Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017
Issued Date
2022-12-01
Resource Type
eISSN
14752875
Scopus ID
2-s2.0-85126219989
Pubmed ID
35279140
Journal Title
Malaria Journal
Volume
21
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Malaria Journal Vol.21 No.1 (2022)
Suggested Citation
Das S., Kérah-Hinzoumbé C., Kebféné M., Srisutham S., Nagorngar T.Y., Saralamba N., Vongpromek R., Khomvarn T., Sibley C.H., Guérin P.J., Imwong M., Dhorda M. Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017. Malaria Journal Vol.21 No.1 (2022). doi:10.1186/s12936-022-04095-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/84862
Title
Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017
Author's Affiliation
WorldWide Antimalarial Resistance Network
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
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
Other Contributor(s)
Abstract
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.