Antifolate drug resistance: Novel mutations and haplotype distribution in dhps and dhfr from Northeast India

Sarmah, Nilanju P; Sarma, K. K.; Bhattacharyya, D. R.; Sultan, Ali A.; Bansal, Devendra; Singh, Neeru; Bharti, Praveen K.; Sehgal, Rakesh; Mohapatra, Pradyumna K.; Parida, Pratap; Mahanta, Jagadish

doi:10.1007/s12038-017-9706-5

Cited by 17 publications

(11 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High level of triple mutant genotypes was also found in the present study among isolates originates from Nigeria and Cameroon, which is in agreement with other studies [32,33]. Among the Indian sub-continent isolates, the double (59R/108N and 51I/108N) mutants genotypes were the most frequent genotypes followed by triple (51I/59R/108N) mutant genotypes, which are in agreement with previous reports from India [21,27,[34][35][36].…”

Section: Discussionsupporting

confidence: 93%

“…Resistance to SP was first reported from the Thai-Cambodian border in the 1960s [24] and has spread to several parts of Southeast Asia, South America and Africa [25][26][27]. Resistance is likely to progress geographically and in intensity at a rising rate, becoming fixed in the population if proper and timely measures are not taken to interrupt it.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular surveillance of putative drug resistance markers of antifolate and artemisinin among importedPlasmodium falciparumin Qatar

Bansal

Bharti

Acharya

et al. 2019

Pathogens and Global Health

View full text Add to dashboard Cite

Malaria remains a significant public health challenge and is of global importance. Imported malaria is a growing problem in non-endemic areas throughout the world and also in Qatar due to a massive influx of migrants from endemic countries. Antimalarial drug resistance is an important deterrent in our fight against malaria today. Molecular markers mirror intrinsic antimalarial drug resistance and their changes precede clinical resistance. Thus, in the present study, molecular markers of sulphadoxine-pyrimethamine (Pfdhfr and Pfdhps) and artemisinin (PfATPase6 and Pfk13) were sequenced to determine the drug resistance genotypes among 118 imported P. falciparum isolates in Qatar, between 2013 and 2016. All the isolates had mutant Pfdhfr alleles, with either double mutant (51I/108N) (59.3%) or triple mutant (51I, 59R and 108N) (30.6%) genotypes. I164L substitution was not found in this study. In case of Pfdhps, majority of the samples were carriers of either single (S436A/ A437G/ K540E) mutant (47.2%) or double (S436A/K540E, A437G/K540E, K540E/A581G) mutant (39.8%). A single novel point mutation (431V) was observed in the samples originated from Nigeria and Ghana. Polymorphisms in PfATPase6 were absent and only one non-synonymous mutation in Pfk13 was found at codon G453A from a sample of Kenyan origin. High levels of sulphadoxinepyrimethamine resistance in the present study provide potential information about the spread of antimalarial drug resistance and will be beneficial for the treatment of imported malaria cases in Qatar.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Molecular surveillance of putative drug resistance markers of antifolate and artemisinin among importedPlasmodium falciparumin Qatar

Bansal

Bharti

Acharya

et al. 2019

Pathogens and Global Health

View full text Add to dashboard Cite

show abstract

“…The frequency of this mutation is comparable to that obtained in isolates collected in Lambaréné in 1996 (28%). Nevertheless, it has over time gradually increased and may reach90% in some areas [25, 31, 35–38]. In contrast, Pfdhps K540E mutation which is not frequent in West and central Africa has not been detected in the isolates.…”

Section: Discussionmentioning

confidence: 99%

Increased Frequency of Pfdhps A581G Mutation in Plasmodium falciparum Isolates from Gabonese HIV-Infected Individuals

