Artemisinin-based combination therapies (ACTs) are first-line treatments for uncomplicated Plasmodium falciparum malaria. ACT resistance is spreading in Asia but not yet in Africa. Reduced effects of ACT partner drugs have been reported but with little information regarding widely used artesunate/amodiaquine (ASAQ). We studied its efficacy in Zanzibar after 14 years as first-line treatment directly by an in vivo, single-armed trial and indirectly by prevalences of different genotypes in the P. falciparum chloroquine-resistance transporter, multidrug-resistance 1, and Kelch 13 propeller domain genes. In vivo efficacy was higher during 2017 (100%; 95% CI 97.4%-100%) than during 2002-2005 (94.7%; 95% CI 91.9%-96.7%) (p = 0.003). Molecular findings showed no artemisinin resistance-associated genotypes and major increases in genotypes associated with high sensitivity/efficacy for amodiaquine than before ASAQ was introduced. Thus, the efficacy of ASAQ is maintained and appears to be increased after long-term use in contrast to what is observed for other ACTs used in Africa.
Keywords: ACT; ASAQ; P. falciparum Kelch 13 propeller domain gene; P. falciparum chloroquine-resistance transporter gene; P. falciparum multidrug-resistance 1 gene; Plasmodium falciparum; Tanzania; Zanzibar; artemisinin-based combination therapy; artesunate/amodiaquine; drug resistance; genotypes; malaria; parasites; pfcrt gene; pfk13 gene; pfmdr1 gene; resistance selection; trends; vector-borne infections; zoonoses.