Reduced Efficacy of Intermittent Preventive Treatment of Malaria in Malnourished Children

Intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) reduces malaria episodes by 20 to 59% across Africa. This protective efficacy, however, may be affected by the high frequency of malnutrition in African infants. We analyzed the impact of malnutrition as defined by anthropometry on the incidence of malaria and on the protective efficacy of IPTi in a cohort of 1,200 children in northern Ghana, where malaria is hyperendemic. These children received IPTi-SP or placebo at 3, 9, and 15 months of age and were monitored until 24 months of age. Malnutrition was present in 32, 40, and 50% of children at ages 3, 9, and 15 months, respectively. It was associated with increased risks of severe anemia and death but not an increased risk of malaria. Although malaria slightly contributed to chronic malnutrition, IPTi did not substantially improve child growth. Importantly, the protective efficacies of IPTi in malnourished children were roughly half or even less of those observed in nonmalnourished children. In the first year of life, IPTi reduced the incidence of malaria to a significantly lesser extent in infants who received both doses in a malnourished condition (25%; 95% confidence interval [CI], −7 to 48%) compared to that of nonmalnourished children (46%; 95% CI, 30 to 58%; P = 0.049). Moreover, in contrast to nutritionally advantaged children, the rate of severe malaria appeared to be increased in malnourished children who took IPTi. IPTi might exhibit reduced efficacy in regions of abundant malnutrition. Concomitant nutrition programs may be needed in these places to achieve the desired impact.Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) appears to be a promising tool of malaria control in young children. The initial IPTi trial in Tanzania reported a protective efficacy (PE) against uncomplicated malaria in infancy of 59% and some degree of protection persisting into the second year of life (28, 29). In subsequent studies at sites of differing endemicity in sub-Saharan Africa, protection in infancy was confirmed; however, the PEs were lower, at 20 to 33% (5, 12, 15, 17, 23). We have reported previously that in Tamale, northern Ghana, IPTi reduced the incidence of asymptomatic parasitemia, uncomplicated malaria, and severe anemia from 3 to 24 months of age by 29, 17, and 15%, respectively. These effects were greatest in the first year of life and less pronounced in the second (23).As in many regions of Africa, malnutrition is abundant in northern Ghana, reaching prevalences as high as 50% in preschool children, depending on seasonality and food availability (32 and http://www.who.int/nutgrowthdb/database/countries/nchs_reference/gha.pdf). Malnutrition causes relative immunosuppression, and repeated or chronic infections may contribute to poor nutritional status (27). However, the effect of malnutrition on malaria is less clear cut than would be expected: protein-energy malnutrition has been associated with greater malaria morbidity and mortality in some areas but not in others (4, 6, 8, 21, 24, 30). Moreover, the risk of antimalarial treatment failure appears to be increased in malnourished children (13, 14, 22, 39). Taken together, these findings suggest that malnutrition is one factor contributing to malaria-associated morbidity and that malaria control strategies without concomitant nutrition programs may not have the desired impact on childhood morbidity on a large scale (8). We hypothesized that malnutrition affects both malaria morbidity and IPTi efficacy. Alternatively, IPTi might improve children''s growth and nutritional status. We reanalyzed data from a cohort from northern Ghana (23) regarding the effect of malnutrition on the PE of IPTi, and here we report the results of this secondary analysis.