scholarly journals Epidemiology of Plasmodium falciparum infection and drug resistance markers in Ota Area, Southwestern Nigeria

2019 ◽  
Vol Volume 12 ◽  
pp. 1941-1949 ◽  
Author(s):  
Grace Olasehinde ◽  
Ruth Diji-geske ◽  
Irawo Fadina ◽  
Damola Arogundade ◽  
Precious Darby ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Southwestern Nigeria ◽  
Resistance Markers

scholarly journals Molecular Surveillance of Plasmodium falciparum Drug Resistance Markers in Clinical Samples from Botswana

2018 ◽  
Vol 99 (6) ◽  
pp. 1499-1503 ◽  
Author(s):  
Leabaneng Tawe ◽  
Michela Menegon ◽  
Pleasure Ramatlho ◽  
Charles W. Muthoga ◽  
Naledi Mutukwa ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Clinical Samples ◽  
Molecular Surveillance ◽  
Resistance Markers

scholarly journals Molecular detection of drug resistant polymorphisms in Plasmodium falciparum isolates from Southwest, Nigeria

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Monday Tola ◽  
Olumide Ajibola ◽  
Emmanuel Taiwo Idowu ◽  
Olusesan Omidiji ◽  
Samson Taiwo Awolola ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug Resistance ◽  
Allelic Discrimination ◽  
Molecular Surveillance ◽  
Malaria Burden ◽  
Two Samples ◽  
Southwest Nigeria ◽  
Resistance Markers ◽  
Drug Interventions

Abstract Objective Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1–61 years old from South-west Nigeria. Results Two Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.

scholarly journals Molecular detection of drug resistant polymorphisms in Plasmodium falciparum isolates from Southwest, Nigeria.

2020 ◽  
Author(s):  
Monday Tola ◽  
Olumide Ajibola ◽  
Taiwo Emmanuel Idowu ◽  
Olusesan Omidiji ◽  
Samson Taiwo Awolola ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug Resistance ◽  
Allelic Discrimination ◽  
Molecular Surveillance ◽  
Malaria Burden ◽  
Two Samples ◽  
Southwest Nigeria ◽  
Resistance Markers ◽  
Drug Interventions

Abstract ObjectiveNigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1-61 years old from South-west Nigeria. ResultsTwo Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.

scholarly journals The Malaria TaqMan Array Card Includes 87 Assays for Plasmodium falciparum Drug Resistance, Identification of Species, and Genotyping in a Single Reaction

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Suporn Pholwat ◽  
Jie Liu ◽  
Suzanne Stroup ◽  
Shevin T. Jacob ◽  
Patrick Banura ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Large Scale ◽  
Limit Of Detection ◽  
Artemisinin Resistance ◽  
Clinical Samples ◽  
Content Type ◽  
Antimalarial Resistance ◽  
Resistance Markers ◽  
Taqman Array

ABSTRACT Antimalarial drug resistance exacerbates the global disease burden and complicates eradication efforts. To facilitate the surveillance of resistance markers in countries of malaria endemicity, we developed a suite of TaqMan assays for known resistance markers and compartmentalized them into a single array card (TaqMan array card, TAC). We included 87 assays for species identification, for the detection of Plasmodium falciparum mutations associated with chloroquine, atovaquone, pyrimethamine, sulfadoxine, and artemisinin resistance, and for neutral single nucleotide polymorphism (SNP) genotyping. Assay performance was first optimized using DNA from common laboratory parasite lines and plasmid controls. The limit of detection was 0.1 to 10 pg of DNA and yielded 100% accuracy compared to sequencing. The tool was then evaluated on 87 clinical blood samples from around the world, and the malaria TAC once again achieved 100% accuracy compared to sequencing and in addition detected the presence of mixed infections in clinical samples. With its streamlined protocol and high accuracy, this malaria TAC should be a useful tool for large-scale antimalarial resistance surveillance.

scholarly journals Evolution of Antimalarial Drug Resistance Markers in the Reservoir of Plasmodium falciparum Infections in the Upper East Region of Ghana

