Molecular markers of resistance to sulphadoxine-pyrimethamine one year after implementation of intermittent preventive treatment of malaria in infants in Mali.
BACKGROUND
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. However, there is a fear that IPTi may result in a rapid increase of parasite resistance to SP.


METHODS
To 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.


RESULTS
Each 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%).


CONCLUSIONS
This study shows no increase in the frequency of molecular markers of SP resistance in areas where IPTi with SP was implemented for one year.
Dicko
Alassane
A
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine Pharmacy and Dentistry, University of Bamako, PO Box 1805 Bamako, Mali. adicko@mrtcbko.org
Sagara
Issaka
I
Djimdé
Abdoulaye A
AA
Touré
Sidy O
SO
Traore
Mariam
M
Dama
Souleymane
S
Diallo
Abdoulbaki I
AI
Barry
Amadou
A
Dicko
Mohamed
M
Coulibaly
Oumar M
OM
Rogier
Christophe
C
de Sousa
Alexandra
A
Doumbo
Ogobara K
OK
D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use*; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D008302:Mali; D010961:Plasmodium / Q000187:drug effects* / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology* / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000494:pharmacology* / Q000627:therapeutic use*; D017211:Treatment Failure
D000962:Antimalarials; D016054:DNA, Protozoan; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine