) or 28 days after (delayed group) antimalarial treatment. All children were followed for the same 56-day period starting at the time of antimalarial treatment (Day 0) and underwent passive and active surveillance for malaria and other morbidity for the entire follow-up period. All ill children were examined and treated by the study physician. In this secondary analysis of morbidity data from the main trial, we report that although the incidence of malaria-specific visits did not differ between the groups, children in the immediate group had a higher incidence rate ratio of all-cause sick-child visits to the clinic during the follow-up period (Incidence Rate Ratio (IRR) immediate/delayed = 1.76; 95%CI: 1.05-3.03, p = 0.033). Although these findings need to be tested in a larger trial powered for malaria-specific morbidity, these preliminary results suggest that delaying iron by 28 days in children with coexisting malaria and iron deficiency is associated with a reduced risk of subsequent all-cause illness.