Efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Northern Papua and Jambi, Indonesia

Dihydroartemisinin-piperaquine (DHA-PPQ) has been adopted as first-line therapy for uncomplicated falciparum malaria in Indonesia since 2010. The efficacy of DHA-PPQ was evaluated in 2 sentinel sites in Keerom District, Papua and Merangin District, Jambi Provinces from April 2017 to April 2018. Clinical and parasitological parameters were monitored over a 42-day period following the WHO standard in vivo protocol and subjects meeting the inclusion criteria were treated with DHA-PPQ once daily for 3 days, administered orally. In Keerom District, 6339 subjects were screened through active and passive cases detection. A total of 114 subjects infected by P. falciparum and 83 subjects infected by P. vivax agreed to take a part through written informed consent. Kaplan-Meier analysis of microscopy readings and PCR-corrected falciparum cases revealed a 93.1% (95%CI:86.4-97.2) and 97.9% (95%CI:92.7-99.7) DHA-PPQ efficacy, respectively and were classified as Adequate Clinical Parasitological Responses (ACPRs). For vivax malaria, the DHA-PPQ efficacy were 89% (95%CI: 80.2-94.9) and 100% (95%CI: 95.1-100) respectively. In Merangin District, 751 subjects were screened and 41 subjects infected by P. vivax were recruited. Microscopy reading and PCR-corrected analysis revealed a 97.4% (95%CI:86.2-99.9) and 100% (95%CI: 90.5-100) DHA-PPQ efficacy, respectively. No severe adverse events were found in both sites. In both sites, there was no delay in parasite clearance and no mutations in the PfK13 and PvK12 genes. Of the 6 recurrent P. falciparum found, 2 indicated recrudescent and 4 cases were re-infection. Analysis of the PfPM2 gene at day 0 and day of recurrence in recrudescent cases revealed the same single copy number, whereas 3 of the 4 re-infection cases carried 2-3 copy numbers. In conclusion, treatment of falciparum and vivax malaria cases with DHA-PPQ showed a high efficacy and safety. DHA-PPQ regimen is also efficacious against P. vivax cases in the absence of primaquine.