Dataset Information

Plasmodium falciparum Chloroquine-pfcrt Resistant Haplotypes in Brazilian Endemic Areas Four Decades after CQ Withdrawn.

ABSTRACT: (1) Background: Malaria is a public health problem worldwide. Despite global efforts to control it, antimalarial drug resistance remains a great challenge. In 2009, our team identified, for the first time in Brazil, chloroquine (CQ)-susceptible Plasmodium falciparum parasites in isolates from the Brazilian Amazon. The present study extends those observations to include survey samples from 2010 to 2018 from the Amazonas and Acre states for the purpose of tracking pfcrt molecular changes in P. falciparum parasites. (2) Objective: to investigate SNPs in the P. falciparum gene associated with chemoresistance to CQ (pfcrt). (3) Methods: Sixty-six P. falciparum samples from the Amazonas and Acre states were collected from 2010 to 2018 in patients diagnosed at the Reference Research Center for Treatment and Diagnosis of Malaria (CPD-Mal/Fiocruz), FMT-HVD and Acre Health Units. These samples were subjected to PCR and DNA Sanger sequencing to identify mutations in pfcrt (C72S, M74I, N75E, and K76T). (4) Results: Of the 66 P. falciparum samples genotyped for pfcrt, 94% carried CQ-resistant genotypes and only 4 showed a CQ pfcrt sensitive-wild type genotype, i.e., 1 from Barcelos and 3 from Manaus. (5) Conclusion: CQ-resistant P. falciparum populations are fixed, and thus, CQ cannot be reintroduced in malaria falciparum therapy.

SUBMITTER: de Abreu-Fernandes R

PROVIDER: S-EPMC10223861 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Plasmodium falciparum Chloroquine-pfcrt Resistant Haplotypes in Brazilian Endemic Areas Four Decades after CQ Withdrawn.

de Abreu-Fernandes Rebecca R Almeida-de-Oliveira Natália Ketrin NK Gama Bianca Ervatti BE Gomes Larissa Rodrigues LR De Lavigne Mello Aline Rosa AR Queiroz Lucas Tavares de LT Barros Jacqueline de Aguiar JA Alecrim Maria das Graças Costa MDGC Medeiros de Souza Rodrigo R Pratt-Riccio Lilian Rose LR Brasil Patrícia P Daniel-Ribeiro Cláudio Tadeu CT Ferreira-da-Cruz Maria de Fátima MF

Pathogens (Basel, Switzerland) 20230517 5

(1) Background: Malaria is a public health problem worldwide. Despite global efforts to control it, antimalarial drug resistance remains a great challenge. In 2009, our team identified, for the first time in Brazil, chloroquine (CQ)-susceptible Plasmodium falciparum parasites in isolates from the Brazilian Amazon. The present study extends those observations to include survey samples from 2010 to 2018 from the Amazonas and Acre states for the purpose of tracking pfcrt molecular cha ...[more]

PMID: 37242401

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Project description:BACKGROUND: In Plasmodium falciparum, resistance to chloroquine (CQ) is conferred by a K to T mutation at amino acid position 76 (K76T) in the P. falciparum CQ transporter (PfCRT). To date, at least 15 pfcrt genotypes, which are represented by combinations of five amino acids at positions 72-76, have been described in field isolates from various endemic regions. To identify novel mutant pfcrt genotypes and to reveal the genetic relatedness of pfcrt genotypes, a large-scale survey over a wide geographic area was performed. METHODS: Sequences for exon 2 in pfcrt, including known polymorphic sites at amino acid positions 72, 74, 75 and 76, were obtained from 256 P. falciparum isolates collected from eight endemic countries in Asia (Bangladesh, Cambodia, Lao P.D.R., the Philippines and Thailand), Melanesia (Papua New Guinea and Vanuatu) and Africa (Ghana). A haplotype network was constructed based on six microsatellite markers located -29 kb to 24 kb from pfcrt in order to examine the genetic relatedness among mutant pfcrt genotypes. RESULTS: In addition to wild type (CVMNK at positions 72-76), four mutant pfcrt were identified; CVIET, CVIDT, SVMNT and CVMNT (mutated amino acids underlined). Haplotype network revealed that there were only three mutant pfcrt lineages, originating in Indochina, Philippines and Melanesia. Importantly, the Indochina lineage contained two mutant pfcrt genotypes, CVIET (n = 95) and CVIDT (n = 14), indicating that CVIDT shares a common origin with CVIET. Similarly, one major haplotype in the Melanesian lineage contained two pfcrt genotypes; SVMNT (n = 71) and CVMNT (n = 3). In Africa, all mutant pfcrt genotypes were the CVIET of the Indochina lineage, probably resulting from the intercontinental migration of CQ resistance from Southeast Asia. CONCLUSIONS: The number of CQ-mutant lineages observed in this study was identical to that found in previous studies. This supports the hypothesis that the emergence of novel CQ resistance is rare. However, in the mutant pfcrt genotypes, amino acid changes at positions 72, 74 and 75 appear to have recently been generated at least several times, producing distinct pfcrt mutant genotypes. The occurrence of new mutations flanking K76T may yield stronger resistance to CQ and/or a higher fitness than the original pfcrt mutant.

Project description:BackgroundIn recent years, there has been an increasing trend in the number of imported Plasmodium falciparum cases in Turkey. To improve treatment success and to better understand malaria epidemiology among imported cases, it is necessary to determine anti-malarial drug resistance. This study aimed to survey polymorphisms of resistance genes in imported P. falciparum patients using archived thin smear preparations and EDTA blood samples.MethodsA total of 100 imported P. falciparum patients admitted to Bakırköy Dr. Sadi Konuk Research and Training Hospital between 2017 and 2022 were included in this study. DNA extraction was performed using an archived slide and EDTA blood samples that were microscopically diagnosed. After confirming the samples by real-time PCR, the pfmdr1, pfcrt, and pfk13 genes were amplified and sequenced. Single nucleotide polymorphisms (SNPs) were screened using Geneious R9 software, with the reference P. falciparum clone 3D7 isolate.ResultsAll studied samples were confirmed to be P. falciparum using real-time PCR. Nested PCR was conducted and the pfcrt (92 samples), pfmdr1 (91 samples), and pfk13 (93 samples) genes were successfully amplified. Sequence analysis revealed the highest mutation rate in the pfmdr1 (74.5%) gene, with the identification of five haplotypes: NYSND (wild-type, 23%), NFSND (56%), NYSDD (2.2%), NFSDD (15.4%), and YFSND (3.4%)]. The pfcrt mutation was identified in 11 samples (12.2%), whereas the pfk13 mutation was found in only two samples.ConclusionThis study is the first molecular survey of anti-malarial drug resistance genes in Turkey. With the increasing number of imported Plasmodium malaria cases and recent reports of sporadic indigenous P. falciparum cases, malaria is becoming a growing concern in Turkey. Although molecular screening for resistance markers in P. falciparum malaria is not routinely conducted, the data from this study will enhance treatment success rates and contribute to global malaria elimination.

Dataset Information

Plasmodium falciparum Chloroquine-pfcrt Resistant Haplotypes in Brazilian Endemic Areas Four Decades after CQ Withdrawn.

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<i>Plasmodium falciparum</i> Chloroquine-<i>pfcrt</i> Resistant Haplotypes in Brazilian Endemic Areas Four Decades after CQ Withdrawn.

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