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1167 Surveillance of parasite populations and patterns of drug resistance, and associated parasite clearance or treatment failure in Tanzania

Location: Tanzania (TZ).


Partner study description

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. The samples for this project were collected in 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. Genomic data of Plasmodium falciparum were generated by whole genome sequencing (WGS) using illumina short reads which was done through the P. falciparum Community Project at the Wellcome Sanger Institute, UK. Of the 509 children enrolled (192 at Muheza and 317 at Ujiji), there was no early treatment failure and 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. The findings confirmed 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. Parasite diversity and population structure, and the profile of drug resistance markers will be determined from the WGS data compared with those of other countries in the Pf6k dataset.