Molecular Epidemiology of Plasmodium Falciparum Resistance to Antimalarial Drugs in Indonesia

Abstract

The extent of gene polymorphisms associated with resistance to chloroquine and sulfadoxinepyrimethamine was examined in field isolates of Plasmodium falciparum from Indonesia. Eight malaria-endemic areas, representing a broad region of the western and eastern Indonesian Archipelago were surveyed. Blood from 20−50 patients was collected at each site, DNA was isolated, and the sequences of four different genes (dihydrofolate reductase [dhfr], dihydropteroate synthase [dhps], P. falciparum multidrug resistance 1 [pfmdr1], and P. falciparum chloroquine resistance transporter [pfcrt]) were analyzed using polymerase chain reaction and restriction fragment length polymorphisms to detect polymorphisms previously shown to be associated with resistance. This analysis identified polymorphisms in dhfr at 108-Asn/Thr, 16-Val, and 59-Arg. Polymorphisms in dhps were found less frequently, either 437-Gly alone or paired with 540-Glu. The pfcrt 76-Thr polymorphism was fixed in all parasite populations and pfmdr1 86-Tyr polymorphisms in all populations except in the most eastern regions. The pfmdr1 1042-Asp polymorphism occurred less frequently. These findings indicate that polymorphisms in genes associated with drug resistance in P. falciparum are found across a broad region of Indonesia.

Two novel mutations of pfdhps K540T and I588F, affecting sulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malaria at Banjar district, South Kalimantan Province, Indonesia

“…They mentioned no mutations were observed at codons 16, 50, 51 and 164 of the pfdhfr gene and at 436, 581 and 613 of the pfshps gene [21]. Syafruddin et al expanded the analysis to eight malaria-endemic areas, representing a broad region of the eastern and western Indonesian archipelago and presented additional polymorphisms in pfdhfr gene at the codons of A16V and S108T from several island parasite samples, the more common distributions being among eastern parts [22]. In this report, they mentioned less frequency of pfdhps polymorphisms; most of the parasites presented wild type pfdhps and about 15% of 437G; less than 5% of K540E mutations were detected [22].…”

Similarities of Antimalarial Resistance Genes in Plasmodium Falciparum Based on Ontology

“…In this research, there are two genes from Plasmodium falciparum which caused resistant to antimalarial chloroquine, they are P. Falciparum Chloroquine Resistant (Pfcrt) and P. Falciparum Multidrug 1 (Pfmdr1) which have been part of this research [8]. Those 2 genes will be counted semantically their similarity based on ontology and graph method by Wang method [15].…”

“…For Malaria, [20] research to predict functions of genes in Plasmodium falcifarum by counting the semantic similarity values based on patch to cluster the genes as well as to conduct its enrichment analysis. While researc h on antimalarial resistance has been done by [8]. Based on the explanation above on semantic similarity counting, many of which to predict function of genes in some species, one of which is malaria.…”

“…The emergence of Plasmodium falciparum that resistence to chloroquin has failed the goal of controlling Malaria [7]. In research of molecular approach using PCR (polymerase chain reaction) technic found the existence of polymorphism on P. falciparum chloroquine resistance transporter (pfcrt) gene and P. falciparum multidrug resistance 1 (pfmdr1) gene that influence the chloroquine [8]. Research in molecular is conducted to locate the mutation position in various genes related to the resistance [9].…”

Anti-Malarial Drug Resistance

“…12 Besides, Pfmrp, which is located on chromosome 1, encodes a protein that is located in the plasma membrane and membrane-bound vesicles of the erythrocytic stages of the parasite. 11 In contrast with mutations of Pfcrt and Pfmdr1 which cause decrease susceptibility of the parasite to antimalarial drugs, mutation in Pfmrp results in an increase anti-malarial susceptibility of the parasites.…”