Molecular Markers of Resistance to Sulfadoxine-Pyrimethamine during Intermittent Preventive Treatment for Malaria in Mozambican Infants

• Published in: The Journal of infectious diseases Vol. 197; no. 12; pp. 1737 - 1742
• Main Authors: Mayor, Alfredo, Serra-Casas, Elisa, Sanz, Sergi, Aponte, John J., Macete, Eusebio, Mandomando, Inacio, Puyol, Laura, Berzosa, Pedro, Dobaño, Carlota, Aide, Pedro, Sacarlal, Jahit, Benito, Agustín, Alonso, Pedro, Menéndez, Clara
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.06.2008; University of Chicago Press
• Subjects: Animals; Antimalarials; Antimalarials - administration & dosage; Antimalarials - pharmacology; Biological and medical sciences; Biomarkers; Blood; Codons; Dosage; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Resistance - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic mutation; Genotypes; Human protozoal diseases; Humans; Infant; Infections; Infectious diseases; Malaria; Malaria, Falciparum - prevention & control; Male; Medical sciences; Microbiology; Mozambique; Mutation; Parasites; Parasitic diseases; Placebos; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Protozoal diseases; Pyrimethamine - administration & dosage; Pyrimethamine - pharmacology; Sulfadoxine - administration & dosage; Sulfadoxine - pharmacology; Mozambique; Human; Antimalarial; Protozoal disease; Microbiology; Malaria; Pyrimethamine; Infant; Parasitosis; Infection; Resistance; Treatment; Sulfonamides; Parasiticide; Antiinfectious; Sulfadoxine; Antibacterial agent
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/588144

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. Conclusion. 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. Trial registration. ClinicalTrials.gov identifier: NCT00209794.