Efficacy of artemether-lumefantrine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso, 2020-2021.

BACKGROUND

Burkina Faso has conducted regular therapeutic efficacy monitoring of artemisinin-based combination therapy (ACT) since its introduction in the early 2000s. Since 2008, artemether-lumefantrine (AL), the most widely used ACT to treat uncomplicated malaria, has shown reduced efficacy in Burkina Faso. To inform national case management policy, investigators conducted a therapeutic efficacy study in 2020-2021.

METHODS

Children aged 6 months to 12 years with microscopically confirmed uncomplicated Plasmodium falciparum malaria were enrolled in three sites, treated with either AL, dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (AS-PYR), and monitored for 28 or 42 days to determine treatment response. Dried blood spots were collected on filter papers to determine recrudescence from new infection in late treatment failures, presence of known molecular markers of antimalarial resistance, and presence of hrp2/3 genes associated with rapid diagnostic test accuracy. Samples collected on day-7 in the AL arm were analysed to determine blood lumefantrine concentrations.

RESULTS

A total of 1078 participants reached the study endpoint. Uncorrected cumulative 28-day efficacy ranged from 57.1% (95% confidence intervals (CI) 49.4-64.0) to 64.4% (95% CI 56.8-71.0) for AL, from 96.6% (95% CI 89.8-98.9) to 98.9% (95% CI 92.2-99.8) for DP, and from 82.2% (95% CI 72.2-88.9) to 90.7% (95% CI 82.3-95.2) for AS-PYR. PCR-corrected efficacy was above the 90% WHO threshold for all drugs and sites except for AL in Nanoro where the per-protocol efficacy was 89.4% (95% CI 82.2-94.4). No molecular markers associated with artemisinin resistance were identified in samples analysed, and there was no statistically significant association between treatment failure and sub-therapeutic day-7 blood lumefantrine levels. One sample was found to harbor a pfhrp3-single deletion.

CONCLUSION

Continued low uncorrected efficacy of AL was observed in all sites, with one half to one third of children returning to the clinic with repeat infection within 28 days. PCR-corrected efficacy was at or below 90% for AL. AS-PYR and DP were associated with low rates of recurrent parasitaemia suggesting a potential for implementing a multiple first-line therapy approach with non-AL ACT. This approach will allow to preserve future use of lumefantrine and improve patient outcomes.