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- Title
Interactions Between Antenatal Sulfadoxine-Pyrimethamine, Drug-Resistant Plasmodium falciparum Parasites, and Delivery Outcomes in Malawi.
- Authors
Taylor, Steve M; Levitt, Brandt; Freedman, Betsy; Madanitsa, Mwayiwawo; Thwai, Kyaw-Lay; Kalilani-Phiri, Linda; Khairallah, Carole; Mwapasa, Victor; Kuile, Feiko O ter; Meshnick, Steven R; Ter Kuile, Feiko O
- Abstract
<bold>Background: </bold>Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients.<bold>Methods: </bold>We measured SP-resistance allele frequencies in Malawian women participating in a trial comparing IPTp with SP against intermittent screening by rapid diagnostic tests (ISTp). We genotyped polymerase chain reaction-detected parasites using deep sequencing of SP-resistance alleles.<bold>Results: </bold>Among 125 placental infections, A581G-bearing parasites were associated with reduced birth weight (mean difference [MD], 252 g; 95% confidence interval [CI], 46-457; P = .017). Relative to ISTp, IPTp-SP was associated with higher birth weights in women with wild-type parasites (MD, 116 g; 95% CI, -40 to 272; P = .142) and lower birth weights in women with A581G-bearing parasites (MD, 192 g; 95% CI, -264 to 648; P = .385) (Pinteraction = .033). Similar associations were noted on gestational age (Pinteraction = .075). Amongst only IPTp-SP recipients, relative to women who last received SP > 4 weeks before delivery, recent SP receipt was associated with lower birth weight in women with wild-type parasites (MD, 118 g; 95% CI, -376 to 139; P = .361) and higher birth weight in women with A581G-bearing parasites (MD, 783 g; 95% CI, -20 to 1586; P = .054) (Pinteraction = .005).<bold>Conclusions: </bold>The effectiveness in birth weight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP.<bold>Isrctn Registry: </bold>www.isrctn.com/ISRCTN69800930.
- Subjects
SUB-Saharan Africa; MALAWI; PLASMODIUM falciparum; BIRTH weight; LOW birth weight; PARASITES; GESTATIONAL age; MALARIA prevention; PROTOZOA; RESEARCH; GENETIC mutation; COMBINATION drug therapy; ANIMAL experimentation; RESEARCH methodology; DRUG resistance; REGRESSION analysis; EVALUATION research; MEDICAL cooperation; MALARIA; COMPARATIVE studies; SULFANILAMIDES; GENOTYPES; ANTIMALARIALS; PARASITIC diseases in pregnancy
- Publication
Journal of Infectious Diseases, 2020, Vol 222, Issue 4, p661
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiaa145