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Furthermore, the upper limits of the self-confidence intervals for efficacy in year 4 exclude an efficacy of more than 31 percent overall and an efficacy of more than 15 percent among children with a high exposure index. The waning of vaccine efficacy observed with our data is usually unlikely to end up being the result of heterogeneity in malaria exposure, because reductions in efficacy over time were similar whether first or all episodes had been analyzed and also because they persisted actually after the exposure index was included in the model. We identified significant interactions between period since vaccination and vaccine efficacy and between degree of exposure to malaria and vaccine efficacy.