scholarly journals Evolution of multidrug resistance in Plasmodium falciparum : a longitudinal study of genetic resistance markers in the Greater Mekong Subregion

2021 ◽  
Author(s):  
Mallika Imwong ◽  
Kanokon Suwannasin ◽  
Suttipat Srisutham ◽  
Ranitha Vongpromek ◽  
Cholrawee Promnarate ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Artemisinin Combination Therapy ◽  
Genetic Resistance ◽  
Lao Pdr ◽  
Treatment Resistance ◽  
Chloroquine Resistance ◽  
High Background ◽  
Greater Mekong Subregion ◽  
Over Time

Increasing drug resistance in Plasmodium falciparum to artemisinins and their ACT partner drugs jeopardises effective antimalarial treatment. Resistance is worst in the Greater Mekong Subregion. Monitoring genetic markers of resistance can help to guide antimalarial therapy. Markers of resistance to artemisinins ( PfKelch mutations), mefloquine (amplification of P. falciparum multidrug resistance-1, PfMDR1, ), and piperaquine ( PfPlasmepsin2/3 amplification and specific P. falciparum chloroquine resistance transporter, PfCRT, mutations) were assessed in 6,722 P. falciparum samples from Vietnam, Lao PDR, Cambodia, Thailand, Myanmar between 2007 and 2019. Against a high background prevalence of PfKelch mutations, PfMDR1 and PfPlasmepsin2/3 amplification closely followed regional drug pressures over time. PfPlasmepsin2/3 amplification preceded piperaquine-resistance associated PfCRT mutations in Cambodia, and reached a peak prevalence of 23/28 (82%) in 2015. This declined to 57/156 (38%) after changing first-line treatment away from dihydroartemisinin-piperaquine to artesunate-mefloquine (ASMQ) between 2014 and 2017. PfMDR1 amplification increased from 0/293 (0%) between 2012 and 2017 to 12/156 (8%) in 2019. Amplification of PfMDR1 and PfPlasmepsin2/3 in the same parasites was extremely rare (4/6,722; 0.06%) and dispersed over time. Mechanisms conferring mefloquine and piperaquine resistance may be counterbalancing. This supports the development of ASMQ plus piperaquine as a triple artemisinin combination therapy.

Detection of antimalarial drug resistance polymorphisms in Plasmodium falciparum chloroquine resistance transporter and Plasmodium falciparum multidrug resistance 1 genes of Plasmodium falciparum found in Kano State, Nigeria

2021 ◽  
Vol 5 ◽  
pp. 8-14
Author(s):  
Al-Mukhtar Yahuza Adamu ◽  
Olayeni Stephen Olonitola ◽  
Helen Ileigo Inabo ◽  
Ahmad Babangida Suleiman
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Antimalarial Drug ◽  
Artemisinin Combination Therapy ◽  
Chloroquine Resistance ◽  
Antimalarial Drug Resistance ◽  
Antimalarial Agents ◽  
Chloroquine Resistance Transporter ◽  
Two Samples

Objectives: In 2018, malaria claimed an estimated 380,000 lives in African region, with Nigeria accounting for 24.0% (91,368) of malaria deaths from the region. Mutations in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr-1) genes had reduced the effective use of artemisinin combination therapy through the development of resistance to these antimalarial agents. Our study set out to determine the antimalarial drug resistance polymorphisms in Pfcrt and Pfmdr-1 genes of P. falciparum isolates among patients in Kano State, Nigeria. Material and Methods: Malaria positive samples were collected across the three senatorial districts of Kano State. The samples were amplified using nested polymerase chain reaction to detect the Pfcrt and Pfmdr-1 genes. The amplicons were sequenced and bioinformatic analysis was done using CLC Sequence viewer 8.0 and BioEdit sequence alignment editor to detect the single-nucleotide polymorphisms. Results: In the Pfcrt gene, CVIET haplotype was seen in 26.2% of the samples while only two samples showed the 86Y mutation in the Pfmdr-1 gene. All the 86Y mutations and majority of the CVIET haplotypes were detected in the patients from rural settings where some of them noted that they consumed modern and traditional (herbs) antimalarial agents. One sample was observed to have the CVIET haplotype and N86Y mutation while the other five CVIET haplotypes were seen in five separate samples. A new mutation V62A was found in the Pfmdr-1 gene as observed in one of the sample. Conclusion: It is imperative to ensure the rational use of the right antimalarial agents and employ continuous resistance surveillance/mapping to ensure synergy in malaria containment and elimination strategies.

scholarly journals Survey of Plasmodium falciparum multidrug resistance-1 and chloroquine resistance transporter alleles in Haiti

