Survey of chloroquine-resistant mutations in the Plasmodium falciparum pfcrt and pfmdr-1 genes in Hadhramout, Yemen

Bamaga, Omar A. A.; Mahdy, Mohammed A. K.; Lim, Yvonne Ai Lian

doi:10.1016/j.actatropica.2015.05.013

Cited by 11 publications

(9 citation statements)

References 25 publications

(31 reference statements)

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“…In some studies, the N86Y mutation was associated with CQ resistance [17] , [18] , [19] , whereas, in other studies this association was not found [20] , [21] , [22] , [23] , [24] . In the present study population, there was no association of N86Y mutation of the pfmdr1 gene with CQ resistance and this non-association was in agreement with previous findings [16] , [20] , [25] , [26] . However, the prevalence of N86Y mutation was high in other Indian P. falciparum isolates [16] , [27] , [28] .…”

Section: Discussionsupporting

confidence: 93%

Sequence analysis of pfcrt and pfmdr1 genes and its association with chloroquine resistance in Southeast Indian Plasmodium falciparum isolates

Antony¹,

Das²,

Parija³

et al. 2016

Genomics Data

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BackgroundDue to the widespread resistance of Plasmodium falciparum to chloroquine drug, artemisinin-based combination therapy (ACT) has been recommended as the first-line treatment. This study aims to evaluate the extent of chloroquine resistance in P. falciparum infection after the introduction of ACT. This study was carried out based on the mutation analysis in P. falciparum chloroquine resistant transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes. Identification of these molecular markers plays a significant role in monitoring and assessment of drug resistance as well as in designing an effective antimalarial drug policy in India.MethodsSixty blood samples were collected from patients infected with P. falciparum from JIPMER, Puducherry and MKCG Medical College, Odisha. Polymerase chain reaction-restriction fragment length polymorphism was performed, targeting the point mutation of K76T in pfcrt and N86Y in pfmdr1 gene. The PCR products were sequenced, genotyped and further analysed for amino acid changes in these codons.ResultsThe frequency of pfcrt mutation at 76th position was dominant for mutant T allele with 56.7% and wild type K, 43.3%. Majority of pfmdr1 86 allele were wild type, with N (90%) and mutant, Y (10%). Additionally, we found three haplotypes for CQ resistance, SVMNT, CVIET and CVIKT in association with the pfcrt gene. However, a poorly studied SNP in pfmdr1 gene (Y184F) associated with CQ resistance showed high frequency (70%) in P. falciparum isolates.ConclusionsThe point mutation K76T of pfcrt is high in P. falciparum suggesting a sustained high CQ resistance even after five years of the introduction of ACTs for antimalarial therapy. The present study suggests a strong association of CQ resistance with pfcrt T76, but not with the pfmdr1 Y86 mutation. However, sequence analysis showed that Y184F mutation on pfmdr1 gene was found to be associated with high resistance. Also, a new pfcrt haplotype ‘CVIKT’ associated with CQ resistance was found to be present in Indian strains of P. falciparum. The data obtained from this study helps in continuous monitoring of drug resistance in malaria and also suggests the need for careful usage of CQ in Plasmodium vivax malarial treatment.

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Section: Discussionsupporting

confidence: 93%

Sequence analysis of pfcrt and pfmdr1 genes and its association with chloroquine resistance in Southeast Indian Plasmodium falciparum isolates

Antony¹,

Das²,

Parija³

et al. 2016

Genomics Data

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“…This is consistent with a previous study conducted in Yemen that reported a high prevalence of mutated alleles for codons 74I and 75E (89%) and 76T (93%) ( Al-Hamidhi et al , 2013 ). The present study found that the overall prevalence of pfcrt 76T was 74%–100%, which is similar to the figure previously reported for isolates from other parts of Yemen ( Al-Mekhlafi et al , 2011 ; Mubjer et al , 2011 ; Bamaga, Mahdy & Lim , 2015 ).…”

Section: Discussionsupporting

confidence: 91%

“…These results are consistent with those of a previous study in Hodeidah that reported a high prevalence (99%) of 184F and a relatively low existence (20%) of the 86Y mutated allele ( Al-Hamidhi et al , 2013 ). Likewise, a recent study conducted in Hadramout in the southeastern part of Yemen, which has low malaria transmission, reported a low frequency (16.7%) of pfmdr1 86 mutated allele ( Bamaga, Mahdy & Lim , 2015 ). However, a high prevalence (70%) for mutations of 1034C and 1042D has been reported for the Taiz, Dhamar, and Hodeidah governorates ( Al-Hamidhi et al , 2013 ).…”

Section: Discussionmentioning

confidence: 87%

Different patterns ofpfcrtandpfmdr1polymorphism inPlasmodium falciparumisolates from Tehama region, Yemen

