Mutational profile of pfdhfr, pfdhps, pfmdr1, pfcrt and pfk13 genes of P. falciparum associated with resistance to different antimalarial drugs in Osun state, southwestern Nigeria
Abstract Background Nigeria accounts for the greatest burden of malaria disease globally. Malaria control requires an effective treatment after diagnosis. The efficacy of antimalarial drugs can be assessed through the analysis of genetic changes associated with reduced drug sensitivity. Methods This...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s41182-025-00732-6 |
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| author | Alexandra Martín Ramírez Akeem Abiodun Akindele Vicenta González Mora Luz García Nicole Lara Eva de la Torre-Capitán Matías Irene Molina de la Fuente Sulaiman Adebayo Nassar Thuy-Huong Ta-Tang Agustín Benito Pedro Berzosa |
| author_facet | Alexandra Martín Ramírez Akeem Abiodun Akindele Vicenta González Mora Luz García Nicole Lara Eva de la Torre-Capitán Matías Irene Molina de la Fuente Sulaiman Adebayo Nassar Thuy-Huong Ta-Tang Agustín Benito Pedro Berzosa |
| author_sort | Alexandra Martín Ramírez |
| collection | DOAJ |
| description | Abstract Background Nigeria accounts for the greatest burden of malaria disease globally. Malaria control requires an effective treatment after diagnosis. The efficacy of antimalarial drugs can be assessed through the analysis of genetic changes associated with reduced drug sensitivity. Methods This study includes the analysis of the markers associated with artemisinin (pfk13), sulfadoxine–pyrimethamine (pfdhfr and pfdhps), and chloroquine and its derivatives (pfmdr1 and pfcrt) resistances, in blood samples collected from asymptomatic children in south-western Nigeria. Results The 25.95% of samples showed a number of mutations in pfk13 gene. Among those, the validated, C580Y, and the candidate, R515K, mutations by WHO were detected. Twenty-seven pfdhps different haplotypes were observed, with the haplotype ISGKAA as the most prevalent (18.80%), followed by IFGKAA (12.78%) and IAGKAA (11.28%). The VAGKGS was the most common haplotype carrying the I431V mutation (10.53%). Combinations of alleles in pfdhfr and pfdhps genes provided a 40.98% of samples with the partially resistant haplotype (IRNG). No samples exhibited the ‘fully resistant’ or ‘super resistant’ pfdhprf–pfdhps combinations, but one sample contained mutations at pfdhfr 51I, 59R, and 108N with pfdhps 431V, 436A, A437G and 540E. The analysis of pfcrt 72–76 variants disclosed a 12.12% of samples with the mutant-type (CVIET). No double mutant pfmdr1 haplotypes 86Y/1246Y (YY) were detected, nor was the haplotype formed by the alleles 86Y pfmdr1 + pfcrt 76 T (YT). Conclusions There was no evidence of parasite genomes harbouring multilocus mutations conferring multidrug resistance, although evidence of a validated (C580Y) and a candidate (R515K) mutation in pfk13 gene, high frequency pfdhfr mutant alleles and high variability of pfdhps haplotypes were found in this study, which provides a baseline information essential in monitoring P. falciparum resistances. |
| format | Article |
| id | doaj-art-2833db782e1f413f8e76c6d0ad5825a7 |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-2833db782e1f413f8e76c6d0ad5825a72025-08-20T02:12:07ZengBMCTropical Medicine and Health1349-41472025-04-0153111510.1186/s41182-025-00732-6Mutational profile of pfdhfr, pfdhps, pfmdr1, pfcrt and pfk13 genes of P. falciparum associated with resistance to different antimalarial drugs in Osun state, southwestern NigeriaAlexandra Martín Ramírez0Akeem Abiodun Akindele1Vicenta González Mora2Luz García3Nicole Lara4Eva de la Torre-Capitán Matías5Irene Molina de la Fuente6Sulaiman Adebayo Nassar7Thuy-Huong Ta-Tang8Agustín Benito9Pedro Berzosa10Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos IIIMedical Laboratory Science Department, Ladoke Akintola University of TechnologyNational Centre of Tropical Medicine, Institute of Health Carlos IIINational Centre of Tropical Medicine, Institute of Health Carlos IIIComplutense University of MadridAlcala UniversityCentro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos IIIMedical Laboratory Science Department, Ladoke Akintola University of