Abstract:
Background: Artemether–lumefantrine (AL) is the recommended first-line artemisinin-based combination therapy
(ACT) for the treatment of uncomplicated falciparum malaria in most of the malaria-endemic countries, including
Tanzania. Recently, dihydroartemisinin–piperaquine (DP) has been recommended as the alternative anti-malarial to
ensure effective case management in Tanzania. This study assessed the parasite clearance rate and efficacy of AL and
DP among patients aged 6 months to 10 years with uncomplicated falciparum malaria in two sites with different
malaria transmission intensity.
Methods: This was an open-label, randomized trial that was conducted at two sites of Muheza Designated District
Hospital and Ujiji Health Centre in Tanga and Kigoma regions, respectively. Patients meeting inclusion criteria were
enrolled, treated with either AL or DP and followed up for 28 (extended to 42) and 42 (63) days for AL and DP, respec
tively. Parasite clearance time was monitored in the first 72 h post treatment and the clearance rate constant and half
life were calculated using an established parasite clearance estimator. The primary outcome was parasitological cure
on days 28 and 42 for AL and DP, respectively, while secondary outcome was extended parasitological cure on days
42 and 63 for AL and DP, respectively.
Results: Of the 509 children enrolled (192 at Muheza and 317 at Ujiji), there was no early treatment failure and PCR
uncorrected cure rates on day 28 in the AL group were 77.2 and 71.2% at Muheza and Ujiji, respectively. In the DP
arm, the PCR uncorrected cure rate on day 42 was 73.6% at Muheza and 72.5% at Ujiji. With extended follow-up (to
day 42 for AL and 63 for DP) cure rates were lower at Ujiji compared to Muheza (AL: 60.2 and 46.1%, p = 0.063; DP: 57.6
and 40.3% in Muheza and Ujiji, respectively, p = 0.021). The PCR corrected cure rate ranged from 94.6 to 100% for all
the treatment groups at both sites. Parasite clearance rate constant was similar in the two groups and at both sites
(< 0.28/h); the slope half-life was < 3.0 h and all but only one patient cleared parasites by 72 h.
Conclusion: These findings confirm high efficacy of the first- and the newly recommended alternative ACT for
treatments for uncomplicated falciparum malaria in Tanzania. The high parasite clearance rate suggests absence of
suspected artemisinin resistance, defined as delayed parasite clearance.
