Protective efficacy of intermittent preventive treatment of malaria in infants (IPTi) using sulfadoxine-pyrimethamine and parasite resistance.
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.


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 50 km 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.
Griffin
Jamie T
JT
MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.
Cairns
Matthew
M
Ghani
Azra C
AC
Roper
Cally
C
Schellenberg
David
D
Carneiro
Ilona
I
Newman
Robert D
RD
Grobusch
Martin P
MP
Greenwood
Brian
B
Chandramohan
Daniel
D
Gosling
Roly D
RD
D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000962:Antimalarials / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control*; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
D000962:Antimalarials; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D000426:Alcohol Dehydrogenase; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine