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

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.

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