Atroosh

Al-Mekhlafi

Al-Jasari

et al. 2016

PeerJ

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Introduction. Despite the efforts of the malaria control programme, malaria morbidity is still a common health problem in Yemen, with 60% of the population at risk. Plasmodium falciparum is responsible for 99% of malaria cases. The emergence in Yemen of parasite resistance to chloroquine (CQ) prompted the adoption of artemisinin combination therapy (ACT) in 2009, which involves the use of artesunate plus sulphadoxine-pyrimethamine (AS + SP). However, CQ was retained as the drug of choice for vivax malaria. To assess the impact of the change in the malaria treatment policy five years after its introduction, the present study investigated the mutations in the CQ resistance transporter (pfcrt) and multidrug resistance 1 (pfmdr1) genes.Method. A molecular investigation of 10 codons of pfcrt (72–76, 220, 271, 326, 356, and 371) and five codons of pfmdr1 (86, 184, 1034, 1042, and 1246) was conducted on P. falciparum isolates from districts with the highest malaria endemicity in the Hodeidah and Al-Mahwit governorates in Tehama region, Yemen. A total of 86 positive cases of falciparum monoinfection were investigated for the presence of mutations related to CQ and other antimalarials using a PCR-RFLP assay.Results. There was a wide prevalence of pfcrt gene mutations with the pfcrt 76T CQ resistance marker being predominant (97.7%). The prevalence of other pfcrt mutations varied from high (75E: 88%) to moderate (74I: 79.1%, 220S: 69.8%, 271E and 371I: 53.5%) or low (326S: 36%, 72S: 10.5%). Mutated pfcrt 72–76 amino acids haplotypes were highly prevalent (98.8%). Among these, the CVIET classic, old-world African/Southeast Asian haplotype was the most predominant, and was mostly found in the isolates from the Khamis Bani Saad district of Al-Mahwit (93.1%) and the AdDahi district of Hodeidah (88.9%). However, it was only found in 26.3% of the isolates from the Bajil district of Hodeidah. Surprisingly, the SVMNT new-world South American haplotype was exclusively detected in 9.3% of the isolates from the Bajil district of Hodeidah. Mutations at Y184F of pfmdr1 were found in all isolates (100%) from all districts. The mutation for codons 1034C and 86Y were found only in the isolates from the AdDahi and Khamis Bani Saad districts. Overall, the AdDahi and Khamis Bani Saad districts were similar in terms of carrying most of the mutations in the pfcrt and pfmdr1 genes, while there was a lower prevalence of mutation in the isolates from the Bajil district.Conclusion. The high prevalence of mutations in pfcrt 5 years after the official cessation of CQ use against P. falciparum suggests that there is sustained CQ pressure on P. falciparum isolates in the study area. Moreover, the low prevalence of mutations in the pfmdr1 gene could be a good indicator of the high susceptibility of P. falciparum isolates to antimalarials other than CQ. A new strategy to ensure the complete nationwide withdrawal of CQ from the private drug market is recommended.

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“…In Yemen, a neighbouring country with high malaria transmission, previous studies showed that the prevalence of the 86Y mutation was higher than that reported by the current study, varying between 16-20% in the governorates of Hadhramoud (southeastern Yemen) and Hodeidah (northwestern Yemen) 34,35,36 . However, striking results were reported in Taiz governorate (southwestern Yemen) in which all of the 50 isolates analysed were found to be carrying the wild N86 allele 37 .…”

Section: Discussioncontrasting

confidence: 82%

Polymorphism Analysis of pfmdr1 Gene in Plasmodium falciparum Isolates 11 Years Post-adoption of Artemisinin-based Combination Therapy in Saudi Arabia

Al-Mekhlafi¹,

Madkhali²,

Atroosh³

et al. 2021

Preprint

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A total of 227 Plasmodium falciparum isolates from Jazan region, southwestern Saudi Arabia were amplified for the P. falciparum multi-drug resistance 1 (pfmdr1) gene to detect point mutations 11 years after the introduction of artemisinin-based combination therapy (ACT) in Saudi Arabia. The pfmdr1 86Y mutation was found in 11.5% (26/227) of the isolates while the N86 wild allele was detected in 88.5%. Moreover, 184F point mutations dominated (86.3%) the instances of pfmdr1 polymorphism while no mutation was observed at codons 1034, 1042 and 1246. Three pfmdr1 haplotypes were identified, NFSND (74.9%), NYSND (13.7%) and YFSND (11.4%). Associations of the prevalence of 86Y mutation and YFSND haplotype with participants’ nationality, residency and parasitaemia level were found to be significant (P < 0.05). The findings revealed significant decline in the prevalence of the pfmdr1 86Y mutation in P. falciparum isolates from Jazan region over a decade after the implementation of ACT treatment. Moreover, the high prevalence of the NFSND haplotype might be indicative of the potential emergence of CQ-sensitive but artemether-lumefantrine-resistant P. falciparum strains since the adoption of ACT. Therefore, continuous monitoring of the molecular markers of antimalarial drug resistance in Jazan region is highly recommended.

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Survey of chloroquine-resistant mutations in the Plasmodium falciparum pfcrt and pfmdr-1 genes in Hadhramout, Yemen

Cited by 11 publications

References 25 publications

Sequence analysis of pfcrt and pfmdr1 genes and its association with chloroquine resistance in Southeast Indian Plasmodium falciparum isolates

Sequence analysis of pfcrt and pfmdr1 genes and its association with chloroquine resistance in Southeast Indian Plasmodium falciparum isolates

Different patterns ofpfcrtandpfmdr1polymorphism inPlasmodium falciparumisolates from Tehama region, Yemen

Polymorphism Analysis of pfmdr1 Gene in Plasmodium falciparum Isolates 11 Years Post-adoption of Artemisinin-based Combination Therapy in Saudi Arabia

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