Molecular analysis demonstrates high prevalence of chloroquine resistance but no evidence of artemisinin resistance in Plasmodium falciparum in the Chittagong Hill Tracts of Bangladesh

Alam, Mohammad Shafiul; Ley, Benedikt; Nima, Maisha Khair; Johora, Fatema Tuj; Hossain, Mohammad Enayet; Thriemer, Kamala; Auburn, Sarah; Marfurt, Jutta; Price, Ric N.; Khan, Wasif Ali

doi:10.1186/s12936-017-1995-5

Cited by 15 publications

(23 citation statements)

References 52 publications

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“…Prevalence of pfmdr1 N86Y mutations in Bangladesh in this study (20.69%) was in moderate range which is in congruence with reports published in past few years 16,17 .This rate for five Sub-Saharan African countries in this study is even lower (2.44%) which is also lower than the finding of few reports published in the recent past 26,29 .…”

Section: Discussionsupporting

confidence: 88%

“…Likewise, recent studies in many African countries reported marked reduction in the prevalence of chloroquine resistant strains of P. falciparum indicating gradual return of the genotypes sensitive to chloroquine and other 4-aminoquinoline derivatives 27,28 . Chloroquine sensitive strains are becoming the predominant strains of P. falciparum in locations where chloroquine has been almost completely removed from the market, including the private sector for 6-10 years 17 .…”

Section: Discussionmentioning

confidence: 99%

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Molecular Pattern of Anti-malarial Drug Resistance of Plasmodium falciparum in Bangladeshi Troops Working in Endemic Areas of Bangladesh and Africa

Amin¹,

Yasmin²,

Akhtar³

et al. 2020

Bangla. J. Microbiol.

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Members of Bangladesh Armed Forces work in two different malaria endemic area, Chittagong Hill Tracts (CHT) in Bangladesh and Sub-Saharan countries in Africa. This under-recognized group remained unexplored for long in respect to drug resistant falciparum malaria they usually suffer from. In this study, a total of 252 ‘dried blood samples on filter paper’ were collected between November 2014 and February 2016, from Plasmodium falciparum positive Bangladeshi troops working in Chittagong Hill Tracts (CHT), Bangladesh and five Sub Saharan African Countries namely, Central African Republic (CAR), Democratic Republic of Congo (DRC), Liberia, Mali and Ivory Coast. After DNA extraction from all these samples (94 from Bangladesh and 138 from African countries), plasmodium species was confirmed by a nested PCR following standard protocol with minor modifications. Thereafter, a multiplex nested PCR followed by restriction fragment length polymorphism (RFLP) method was employed to investigate the presence of chloroquine resistance marker ‘K76T mutation’ in P. falciparum chloroquine resistance transporters (pfcrt) gene and lumifantrine and mefloquine resistance marker ‘N86Y mutation’ in P. falciparum multidrug resistance1 (pfmdr1) gene. The P. falciparum DNA was confirmed in 35 (37.23%) Bangladeshi and 45 (28.48%) African samples. The ‘pfcrt (K76T) mutation’ that confers resistance to chloroquine, was detected in 93.10% Bangladeshi and 29.27% African samples. The ‘pfmdr1 (N86Y) mutation’ that confers resistance to lumifantrine and mefloquine, was detected in 20.69% Bangladeshi and only 2.44% African samples. The higher prevalence of chloroquine resistance of P. falciparum in Bangladesh than in African countries revealed that possible withdrawal of chloroquine from endemic areas and also periodic molecular survey to monitor pf resistance to chloroquine, mefloquine, lumefantrine and artemisinin among these troops working in both endemic areas. Bangladesh J Microbiol, Volume 37 Number 1 June 2020, pp 1-6

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Molecular Pattern of Anti-malarial Drug Resistance of Plasmodium falciparum in Bangladeshi Troops Working in Endemic Areas of Bangladesh and Africa

Amin¹,

Yasmin²,

Akhtar³

et al. 2020

Bangla. J. Microbiol.

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“…Furthermore, there was no chloroquine drug pressure on the P. falciparum population which allowed the more t CQ sensitive parasites to thrive. This is not the case in Southeast Asia and South America, where the parasites carrying the mutation have become xed in the population due to continued use of chloroquine in the treatment of vivax malaria [23,31].…”

Section: Discussionmentioning

confidence: 99%

Decreased Prevalence of the Plasmodium Falciparum Pfcrt K76T and Pfmdr1 N86Y Mutations Post- Chloroquine Treatment Withdrawal in Katete District, Eastern Zambia

