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The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women.

Publication ,  Journal Article
Gutman, J; Kalilani, L; Taylor, S; Zhou, Z; Wiegand, RE; Thwai, KL; Mwandama, D; Khairallah, C; Madanitsa, M; Chaluluka, E; Dzinjalamala, F ...
Published in: J Infect Dis
June 15, 2015

BACKGROUND: The A581 G: mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called sextuple mutant, has been associated with increased placental inflammation and decreased infant birth weight among women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) during pregnancy. METHODS: Between 2009 and 2011, delivering women without human immunodeficiency virus infection were enrolled in an observational study of IPTp-SP effectiveness in Malawi. Parasites were detected by polymerase chain reaction (PCR); positive samples were sequenced to genotype the dhfr and dhps loci. The presence of K540 E: in dhps was used as a marker for the quintuple mutant. RESULTS: Samples from 1809 women were analyzed by PCR; 220 (12%) were positive for P. falciparum. A total of 202 specimens were genotyped at codon 581 of dhps; 17 (8.4%) harbored the sextuple mutant. The sextuple mutant was associated with higher risks of patent infection in peripheral blood (adjusted prevalence ratio [aPR], 2.76; 95% confidence interval [CI], 1.82-4.18) and placental blood (aPR 3.28; 95% CI, 1.88-5.78) and higher parasite densities. Recent SP use was not associated with increased parasite densities or placental pathology overall and among women with parasites carrying dhps A581 G: . CONCLUSIONS: IPTp-SP failed to inhibit parasite growth but did not exacerbate pathology among women infected with sextuple-mutant parasites. New interventions to prevent malaria during pregnancy are needed urgently.

Duke Scholars

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

June 15, 2015

Volume

211

Issue

12

Start / End Page

1997 / 2005

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Tetrahydrofolate Dehydrogenase
  • Sulfadoxine
  • Sequence Analysis, DNA
  • Pyrimethamine
  • Pregnancy
  • Polymerase Chain Reaction
  • Point Mutation
  • Plasmodium falciparum
  • Mutation, Missense
 

Citation

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MLA
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Gutman, J., Kalilani, L., Taylor, S., Zhou, Z., Wiegand, R. E., Thwai, K. L., … ter Kuile, F. O. (2015). The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women. J Infect Dis, 211(12), 1997–2005. https://doi.org/10.1093/infdis/jiu836
Gutman, Julie, Linda Kalilani, Steve Taylor, Zhiyong Zhou, Ryan E. Wiegand, Kyaw L. Thwai, Dyson Mwandama, et al. “The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women.J Infect Dis 211, no. 12 (June 15, 2015): 1997–2005. https://doi.org/10.1093/infdis/jiu836.
Gutman J, Kalilani L, Taylor S, Zhou Z, Wiegand RE, Thwai KL, Mwandama D, Khairallah C, Madanitsa M, Chaluluka E, Dzinjalamala F, Ali D, Mathanga DP, Skarbinski J, Shi YP, Meshnick S, ter Kuile FO. The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women. J Infect Dis. 2015 Jun 15;211(12):1997–2005.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

June 15, 2015

Volume

211

Issue

12

Start / End Page

1997 / 2005

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Tetrahydrofolate Dehydrogenase
  • Sulfadoxine
  • Sequence Analysis, DNA
  • Pyrimethamine
  • Pregnancy
  • Polymerase Chain Reaction
  • Point Mutation
  • Plasmodium falciparum
  • Mutation, Missense