High efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated falciparum malaria in Muheza and Kigoma Districts, Tanzania

Abstract

BackgroundArtemether–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.MethodsThis 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, respectively. 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.ResultsOf 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.ConclusionThese 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.Trial registration This trial is registered at ClinicalTrials.gov under registration number NCT02590627

Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade of its use in Kenya

“…This outcome correlate to a number of studies undertaken earlier in Kenya, Uganda, Somalia, Mali, and several other African countries indicating that Artemisinin resistance has not appeared in the African continent [19,34]. The component drug, lumefantrine, is a gradually acting drug with a long half-life time ranging from 4-7 days [48].…”

“…In this study, AL has shown high efficacy similar to one carried in Tanzania and other parts of Africa primarily supporting the high efficacy rates of AL despite its use in the continent for over ten years [19,47]. The elevated parasite clearance rates may possibly be described by the steadfast act of artemether to clear parasites biomass leading to a quick resolution of clinical manifestation.…”

“…Artemisinin resistance which is the cornerstone of ACTs was reported in western Cambodia and subsequently spreading several neighboring countries in the Greater Mekong sub region of Southeast Asia in recent years [16][17][18][19][20]. The World Health Organization recommends that malaria-endemic countries should monitor the efficacy of nationally recommended ACT to guide national treatment guidelines [11].…”

“…The following artemisinin-based combinations are recommended; artemether-lumefantrine (AL), artesunate-amodiaquine (AS + AQ), artesunate-mefloquine (AS + MQ), artesunatesulfadoxine/pyrimethamine (AS + SP), and dihydroartemisinin-piperaquine (DP) with AL being the most widely used combination and is currently the first-line antimalarial drug in most malaria endemic countries in the WHO African region [2,19,22]. AL which is a co-formulation Artemether and lumefantrine which, is an aryl related alcohol linked to quinine, mefloquine and halofantrine that is commercially accessible in fixed-dose combination.…”

Clinical efficacy of artemisinin-lumefantrine and status of antifolate drug resistance markers in western Kenya

“…Immediately, resistance to SP emerged and in 2006, AL was adopted and the implementation of the new policy started in 2007 [12][13][14][15].…”