2013 ◽  
Vol 12 (1) ◽  
pp. 426 ◽  
Author(s):  
Maha A ElBadry ◽  
Alexandre Existe ◽  
Yves S Victor ◽  
Gladys Memnon ◽  
Mark Fukuda ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Chloroquine Resistance ◽  
Chloroquine Resistance Transporter

scholarly journals Large-Scale Surveillance of Plasmodium falciparum crt(K76T) in Northern Ghana

2007 ◽  
Vol 51 (9) ◽  
pp. 3407-3409 ◽  
Author(s):  
Stephan Ehrhardt ◽  
Teunis A. Eggelte ◽  
Sarah Kaiser ◽  
Lydia Adjei ◽  
Gerd D. Burchard ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Life Span ◽  
Large Scale ◽  
Artemisinin Combination Therapy ◽  
Dry Season ◽  
Chloroquine Resistance ◽  
Northern Ghana ◽  
Resistance Marker

ABSTRACT Surveillance of Plasmodium falciparum crt(K76T) [Pfcrt(K76T)], a resistance marker of chloroquine and, limitedly, amodiaquine, in >4,000 children in northern Ghana revealed a prevalence of 79%. Pfcrt(K76T) was heterogeneously distributed and associated with chloroquine use, low parasitemia, and the dry season. Widespread chloroquine resistance challenges the regional life span of amodiaquine as a partner drug in artemisinin combination therapy.

Transcripts of the multidrug resistance genes in chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

Parasitology ◽  
1993 ◽  
Vol 106 (2) ◽  
pp. 107-115 ◽  
Author(s):  
R. M. Ekong ◽  
K. J. H. Robson ◽  
D. A. Baker ◽  
D. C. Warhurst
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Copy Number ◽  
Chloroquine Resistance ◽  
Multidrug Resistance Gene ◽  
Genetic Cross ◽  
Multidrug Resistance Genes

SUMMARYHomologues of the mammalian multidrug resistance gene have been identified in isolates and clones of Plasmodium falciparum and designated pfmdr1 and pfmdr2. Mutations in pfmdr1 have been associated with chloroquine resistance but confirmation could not be obtained in a genetic cross. We have examined the copy number and expression of pfmdr1 and pfmdr2 in chloroquine-sensitive and -resistant P. falciparum and have found no relationship between the copy number of either gene and chloroquine resistance. However, a marked correlation was seen between levels of mRNA transcribed for each gene and chloroquine resistance. Two transcripts of pfmdr1 were detected, and in the asexual blood cycle an 8 kb transcript appeared first, followed by the appearance of a 7 kb species.

Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum

Nature ◽  
1990 ◽  
Vol 345 (6272) ◽  
pp. 255-258 ◽  
Author(s):  
S. J. Foote ◽  
D. E. Kyle ◽  
R. K. Martin ◽  
A. M. J. Oduola ◽  
K. Forsyth ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Chloroquine Resistance ◽  
Multidrug Resistance Gene

Amplification of the multidrug resistance gene pfmdr1 in Plasmodium falciparum has arisen as multiple independent events

1991 ◽  
Vol 11 (10) ◽  
pp. 5244-5250
Author(s):  
T Triglia ◽  
S J Foote ◽  
D J Kemp ◽  
A F Cowman
Keyword(s):  
Polymerase Chain Reaction ◽  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Tumor Cells ◽  
Yeast Artificial Chromosome ◽  
Chloroquine Resistance ◽  
Chain Reaction ◽  
Pfmdr1 Gene ◽  
Independent Events ◽  
Polymerase Chain

The multidrug resistance (MDR) phenotype in mammalian tumor cells can involve amplification of mdr genes that results in overexpression of the protein product termed P-glycoprotein. Chloroquine resistance (CQR) in Plasmodium falciparum has similarities with the MDR phenotype in tumor cells, and some isolates of P. falciparum have amplified levels of the pfmdr1 gene. To investigate the nature and origin of pfmdr1 amplicons, we have cloned large regions of a 110-kb amplicon from the CQR cloned isolate B8 by using the yeast artificial chromosome system. We have identified and sequenced the breakpoints of the amplicon by a novel method employing inverted polymerase chain reaction that is applicable to analysis of any large-scale repeat. We show that the five copies of the amplicon in this isolate are in a head to tail configuration. A string of 30 A's flank the breakpoints on each side of the amplified segment, suggesting a mechanism for the origin of the tandem amplification. Polymerase chain reaction analysis with oligonucleotides that cross the B8 breakpoint has shown in 26 independent CQR isolates, 16 of which contain amplified copies of pfmdr1, that amplification of the pfmdr1 gene in P. falciparum has arisen as multiple independent events. These results suggest that this region of the genome is under strong selective pressure.

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