2020 ◽  
Vol 222 (10) ◽  
pp. 1692-1701
Author(s):  
Charles A Narh ◽  
Anita Ghansah ◽  
Michael F Duffy ◽  
Shazia Ruybal-Pesántez ◽  
Christiana O Onwona ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Therapy Resistance ◽  
Multidrug Resistant ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
East Region ◽  
Antimalarial Resistance ◽  
Upper East Region ◽  
Resistance Markers

Abstract Background The majority of Plasmodium falciparum infections, constituting the reservoir in all ages, are asymptomatic in high-transmission settings in Africa. The role of this reservoir in the evolution and spread of drug resistance was explored. Methods Population genetic analyses of the key drug resistance–mediating polymorphisms were analyzed in a cross-sectional survey of asymptomatic P. falciparum infections across all ages in Bongo District, Ghana. Results Seven years after the policy change to artemisinin-based combination therapies in 2005, the pfcrt K76 and pfmdr1 N86 wild-type alleles have nearly reached fixation and have expanded via soft selective sweeps on multiple genetic backgrounds. By constructing the pfcrt-pfmdr1-pfdhfr-pfdhps multilocus haplotypes, we found that the alleles at these loci were in linkage equilibrium and that multidrug-resistant parasites have not expanded in this reservoir. For pfk13, 32 nonsynonymous mutations were identified; however, none were associated with artemisinin-based combination therapy resistance. Conclusions The prevalence and selection of alleles/haplotypes by antimalarials were similar to that observed among clinical cases in Ghana, indicating that they do not represent 2 subpopulations with respect to these markers. Thus, the P. falciparum reservoir in all ages can contribute to the maintenance and spread of antimalarial resistance.

scholarly journals Role of Known Molecular Markers of Resistance in the Antimalarial Potency of Piperaquine and Dihydroartemisinin In Vitro

2009 ◽  
Vol 53 (4) ◽  
pp. 1362-1366 ◽  
Author(s):  
Sant Muangnoicharoen ◽  
David J. Johnson ◽  
Sornchai Looareesuwan ◽  
Srivicha Krudsood ◽  
Stephen A. Ward
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Artemisinin Combination Therapy ◽  
Parasite Line ◽  
South American ◽  
Resistance Markers ◽  
Positive Correlations ◽  
The Individual

ABSTRACT Using a range of laboratory-adapted and genetically modified Plasmodium falciparum parasite isolates, we investigated the interaction between dihydroartemisinin and piperaquine (PIP), the individual components of an artemisinin combination therapy currently under development, in addition to the role of known drug resistance genes in parasite susceptibility in vitro. All but one parasite line investigated displayed an interaction of dihydroartemisinin and PIP that was antagonistic, although the degree of antagonism was isolate dependent. In terms of resistance markers, the pfcrt haplotypes CVIET and SVMNT were positively associated with reduced sensitivity to PIP, with parasites carrying the South American CQR (SVMNT) allele being generally less sensitive than CVIET parasites. Parasites carrying the CQS (CVMNK) allele displayed a further increase in PIP sensitivity compared with CVIET and SVMNT parasites. Our data indicate that PIP sensitivity was not affected by pfmdr1 sequence status, despite positive correlations between the structurally related compound amodiaquine and pfmdr1 mutations in other studies. In contrast, neither the pfcrt nor pfmdr1 sequence status had any significant impact on susceptibility to dihydroartemisinin.

scholarly journals Molecular surveillance of chloroquine drug resistance markers (Pfcrt and Pfmdr1) among imported Plasmodium falciparum malaria in Qatar

2017 ◽  
Vol 112 (2) ◽  
pp. 57-62 ◽  
Author(s):  
Anushree Acharya ◽  
Devendra Bansal ◽  
Praveen K. Bharti ◽  
Fahmi Y. Khan ◽  
Salem Abusalah ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Surveillance ◽  
Resistance Markers

scholarly journals Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis protocol

2020 ◽  
Author(s):  
Peter Thelma Ngwa Niba ◽  
Akindeh M. Nji ◽  
Marie-Solange Evehe ◽  
Innocent M. Ali ◽  
Palmer Masumbe Netongo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Meta Analysis ◽  
Rapid Development ◽  
Gene Mutations ◽  
Pool Data ◽  
Mesh Terms ◽  
Resistance Markers

