Meghna Desai1,2, Julie Gutman1, Steve M Taylor3,4, Ryan E Wiegand1, Carole Khairallah5, Kassoum Kayentao5,6, Peter Ouma2, Sheick O Coulibaly7, Linda Kalilani8, Kimberly E Mace1, Emmanuel Arinaitwe9, Don P Mathanga8, Ogobara Doumbo6, Kephas Otieno2, Dabira Edgar7, Ebbie Chaluluka8, Mulakwa Kamuliwo10, Veronica Ades11, Jacek Skarbinski1, Ya Ping Shi1, Pascal Magnussen12, Steve Meshnick4, Feiko O Ter Kuile5. 1. Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia. 2. Malaria Branch, Center for Global Health Research, Kenya Medical Research Institute, Kisumu. 3. Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina. 4. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill. 5. Department of Clinical Sciences, Liverpool School of Tropical Medicine, United Kingdom. 6. Malaria Research and Training Center, University of Sciences, Technics and Technologies of Bamako, Mali. 7. University of Ouagadougou, Burkina Faso. 8. College of Medicine, University of Malawi, Blantyre. 9. Infectious Disease Research Collaboration, Kampala, Uganda. 10. National Malaria Control Center, Lusaka, Zambia. 11. New York University Langone Medical Center, New York. 12. Centre for Medical Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Abstract
BACKGROUND: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. METHODS: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. RESULTS: Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02). CONCLUSIONS: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
BACKGROUND: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. METHODS: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. RESULTS: Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02). CONCLUSIONS: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Entities:
Keywords:
effectiveness; intermittent preventive treatment; malaria in pregnancy; sulfadoxine-pyrimethamine resistance
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