Decreased susceptibility of Plasmodium falciparum parasites in Southeast Asia to artemisinin drugs and recently to one of its partner drugs; piperaquine, threatens the control and elimination efforts of malaria. Western Indonesia used artesunate-amodiaquine between 2004 and 2012, and treatment failures were frequently observed. Dihydroartemisinin-piperaquine (DP) has been deployed as the first-line treatment since 2012.
We enrolled 302 adults and children with uncomplicated falciparum malaria in three regencies in North Sumatera province, western Indonesia. Patients were randomised to receive either the standard 3-dose of DP or 6-dose of artemether-lumefantrine (AL). Patients were followed-up for 6 weeks. Primary endpoint was the PCR-corrected efficacy of DP and AL at day-42, and the secondary endpoints were parasite clearance times, and the proportion of patients with submicroscopic Plasmodium falciparum recurrences at day-42.
Baseline genetic characterisations of P. falciparum parasites revealed high frequency of pfcrt-SVMNT haplotype (88.7%, 63/71), pfmdr1 86Y/184Y (72.8%, 67/92), and pfkelch13 wild-type allele (96%, 72/75). A small proportion of patients (3/75, 4%) had mixed wild-type and mutant T474A in the pfkelch13. The parasite clearance times were 1.6 and 1.9 days for DP and AL, respectively. The uncorrected-PCR efficacy at day-42 were 84% for DP and 90.4% for AL (P=0.09). However, PCR-corrected efficacy remain excellent at 99.3% and 100% for DP and AL (P=0.31), respectively. Nevertheless, at day 42, submicroscopic P. falciparum recurrences were significantly noted at 31.5% for DP and 30.4% for AL (P=0.741). Both treatment selected parasites carrying pfmdr1 86N/184F (OR 13.3, 95% CI 2.7-81.4, P=0.0001 for DP and OR 28.6, 95% CI 5.1-277.7, P<0.0001 for AL).
DP and AL appear to remain effective for the treatment of uncomplicated P. falciparum infection in western Indonesia. However, both combinations gave limited post-treatment prophylaxis at day 42 which potentially contribute to continuous malaria transmission and hinders the malaria elimination efforts in the region.