Progressive increase in point mutations associates chloroquine resistance: Even after withdrawal of chloroquine use in India

Das, Sabyasachi; Tripathy, Satyajit; Chattopadhayay, S.; Das, Balaram; Mahapatra, Santanu Kar; Hati, Amiya Kumar; Roy, Somenath

doi:10.1016/j.ijpddr.2017.06.002

Cited by 17 publications

(27 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analysis indicates that 67.1% of samples with CVIET haplotype also carried N86Y mutation. A similar pattern had been observed in parts of India [37], Asia [38,[50][51][52] and Africa [35,53,54].…”

Section: Discussionsupporting

confidence: 83%

“…4). Perhaps this is because CQ (the current the treatment for P. vivax infection) could be employed for treating unrecognized mixed infections, thereby making P. falciparum vulnerable to the drug [37]. In addition, the present study on pfcrt polymorphisms indicated that CQS (41.5%) and CQR (58.5%) co-existed, albeit when CQ treatment ceased, in a manner similar to other parts of Asia [38,39] (Fig.…”

Section: Discussionmentioning

confidence: 49%

See 1 more Smart Citation

Epidemiology of malaria and chloroquine resistance in Mizoram, northeastern India, a malaria-endemic region bordering Myanmar

Zomuanpuii

Hmar

Lallawmzuala

et al. 2020

Malar J

View full text Add to dashboard Cite

Background: Mizoram, a northeastern state in India, shares international borders with Myanmar and Bangladesh and is considered to be one of the key routes through which drug-resistant parasites of Southeast Asia enter mainland India. Despite its strategic location and importance, malaria epidemiology and molecular status of chloroquine resistance had not been well documented, and since chloroquine (CQ), as the first-line treatment in Plasmodium falciparum infection was discontinued since 2008, it was expected that CQ-sensitive haplotype would be more abundant. Methods: Malaria epidemiology data for the period 2010 to 2018 was collected from the office of State Vector Disease Control Programme. Plasmodium falciparum-positive blood samples were collected from government district hospitals, community health centres, primary health centres, sub-centres, and diagnostic centres from six malariaprone districts. The samples were processed and analysed using genes-P. falciparum chloroquine-resistant transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) via sequencing of PCR amplicon from 2015 to 2017. Results: Malaria occurred throughout the year and P. falciparum accounted for > 89% of total malaria cases. During 2010-2018, the highest number of malaria incidence was recorded in Lawngtlai (36% of total malaria cases; average API 2010-2018 of 34.8) while Champhai remained consistently low (0.4%; average API 2010-2018 of 0.04). Males of ≥ 15 years old contributed maximum (35.7%) among gender and age malarial distribution recorded during 2014-2018. Death due to malaria gradually decreased over the years. A higher abundance of mutated pfcrt (58.5% of the total sample analysed) and a lower prevalence of mutated pfmdr1 (48.7%) were observed. All mutations identified for pfcrt belong to the Southeast Asian CVIET haplotype. Only a single point mutation was observed at 86 (N → Y) position in pfmdr1 (48.7%). The key N86Y mutation in pfmdr1 that had been shown to modulate CQR was found in 67.1% of the samples positive for the CVIET haplotype. Conclusions: This is the first report that details malaria epidemiology and also the molecular status of CQ-resistance in P. falciparum population of the region. The efforts of the State Vector Borne Disease Control Programme have proved to be quite effective in controlling the malaria burden in the state. Despite the discontinuation of CQ for a decade, local P. falciparum is observed with decreased CQ-sensitive haplotype. It is believed that the present findings will form a basis for further studies on genetic diversity in P. falciparum, which could confer better understanding of the complexity of the disease in Southeast Asia.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 49%

Epidemiology of malaria and chloroquine resistance in Mizoram, northeastern India, a malaria-endemic region bordering Myanmar

Zomuanpuii

Hmar

Lallawmzuala

et al. 2020

Malar J

View full text Add to dashboard Cite

show abstract

“…Some reports have associated a rise in the prevalence of pfmdr1 86Y alleles with increasing CQ resistance [11][12]25]. The low prevalence of pfmdr1 86Y in Adamawa and Yobe raises the possibility that CQ may be effective against P. falciparum malaria in North-Eastern Nigeria once again, although this would be presumably tempered by CQ-resistance associated mutations in pfcrt, which we have not assayed here.…”

Section: Discussionmentioning

confidence: 79%

“…Mutations in PfMDR1 are associated with enhanced e ux of diverse antimalarial drugs reducing their intracellular accumulation [17,42]. Single nucleotide polymorphisms (SNPs) in pfmdr1 are associated with resistance to multiple antimalarial drugs [12,44]. Several codons in pfmdr1 have been putatively linked with changes in the parasite's sensitivity to antimalarial drugs, but codons N86Y, Y184F and D1246Y are uniquely associated with changes in artemether-lumefantrine (AL) and artesunateamodiaquine (AS-AQ) e cacies in sub-Saharan Africa [14].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium Falciparum Multidrug Resistance Gene-1 N86Y-Y184F-D1246Y Polymorphisms in Northern Nigeria: Implications for the Continued Use of Artemether-Lumefantrine in the Region

