Silvie Huijben1,2, Eusebio Macete3, Ghyslain Mombo-Ngoma4,5,6, Michael Ramharter4,6, Simon Kariuki7, Meghna Desai8, Ya Ping Shi8, Grace Mwangoka9, Achille Massougbodji10, Michel Cot11, Nicaise Tuikue Ndam11, Estefania Uberegui1, Himanshu Gupta1, Pau Cisteró1, John J Aponte1,3, Raquel González1,3, Clara Menéndez1,3, Alfredo Mayor1,3. 1. ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain. 2. Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, Arizona, USA. 3. Centro de Investigação em Saúde da Manhiça, Manhiça, Mozambique. 4. Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon. 5. Institut für Tropenmedizin, Universität Tübingen, und Deutsches Zentrum für Infektionsforschung, Tübingen, Germany. 6. Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 7. Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya. 8. Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 9. Ifakara Health Institute, Bagamoyo, Tanzania. 10. Unité d'Enseignement et de Recherche de Parasitologie Mycologie, Faculté des Sciences de la Santé, Cotonou, Bénin. 11. Université de Paris, MERIT, IRD, Paris, France.
Abstract
BACKGROUND: Innovative approaches are needed to limit antimalarial resistance evolution. Understanding the role of intermittent preventive treatment in pregnancy (IPTp) on the selection for resistance and the impact such selection has on pregnancy outcomes can guide future interventions. METHODS: Plasmodium falciparum isolates (n = 914) from 2 randomized clinical trials were screened for pfmdr1 copy number variation and pfcrt, pfmdr1, pfdhfr, and pfdhps resistance markers. The trials were conducted between 2010 and 2013 in Benin, Gabon, Kenya, and Mozambique to establish the efficacy of IPTp-mefloquine (MQ) compared with IPTp-sulphadoxine-pyrimethamine (SP) in human immunodeficiency virus (HIV)-uninfected and to IPTp-placebo in HIV-infected women. RESULTS: In HIV-uninfected women, the prevalence of pfcrt mutants, pfdhfr/pfdhps quintuple mutants, and pfmdr1 copy number was similar between women receiving IPT-SP and IPTp-MQ. However, prevalence of pfmdr1 polymorphism 86Y was lower in the IPTp-MQ group than in the IPTp-SP group, and within the IPTp-MQ group it was lower at delivery compared with recruitment. No effect of IPTp-MQ on resistance markers was observed among HIV-infected women. The carriage of resistance markers was not associated with pregnancy outcomes. CONCLUSIONS: Selection of wild-type pfmdr1 polymorphism N86 by IPTp-MQ highlights the strong selective pressure IPTp can exert and the opportunity for using negative cross-resistance in drug choice for clinical treatment and IPTp.
BACKGROUND: Innovative approaches are needed to limit antimalarial resistance evolution. Understanding the role of intermittent preventive treatment in pregnancy (IPTp) on the selection for resistance and the impact such selection has on pregnancy outcomes can guide future interventions. METHODS:Plasmodium falciparum isolates (n = 914) from 2 randomized clinical trials were screened for pfmdr1 copy number variation and pfcrt, pfmdr1, pfdhfr, and pfdhps resistance markers. The trials were conducted between 2010 and 2013 in Benin, Gabon, Kenya, and Mozambique to establish the efficacy of IPTp-mefloquine (MQ) compared with IPTp-sulphadoxine-pyrimethamine (SP) in human immunodeficiency virus (HIV)-uninfected and to IPTp-placebo in HIV-infected women. RESULTS: In HIV-uninfected women, the prevalence of pfcrt mutants, pfdhfr/pfdhps quintuple mutants, and pfmdr1 copy number was similar between women receiving IPT-SP and IPTp-MQ. However, prevalence of pfmdr1 polymorphism 86Y was lower in the IPTp-MQ group than in the IPTp-SP group, and within the IPTp-MQ group it was lower at delivery compared with recruitment. No effect of IPTp-MQ on resistance markers was observed among HIV-infected women. The carriage of resistance markers was not associated with pregnancy outcomes. CONCLUSIONS: Selection of wild-type pfmdr1 polymorphism N86 by IPTp-MQ highlights the strong selective pressure IPTp can exert and the opportunity for using negative cross-resistance in drug choice for clinical treatment and IPTp.
Authors: Aaron M Samuels; Oliver Towett; Brian Seda; Ryan E Wiegand; Kephas Otieno; Miriam Chomba; Naomi Lucchi; Dragan Ljolje; Kammerle Schneider; Patrick G T Walker; Titus K Kwambai; Laurence Slutsker; Feiko O Ter Kuile; Simon K Kariuki Journal: J Infect Dis Date: 2022-09-04 Impact factor: 7.759
Authors: Steve M Taylor; Brandt Levitt; Betsy Freedman; Mwayiwawo Madanitsa; Kyaw-Lay Thwai; Linda Kalilani-Phiri; Carole Khairallah; Victor Mwapasa; Feiko O Ter Kuile; Steven R Meshnick Journal: J Infect Dis Date: 2020-07-23 Impact factor: 5.226
Authors: Zhiyong Zhou; John E Gimnig; Sheila B Sergent; Ying Liu; Bernard Abong'o; Kephas Otieno; Winnie Chebore; Monica P Shah; John Williamson; Feiko O Ter Kuile; Mary J Hamel; Simon Kariuki; Meghna Desai; Aaron M Samuels; Edward D Walker; Ya Ping Shi Journal: Malar J Date: 2022-09-13 Impact factor: 3.469