FIGURE 1 Incidence of first clinical malaria episodes over the course of the malaria season among subjects who received curative sulfadoxine-pyrimethamine.

SOURCE: Coulibaly et al., 2002. Reprinted with permission from the American Journal of Tropical Medicine and Hygiene. Copyright 2002 by the American Society of Tropical Medicine and Hygiene.

In the six IPTi-SP studies, all infants received a dose of SP or of placebo at 9 months of age, as either the second or the third SP (or placebo) dose. Notably, the previous dose of SP or of placebo had been administered at either 3 or 4 months of age, depending on the study (Table 2). In each study, therefore, the infants had 5–6 months of follow-up between doses, a follow-up time that is considerably longer than the 1–2 months during which drug levels of SP would be expected to remain protective and including early post-therapy period when rebound would be most likely to manifest (Coulibaly et al., 2002; White, 2005). Similarly, in the three studies in which children received their SP or placebo doses at 3, 9 and 15 months of age, the period between 9 and 15 months is far longer than one would expect the drug’s protective effect to have lasted and to have been the only factor responsible for providing protection against the disease. Stated in another way, whatever the protective effect of SP during the intervention period, because of the long periods of time between the last two doses (either the time between the ages of 4 and 9 months or the time between the ages 9 and 15 months), one would expect the children to have considerable exposure to infected mosquitoes during periods when they do not have protective blood levels of the drug, and therefore they presumably will have repetitive immunologic stimulation by Plasmodium.

The ideal approach to assessing the efficacy of IPTi-SP would have been to have reviewed an array of large, randomized clinical trials conducted under several geographic and epidemiologic scenarios. These trials would have studied various clinical outcomes, including total burden of morbidity both during the period of SP use and for a subsequent period during which rebound could occur. The data available to the IOM committee were not ideal in all these