Introduction. Artemisinin derivatives are the WHO first-line treatment for severe and uncomplicated falciparum malaria. Spreading artemisinin drug-resistance threatens Southeast Asian malaria elimination goals. In Malaysia, the Ministry of Health is implementing drug response surveillance of artemisinin treatment efficacy for falciparum malaria, but there is only limited evaluation of P. falciparum-molecular artemisinin-resistance markers.
Methods. This was a multi-centre open-label study conducted in three adjacent district hospitals in northwest Sabah, Malaysia, to assess clearance rates of P. falciparum parasitaemia in patients with acute uncomplicated malaria. Febrile non-pregnant patients with a positive Pf-HRP2 rapid diagnostic test, microscopic monoinfection with P. falciparum and a parasite count of 1,000-100,000/µL were enrolled, with Plasmodium species subsequently confirmed by PCR. Patients received oral artesunate alone (total target dose 12mg/kg) for 3 days, followed by oral mefloquine. Blood slides were taken 6-hourly to calculate microscopic parasite clearance. Molecular surveillance of 20 SNPs in the P. falciparum K13 propeller domain associated with artemisinin-resistance were evaluated by PCR, including in additional patients with falciparum malaria enrolled in a prospective tertiary-referral hospital study for the western area of Sabah.
Results. From 2012-15, 59 patients with falciparum malaria were enrolled in the artemisinin in vivo efficacy study. Median age was 21 years (IQR 12-31; range 3-62), with 15 (25%) being children ≤12 years. Median parasite count at presentation was 9,074/µL. The median parasite clearance time was 24 hours (IQR 18-42; range 6-72), and median time to 50% parasite clearance was 4.2 hours. All patients were microscopy-negative for parasites by 72 hours. For the molecular surveillance study, a total of 264 patients with falciparum malaria from western Sabah were evaluated for K13 drug-resistance markers, with all SNPs found to be wild-type.
Conclusion. Artemisinin derivatives remain highly efficacious for the treatment of falciparum malaria in Sabah, Malaysia, with no K13 drug-resistance markers detected.