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. 2021 Jul 16;65(8):e0087321.
doi: 10.1128/AAC.00873-21. Epub 2021 Jul 16.

Persistent Submicroscopic Plasmodium falciparum Parasitemia 72 Hours after Treatment with Artemether-Lumefantrine Predicts 42-Day Treatment Failure in Mali and Burkina Faso

Khalid B Beshir  1 , Nouhoum Diallo  2 , Fabrice A Somé  3 , Salif Sombie  4 , Issaka Zongo  3 , Bakary Fofana  2 , Aliou Traore  2 , Souleymane Dama  2 , Amadou Bamadio  2 , Oumar B Traore  2 , Sam A Coulibaly  4 , Ouattara S Maurice  5 , Amidou Diarra  5 , Jean Moise Kaboré  5 , Aly Kodio  2 , Amadou Hamidou Togo  2 , Niawanlou Dara  2 , Moctar Coulibaly  2 , Francois Dao  2 , Frederic Nikiema  3 , Yves D Compaore  3 , Naomie T Kabore  3 , Nouhoun Barry  3 , Issiaka Soulama  4 , Issaka Sagara  2 , Sodiomon B Sirima  5 , Jean-Bosco Ouédraogo  3 , Abdoulaye Djimde  2 , Colin J Sutherland  1
Affiliations

Persistent Submicroscopic Plasmodium falciparum Parasitemia 72 Hours after Treatment with Artemether-Lumefantrine Predicts 42-Day Treatment Failure in Mali and Burkina Faso

Khalid B Beshir et al. Antimicrob Agents Chemother. .

Abstract

A recent randomized controlled trial, the WANECAM (West African Network for Clinical Trials of Antimalarial Drugs) trial, conducted at seven centers in West Africa, found that artemether-lumefantrine, artesunate-amodiaquine, pyronaridine-artesunate, and dihydroartemisinin-piperaquine all displayed good efficacy. However, artemether-lumefantrine was associated with a shorter interval between clinical episodes than the other regimens. In a further comparison of these therapies, we identified cases of persisting submicroscopic parasitemia by quantitative PCR (qPCR) at 72 h posttreatment among WANECAM participants from 5 sites in Mali and Burkina Faso, and we compared treatment outcomes for this group to those with complete parasite clearance by 72 h. Among 552 evaluable patients, 17.7% had qPCR-detectable parasitemia at 72 h during their first treatment episode. This proportion varied among sites, reflecting differences in malaria transmission intensity, but did not differ among pooled drug treatment groups. However, patients who received artemether-lumefantrine and were qPCR positive at 72 h were significantly more likely to have microscopically detectable recurrent Plasmodium falciparum parasitemia by day 42 than those receiving other regimens and experienced, on average, a shorter interval before the next clinical episode. Haplotypes of pfcrt and pfmdr1 were also evaluated in persisting parasites. These data identify a possible threat to the parasitological efficacy of artemether-lumefantrine in West Africa, over a decade since it was first introduced on a large scale.

Keywords: Plasmodium falciparum; antimalarial agents.

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Figures

FIG 1
FIG 1
Proportion of participants qPCR positive at day 3 for episodes 1 and 2. Colored bars represent proportion of slow-clearing P. falciparum infections for each of the 4 treatment groups in the primary malaria episode, and inlaid white bars represent proportion for episode 2 in the same patient group. Denominators are given for episode 1 and episode 2.
FIG 2
FIG 2
Prevalence of pfcrt CVMNK and pfmdr1 codon 86Asn alleles among day 0 and day 3 isolates by study site. Denominators shown are for day 0 and day 3.
See this image and copyright information in PMC

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