Plasmodium falciparumMutant Haplotype Infection during Pregnancy Associated with Reduced Birthweight, Tanzania

• DOI: 10.3201/eid1909.130133
• Publication Date: 2013-06-26T18:33:29Z
• Authors: Daniel T. R. Minja; Christentze Schmi...; Bruno Mmbando; Stéphanie Boström; Mayke Oesterholt; Pamela Magistrado; Caroline Pehrson; Davis John; Ali Salanti; Adrian J.F. Luty; Martha Lemnge; Thor Theander; John Lusingu; Michael Alifrangis
• Keywords: Adult; haplotype; Adolescent; Plasmodium falciparum; malaria; Gestational Age; Infectious and parasitic diseases; RC109-216; Polymorphism, Single Nucleotide; Tanzania; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Pregnancy; Humans; Prospective Studies; Malaria, Falciparum; Alleles; drug resistance; Research; R; Pregnancy Outcome; Infant, Low Birth Weight; mutations; 3. Good health; Tetrahydrofolate Dehydrogenase; Haplotypes; Pregnancy Complications, Parasitic; Mutation; Medicine; Female; pregnancy

Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is a key strategy in the control of pregnancy-associated malaria. However, this strategy is compromised by widespread drug resistance from single-nucleotide polymorphisms in the Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthetase genes. During September 2008-October 2010, we monitored a cohort of 924 pregnant women in an area of Tanzania with declining malaria transmission. P. falciparum parasites were genotyped, and the effect of infecting haplotypes on birthweight was assessed. Of the genotyped parasites, 9.3%, 46.3%, and 44.4% had quadruple or less, quintuple, and sextuple mutated haplotypes, respectively. Mutant haplotypes were unrelated to SP doses. Compared with infections with the less-mutated haplotypes, infections with the sextuple haplotype mutation were associated with lower (359 g) birthweights. Continued use of the suboptimal IPTp-SP regimen should be reevaluated, and alternative strategies (e.g., intermittent screening and treatment or intermittent treatment with safe and effective alternative drugs) should be evaluated.