Abstract
BackgroundIntermittent 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 ResultsWe 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.ConclusionsA 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.
Highlights
Intermittent preventive treatment of malaria with sulfadoxinepyrimethamine (SP) in infants (SP- IPTi) reduced the incidence of clinical malaria in areas of sub-Saharan Africa with low to moderate SP resistance in sub-Saharan Africa [1,2,3,4,5] but had no significant protective effect in one area of high SP resistance [6] and one area of low transmission [7]
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
Based on the findings from these 7 randomised trials, a technical Expert Group convened by the World Health Organization (WHO) in 2009 recommended SP-IPTi for use as a malaria control tool in sub-Saharan Africa under certain conditions [8]
Summary
Intermittent preventive treatment of malaria with sulfadoxinepyrimethamine (SP) in infants (SP- IPTi) reduced the incidence of clinical malaria in areas of sub-Saharan Africa with low to moderate SP resistance in sub-Saharan Africa [1,2,3,4,5] but had no significant protective effect in one area of high SP resistance [6] and one area of low transmission [7]. The aim of this study was to explore the relationship between protective efficacy of SP-IPTi and measures of resistance to SP in order to better define this relationship. 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. We examine the relationship between the protective efficacy of SP-IPTi and measures of SP resistance
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