Abstract
BackgroundIntermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) given during routine vaccinations is efficacious in preventing malaria disease and shows no interaction with the vaccines. However, there is a fear that IPTi may result in a rapid increase of parasite resistance to SP.MethodsTo evaluate the impact of IPTi on SP-resistance point mutations, the 22 health sub-districts in the district of Kolokani, Mali, were randomized in a 1:1 ratio and starting in December 2006, IPTi with SP was implemented in 11 health sub-districts (intervention zone), while the other 11 health sub-districts served as the control (non-intervention zone). Blood smears and blood dots on filter paper were obtained from children aged 0-5 years, randomly selected in each of heath sub-districts during two cross-sectional surveys. The first survey was conducted in May 2007 before the start of the transmission season to collect baseline prevalence of the molecular markers of resistance to SP and the second in December 2007 after the end of the transmission season and one year after implementation of IPTi. A total of 427 and 923 randomly selected blood samples from the first and second surveys respectively were analysed by PCR for dhfr and dhps mutations.ResultsEach of the three dhfr mutations at codons 51, 59 and 108 was present in 35% and 57% of the samples during the two surveys with no significant differences between the two zones. Dhps mutations at codons 437 and 540 were present respectively in about 20% and 1% of the children during the two surveys in both zones at similar proportion. The prevalence of quadruple mutants (triple dhfr-mutants + dhps-437G) associated with in-vivo resistance to SP in Mali after one year implementation of IPTi was also similar between the two zones (11.6% versus 11.2%, p = 0.90) and to those obtained at baseline survey (10.3% versus 8.1%).ConclusionThis study shows no increase in the frequency of molecular markers of SP resistance in areas where IPTi with SP was implemented for one year.
Highlights
Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) given during routine vaccinations is efficacious in preventing malaria disease and shows no interaction with the vaccines
Several randomized controlled trials have demonstrated that Intermittent Preventive Treatment of malaria in infants (IPTi) with sulphadoxine-pyrimethamine (SP) given during routine vaccinations of the Expanded Programme of Immunization (EPI) at approximately two, three and nine months of age, result in a reduction of the incidence of clinical malaria by 22 to 59% [2,3,4,5,6,7,8], without showing interactions with EPI vaccines [2,4,9]
The efficacy and safety as well as the lack of interaction with EPI vaccines of IPTi in various endemic areas were well established [10,11,12], there have been concerns regarding the possibility that this strategy may cause an increase of Plasmodium falciparum resistance to SP, jeopardizing the use of SP for the prevention of malaria in infants, and in pregnant women [13,14,15], an intervention widely adopted in many countries in sub-Saharan Africa
Summary
Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) given during routine vaccinations is efficacious in preventing malaria disease and shows no interaction with the vaccines. Several randomized controlled trials have demonstrated that Intermittent Preventive Treatment of malaria in infants (IPTi) with sulphadoxine-pyrimethamine (SP) given during routine vaccinations of the Expanded Programme of Immunization (EPI) at approximately two, three and nine months of age, result in a reduction of the incidence of clinical malaria by 22 to 59% [2,3,4,5,6,7,8], without showing interactions with EPI vaccines [2,4,9]. This study evaluated the impact of IPTi on the selection SPresistant dhfr and dhps mutations in P. falciparum after 12 months of implementation of IPTi in the district of Kolokani, Mali, where UNICEF pilot implementation of IPTi with SP was undertaken as part of a large operational research study in six African malaria endemic countries
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