TY - JOUR
T1 - Counter-selection of antimalarial resistance polymorphisms by intermittent preventive treatment in pregnancy
AU - Huijben, Silvie
AU - Macete, Eusebio
AU - Mombo-Ngoma, Ghyslain
AU - Ramharter, Michael
AU - Kariuki, Simon
AU - Desai, Meghna
AU - Shi, Ya Ping
AU - Mwangoka, Grace
AU - Massougbodji, Achille
AU - Cot, Michel
AU - Ndam, Nicaise Tuikue
AU - Uberegui, Estefania
AU - Gupta, Himanshu
AU - Cisteró, Pau
AU - Aponte, John J.
AU - González, Raquel
AU - Menéndez, Clara
AU - Mayor, Alfredo
N1 - Funding Information:
Financial support. This work was funded by the European Developing Countries Clinical Trials Partnership (IP.2007.31080.002); the Malaria in Pregnancy Consortium; Marie Curie Incoming Fellowship (623703; to S. H.); Branco Weiss Fellowship – Society in Science (to S. H.); Departament d'Universitats i Recerca de la Generalitat de Catalunya (2017SGR664 to A. M.); and the Overseas Postdoctoral Fellowship by the Department of Science & Technology, Government of India (SB/OS/PDF043/201516; to H. G.). The MiP Consortium is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. The Centro de Investigacao em Saude da Manhica receives core support from the Spanish Agency for International Cooperation and Development.
Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - Intermittent preventive therapy
KW - Malaria
KW - Mefloquine
KW - Pfmdr
KW - Pregnancy
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U2 - 10.1093/infdis/jiz451
DO - 10.1093/infdis/jiz451
M3 - Article
C2 - 31677349
AN - SCOPUS:85077346322
SN - 0022-3166
VL - 149
SP - 293
EP - 303
JO - Journal of Nutrition
JF - Journal of Nutrition
ER -