Exploring Plasmodium falciparum multidrug resistance 1 gene polymorphisms and clinical outcomes after treatment with artemether-lumefantrine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine Open Access

Laird, Veronika (Spring 2022)

Permanent URL: https://etd.library.emory.edu/concern/etds/sq87bv750?locale=en%255D
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Abstract

The Plasmodium falciparum multidrug resistance transporter 1 gene (pfmdr1) is associated with altered response to artemisinin-based combination therapies (ACTs), particularly those 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 treatment responses to AL and ASAQ. To determine whether patients infected with parasites carrying specific pfmdr1 SNPs are at increased risk of recurrent parasitemia or treatment failure, patient data on molecular markers of P. falciparum from 16 therapeutic efficacy studies in 13 African countries from 2013 to 2019 were analyzed. Conditional logistic regression was used to estimate the exposure odds ratio by treatment arm when the data from all studies were compiled. This exposure odds ratio represented the odds of recurrent infections or recrudescent infections with a specific allele found at baseline compared to the odds of successfully treated infections with that same allele found at baseline. After controlling for study site, the presence of parasites in the initial infection that carried pfmdr1 N86 (alone or a mixed infection with 86Y) was strongly and negatively associated with recurrent infection occurring between days 14 and 28 after AL treatment (adjusted odds ratio [OR]=0.22, 95% CI=0.05, 0.94, P < 0.001). For those treated with ASAQ, the presence of parasites in the initial infection that carried pfmdr1 N86 (alone or a mixed infection with 86Y) was strongly and negatively associated with recrudescence occurring between days 14 and 28 after ASAQ treatment ([OR]=0.09; 95% CI=0.01, 0.72; P = 0.02). There were no statistically significant associations detected between recurrent or recrudescent infections and pfmdr1 codons 184 and 1246. These findings suggest that administering AL and pfmdr1 genotype may influence treatment outcome after P. falciparum infection.

Table of Contents

1. Introduction. 1

2. Methods. 3

3. Results. 7

4. Discussion. 9

5. References. 13

6. Tables. 18

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