Antimalarial Drug Resistance: A Brief History of Its Spread in Indonesia.

Malaria remains to be a national and global challenge and priority, as stated in the strategic plan of the Indonesian Ministry of Health and Sustainable Development Goals. In Indonesia, it is targeted that malaria elimination can be achieved by 2030. Unfortunately, the development and spread of antimalarial resistance inflicts a significant risk to the national malaria control programs which can lead to increased malaria morbidity and mortality. In Indonesia, resistance to widely used antimalarial drugs has been reported in two human species, Plasmodium falciparum and Plasmodium vivax. With the exception of artemisinin, resistance has surfaced towards all classes of antimalarial drugs. Initially, chloroquine, sulfadoxine-pyrimethamine, and primaquine were the most widely used antimalarial drugs. Regrettably, improper use has supported the robust spread of their resistance. Chloroquine resistance was first reported in 1974, while sulfadoxine-pyrimethamine emerged in 1979. Twenty years later, most provinces had declared treatment failures of both drugs. Molecular epidemiology suggested that variations in pfmdr1 and pfcrt genes were associated with chloroquine resistance, while dhfr and dhps genes were correlated with sulfadoxine-pyrimethamine resistance. Additionally, G453W, V454C and E455K of pfk13 genes appeared to be early warning sign to artemisinin resistance. Here, we reported mechanisms of antimalarial drugs and their development of resistance. This insight could provide awareness toward designing future treatment guidelines and control programs in Indonesia.

Fractions 14 and 36K of Metabolite Extract Streptomyces hygroscopicus subsp. Hygroscopicus Have Antimalarial Activities Against Plasmodium berghei in vitro.

Purpose: The study was conducted to investigate the effectivity and the cytotoxicity of fractions 14 and 36K of metabolite extract of Streptomyces hygroscopicus subsp. Hygroscopicus as an antimalarial compounds against Plasmodium berghei in vitro. Methods: Fractions 14 and 36K of metabolite extract of Streptomyces hygroscopicus subsp. Hygroscopicus produced by the fractionation process utilizing the Flash Column Chromatography (FCC) BUCHI Reveleris® PREP. Plasmodium berghei culture was used to assess the antimalarial activity of fractions 14 and 36K. Parasite densities and the ability of parasite growth were determined under microscopic. The cytotoxicity of the fractions was assessed using MTT assays on the MCF-7 cell line. Results: Streptomyces hygroscopicus subsp. Hygroscopicus fractions 14 and 36K have antimalarial activity against Plasmodium berghei, with fraction 14 having the more potent activity. The percentage of Plasmodium berghei-infected erythrocytes was decreased as well as the increase of fraction concentration. Fraction 14 has the highest inhibition of parasite growth at a concentration of 156,25 µg/mL, with an inhibition percentage of 67.73% (R2 = 0.953, p = 0.000). IC50 of fractions 14 and 36K were found at 10.63 µg/mL and 135,91 µg/mL, respectively. The fractions caused morphological damage in almost all asexual stages of the parasite. Both fractions were not toxic against MCF-7, indicating that the fractions have a safe active metabolite. Conclusion: Fractions 14 and 36K of metabolite extract Streptomyces hygroscopicus subsp. Hygroscopicus contains non-toxic compounds that could damage the morphology and inhibit the growth of Plasmodium berghei in vitro.