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Background  Intermittent Preventive Treatment of malaria in infants using sulfadoxine-pyrimethamine (SP-IPTi) is recommended by WHO for implementation in settings where resistance to SP is not high. Here we examine the relationship between the protective efficacy of SP-IPTi and measures of SP resistance.    Methods and Results  We analysed the relationship between protective efficacy reported in the 7 SP-IPTi trials and contemporaneous data from 6  in vivo  efficacy studies using SP and 7 molecular studies reporting frequency of  dhfr  triple and  dhps  double mutations within 50km of the trial sites. We found a borderline significant association between frequency of the  dhfr  triple mutation and protective efficacy to 12 months of age of SP-IPTi. This association is significantly biased due to differences between studies, namely number of doses of SP given and follow up times. However, fitting a simple probabilistic model to determine the relationship between the frequency of the  dhfr  triple,  dhps  double and  dhfr/dhps  quintuple mutations associated with resistance to SP and protective efficacy, we found a significant inverse relationship between the  dhfr  triple mutation frequency alone and the  dhfr/dhps  quintuple mutations and efficacy at 35 days post the 9 month dose and up to 12 months of age respectively.    Conclusions  A significant relationship was found between the frequency of the  dhfr  triple mutation and SP-IPTi protective efficacy at 35 days post the 9 month dose. An association between the protective efficacy to 12 months of age and  dhfr  triple and  dhfr/dhps  quintuple mutations was found but should be viewed with caution due to bias. It was not possible to define a more definite relationship based on the data available from these trials.

Protective Efficacy of Intermittent Preventive Treatment of Malaria in Infants (IPTi) Using Sulfadoxine-Pyrimethamine and Parasite Resistance