Interactions between Age and ITN Use Determine the Risk of Febrile Malaria in Children

Abstract

BackgroundControl measures which reduce individual exposure to malaria are expected to reduce disease, but also to eventually reduce immunity. Reassuringly, long term data following community wide ITN distribution show sustained benefits at a population level. However, the more common practice in Sub-Saharan Africa is to target ITN distribution on young children. There are few data on the long term outcomes of this practice.Methodology/Principal FindingsEpisodes of febrile malaria were identified by active surveillance in 383 children over 18 months of follow up. In order to compare the short and long term outcomes of ITN use, we examined interactions between ITN use and age (12–42 months of age versus 42–80 months) in determining the risk of febrile malaria. ITN use and older age protected against the first or only episode of malaria (Hazard Ratio [HR] = 0.33, 95%CI 0.17–0.65 and HR = 0.30, 95%CI 0.17–0.51, respectively). The interaction term between ITN use and older age was HR = 2.91, 95%CI 1.02–8.3, p = 0.045, indicating that ITNs did not protect older children. When multiple episodes were included in analysis, ITN use and older age were again protective against malaria episodes (Incident Rate Ratio [IRR] = 0.43 95%CI 0.27–0.7) and IRR = 0.23, 95%CI 0.13–0.42, respectively) and the interaction term indicated that ITNs did not protect older children (IRR = 2.71, 95%CI 1.3–5.7, p = 0.008).Conclusions/SignificanceThese data on age interactions with ITN use suggest that larger scale studies on the long term individual outcomes should be undertaken if the policy of targeted ITN use for vulnerable groups is to continue.

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“…90 Misclassification of unexposed individuals as "protected" will significantly bias interpretation of the immune response measured. 33,90 This is a particular problem for studies using GIA since the acquisition of growth inhibitory antibodies appears to be linked to exposure (see Table 1). The use of more clinically relevant endpoints such as protection against clinical disease (defined as parasitemia with clinical symptoms vs. asymptomatic parasitemia) may be more informative.…”

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