RESUMEN
BACKGROUND: Resistance against artemisinin-based combination therapy is one of the challenges to malaria control and elimination globally. Mutations in different genes (Pfdhfr, Pfdhps, Pfk-13 and Pfmdr1) confer resistance to artesunate and sulfadoxine-pyrimethamine (AS + SP) were analysed from Mandla district, Madhya Pradesh, to assess the effectiveness of the current treatment regimen against uncomplicated Plasmodium falciparum. METHODS: Dried blood spots were collected during the active fever survey and mass screening and treatment activities as part of the Malaria Elimination Demonstration Project (MEDP) from 2019 to 2020. Isolated DNA samples were used to amplify the Pfdhfr, Pfdhps, Pfk13 and Pfmdr1 genes using nested PCR and sequenced for mutation analysis using the Sanger sequencing method. RESULTS: A total of 393 samples were subjected to PCR amplification, sequencing and sequence analysis; 199, 215, 235, and 141 samples were successfully sequenced for Pfdhfr, Pfdhps, Pfk13, Pfmdr1, respectively. Analysis revealed that the 53.3% double mutation (C59R, S108N) in Pfdhfr, 89.3% single mutation (G437A) in Pfdhps, 13.5% single mutants (N86Y), and 51.1% synonymous mutations in Pfmdr1 in the study area. Five different non-synonymous and two synonymous point mutations found in Pfk13, which were not associated to artemisinin resistance. CONCLUSION: The study has found that mutations linked to SP resistance are increasing in frequency, which may reduce the effectiveness of this drug as a future partner in artemisinin-based combinations. No evidence of mutations linked to artemisinin resistance in Pfk13 was found, suggesting that parasites are sensitive to artemisinin derivatives in the study area. These findings are a baseline for routine molecular surveillance to proactively identify the emergence and spread of artemisinin-resistant parasites.
Asunto(s)
Antimaláricos , Artemisininas , Malaria Falciparum , Malaria , Humanos , Plasmodium falciparum , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéutico , Artemisininas/farmacología , Artemisininas/uso terapéutico , Malaria/tratamiento farmacológico , Biomarcadores , Resistencia a Medicamentos/genética , India , Combinación de Medicamentos , Malaria Falciparum/parasitología , Proteínas Protozoarias/genética , Proteínas Protozoarias/uso terapéuticoRESUMEN
India contributed approximately 66% of the malaria cases in the WHO South-East Asia region in 2022. In India, approximately 44% of cases have been reported to be disproportionately contributed by approximately 27 districts. A comparative analysis of reported malaria cases between January 2017 and December 2022 was performed in Mandla district, which is the site of a model malaria elimination demonstration project (MEDP) in Madhya Pradesh (MP), India. Compared to 2017, the decrease in malaria cases in Mandla from 2018 to 2022 was higher than MP and the rest of the country. The reduction of cases was significant in 2018, 2019, and 2021 (p < 0.01) (Mandla vs. MP) and was highly significant during 2018-2022 (p < 0.001) (Mandla vs. India). Robust surveillance and real-time data-based decisions accompanied by appropriate management, operational controls, and independent reviews, all designed for resource optimisation, were the reasons for eliminating indigenous malaria in Mandla district. The increase in infection rates during the months immediately following rains suggests that surveillance, vector control, and case management efforts should be specifically intensified for eliminating imported and indigenous cases in the near-elimination districts to work towards achieving the national elimination goal of 2030.