Molecular markers of resistance to sulfadoxine-pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants.
BACKGROUND
Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a potential malaria control strategy. There is concern about the impact that increasing in vivo resistance to SP has on the efficacy of IPTi, as well as about the potential contribution of IPTi to increases in resistance.


METHODS
We compared the frequency of clinical episodes of malaria caused by P. falciparum parasites with mutations in dhfr and dhps among sick children who received SP or placebo in the context of a randomized, double-blind, placebo-controlled IPTi trial in Mozambique.


RESULTS
Half of the children who received placebo harbored quintuple-pure mutant parasites. Nevertheless, the protective efficacy of IPTi within the 35 days after the third dose was 70.8% (95% confidence interval [CI], 40.7%-85.6%). Between month 2 after the third IPTi dose and the end of the follow-up period, children receiving SP harbored more dhps codon 437 mixed infections (odds ratio [OR], 10.56 [95% CI, 1.30-86.14]) and fewer dhps double-pure mutant parasites (OR, 0.43 [95% CI, 0.22-0.84]) than did placebo recipients.


CONCLUSIONS
IPTi appears to be associated with some changes in the prevalence of genotypes involved in SP resistance. In the face of a high prevalence of quintuple-mutant parasites, SP exhibited a high level of efficacy in the prevention of new episodes of malaria in infants.
Mayor
Alfredo
A
Centre de Recerca en Salut Internacional de Barcelona, Hospital Clínic/Institut d'Investigacions Biomèdicas August Pí i Sunyer, Universitat de Barcelona, Barcelona, Spain. agmayor@clinic.ub.es
Serra-Casas
Elisa
E
Sanz
Sergi
S
Aponte
John J
JJ
Macete
Eusebio
E
Mandomando
Inacio
I
Puyol
Laura
L
Berzosa
Pedro
P
Dobaño
Carlota
C
Aide
Pedro
P
Sacarlal
Jahit
J
Benito
Agustín
A
Alonso
Pedro
P
Menéndez
Clara
C
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000494:pharmacology*; D015415:Biomarkers; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D009073:Mozambique; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000494:pharmacology*; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000494:pharmacology*
D000962:Antimalarials; D015415:Biomarkers; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine