Background The emergence and spread of Plasmodium falciparum resistance to artemisinin and its partner drugs pose a major challenge to malaria elimination efforts. Continuous monitoring of resistance-associated molecular markers provides valuable insights into the emergence of resistant genotypes and their geographical distribution. Methods In this study, we investigated mutations linked to antimalarial drug resistance in the pfcrt, pfmdr1, and pfmrp1 genes among 100 P. falciparum isolates collected from southeastern Iran during 2022–2023 and compared the findings with data from the same region a decade earlier. Point mutations were genotyped using PCR–RFLP. Results Molecular analysis demonstrated a high prevalence (95%) of the pfcrt K76T mutation. In pfmdr1, no mutations were observed at codons 1034, 1042, or 1246; however, the N86Y and Y184F mutations were detected in 3.75% and 51.25% of isolates, respectively. Comparative analysis between the previous (2007–2010) and current (2022–2023) studies revealed a significant increase in the wild-type allele for N86Y and the mutant allele for Y184F. In pfmrp1, mutations at H191Y, S437A, I876V, and F1390I were identified in 68.75%, 85%, 78.75%, and 46.25% of isolates, respectively, while no mutation was observed at K1466R. The predominant pfmdr1 haplotype shifted from wild-type (50%) in the previous study to the single-mutation haplotype N86F184S1034N1042D1246 (50%) in the current study. Combined haplotype analysis of all three genes revealed a decrease in one major haplotype T76N86Y184S1043N1042D1246Y191A437V876F1390K1466 (from 23.5 to 3.75%) and an increase in haplotype T76N86Y184S1043N1042D1246Y191A437V876I1390K1466 (from 7 to 23.75%) over the same period. Conclusions The persistence of the pfcrt K76T mutant allele despite the withdrawal of Chloroquine from the treatment policy in Iran may be attributable to the co-endemicity of P. vivax in the study area. The increasing prevalence of the N86F184S1034N1042D1246 pfmdr1 haplotype is of concern, given its reported association with reduced susceptibility to lumefantrine. Although mutant pfmrp1 alleles were detected at relatively high frequencies, current evidence does not suggest an immediate threat to the efficacy of artemether–lumefantrine in the studied population.

Molecular surveillance of antimalarial drug resistance markers in the pfcrt, pfmdr1 and pfmrp1 genes of Plasmodium falciparum isolates from southeastern Iran

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2026年6月19日

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Mohadeseh Jafari,
Romina Rezapour,
Fahimeh Nemati,
Akram Abouie Mehrizi,
Sakineh Pirahmadi

摘要

Background

The emergence and spread of Plasmodium falciparum resistance to artemisinin and its partner drugs pose a major challenge to malaria elimination efforts. Continuous monitoring of resistance-associated molecular markers provides valuable insights into the emergence of resistant genotypes and their geographical distribution.

Methods

In this study, we investigated mutations linked to antimalarial drug resistance in the pfcrt, pfmdr1, and pfmrp1 genes among 100 P. falciparum isolates collected from southeastern Iran during 2022–2023 and compared the findings with data from the same region a decade earlier. Point mutations were genotyped using PCR–RFLP.

Results

Molecular analysis demonstrated a high prevalence (95%) of the pfcrt K76T mutation. In pfmdr1, no mutations were observed at codons 1034, 1042, or 1246; however, the N86Y and Y184F mutations were detected in 3.75% and 51.25% of isolates, respectively. Comparative analysis between the previous (2007–2010) and current (2022–2023) studies revealed a significant increase in the wild-type allele for N86Y and the mutant allele for Y184F. In pfmrp1, mutations at H191Y, S437A, I876V, and F1390I were identified in 68.75%, 85%, 78.75%, and 46.25% of isolates, respectively, while no mutation was observed at K1466R. The predominant pfmdr1 haplotype shifted from wild-type (50%) in the previous study to the single-mutation haplotype N₈₆F₁₈₄S₁₀₃₄N₁₀₄₂D₁₂₄₆ (50%) in the current study. Combined haplotype analysis of all three genes revealed a decrease in one major haplotype T₇₆N₈₆Y₁₈₄S₁₀₄₃N₁₀₄₂D₁₂₄₆Y₁₉₁A₄₃₇V₈₇₆F₁₃₉₀K₁₄₆₆ (from 23.5 to 3.75%) and an increase in haplotype T₇₆N₈₆Y₁₈₄S₁₀₄₃N₁₀₄₂D₁₂₄₆Y₁₉₁A₄₃₇V₈₇₆I₁₃₉₀K₁₄₆₆ (from 7 to 23.75%) over the same period.

Conclusions

The persistence of the pfcrt K76T mutant allele despite the withdrawal of Chloroquine from the treatment policy in Iran may be attributable to the co-endemicity of P. vivax in the study area. The increasing prevalence of the N₈₆F₁₈₄S₁₀₃₄N₁₀₄₂D₁₂₄₆ pfmdr1 haplotype is of concern, given its reported association with reduced susceptibility to lumefantrine. Although mutant pfmrp1 alleles were detected at relatively high frequencies, current evidence does not suggest an immediate threat to the efficacy of artemether–lumefantrine in the studied population.