title: Plasmodium falciparum mutant haplotype infection during pregnancy associated with reduced birthweight, Tanzania.
abstract: 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.
authors: National Institute for Medical Research, Tanga Centre, Tanga, United Republic of Tanzania. minjartd@gmail.com
authors: Daniel T R
authors: DT
authors: Minja
authors: Christentze
authors: C
authors: Schmiegelow
authors: Bruno
authors: B
authors: Mmbando
authors: Stéphanie
authors: S
authors: Boström
authors: Mayke
authors: M
authors: Oesterholt
authors: Pamela
authors: P
authors: Magistrado
authors: Caroline
authors: C
authors: Pehrson
authors: Davis
authors: D
authors: John
authors: Ali
authors: A
authors: Salanti
authors: Adrian J F
authors: AJ
authors: Luty
authors: Martha
authors: M
authors: Lemnge
authors: Thor
authors: T
authors: Theander
authors: John
authors: J
authors: Lusingu
authors: Michael
authors: M
authors: Alifrangis
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D005260:Female; D005865:Gestational Age; D006239:Haplotypes; D006801:Humans; D007230:Infant, Low Birth Weight; D016778:Malaria, Falciparum / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control; D011256:Pregnancy Outcome; D011446:Prospective Studies; D013636:Tanzania; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D055815:Young Adult
chemical_list: D013762:Tetrahydrofolate Dehydrogenase
keywords: Plasmodium falciparum; Tanzania; dihydrofolate reductase; dihydropteroate synthetase; drug resistance; haplotype; intermittent preventive treatment; low birth weight; malaria; mutations; parasites; polymorphisms; pregnancy; sextuple; sulfadoxine-pyrimethamine
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