Abstract Background: Cameroon remains a country faced with high malaria burden despite enormous efforts made in the control of the disease. The rapid development and dispersal of mutations associated with anti-malarial drug resistance influenced policy changes from the use of chloroquine, amodiaquine and sulphadoxine-pyrimethamine to the adoption of artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Different studies have identified the frequency of key markers in Plasmodium falciparum associated with drug resistance without a clear picture on the localisation of potential hotspots that may drive the emergence of resistance to the currently used ACTs. This systematic review and meta-analysis aims to determine the prevalence and distribution of P. falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from 1990 to present. Methods: The PRISMA, PRISMA-P and STREGA statements will be adopted in the quality assessments of studies to be included in this review. The electronic databases of Medline via Pubmed, EMBASE, Google Scholar and Science Direct will be searched by two independent researchers using different MeSH terms and Boolean operators (AND, OR). More so, unpublished data that will be sourced from academic libraries will also be extracted. Quantitative syntheses will be done using the “metaphor” and “meta” commands in the R statistical software package version 3.5.2. Heterogeneity will be assessed using the Cochrane Q and I2 statistics. The random effects model will be used as benchmark in the determination of heterogeneity between studies. Discussion: The primary outcome of this review is to identify and describe molecular markers conferring drug resistance in Plasmodium falciparum parasites that have been circulating for a period of over 30 years in Cameroon. This review will be able to pool data from previously published and unpublished studies on anti-malarial drug resistance gene mutations. This will provide evidence to support the continuous use of ACTs in the treatment of uncomplicated P. falciparum malaria. Moreover, it is also hoped that potential hotspots driving the emergence and spread of anti-malarial resistance markers will be identified. Systematic review registration: PROSPERO CRD42020162620

scholarly journals Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis protocol

2020 ◽  
Author(s):  
Peter Thelma Ngwa Niba ◽  
Akindeh M. Nji ◽  
Marie-Solange Evehe ◽  
Innocent M. Ali ◽  
Palmer Masumbe Netongo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Meta Analysis ◽  
Rapid Development ◽  
Random Effect ◽  
Random Effect Model ◽  
Pool Data ◽  
Mesh Terms ◽  
Resistance Markers

Abstract Background: Cameroon remains a country faced with high malaria burden despite enormous efforts made in the control of the disease. The rapid development and dispersal of mutations associated with anti-malarial drug resistance influenced policy changes from the use of chloroquine, amodiaquine and sulphadoxine-pyrimethamine to the adoption of artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Different studies have identified the frequency of key markers in Plasmodium falciparum associated with drug resistance without a clear picture on the localisation of potential hotspots that may drive the emergence of resistance to the currently used ACTs. This systematic review and meta-analysis aims to determine the prevalence and distribution of P. falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from 1990 to present.Methods: The PRISMA, PRISMA-P and STREGA statements will be adopted in the quality assessments of studies to be included in this review. The electronic databases of Medline via Pubmed, EMBASE, Google Scholar and Science Direct will be searched by two independent researchers using different MeSH terms and Boolean operators (AND, OR). More so, unpublished data that will be sourced from academic libraries will also be extracted. Quantitative syntheses will be done using the “metaphor” and “meta” commands in the R statistical software package version 3.5.2. Heterogeneity will be assessed using Cochrane Q and the I2. The random effect model will be used as benchmark to combine studies showing heterogeneity.Discussion: The primary outcome of this review is to identify and describe molecular markers conferring drug resistance in Plasmodium falciparum parasites that have been circulating for a period of over 30 years in Cameroon. This review will be able to pool data from previously published and unpublished studies on anti-malarial drug resistance gene mutations. This will provide evidence to support the continuous use of ACTs in the treatment of uncomplicated P. falciparum malaria. Moreover, it is also hoped that potential hotspots driving the emergence and spread of anti-malarial resistance markers will be identified. Systematic review registration: PROSPERO CRD42020162620

scholarly journals Historical literature review and molecular analysis of malaria drug resistance markers of Plasmodium falciparum field-isolates from Sudan.

