Emergence of sulfadoxine–pyrimethamine resistance in Indian isolates of Plasmodium falciparum in the last two decades

Kumar, Amit; Moirangthem, Romilla; Gahlawat, Suresh Kumar; Chandra, Jagdish; Gupta, Purva; Valecha, Neena; Anvikar, Anup; Singh, Vineeta

doi:10.1016/j.meegid.2015.08.027

Cited by 11 publications

(17 citation statements)

References 25 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%

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%

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

“…However, some deviations exist; for example, the Pfdhps gene harbours high diversity in both the type and number of mutations and therefore the corresponding haplotypes. All the four commonly reported amino acid mutations that confer resistance to sulfadoxine-pyrimethamine (S 436 A 437 K 540 A 581 ) could be found in the present study, except one (A 613 S) that is rare in India (Biswas et al, 2000; Kumar et al, 2015). The present findings therefore substantiate similar outcomes from other Indian states including Odisha with respect to the mutational pattern at the Pfdhps gene (Sharma, D. et al, 2015).…”

Section: Discussionsupporting

confidence: 57%

“…For the Pfdhps gene, as many as 11 nucleotide substitutions (resulting in two synonymous substitutions and nine non-synonymous, including three stop codons) could be found. Out of these two synonymous substitutions one has been recently reported from Odisha (Kumar et al, 2015). On the whole, the HF contains two stop codons; two synonymous and three non-synonymous substitutions and the RP comprises two stop codons (one common with HF) and six non-synonymous substitutions.…”

Section: Discussionmentioning

confidence: 97%

“… * Reported in earlier studies *(Okombo et al, 2014) ** (Kumar et al, 2015), # Unique to HF; $ Unique to RP; ‘Z’ represents a stop codon. …”

Section: Figurementioning

confidence: 99%

“…Several studies following these methodologies in genes conferring resistance to antimalarials in P. falciparum have indicated evolutionary potential of these genes both at the global scale and also in India (Awasthi et al, 2011; Brown et al, 2015; Das and Dash, 2007; Kumar et al, 2015; Li et al, 2015; Rouhani et al, 2015). Mutations in the gene encoding a P. falciparum CQ resistance transporter ( Pfcrt ) and resulting change in single amino acid (AA) locus 76 from K to T (K76T) were proven a strong marker for CQ (Fidock et al, 2000; Valderramos et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative assessment on the prevalence of mutations in the Plasmodium falciparum drug-resistant genes in two different ecotypes of Odisha state, India

Kar

Chauhan

Nanda

et al. 2016

Infection, Genetics and Evolution

View full text Add to dashboard Cite

Considering malaria as a local and focal disease, epidemiological understanding of different ecotypes of malaria can help in devising novel control measures. One of the major hurdles in malaria control lies on the evolution and dispersal of the drug-resistant malaria parasite, Plasmodium falciparum. We herewith present data on genetic variation at the Single Nucleotide Polymorphism (SNP) level in four different genes of P. falciparum (Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps) that confer resistance to different antimalarials in two different eco-epidemiological settings, i.e. Hilly-Forest (HF) and Riverine-Plain (RP), in a high malaria endemic district of Odisha state, India. Greater frequency of antimalarial resistance conferring SNPs and haplotypes was observed in all four genes in P. falciparum, and Pfdhps was the most variable gene among the four. No significant genetic differentiation could be observed in isolates from HF and RP ecotypes. Twelve novel, hitherto unreported nucleotide mutations could be observed in the Pfmdr1 and Pfdhps genes. While the Pfdhps gene presented highest haplotype diversity, the Pfcrt gene displayed the highest nucleotide diversity. When the data on all the four genes were complied, the isolates from HF ecotype were found to harbour higher average nucleotide diversity than those from RP ecotype. High and positive Tajima’s D values were obtained for the Pfcrt and Pfdhfr genes in isolates from both the HF and RP ecotypes, with statistically significant deviation from neutrality in the RP ecotype. Different pattern of Linkage Disequilibrium (LD) among SNPs located in different drug-resistant genes was found in the isolates collected from HF and RP ecotypes. Whereas in the HF ecotype, SNPs in the Pfmdr1 and Pfdhfr were significantly associated, in the RP ecotype, SNPs located in Pfcrt were associated with Pfmdr1, Pfdhfr and Pfdhps. These findings provide a baseline understanding on how different micro eco-epidemiological settings influence evolution and spread of different drug resistance alleles. Our findings further suggest that drug resistance to chloroquine and sulfadoxine-pyrimethamine is approaching fixation level, which requires urgent attention of malaria control program in India.

show abstract

Repurposing FDA‐approved drugs to target malaria through inhibition of dihydrofolate reductase in the folate biosynthesis pathway: A prospective approach

Verma,

Chaturvedi,

Lahariya

et al. 2024

J of Cellular Biochemistry

View full text Add to dashboard Cite

Dihydrofolate reductase (DHFR) is a ubiquitous enzyme that regulates the biosynthesis of tetrahydrofolate among various species of Plasmodium parasite. It is a validated target of the antifolate drug pyrimethamine (Pyr) in Plasmodium falciparum (Pf), but its clinical efficacy has been hampered due to the emergence of drug resistance. This has made the attempt to screen Food & Drug Administration‐approved drugs against wild‐ and mutant PfDHFR by employing an in‐silico pipeline to identify potent candidates. The current study has followed a virtual screening approach for identifying potential DHFR inhibitors from DrugBank database, based on a structure similarity search of candidates, followed by absorption, distribution, metabolism, and excretion estimation. The screened drugs were subjected to various parameters like docking, molecular mechanics with generalized born and surface area solvation calculations, and molecular simulations. We have thus identified two potential drug candidates, duloxetine and guanethidine, which can be repurposed to be tested for their efficacy against wild type and drug resistant falciparum malaria.

show abstract

Emergence of sulfadoxine–pyrimethamine resistance in Indian isolates of Plasmodium falciparum in the last two decades

Cited by 11 publications

References 25 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

Comparative assessment on the prevalence of mutations in the Plasmodium falciparum drug-resistant genes in two different ecotypes of Odisha state, India

Repurposing FDA‐approved drugs to target malaria through inhibition of dihydrofolate reductase in the folate biosynthesis pathway: A prospective approach

Contact Info

Product

Resources

About