Genetic Profiles of Plasmodium falciparum Isolates from a Therapeutic Efficacy Study on the Antimalarial Drug Dihydroartemisinin-Piperaquine in the West Sumba and Kupang Districts of East Nusa Tenggara Province, Indonesia

¹ Master Program, Department of Biochemistry, Faculty of Mathematics and Natural Science, IPB University, Bogor, Indonesia (E-mail: irdayanti52@gmail.com)
² Hasanuddin University Medical Research Center, Makassar, Indonesia. (E-mail: irdayanti52@gmail.com; hijral.aswad87@gmail.com; yenniyusuf82@gmail.com; dinkarim@yahoo.com)
³ Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong, Indonesia. (E-mail: puji008@brin.go.id; isma005@brin.go.id)
⁴ World Health Organization, Country Office for Indonesia, Jakarta, Indonesia. (Email: basrih@who.int; diptynusaa@who.int)
⁵ Malaria Team Work, Ministry of Health, Jakarta, Republic of Indonesia. (E-mail: helendewi@yahoo.com)
⁶ Department of Parasitology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. (E-mail: yenniyusuf82@gmail.com; rhany72blue@gmail.com; dinkarim@yahoo.com)
⁷ Biomedical Science Study Program, Graduate School of Hasanuddin University, Makassar, Indonesia (Email: najdahhidayah@unhas.ac.id)
⁸ Department of Biochemistry, Faculty of Mathematics and Natural Science, IPB University, Bogor, Indonesia. (Email: imart@apps.ipb.ac.id)

^* Corresponding author: Puji BS Asih

Abstract

Artemisinin resistance, first reported on the Thai-Cambodian border in 2009, has spread across Southeast Asia, characterized by delayed parasite clearance. Extended artemisinin-based combination therapy (ACT) regimens have shown efficacy where standard 3-day treatments failure. In Indonesia, dihydroartemisinin-piperaquine (DHA-PPQ) has been the first-line treatment for uncomplicated Plasmodium falciparum malaria since 2010. This study evaluates the efficacy, safety, and parasite clearance times of DHA-PPQ in West Sumba and Kupang Districts, East Nusa Tenggara, while assessing single-nucleotide polymorphisms (SNPs) in the Pfk13 and Pfcrt genes, which are linked to artemisinin and piperaquine resistance, respectively. Following WHO guidelines, 382 cases were screened, with 41 eligible for 42-day clinical and parasitological monitoring. Molecular analyses utilized PCR and real-time PCR. All cases demonstrated adequate clinical and parasitological response (100% APCR). No mutations were detected in 21 Pfk13 SNPs associated with artemisinin resistance or in Pfcrt codons M343L, C350R, G353V, and I356L linked to piperaquine resistance. However, 10 of 41 samples (24.39%) exhibited Pfpm2 gene amplification, indicating early piperaquine selection pressure. DHA-PPQ remains effective, but Pfpm2 amplification underscores the need for continuous molecular surveillance and exploration of extended ACT regimens to sustain malaria control.