2020 ◽  
Author(s):  
Nouh S. Mohamed ◽  
Hanadi Abdelbagi ◽  
Hussam A. Osman ◽  
Abdallah E. Ahmed ◽  
Alaa M. Yousif ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Frequency Distribution ◽  
Malaria Infection ◽  
Pearson Correlation ◽  
Treatment Protocol ◽  
Public Health Problem ◽  
Historical Literature ◽  
Resistance Markers

Abstract Background Malaria infection is still known to be a worldwide public health problem, especially in tropical and sub-tropical African countries like Sudan. The fight against malaria is still taking place due to many factors. One of these factors is the presence of Plasmodium falciparum drug resistant parasites. This study is aiming at studying the P. falciparum drug resistance markers and analyzing the historical literature on these markers in Sudan. Methods A descriptive cross-sectional healthcare-centers based study conducted in Khartoum state between December 2017 and July 2018. Febrile patients diagnosed with P. falciparum malaria infection were recruited. Two ml blood samples were collected prior to start treatment. Genotyping of the specific point mutations in the P. falciparum genome was done using Sanger sequencing method for the Pfcrt, Pfmdr-1, Pfdhfr, and Pfdhps genes. Data deposited by the worldwide antimalarial resistance network was consulted and the molecular markers previously reported from Sudan were identified, collected, and analyzed to compare between past and present frequency of malaria drug resistance mutations. One-way ANOVA test was used to calculate the least significance of frequency distribution in the molecular markers collected from the previous reports from Sudan in comparison to this study. Pearson correlation was used to investigate the association between the different drug resistance markers. Results Drug molecular markers analysis was successfully done on the 20 P. falciparum isolates. the Pfcrt K76 showed the highest frequency; 16 (80%). Pfcrt 76T was 4 (20%). For the Pfmdr-1 marker, 9 (45%) isolates were carrying the N86 allele and 11 (55%) were 86Y allele. While the Y184F of the Pfmdr-1 showed higher frequency of 184F compared to Y184; 16 (80%) and 4 (20%), respectively. Concerning the double Pfmdr-1 haplotype, NY haplotype was 2 (10%), NF was 7 (35%), YF was 9 (45%), and YY was 2 (10%). In the Pfdhfr , 51I allele showed higher frequency compared to N51; 18 (90%) and 2 (10%), respectively. Whereas for C59R, C59 was 18 (90%), and 59R was 2 (10%). For S108N, 18 (90%) for 108N and 2 (10%) for S108. The triplet haplotype ICN of the Pfdhfr ; was the most frequent haplotype; 16 (80%). Concerning the Pfdhps , all the 20 (100%) isolates were carrying the mutant alleles; 437G and 540E. the Pfdhps haplotype present was the double GE haplotype only. No statistically significant correlation was found for the Pfcrt , Pfmdr-1 , Pfdhfr , and Pfdhps . Historical reports on P. falciparum multidrug resistant collected from 1989 to 2016 showed extreme fluctuation. High prevalence of Pfcrt 76T allele was observed in Khartoum throughout all years of previous studies, while in Gedaref Pfcrt 76T showing increased prevalence each year. All studied genes were showing increase prevalence of the mutant alleles and reduction of the wildtype alleles. In this study, the GE mutant haplotype was prevalent in all the studied samples. Frequency distribution of the Pfcrt K76T and Pfmdr-1 N86Y alleles, Pfmdr-1 ; N86Y and Y184F, Pfdhfr ; N51I and S108N, and Pfdhps ; A437G and K540E double haplotypes was significantly different across the whole years in Sudan. Conclusion This study describes the distribution of P. falciparum multidrug resistance markers throughout Sudan providing a solid baseline data of the status of these markers which could be very useful for the malaria control program not only for establishing surveillance system that monitor the change in and/or the emergence of malaria drug resistance but it will also offer a guidance for the evidence-base decision-making regarding the treatment protocol national and regional wise.

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