Efficacy and safety of artemisinin-based combination therapy, and molecular markers for artemisinin and piperaquine resistance in Mainland Tanzania

• Published in: Malaria Journal
• Main Authors: Mwaka A. Kakolwa, Muhidin K. Mahende, Deus S. Ishengoma, Celine I. Mandara, Billy Ngasala, Erasmus Kamugisha, Johannes B. Kataraihya, Renata Mandike, Sigsbert Mkude, Frank Chacky, Ritha Njau, Zul Premji, Martha M. Lemnge, Marian Warsame, Didier Menard, Abdunoor M. Kabanywanyi
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2018
• Subjects: Artemisinin-based combination therapy; Efficacy; Safety; Malaria; Molecular markers; Artemisinin; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-018-2524-x; https://doaj.org/article/ee9da9dfdea34557ac4cebb6d5599354

Abstract Background Artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment of uncomplicated malaria in most malaria endemic countries, including Tanzania. Unfortunately, there have been reports of artemisinin resistance and ACT failure from South East Asia highlighting the need to monitor therapeutic efficacy of ACT in these countries as recommended by World Health Organization. Methods Open-label single arm studies in mainland Tanzania were conducted in nine sentinel sites in 2011, 2012 and 2015 to assess the efficacy and safety of artemether/lumefantrine (AL) and artesunate/amodiaquine (ASAQ) using 28 days follow-up and dihydroartemisinin/piperaquine (DHAPQ) using 42 days follow-up. Mutations in the propeller domain of the Plasmodium falciparum kelch 13 (k13) gene and amplification of the P. falciparum plasmepsin 2 (pm2) gene, associated with artemisinin and piperaquine (PQ) resistance, were also investigated. Results Of the 428 patients enrolled, 328 patients provided study endpoint. For AL, the PCR corrected per-protocol analysis showed adequate clinical and parasitological response (ACPR) of 90.3% (n = 28; 95% CI 74.2–98.0) in Kyela 2012, 95.7% (n = 22; 95% CI 78.1–99.0) in Chamwino, 100% in Muheza (n = 29; 95% CI 88.1–100), 100% in Nagaga (n = 39; 95% CI 91.0–100) and Kyela 2015 (n = 60; 95% CI 94.0–100). For ASAQ, PCR corrected ACPR of 98% (n = 49; 95% CI 89.4–99.9) and 100% (n = 25; 95% CI 86.3–100) were observed in 2011 in Ujiji and Kibaha, respectively. For DHAPQ, the ACPR was 100% (n = 71; 95% CI 94.9–100). Of the 235 samples with genetic interpretable results, only 7 (3%) had non-synonymous k13 mutations. None of these are candidate or validated markers of artemisinin resistance and all patients carrying these alleles cleared the parasites on day 3. Of the DHAPQ group, 10% (3/29) of the samples with interpretable results had pm2 multiple copies and none of them was associated with treatment failure. Conclusion All the tested ACT in mainland Tanzania were highly ...