BACKGROUND: Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the first-line treatments against malaria in Mozambique. Dihydroartemisinin-piperaquine (DP) has been used in-country for mass drug administration campaigns, and artesunate-pyronaridine (AS-PY) is considered an alternative drug to delay AL resistance in the country. To assess whether AL and AS-AQ remain efficacious and to confirm that DP and AS-PY are potential alternatives for uncomplicated malaria treatment, an in vivo therapeutic efficacy study was conducted in Mozambique at five sentinel sites.
METHODS: This study was conducted in the districts of Montepuez (AL), Dondo (AL and AS-AQ), Mopeia (AL and AS-PY), Moatize (AL and AS-AQ), and Massinga (AL and DP) following the 2009 World Health Organization (WHO)-recommended protocol. Patients aged 6 months to 11 years with uncomplicated Plasmodium falciparum malaria (1000-200,000 parasites/µl) were enrolled, followed, and assessed for 28 days (AL and AS-AQ) or 42 days (DP and AS-PY). Genotyping for msp1/msp2/poly-α markers and match counting via the WHO/Medicines for Malaria Venture (MMV) 3/3 algorithm were used to differentiate recrudescences from new infections. The primary outcome was polymerase chain reaction corrected efficacy for each drug.
RESULTS: In total, 828 participants were enrolled in the four study arms: AL (462), AS-AQ (183), DP (91), and AS-PY (92). Among the recruited participants, 10.2% (85/828) were lost to follow-up or withdrew, and 60 had recurrent malaria infections, 55 of which were considered new infections and five recrudescences. Day 28 corrected AL efficacy was 100% (95% CI 94.3-100) in Massinga, 100% in Dondo, 100% (95% CI 95.5-100) in Moatize, 97.63% (95% CI 94.4-100) in Mopeia, and 98.68% (95% CI 96.2-100) in Montepuez. Day 28 corrected AS-AQ efficacy was 100% in Dondo and 100% (95% CI 95.4-100) in Moatize. For DP, the corrected efficacy on day 42 was 100% (95% CI 94.1-100) in Massinga, and that on day 42 was 97.75% (95% CI 94.7-100) in Mopeia. All drugs were well tolerated, with adverse events reported in less than 2% of the participants.
CONCLUSION: AL and AS-AQ remain effective, as their efficacy remained above the 90% WHO-recommended cut-off. DP and AS-PY also showed therapeutic efficacy above the WHO-acceptable cut-off and could be used as first-line treatments when needed. All four artemisinin-based combinations were well tolerated, with minimal safety concerns.
TRIAL REGISTRATION: Clinicaltrials.gov: NCT05343312.
