Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017
Background: Resistance to anti-malarials is a serious threat to the efforts to control and eliminate malaria. Surveillance based on simple field protocols with centralized testing to detect molecular markers associated with anti-malarial drug resistance can be used to identify locations where furthe...
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th-mahidol.740762022-08-04T11:14:37Z Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017 Sukanta Das Clément Kérah-Hinzoumbé Moundiné Kebféné Suttipat Srisutham Tog Yeum Nagorngar Naowarat Saralamba Ranitha Vongpromek Teeradet Khomvarn Carol H. Sibley Philippe J. Guérin Mallika Imwong Mehul Dhorda Faculty of Tropical Medicine, Mahidol University Chulalongkorn University University of Washington Nuffield Department of Medicine ExxonMobil Programme National de Lutte Contre le Paludisme au Tchad WorldWide Antimalarial Resistance Network – Asia-Pacific Regional Centre WorldWide Antimalarial Resistance Network Immunology and Microbiology Medicine Background: Resistance to anti-malarials is a serious threat to the efforts to control and eliminate malaria. Surveillance based on simple field protocols with centralized testing to detect molecular markers associated with anti-malarial drug resistance can be used to identify locations where further investigations are needed. Methods: Dried blood spots were collected from 398 patients (age range 5–59 years, 99% male) with Plasmodium falciparum infections detected using rapid diagnostic tests over two rounds of sample collection conducted in 2016 and 2017 in Komé, South-West Chad. Specimens were genotyped using amplicon sequencing or qPCR for validated markers of anti-malarial resistance including partner drugs used in artemisinin-based combination therapy (ACT). Results: No mutations in the pfk13 gene known to be associated with artemisinin resistance were found but a high proportion of parasites carried other mutations, specifically K189T (190/349, 54.4%, 95%CI 49.0–59.8%). Of 331 specimens successfully genotyped for pfmdr1 and pfcrt, 52% (95%CI 46.4–57.5%) carried the NFD-K haplotype, known to be associated with reduced susceptibility to lumefantrine. Only 20 of 336 (6.0%, 95%CI 3.7–9.0%) had parasites with the pfmdr1-N86Y polymorphism associated with increased treatment failures with amodiaquine. Nearly all parasites carried at least one mutation in pfdhfr and/or pfdhps genes but ‘sextuple’ mutations in pfdhfr—pfdhps including pfdhps -A581G were rare (8/336 overall, 2.4%, 95%CI 1.2–4.6%). Only one specimen containing parasites with pfmdr1 gene amplification was detected. Conclusions: These results provide information on the likely high efficacy of artemisinin-based combinations commonly used in Chad, but suggest decreasing levels of sensitivity to lumefantrine and high levels of resistance to sulfadoxine-pyrimethamine used for seasonal malaria chemoprevention and intermittent preventive therapy in pregnancy. A majority of parasites had mutations in the pfk13 gene, none of which are known to be associated with artemisinin resistance. A therapeutic efficacy study needs to be conducted to confirm the efficacy of artemether-lumefantrine. 2022-08-04T04:06:26Z 2022-08-04T04:06:26Z 2022-12-01 Article Malaria Journal. Vol.21, No.1 (2022) 10.1186/s12936-022-04095-9 14752875 2-s2.0-85126219989 https://repository.li.mahidol.ac.th/handle/123456789/74076 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85126219989&origin=inward |
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Immunology and Microbiology Medicine Sukanta Das Clément Kérah-Hinzoumbé Moundiné Kebféné Suttipat Srisutham Tog Yeum Nagorngar Naowarat Saralamba Ranitha Vongpromek Teeradet Khomvarn Carol H. Sibley Philippe J. Guérin Mallika Imwong Mehul Dhorda Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017 |
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Background: Resistance to anti-malarials is a serious threat to the efforts to control and eliminate malaria. Surveillance based on simple field protocols with centralized testing to detect molecular markers associated with anti-malarial drug resistance can be used to identify locations where further investigations are needed. Methods: Dried blood spots were collected from 398 patients (age range 5–59 years, 99% male) with Plasmodium falciparum infections detected using rapid diagnostic tests over two rounds of sample collection conducted in 2016 and 2017 in Komé, South-West Chad. Specimens were genotyped using amplicon sequencing or qPCR for validated markers of anti-malarial resistance including partner drugs used in artemisinin-based combination therapy (ACT). Results: No mutations in the pfk13 gene known to be associated with artemisinin resistance were found but a high proportion of parasites carried other mutations, specifically K189T (190/349, 54.4%, 95%CI 49.0–59.8%). Of 331 specimens successfully genotyped for pfmdr1 and pfcrt, 52% (95%CI 46.4–57.5%) carried the NFD-K haplotype, known to be associated with reduced susceptibility to lumefantrine. Only 20 of 336 (6.0%, 95%CI 3.7–9.0%) had parasites with the pfmdr1-N86Y polymorphism associated with increased treatment failures with amodiaquine. Nearly all parasites carried at least one mutation in pfdhfr and/or pfdhps genes but ‘sextuple’ mutations in pfdhfr—pfdhps including pfdhps -A581G were rare (8/336 overall, 2.4%, 95%CI 1.2–4.6%). Only one specimen containing parasites with pfmdr1 gene amplification was detected. Conclusions: These results provide information on the likely high efficacy of artemisinin-based combinations commonly used in Chad, but suggest decreasing levels of sensitivity to lumefantrine and high levels of resistance to sulfadoxine-pyrimethamine used for seasonal malaria chemoprevention and intermittent preventive therapy in pregnancy. A majority of parasites had mutations in the pfk13 gene, none of which are known to be associated with artemisinin resistance. A therapeutic efficacy study needs to be conducted to confirm the efficacy of artemether-lumefantrine. |
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Faculty of Tropical Medicine, Mahidol University |
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Faculty of Tropical Medicine, Mahidol University Sukanta Das Clément Kérah-Hinzoumbé Moundiné Kebféné Suttipat Srisutham Tog Yeum Nagorngar Naowarat Saralamba Ranitha Vongpromek Teeradet Khomvarn Carol H. Sibley Philippe J. Guérin Mallika Imwong Mehul Dhorda |
format |
Article |
author |
Sukanta Das Clément Kérah-Hinzoumbé Moundiné Kebféné Suttipat Srisutham Tog Yeum Nagorngar Naowarat Saralamba Ranitha Vongpromek Teeradet Khomvarn Carol H. Sibley Philippe J. Guérin Mallika Imwong Mehul Dhorda |
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Sukanta Das |
title |
Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017 |
title_short |
Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017 |
title_full |
Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017 |
title_fullStr |
Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017 |
title_full_unstemmed |
Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017 |
title_sort |
molecular surveillance for operationally relevant genetic polymorphisms in plasmodium falciparum in southern chad, 2016–2017 |
publishDate |
2022 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/74076 |
_version_ |
1763487427021766656 |