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 DOI Creative Commons
Alexandra Martín Ramírez,

Akeem Abiodun Akindele,

Vicenta González Mora

et al.

Tropical Medicine and Health, Journal Year: 2025, Volume and Issue: 53(1)

Published: April 8, 2025

Abstract Background Nigeria accounts for the greatest burden of malaria disease globally. Malaria control requires an effective treatment after diagnosis. The efficacy antimalarial drugs can be assessed through analysis genetic changes associated with reduced drug sensitivity. Methods This study includes markers artemisinin ( pfk13 ), sulfadoxine–pyrimethamine pfdhfr and pfdhps chloroquine its derivatives pfmdr1 pfcrt ) resistances, in blood samples collected from asymptomatic children south-western Nigeria. Results 25.95% showed a number mutations gene. Among those, validated, C580Y, candidate, R515K, by WHO were detected. Twenty-seven different haplotypes observed, haplotype IS G KAA as most prevalent (18.80%), followed I FG (12.78%) AG (11.28%). VAG K GS was common carrying I431V mutation (10.53%). Combinations alleles genes provided 40.98% partially resistant IRNG ). No exhibited ‘fully resistant’ or ‘super pfdhprf – combinations, but one sample contained at 51I, 59R, 108N 431V, 436A, A437G 540E. 72–76 variants disclosed 12.12% mutant-type (CV IET double mutant 86Y/1246Y (YY) detected, nor formed 86Y + 76 T (YT). Conclusions There no evidence parasite genomes harbouring multilocus conferring multidrug resistance, although validated (C580Y) candidate (R515K) gene, high frequency variability found this study, which provides baseline information essential monitoring P. falciparum resistances.

Language: Английский

High frequency of artemisinin partial resistance mutations in the great lake region revealed through rapid pooled deep sequencing DOI Creative Commons
Neeva Wernsman Young, Pierre Gashema, David Giesbrecht

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Abstract In Africa, the first Plasmodium falciparum Kelch13 (K13) artemisinin partial resistance mutation 561H was detected and validated in Rwanda. Surveillance to better define extent of emergence Rwanda neighboring countries as other mutations arise East Africa is critical. We employ a novel scheme liquid blood drop preservation combined with pooled sequencing provide cost-effective rapid assessment frequencies at multiple collection sites across countries. Malaria-positive samples (n=5,465) were collected from 39 health facilities Rwanda, Uganda, Tanzania, Democratic Republic Congo (DRC) between May 2022 March 2023 sequenced 199 pools. K13 675V 90% 65% an average frequency 19.0% (0-54.5%) 5.0% (0-35.5%), respectively. had high while it absent DRC although seen low frequency. Conceringly candidate observed: 441L, 449A, 469F co-occurred suggesting they are arising under same pressures. Other markers associated artemether-lumefantrine common: P. multidrug protein 1 N86 98.0% 184F 47.0% (0-94.3%) chloroquine transporter 76T 14.7% (0-58.6%). Additionally, sulfadoxine-pyrimethamine-associated show frequencies. Overall, rapidly expanding region further endangering control efforts potential engendering partner drug resistance.

Language: Английский

Citations

11
High frequency of artemisinin partial resistance mutations in the Great Lakes region revealed through rapid pooled deep sequencing DOI
Neeva Wernsman Young, Pierre Gashema, David Giesbrecht

et al.

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 5, 2024

Abstract Background In Africa, the first Plasmodium falciparum artemisinin partial resistance mutation was Kelch13 (K13) 561H, detected and validated at appreciable frequency in Rwanda 2014. Surveillance to better define extent of emergence neighboring countries is critical. Methods We used novel liquid blood drop preservation with pooled sequencing provide cost-effective rapid assessment frequencies multiple collection sites across regions Uganda, Tanzania, Democratic Republic Congo. Malaria-positive samples (N = 5465) from 39 health facilities collected between May 2022 March 2023 were sequenced 199 pools. Results Rwanda, K13 561H 675V 90% 65% sites, an average 19.0% (range, 0%–54.5%) 5.0% (0%–35.5%), respectively. had high sites. appeared 1.6% Uganda. absent Congo, although seen low frequency. Concerningly, candidate mutations observed: 441L, 449A, 469F co-occurred mutations, suggesting that they are arising under same pressures. Other markers for decreased susceptibility artemether-lumefantrine common: P multidrug protein 1 N86 98.0% 63.3%–100%) 184F 47.0% (0%–94.3%) chloroquine transporter 76T 14.7% (0%–58.6%). Additionally, sulfadoxine-pyrimethamine–associated show frequencies. Conclusions rapidly expanding region, further endangering control efforts potential engendering partner drug resistance.

Language: Английский

Citations

10
Artemisinin-resistant malaria DOI
Nicholas J. White, Kesinee Chotivanich

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(4)

Published: Oct. 15, 2024

SUMMARYThe artemisinin antimalarials are the cornerstone of current malaria treatment. The development resistance in

Language: Английский

Citations

10
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 DOI Creative Commons
Alexandra Martín Ramírez,

Akeem Abiodun Akindele,

Vicenta González Mora

et al.

Tropical Medicine and Health, Journal Year: 2025, Volume and Issue: 53(1)

Published: April 8, 2025

Abstract Background Nigeria accounts for the greatest burden of malaria disease globally. Malaria control requires an effective treatment after diagnosis. The efficacy antimalarial drugs can be assessed through analysis genetic changes associated with reduced drug sensitivity. Methods This study includes markers artemisinin ( pfk13 ), sulfadoxine–pyrimethamine pfdhfr and pfdhps chloroquine its derivatives pfmdr1 pfcrt ) resistances, in blood samples collected from asymptomatic children south-western Nigeria. Results 25.95% showed a number mutations gene. Among those, validated, C580Y, candidate, R515K, by WHO were detected. Twenty-seven different haplotypes observed, haplotype IS G KAA as most prevalent (18.80%), followed I FG (12.78%) AG (11.28%). VAG K GS was common carrying I431V mutation (10.53%). Combinations alleles genes provided 40.98% partially resistant IRNG ). No exhibited ‘fully resistant’ or ‘super pfdhprf – combinations, but one sample contained at 51I, 59R, 108N 431V, 436A, A437G 540E. 72–76 variants disclosed 12.12% mutant-type (CV IET double mutant 86Y/1246Y (YY) detected, nor formed 86Y + 76 T (YT). Conclusions There no evidence parasite genomes harbouring multilocus conferring multidrug resistance, although validated (C580Y) candidate (R515K) gene, high frequency variability found this study, which provides baseline information essential monitoring P. falciparum resistances.

Language: Английский

Citations

1