Mwenda

Sitali

Ciubotariu

et al. 2021

Preprint

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Background: In 2002, Zambia withdrew chloroquine as first line treatment for Plasmodium falciparum malaria due to increased treatment failure and world-wide spread of chloroquine resistance. The artemisinin combination regimen artemether-lumefantrine replaced chloroquine as first choice malaria treatment. The present study determined the prevalence of chloroquine resistance molecular markers in the malaria parasite Pfcrt and Pfmdr1 genes in Eastern Zambia at nine and thirteen years after the removal of drug pressure.Methods: We assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) the prevalence of the genetic mutations, K76T on the Pfcrt gene and N86Y on the Pfmdr1 gene in samples collected from Katete District during drug therapeutic efficacy assessments conducted in 2012 and 2016.Results: A total of 204 P. falciparum positive samples from 2012 and 2016 were further analysed for Pfcrt K76T and Pfmdr1 N86Y. 112 P. falciparum infected samples collected in 2012 were successfully amplified for Pfcrt and Pfmdr1, while 69 (65.7%) and 72 (68.6%) samples from 2016 were successfully amplified for Pfcrt and Pfmdr1. In 2012, the prevalence of Pfcrt 76K was 97.3%, 76T was 1.8%, and 0.8% had both 76K and 76T codons. The prevalence of Pfmdr1 86N was 97.9% and 86Y was 2.1%. In the 2016 samples, the prevalence of the respective parasite genotypes was 100% Pfcrt 76K and Pfmdr1 86N.Conclusion: This study shows that there was a complete recovery of chloroquine-sensitive parasites by 2016 in Katete District, thirteen years following the withdrawal of CQ. These findings add to the body of evidence for a fitness cost in chloroquine-resistant P. falciparum in Zambia and elsewhere. Further studies are recommended to explore the feasibility of integration of the former best antimalarial in combination therapy in the future.

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“…[21][22][23][24][25] Although AL is the mandated treatment for uncomplicated malaria, CQ remains available as an over-thecounter medication for self-treatment of malaria, as well as for vivax malaria treatment in some parts of the country. 26,27 Several drug resistance mechanisms have been reported in P. falciparum; CQ resistance (CQR) has been linked to the mutation in the P. falciparum chloroquine resistance transporter gene (pfcrt) at codon 76. 28 A single nucleotide polymorphism in the P. falciparum multidrug resistance transporter 1 gene (pfmdr1) at codon 86 is associated with hypersensitivity to LUM, MQ, and also to DHA, an active artemisinin metabolite.…”

Section: Introductionmentioning

confidence: 99%

Persistence of Markers of Chloroquine Resistance in Plasmodium falciparum in Bangladesh

Johora

Elahi

Nima

et al. 2021

The American Journal of Tropical Medicine and Hygiene

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The control of malaria, in terms of drug resistance, remains a significant global challenge, with Bangladesh, a malaria-endemic country, being no exception. The aim of this study was to explore antimalarial resistance in Bangladesh by molecular analysis of Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance transporter 1 (pfmdr1) genetic markers of P. falciparum. Samples were obtained from uncomplicated malaria patients between 2009 and 2014 from six malaria-endemic districts. Based on parasite transmission intensity, the endemic districts were divided into high-transmission (Chittagong Hill Tracts [CHT]) and low-transmission (non-CHT) regions. Falciparum malaria-positive isolates were genotyped for K76T of the pfcrt gene, and N86Y and Y184F of the pfmdr1 gene: in total, 262 P. falciparum clinical isolates were analyzed. In CHT areas, the prevalence of polymorphisms was 70.6% for 76T, 14.4% for 86Y, and 7.8% for 184F. In non-CHT areas, 76T and 86Y mutations were found in 78.0% and 19.5% of the samples, respectively, whereas no 184F mutations were observed. We compared our data with previous similar molecular observations, which shows a significant decrease in pfcrt 76T mutation prevalence. No pfmdr1 amplification was observed in any of the samples suggesting an unaltered susceptibility to amino alcohol drugs such as mefloquine and lumefantrine. This study provides an updated assessment of the current status of pfcrt and pfmdr1 gene mutations in Bangladesh, and suggests there is persistent high prevalence of markers of resistance to aminoquinoline drugs.

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Molecular analysis demonstrates high prevalence of chloroquine resistance but no evidence of artemisinin resistance in Plasmodium falciparum in the Chittagong Hill Tracts of Bangladesh

Cited by 15 publications

References 52 publications

Molecular Pattern of Anti-malarial Drug Resistance of Plasmodium falciparum in Bangladeshi Troops Working in Endemic Areas of Bangladesh and Africa

Molecular Pattern of Anti-malarial Drug Resistance of Plasmodium falciparum in Bangladeshi Troops Working in Endemic Areas of Bangladesh and Africa

Decreased Prevalence of the Plasmodium Falciparum Pfcrt K76T and Pfmdr1 N86Y Mutations Post- Chloroquine Treatment Withdrawal in Katete District, Eastern Zambia

Persistence of Markers of Chloroquine Resistance in Plasmodium falciparum in Bangladesh

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