Effect of sulfadoxine-pyrimethamine chemoprophylaxis in pregnant women on selection of the new P. falciparum dhps quintuple mutant carrying the I431V mutation.

Autor:	Cohen O; Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France.; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France., Guemas E; Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France.; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France., Menard S; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France., Tsague Kenfack M; Centre d'Animation Sociale et Sanitaire (CASS) of Nkolndongo, Yaounde, Cameroon., Talom Ngassa C; Centre d'Animation Sociale et Sanitaire (CASS) of Nkolndongo, Yaounde, Cameroon., Iriart X; Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France.; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France., Bidzogo Lebobo M; Centre d'Animation Sociale et Sanitaire (CASS) of Nkolndongo, Yaounde, Cameroon., Ondobo Ekae C; Centre d'Animation Sociale et Sanitaire (CASS) of Nkolndongo, Yaounde, Cameroon., Eboumbou C; Faculté de Médecine et des Sciences Pharmaceutiques, Université de Douala, Douala, Cameroon.; Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroon., Tiyou Kenmeni C; Centre d'Animation Sociale et Sanitaire (CASS) of Nkolndongo, Yaounde, Cameroon.; University Hospital of Yaoundé, Yaoundé, Cameroon., Berry A; Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France.; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2023 Mar 02; Vol. 78 (3), pp. 665-668.
DOI:	10.1093/jac/dkac432
Abstrakt:	Background: A new mutation in the Plasmodium falciparum dihydropteroate synthetase gene (pfdhps), I431V, has been identified in several countries of Central and West Africa. This mutation is mostly found in association with four other SNPs on pfdhps (S436A, A437G, A581G and A613S), forming a quintuple mutant (vagKgs) and almost always associated with the Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) CirnI (C50R, N51I, S108N) triple mutant. To date, nothing is known about the impact of this new pfdhps genotype on sulfadoxine-pyrimethamine (SP) resistance. Objectives: We sought to assess the prevalence of this pfdhps vagKgs quintuple mutant in two groups of pregnant women with malaria, one that took intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and one that did not. Methods: The pfdhfr and pfdhps genes from Plasmodium falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria under IPTp-SP or not, were sequenced. Results: Of 159 patients evaluated, 70 had already taken SP during pregnancy and 89 had never taken SP. Only the vagKgs allele was significantly overrepresented in the SP+ group (21.4% versus 3.4%; P < 0.001), whereas the ISgKAA mutant, widely distributed in this area and known to be less susceptible to SP, tended to be less abundant in this group (48.6% versus 64.0%; P = 0.0503). Conclusions: We found a strong overrepresentation of the CirnI/vagKgs haplotype in the IPTp-SP pregnant group, suggesting a high level of resistance of this mutant to SP. This could compromise not only the effectiveness of IPTp-SP but also the seasonal malaria chemoprevention of young children, now widely implemented. (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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