Adamu

Jada

Haruna

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of antimalarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria. Methods Plasmodium falciparum-positive blood samples on Whatman-3MM filter papers were collected from 750 symptomatic patients from four states (Kano, Kaduna, Yobe and Adamawa) in Northern Nigeria, and genotyped via BigDye (v3.1) terminator cycle sequencing for the presence of three SNPs in pfmdr1. SNPs in pfmdr1 were used to construct NYD, NYY, NFY, NFD, YYY, YYD, YFD and YFY haplotypes, and all data were analyzed using Pearson Chi-square and Fisher's exact (FE) tests. Results The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.5%, 𝜒² = 10.47, P < 0.05), whilst the 184F allele was highest in Kano (73.1%, 𝜒² = 13.20, P < 0.05), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, 𝜒² = 9.18, P < 0.05). The NFD haplotype had the highest prevalence of 69.81% in Kano (𝜒² = 36.05, P < 0.05), followed by NYD with a prevalence of 49% in Adamawa, then YFD with prevalence of 11.46% in Kaduna. The YYY haplotype was not observed in any of the studied states. Conclusion The present study shows that P. falciparum strains with reduced sensitivity to artemether-lumefantrine exist in Northern Nigeria and predominate in the North-West region.

show abstract

“…Thus, the risk of severe falciparum malaria would increase as the RDTs will have failed to detect P. falciparum. This fact is particularly important in malaria-endemic areas where both the circulation of chloroquine-resistant P. falciparum isolates and chloroquine is preferentially used for treating vivax malaria, as this is the case in India [56][57][58][59][60]. In most endemic countries, chloroquine is firstline treatment of vivax malaria [1].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Plasmodium falciparum field isolates with deletions in histidine-rich protein 2 and 3 genes in context with sub-Saharan Africa and India: a systematic review and meta-analysis

Kojom

Singh

2020

Malar J

View full text Add to dashboard Cite

Background: In 2017, nearly 80% of malaria morbidity and mortality occurred in sub-Saharan African (SSA) countries and India. Rapid diagnostic tests (RDTs), especially those targeting histidine-rich protein 2 (PfHRP2) of Plasmodium falciparum, have become an important diagnostic tool in these malaria-endemic areas. However, the chances of RDToriented successful treatment are increasingly jeopardized by the appearance of mutants with deletions in pfhrp2 and pfhrp3 genes. This systematic review and meta-analysis determines the prevalence of field P. falciparum isolates with deletion in pfhrp2 and/or pfhrp3 genes and their proportion among false-negative results in the PfHRP2-based RDTs in SSA and India.Methods: Eight electronic databases were used for searching potentially relevant publications for the systematic review analysis, wherein the main methodological aspects of included studies were analysed and some missing links in the included studies were identified. Results:A total of 19 studies were included, 16 from SSA and 3 from India. The pooled prevalence of pfhrp2 deletions was 8 and 5% while 16 and 4% for pfhrp3 gene deletions in Africa and India, respectively. The pooled proportion of pfhrp2 gene deletions found among false negative PfHRP2-based RDTs results was about 27.0 and 69.0% in Africa and India, respectively. Conclusions:This review study indicates a relatively high proportion of both pfhrp2/3 genes deletions in P. falciparum isolates and among false-negative malaria cases using PfHRP2-based RDT results in SSA and India. Recently the deletions in pfhrp2/3 genes have also been reported from two African countries (Nigeria and Sudan). This review emphasizes the importance of more extensive studies and standardization of studies addressing the pfhrp2/3 gene deletions in malarious areas.

show abstract

Progressive increase in point mutations associates chloroquine resistance: Even after withdrawal of chloroquine use in India

Cited by 17 publications

References 28 publications

Epidemiology of malaria and chloroquine resistance in Mizoram, northeastern India, a malaria-endemic region bordering Myanmar

Epidemiology of malaria and chloroquine resistance in Mizoram, northeastern India, a malaria-endemic region bordering Myanmar

Plasmodium Falciparum Multidrug Resistance Gene-1 N86Y-Y184F-D1246Y Polymorphisms in Northern Nigeria: Implications for the Continued Use of Artemether-Lumefantrine in the Region

Prevalence of Plasmodium falciparum field isolates with deletions in histidine-rich protein 2 and 3 genes in context with sub-Saharan Africa and India: a systematic review and meta-analysis

Contact Info

Product

Resources

About