PROFIL GENETIK ISOLAT Plasmodium falciparum DAN P. vivax PADA EFIKASI OBAT ANTIMALARIA DIHIDROARTEMISININ PIPERAKUIN PROVINSI NUSA TENGGARA TIMUR

Abstract

Malaria masih menjadi masalah kesehatan masyarakat di Indonesia, terutama di wilayah endemis seperti Provinsi Nusa Tenggara Timur. Salah satu program pengendalian malaria mengenai pengobatan masih sangat bergantung pada artemisinin-based combination therapy (ACT). Obat antimalaria dihydroartemisinin-piperaquine (DHA-PPQ) merupakan obat antimalaria lini pertama di Indonesia. Adanya kasus resistansi terhadap artemisinin di negara Kamboja (Greater Mekong Region) menimbulkan kekhawatiran akan meluas potensi berkembangnya resistansi tersebut di Indonesia. Penelitian ini bertujuan untuk menilai efikasi DHA-PPQ serta mengevaluasi penanda genetik resistansi antimalaria pada isolat Plasmodium falciparum dan P. vivax di Kabupaten Sumba Barat dan Kupang, Provinsi Nusa Tenggara Timur. Hasil penelitian menunjukkan bahwa seluruh pasien sembuh total atau 100% Adequate Clinical and Parasitological Response (ACPR). Analisis molekuler meliputi deteksi single-nucleotide polymorphisms (SNP) pada gen Pfk13 dan Pfcrt pada Plasmodium falciparum, serta gen Pvk12 pada P. vivax menggunakan metode PCR sekuensing. Analisis copy number variation (CNV) gen Pfmdr1 dan Pfpm2 menggunakan metode real-time PCR. Secara molekuler, seluruh isolat P. falciparum dan P. vivax menunjukkan alel tipe normal (wild type) pada gen Pfk13, Pfcrt, dan Pvk12. Namun, ditemukan peningkatan CNV gen Pfmdr1 (12,19%) dan Pfpm2 (24,39%). Temuan ini menunjukkan bahwa DHA-PPQ masih efektif di wilayah penelitian, meskipun terjadi peningkatan CNV gen Pfmdr1 dan Pfpm2. Pemantauan molekuler berkelanjutan tetap diperlukan untuk mendeteksi dini potensi resistansi antimalaria.

Malaria continues to pose a significant public health challenge in Indonesia, particularly in regions where it is endemic, such as East Nusa Tenggara Province. It is evident that one of the malaria control programmes, with regard to treatment, continues to rely heavily on artemisinin-based combination therapy (ACT). The antimalarial drug dihydroartemisinin-piperaquine (DHA-PPQ) is the first-line antimalarial drug in Indonesia. The emergence of artemisinin resistance in Cambodia (The Greater Mekong Region) is a concern, particularly given the potential for its dissemination to Indonesia. The objective of this study is to assess the efficacy of DHA-PPQ and to evaluate the genetic markers of antimalarial resistance in Plasmodium falciparum and P. vivax isolates in West Sumba and Kupang Districts, East Nusa Tenggara Province. The results demonstrated that all patients exhibited a complete cure or an adequate clinical and parasitological response (ACPR) of 100%. The molecular analysis encompassed the detection of single-nucleotide polymorphisms (SNPs) in the Pfk13 and Pfcrt genes in Plasmodium falciparum, and in the Pvk12 gene in P. vivax, utilising PCR sequencing. Copy number variation (CNV) analysis of the Pfmdr1 and Pfpm2 genes was performed using real-time PCR. Molecularly, all P. falciparum and P. vivax isolates exhibited normal (wild type) alleles in the Pfk13, Pfcrt, and Pvk12 genes. However, an increase in CNV was identified in the Pfmdr1 (12.19%) and Pfpm2 (24.39%) genes. These findings suggest that DHA-PPQ remains effective in the study area, despite the increase in CNV observed in the Pfmdr1 and Pfpm2 genes. Continuous molecular monitoring remains necessary to detect early potential antimalarial resistance.