TechnologyCentro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos IIICentro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos IIICentro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos IIIAbstract Background Nigeria accounts for the greatest burden of malaria disease globally. Malaria control requires an effective treatment after diagnosis. The efficacy of antimalarial drugs can be assessed through the analysis of genetic changes associated with reduced drug sensitivity. Methods This study includes the analysis of the markers associated with artemisinin (pfk13), sulfadoxine–pyrimethamine (pfdhfr and pfdhps), and chloroquine and its derivatives (pfmdr1 and pfcrt) resistances, in blood samples collected from asymptomatic children in south-western Nigeria. Results The 25.95% of samples showed a number of mutations in pfk13 gene. Among those, the validated, C580Y, and the candidate, R515K, mutations by WHO were detected. Twenty-seven pfdhps different haplotypes were observed, with the haplotype ISGKAA as the most prevalent (18.80%), followed by IFGKAA (12.78%) and IAGKAA (11.28%). The VAGKGS was the most common haplotype carrying the I431V mutation (10.53%). Combinations of alleles in pfdhfr and pfdhps genes provided a 40.98% of samples with the partially resistant haplotype (IRNG). No samples exhibited the ‘fully resistant’ or ‘super resistant’ pfdhprf–pfdhps combinations, but one sample contained mutations at pfdhfr 51I, 59R, and 108N with pfdhps 431V, 436A, A437G and 540E. The analysis of pfcrt 72–76 variants disclosed a 12.12% of samples with the mutant-type (CVIET). No double mutant pfmdr1 haplotypes 86Y/1246Y (YY) were detected, nor was the haplotype formed by the alleles 86Y pfmdr1 + pfcrt 76 T (YT). Conclusions There was no evidence of parasite genomes harbouring multilocus mutations conferring multidrug resistance, although evidence of a validated (C580Y) and a candidate (R515K) mutation in pfk13 gene, high frequency pfdhfr mutant alleles and high variability of pfdhps haplotypes were found in this study, which provides a baseline information essential in monitoring P. falciparum resistances.https://doi.org/10.1186/s41182-025-00732-6MalariaDrug-resistant P. falciparumAntimalarial drug resistanceNigeriapfk13Antimalarial drug resistance |
| spellingShingle | Alexandra Martín Ramírez Akeem Abiodun Akindele Vicenta González Mora Luz García Nicole Lara Eva de la Torre-Capitán Matías Irene Molina de la Fuente Sulaiman Adebayo Nassar Thuy-Huong Ta-Tang Agustín Benito Pedro Berzosa Mutational profile of pfdhfr, pfdhps, pfmdr1, pfcrt and pfk13 genes of P. falciparum associated with resistance to different antimalarial drugs in Osun state, southwestern Nigeria Tropical Medicine and Health Malaria Drug-resistant P. falciparum Antimalarial drug resistance Nigeria pfk13 Antimalarial drug resistance |
| title | Mutational profile of pfdhfr, pfdhps, pfmdr1, pfcrt and pfk13 genes of P. falciparum associated with resistance to different antimalarial drugs in Osun state, southwestern Nigeria |
| title_full | Mutational profile of pfdhfr, pfdhps, pfmdr1, pfcrt and pfk13 genes of P. falciparum associated with resistance to different antimalarial drugs in Osun state, southwestern Nigeria |
| title_fullStr | Mutational profile of pfdhfr, pfdhps, pfmdr1, pfcrt and pfk13 genes of P. falciparum associated with resistance to different antimalarial drugs in Osun state, southwestern Nigeria |
| title_full_unstemmed | Mutational profile of pfdhfr, pfdhps, pfmdr1, pfcrt and pfk13 genes of P. falciparum associated with resistance to different antimalarial drugs in Osun state, southwestern Nigeria |
| title_short | Mutational profile of pfdhfr, pfdhps, pfmdr1, pfcrt and pfk13 genes of P. falciparum associated with resistance to different antimalarial drugs in Osun state, southwestern Nigeria |
| title_sort | mutational profile of pfdhfr pfdhps pfmdr1 pfcrt and pfk13 genes of p falciparum associated with resistance to different antimalarial drugs in osun state southwestern nigeria |
| topic | Malaria Drug-resistant P. falciparum Antimalarial drug resistance Nigeria pfk13 Antimalarial drug resistance |
| url | https://doi.org/10.1186/s41182-025-00732-6 |
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