Lengongo

Ndiaye

Mbuyi

et al. 2019

Malaria Research and Treatment

View full text Add to dashboard Cite

Background. Studying malaria parasites cross resistance to sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (cotrimoxazole, CTX) is necessary in areas coendemic for malaria and HIV. Polymorphism and frequency of drug resistance molecular markers, Pfdhfr and Pfdhps genes have been assessed in Plasmodium falciparum isolates from HIV-infected adults, in Gabon. Materiel and Methods. A cross-sectional study was conducted in three HIV care and treatment centers, at Libreville, the capital city of Gabon and at Oyem and Koulamoutou, two rural cities between March 2015 and June 2016. P. falciparum-infected HIV adults were selected. Analysis of Pfdhfr and Pfdhps genes was performed using high resolution melting (HRM) technique. Results. Pfdhps A581G mutation was found in 23.5% (8/34) of the isolates. Triple Pfdhfr mutation (51I-59R-108N) was predominant (29.4%; n=10) while 17.6% (n=6) of the isolates carried a quadruple mutation (Pfdhfr 51I-59R-108N + Pfdhps 437G; Pfdhfr 51I-108N + Pfdhps 437G-Pfdhps581G; Pfdhfr 51I-59R-108N + Pfdhps 581G). Highly resistant genotype was detected in around 10% (n=3) of the isolates. The quintuple mutation (triple Pfdhfr 51I-59R-108N and double Pfdhps437-581) was only found in isolates from two patients who did not use CTX. The most frequent haplotypes were those with a single mutation (NCNIAKA) (36%) and a quadruple mutation (NCIIGKG, NRIIGKA, and NRIIAKG). Mixed unknown genotypes were found at codon 164 in three isolates. Mixed genotypes were more frequent at codons 51 (23.5%; n=8) and 59 (20.5%; n=7) (p<0.01). Conclusion. Pfdhps A581G mutation as well as new combination of quintuple mutations is found for the first time in isolates from HIV-infected patients in Gabon in comparison to a previous study. The detection of these genotypes at a nonnegligible frequency underlines the need of a regular surveillance of antifolates drug resistance.

show abstract

“…To avoid technical contamination, all PCR and sequencing assays include positive control (MRA-41 Sal I, gDNA, MR4/Bei resources) and negative controls (uninfected samples and water). Mutations were scored only when confirmed by each bidirectional sequencing read with high quality BioEdit (v.7.2.5) ( Sarmah et al., 2017 ) was used to compare individual sequences with the reference sequences pvdhfr (PVX_089950) and pvdhps (PVX_123230). Nucleotide sequences were translated into amino acid sequences to examine mutant codons.…”

Section: Methodsmentioning

confidence: 99%

Polymorphism of Antifolate Drug Resistance in Plasmodium vivax From Local Residents and Migrant Workers Returned From the China-Myanmar Border

Zeng

Wang

Shi

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Drug-resistant Plasmodium vivax malaria impedes efforts to control, eliminate, and ultimately eradicate malaria in Southeast Asia. P. vivax resistance to antifolate drugs derives from point mutations in specific parasite genes, including the dihydropteroate synthase (pvdhps), dihydrofolate reductase (pvdhfr), and GTP cyclohydrolase I (pvgch1) genes. This study aims to investigate the prevalence and spread of drug resistance markers in P. vivax populating the China-Myanmar border. Blood samples were collected from symptomatic patients with acute P. vivax infection. Samples with single-clone P. vivax infections were sequenced for pvdhps and pvdhfr genes and genotyped for 6 flanking microsatellite markers. Copy number variation in the pvgch1 gene was also examined. Polymorphisms were observed in six different codons of the pvdhps gene (382, 383, 512, 549, 553, and 571) and six different codons of the pvdhfr gene (13, 57, 58, 61, 99, 117) in two study sites. The quadruple mutant haplotypes 57I/L/58R/61M/117T of pvdhfr gene were the most common (comprising 76% of cases in Myitsone and 43.7% of case in Laiza). The double mutant haplotype 383G/553G of pvdhps gene was also prevalent at each site (40.8% and 31%). Microsatellites flanking the pvdhfr gene differentiated clinical samples from wild type and quadruple mutant genotypes (FST= 0.259-0.3036), as would be expected for a locus undergoing positive selection. The lack of copy number variation of pvgch1 suggests that SP-resistant P. vivax may harbor alternative mechanisms to secure sufficient folate.

show abstract

Antifolate drug resistance: Novel mutations and haplotype distribution in dhps and dhfr from Northeast India

Cited by 17 publications

References 13 publications

Molecular surveillance of putative drug resistance markers of antifolate and artemisinin among importedPlasmodium falciparumin Qatar

Molecular surveillance of putative drug resistance markers of antifolate and artemisinin among importedPlasmodium falciparumin Qatar

Increased Frequency of Pfdhps A581G Mutation in Plasmodium falciparum Isolates from Gabonese HIV-Infected Individuals

Polymorphism of Antifolate Drug Resistance in Plasmodium vivax From Local Residents and Migrant Workers Returned From the China-Myanmar Border

Contact Info

Product

Resources

About