Introduction: Following deployment of artemisinin-based combination therapies (ACTs) in most malaria endemic countries and the emergence and spread of resistance to artemisinins and partner drugs in South-East Asia (SEA), the World Health Organization (WHO) recommends regular therapeutic efficacy studies (TES) to monitor the performance of these drugs. This review assessed the trends of therapeutic efficacy and molecular makers of artemisinins and partner drugs resistance (K-13 and Pfmdr1) after using ACTs for more than one decade in Tanzania.
Methods: Data from published and unpublished TES and studies of molecular markers were assembled and analysed. Efficacy data included TES of artemether-lumefantrine (AL), artesunate - amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP); while data of K-13 and Pfmdr1 were obtained from TES and cross-sectional surveys conducted in different parties of Tanzania from 2000 to 2017.
Results: Efficacy of AL was assessed in 14 studies and PCR corrected adequate clinical and parasitological response (ACPR) ranged from 95.1% to 100% between 2003 and 2017. Five studies tested ASAQ and ACPR increased from 88% to 100 in 2004 and 2017, respectively. Three studies assessed DP between 2014 and 2017, and all had ACPR of 100%. Non-synonymous mutations in the K-13 gene were <3% between 2006 and 2016 and none of these mutations have been associated with artemisinin resistance in SEA. For mutations in Pfmdr1 associated with lumefantrine resistance, N86 was 6% - 10% between 2002 and 2006, but increased to 99.1% in 2016; and 184F increased from 6% in 2002 to 10% in 2006, and was 40 - 65% between 2011 and 2016.
Conclusion: The ACTs are still efficacious with no known K-13 mutations associated with artemisinin resistance. However, the increasing Pfmdr1 markers associated with lumefantrine resistance is a cause of concern and argue for continued surveillance in order to support TES and provide evidence-based malaria treatment policies.