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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ACTRN12616001533482 ### Funding Statement Samples collection and molecular assays for all samples collected were supported by WHO TSA PO 201684642. Several parts of molecular assays were supported by Government of Indonesia, Ministry of Health and Ministry of Research and Technology/National Research and Innovation Agency, through Eijkman Institute for Molecular Biology, Jakarta. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethics Committee of Research in Health, Medical Faculty of Hasanuddin University, Makassar, Indonesia (No. 663/H4.8.4.5.31/PP36-KOMETIK/2016 and No. 356/H4.8.4.5.31/PP36-KOMETIK/2017). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All relevant data are within the manuscript