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. 2025 Jun 12;24(1):186.
doi: 10.1186/s12936-025-05248-2.

Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment

Veronika R Laird  1   2   3 , Mateusz M Plucinski  4 , Meera Venkatesan  5 , Kelsey A Rondini  6   4 , Milijaona Randrianarivelojosia  7   8 , Mauricette N Andriamananjara  9 , Hawela Moonga  10 , Deus S Ishengoma  11 , Arlindo Chidimatembue  12 , Pedro Rafael Dimbu  13 , Adicatou-Laï Adeothy  14 , Abdoul Habib Beavogui  15 , Simon Kariuki  16 , Sam L Nsobya  17 , Aline Uwimana  18 , Gauthier Mesia Kahunu  19   20 , Ashenafi Assefa  21   22 , Ousmane A Koita  23 , Naomi W Lucchi  24   25 , Samaly S Svigel Souza  25 , Zhiyong Zhou  25 , Leah F Moriarty  4 , Eric S Halsey  26
Affiliations

Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment

Veronika R Laird et al. Malar J. .

Abstract

Background: Plasmodium falciparum multidrug resistance transporter 1 (Pfmdr1) gene mutations are associated with altered response to artemisinin-based combination therapy (ACT), particularly the combinations containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Past studies of Pfmdr1 single nucleotide polymorphisms (SNPs) at codons 86, 184, and 1246 have shown different responses to AL and ASAQ.

Methods: To determine whether infection with parasites carrying specific Pfmdr1 SNPs leads to increased risk of recurrent parasitaemia (recrudescent or new infection), data from 3,915 samples from 16 therapeutic efficacy studies from 13 African countries between 2013 and 2019 were analysed.

Results: Patients treated with AL and infected with parasites carrying Pfmdr1 N86 were at greater risk of recurrent infection than those whose parasites carried 86Y. After treatment with ASAQ, individuals infected with parasites that carried Pfmdr1 86Y were more likely to experience a recurrent infection.

Conclusions: These results support prior studies that suggested: (1) patients given AL and infected with parasites carrying N86 were more likely to experience a recurrent infection; (2) patients given ASAQ and infected with parasites carrying 86Y were more likely to experience a recurrent infection. These findings suggest that ACT and Pfmdr1 genotype may influence outcome after Plasmodium falciparum infection.

Keywords: Plasmodium falciparum; Africa; Antimalarials; Drug resistance; Malaria.

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Conflict of interest statement

Declarations. Disclaimer: The opinions expressed herein are those of the author(s) and do not necessarily reflect the views of any collaborating institute including the Centers for Disease Control and Prevention or the US Agency for International Development. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Countries and sites contributing data to this Pfmdr1 meta-analysis
Fig. 2
Fig. 2
a Forest plot of recurrent parasitemia in patients treated with AL. Odds ratio of N86 among patients with recurrent parasitemia compared to the odds ratio of N86 among patients who successfully cleared the infection. b Forest plot of recurrent parasitemia in patients treated with ASAQ. Odds ratio of 86Y among patients with recurrent parasitemia compared to the odds ratio of 86Y among those who successfully cleared the infection. c Forest plot of recurrent parasitemia in patients treated with DP. Odds ratio of 86Y among patients with recurrent parasitemia compared to the odds ratio of 86Y among patients who successfully cleared the infection. AL: artemether-lumefantrine; ASAQ: artesunate-amodiaquine; CL: confidence interval; DP: dihydroartemisinin-piperaquine; OR: odds ratio
Fig. 3
Fig. 3
a Forest plot of recurrent parasitemia in patients treated with AL. Odds ratio of 184F among patients with recurrent parasitemia compared to the odds ratio of 184F among patients who successfully cleared the infection. b Forest plot of recurrent parasitemia in patients treated with ASAQ. Odds ratio of Y184 among patients with recurrent parasitemia compared to the odds ratio of Y184 among those who successfully cleared the infection. c Forest plot of recurrent parasitemia in patients treated with DP. Odds ratio of 86Y among patients with recurrent parasitemia compared to the odds ratio of Y184 among patients who successfully cleared the infection. AL: artemether-lumefantrine; ASAQ: artesunate-amodiaquine; CL: confidence interval; DP: dihydroartemisinin-piperaquine; OR: odds ratio
Fig. 4
Fig. 4
a Forest plot of recurrent parasitemia in patients treated with AL. Odds ratio of D1246 among patients with recurrent parasitemia compared to the odds ratio of D1246 among patients who successfully cleared the infection. b Forest plot of recurrent parasitemia in patients treated with ASAQ. Odds ratio of 1246Y among patients with recurrent parasitemia compared to the odds ratio of 1246Y among those who successfully cleared the infection. c Forest plot of recurrent parasitemia in patients treated with DP. Odds ratio of 1246Y among patients with recurrent parasitemia compared to the odds ratio of 1246Y among patients who successfully cleared the infection. AL: artemether-lumefantrine; ASAQ: artesunate-amodiaquine; CL: confidence interval; DP: dihydroartemisinin-piperaquine; OR: odds ratio
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