Steve M Taylor1,2,3, Brandt Levitt4, Betsy Freedman1, Mwayiwawo Madanitsa5,6, Kyaw-Lay Thwai3, Linda Kalilani-Phiri5, Carole Khairallah6, Victor Mwapasa5, Feiko O Ter Kuile6, Steven R Meshnick3. 1. Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA. 2. Duke Global Health Institute, Durham, North Carolina, USA. 3. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. 4. Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA. 5. Department of Public Health, School of Public Health and Family Medicine, College of Medicine, Blantyre, Malawi. 6. Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Abstract
BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. ISRCTN REGISTRY: www.isrctn.com/ISRCTN69800930.
RCT Entities:
BACKGROUND:Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhpsA581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. ISRCTN REGISTRY: www.isrctn.com/ISRCTN69800930.
Authors: C H Sibley; J E Hyde; P F Sims; C V Plowe; J G Kublin; E K Mberu; A F Cowman; P A Winstanley; W M Watkins; A M Nzila Journal: Trends Parasitol Date: 2001-12
Authors: Whitney E Harrington; Theonest K Mutabingwa; Edward Kabyemela; Michal Fried; Patrick E Duffy Journal: Clin Infect Dis Date: 2011-08-01 Impact factor: 9.079
Authors: Meghna Desai; Julie Gutman; Steve M Taylor; Ryan E Wiegand; Carole Khairallah; Kassoum Kayentao; Peter Ouma; Sheick O Coulibaly; Linda Kalilani; Kimberly E Mace; Emmanuel Arinaitwe; Don P Mathanga; Ogobara Doumbo; Kephas Otieno; Dabira Edgar; Ebbie Chaluluka; Mulakwa Kamuliwo; Veronica Ades; Jacek Skarbinski; Ya Ping Shi; Pascal Magnussen; Steve Meshnick; Feiko O Ter Kuile Journal: Clin Infect Dis Date: 2015-10-20 Impact factor: 9.079
Authors: Steve M Taylor; Christian M Parobek; Derrick K DeConti; Kassoum Kayentao; Sheick Oumar Coulibaly; Brian M Greenwood; Harry Tagbor; John Williams; Kalifa Bojang; Fanta Njie; Meghna Desai; Simon Kariuki; Julie Gutman; Don P Mathanga; Andreas Mårtensson; Billy Ngasala; Melissa D Conrad; Philip J Rosenthal; Antoinette K Tshefu; Ann M Moormann; John M Vulule; Ogobara K Doumbo; Feiko O Ter Kuile; Steven R Meshnick; Jeffrey A Bailey; Jonathan J Juliano Journal: J Infect Dis Date: 2014-09-01 Impact factor: 5.226
Authors: Esmée Ruizendaal; Marc C Tahita; Ronald B Geskus; Inge Versteeg; Susana Scott; Umberto d'Alessandro; Palpouguini Lompo; Karim Derra; Maminata Traore-Coulibaly; Menno D de Jong; Henk D F H Schallig; Halidou Tinto; Petra F Mens Journal: Malar J Date: 2017-04-28 Impact factor: 2.979
Authors: 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 Journal: Emerg Infect Dis Date: 2013 Impact factor: 6.883
Authors: Mwayiwawo Madanitsa; Linda Kalilani; Victor Mwapasa; Anna M van Eijk; Carole Khairallah; Doreen Ali; Cheryl Pace; James Smedley; Kyaw-Lay Thwai; Brandt Levitt; Duolao Wang; Arthur Kang'ombe; Brian Faragher; Steve M Taylor; Steve Meshnick; Feiko O Ter Kuile Journal: PLoS Med Date: 2016-09-13 Impact factor: 11.069
Authors: Julie R Gutman; Carole Khairallah; Kasia Stepniewska; Harry Tagbor; Mwayiwawo Madanitsa; Matthew Cairns; Anne Joan L'lanziva; Linda Kalilani; Kephas Otieno; Victor Mwapasa; Steve Meshnick; Simon Kariuki; Daniel Chandramohan; Meghna Desai; Steve M Taylor; Brian Greenwood; Feiko O Ter Kuile Journal: EClinicalMedicine Date: 2021-10-25
Authors: Patience Nayebare; Victor Asua; Melissa D Conrad; Richard Kajubi; Abel Kakuru; Joaniter I Nankabirwa; Dennis Muhanguzi; Grant Dorsey; Moses R Kamya; Sam Nsobya; Philip J Rosenthal Journal: Antimicrob Agents Chemother Date: 2020-11-17 Impact factor: 5.938