Short Report: Polymorphisms in the Chloroquine Resistance Transporter Gene in Plasmodium Falciparum Isolates From Lombok, Indonesia

Huaman, Maria Cecilia; Yoshinaga, Kazumi; Suryanatha, Aan; Suarsana, I Nyoman; Kanbara, Hiroji

doi:10.4269/ajtmh.2004.71.40

Cited by 30 publications

(24 citation statements)

References 16 publications

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“…The clinical success of the malaria drug regimen in Suriname is Table 1 Profile of polymorphisms in pfmdr1 and pfcrt and copy number results from two time periods in Suriname consistent with this characterization, because isolates in categories IV and II (N86Y) were reported to be less resistant to MQ, artesunate, and artemisinin than isolates in categories I (wild type) and III (Y184F). 9 Most of the investigated samples (97%) match the allelic variation revealed in the pfmdr1 polymorphisms in MQ-sensitive isolates from Brazil, 24 but they are in contrast with the high prevalence of mutant type N86Y in Indonesia, Nigeria, and subSaharan Africa [31][32][33] and the wild-type Y184, S1034, and N1042 genotype dominating in Angola and Gabon. 34,35 Also, the fixed occurrence of 1246Y found in this study is in contrast with data from Africa, where a low prevalence of the pfmdr1 1246Y allele occurs, 36 but consistent with prior data from the neighboring countries Brazil 24 and Guyana.…”

Section: Discussionmentioning

confidence: 84%

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Adhin

Labadie-Bracho²,

Bretas³

2013

The American Society of Tropical Medicine and Hygiene

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Abstract. The aim of this translational study was to show the use of molecular surveillance for polymorphisms and copy number as a monitoring tool to track the emergence and dynamics of Plasmodium falciparum drug resistance. A molecular baseline for Suriname was established in 2005, with P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance (pfmdr1) markers and copy number in 40 samples. The baseline results revealed the existence of a uniformly distributed mutated genotype corresponding with the fully mefloquine-sensitive 7G8-like genotype (Y184F, S1034C, N1042D, and D1246Y) and a fixed pfmdr1 N86 haplotype. All samples harbored the pivotal pfcrtK76T mutation, showing that chloroquine reintroduction should not yet be contemplated in Suriname. After 5 years, 40 samples were assessed to trace temporal changes in the status of pfmdr1 polymorphisms and copy number and showed minor genetic alterations in the pfmdr1 gene and no significant changes in copy number, thus providing scientific support for prolongation of the current drug policy in Suriname.

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Section: Discussionmentioning

confidence: 84%

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Adhin

Labadie-Bracho²,

Bretas³

2013

The American Society of Tropical Medicine and Hygiene

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“…One likely influence is the history of AQ and CQ use in these regions and the consequent selective pressure for pfcrt and pfmdr1 polymorphisms of one type or another. Haplotypes of pfcrt-encoding polymorphisms similar to those of the pfcrt alleles in South America and PNG have been reported from East Timor, Indonesia, the Philippines, Laos, India, and Iran (40)(41)(42)(43)(44)(45)(46)(47)(48)(49). In many of these regions AQ was widely used in the 1940s (50) and early 1950s before the advent of CQR (Fig.…”

Section: G8mentioning

confidence: 76%

Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

Sá

Twu

Hayton

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

247

230

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Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum originated from at least six foci in South America, Asia, and Oceania. Malaria parasites from these locations exhibit contrasting resistance phenotypes that are distinguished by point mutations and microsatellite polymorphisms in and near the CQR transporter gene, pfcrt, and the multidrug resistance transporter gene, pfmdr1. Amodiaquine (AQ), a 4-aminoquinoline related to CQ, is recommended and often used successfully against CQ-resistant P. falciparum in Africa, but it is largely ineffective across large regions of South America. The relationship of different pfcrt and pfmdr1 combinations to these drug-resistant phenotypes has been unclear. In two P. falciparum genetic crosses, particular pfcrt and pfmdr1 alleles from South America interact to yield greater levels of resistance to monodesethylamodiaquine (MDAQ; the active metabolite of AQ) than to CQ, whereas a pfcrt allele from Southeast Asia and Africa is linked to greater CQ than MDAQ resistance with all partner pfmdr1 alleles. These results, together with (i) available haplotype data from other parasites; (ii) evidence for an emerging focus of AQ resistance in Tanzania; and (iii) the persistence of 4-aminoquinoline-resistant parasites in South America, where CQ and AQ use is largely discontinued, suggest that different histories of drug use on the two continents have driven the selection of distinct suites of pfcrt and pfmdr1 mutations. Increasing use of AQ in Africa poses the threat of a selective sweep of highly AQ-resistant, CQ-resistant parasites with pfcrt and pfmdr1 mutations that are as advantaged and persistent as in South America.

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“…In Philippines, CVMNT is the major haplotype in CQ resistant P. falciparum [122]. Different haplotypes are identified according to geographical areas : SVMNT in Brazil and Papua New Guinea [126]; CVMNT and SVMNT in Peruvian Amazon [127]; SVMNT and CVIET in Indonesia [128]. It has four different haplotypes have been recently found in Brazil, SVMNT, CVMNT, CVMET and CVIET, including one previously found in Asian/African isolates, suggesting that parasites with CVIEt alleles were likely to have been introduced into Brazil from Asia or Africa [129,130].…”

Section: Drug/metabolite Transporter (Dmt) Proteinsmentioning

confidence: 99%

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Henry¹,

Alibert²,

Orlandi-Pradines³

et al. 2006

CDT

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The development and spread of resistance to antimalarial drugs poses a severe and increasing public health threat. Failures of prophylaxis or treatment with quinolines, hydroxynaphthoquinones, sesquiterpene lactones, antifolate drugs and sulfamides are involved in a return malaria-related morbidity and mortality. Resistance is associated with a decrease in accumulation of drugs into the vacuole, which results from a reduced uptake of the drug, an increased efflux or a combination of both. A number of candidate genes in P. falciparum have been proposed to be involved in antimalarial resistance, each concerned in membrane transport. Weaker or stronger associations are seen in P. falciparum between the resistance to quinolines or artemisinin derivatives and codon changes in Pfmdr1, a gene which encodes Pgh-1, an ortholog of one of the P-glycoproteins expressed in multi-drug resistant human cancer cells (ABC transporter). Further analysis has revealed a new gene, Pfcrt, encoding a PfCRT protein, which resembles an anion channel. Codon changes found in the Pfcrt sequence in drug resistant isolates could facilitate the drug efflux through a putative channel. It has been proposed that the reversal of quinoline resistance by verapamil is due to hydrophobic binding to the mutated PfCRT protein. Several compounds have demonstrated in the past decade a promising capability to reverse the antimalarial drug resistance in vitro in parasite isolates, in animal models and in human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic and antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and anthracenic derivatives. Here we summarize the progress made in biochemical and genetic basis of antimalarial resistance, emphasizing the recent developments on drugs, which interfere with trans membrane proteins involved in drug efflux or uptake.

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Short Report: Polymorphisms in the Chloroquine Resistance Transporter Gene in Plasmodium Falciparum Isolates From Lombok, Indonesia

Cited by 30 publications

References 16 publications

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

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