Plasmodium falciparum mutant haplotype infection during pregnancy associated with reduced birthweight, Tanzania

Daniel T R Minja; Christentze Schmiegelow; 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

doi:10.3201/eid1909.130133

Plasmodium falciparum mutant haplotype infection during pregnancy associated with reduced birthweight, Tanzania

Daniel T R Minja, Christentze Schmiegelow, 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

53 Citations (Scopus)

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.

Original language	English
Journal	Emerging Infectious Diseases (Print Edition)
Volume	19
Issue number	9
Pages (from-to)	1446-1454
ISSN	1080-6040
DOIs	https://doi.org/10.3201/eid1909.130133
Publication status	Published - Sept 2013

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10.3201/eid1909.130133

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Minja, D. T. R., Schmiegelow, C., Mmbando, B., Boström, S., Oesterholt, M., Magistrado, P., Pehrson, C., John, D., Salanti, A., Luty, A. J. F., Lemnge, M., Theander, T., Lusingu, J., & Alifrangis, M. (2013). Plasmodium falciparum mutant haplotype infection during pregnancy associated with reduced birthweight, Tanzania. Emerging Infectious Diseases (Print Edition), 19(9), 1446-1454. https://doi.org/10.3201/eid1909.130133

Minja, DTR, Schmiegelow, C, Mmbando, B, Boström, S, Oesterholt, M, Magistrado, P, Pehrson, C, John, D, Salanti, A, Luty, AJF, Lemnge, M, Theander, T, Lusingu, J & Alifrangis, M 2013, 'Plasmodium falciparum mutant haplotype infection during pregnancy associated with reduced birthweight, Tanzania', Emerging Infectious Diseases (Print Edition), vol. 19, no. 9, pp. 1446-1454. https://doi.org/10.3201/eid1909.130133

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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.",

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AU - Boström, Stéphanie

AU - Oesterholt, Mayke

AU - Magistrado, Pamela

AU - Pehrson, Caroline

AU - John, Davis

AU - Salanti, Ali

AU - Luty, Adrian J F

AU - Lemnge, Martha

AU - Theander, Thor

AU - Lusingu, John

AU - Alifrangis, Michael

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N2 - 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.

AB - 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.

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DO - 10.3201/eid1909.130133

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JO - Emerging Infectious Diseases (Print Edition)

JF - Emerging Infectious Diseases (Print Edition)

IS - 9

ER -

Plasmodium falciparum mutant haplotype infection during pregnancy associated with reduced birthweight, Tanzania

Abstract

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