scholarly journals Screening for antifolate and artemisinin resistance in Plasmodium falciparum clinical isolates from three hospitals of Eritrea

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 628
Author(s):  
Harriet Natabona Mukhongo ◽  
Johnson Kang'ethe Kinyua ◽  
Yishak Gebrekidan Weldemichael ◽  
Remmy Wekesa Kasili
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Point Mutations ◽  
Artemisinin Resistance ◽  
Pcr Amplification ◽  
Clinical Isolates ◽  
Genetic Mechanism ◽  
Dried Blood Spot ◽  
Nested Polymerase Chain Reaction ◽  
Blood Spot

Background: Antimalarial drug resistance is a major challenge hampering malaria control and elimination. Plasmodium falciparum, the leading causative parasite species, has developed resistance to basically all antimalarials. Continued surveillance of drug resistance using genetic markers provides important molecular data for treatment policies. This study sought to verify the genetic mechanism of resistance to sulfadoxine-pyrimethamine and assess the occurrence of point mutations associated with artemisinin resistance in P. falciparum clinical isolates from Eritrea. Methods: Nineteen dried blood spot samples were collected from patients visiting Adi Quala, Keren and Gash Barka Hospitals, Eritrea. The patients were followed up after receiving treatment with first line artesunate-amodiaquine. Nested polymerase chain reaction and Sanger sequencing techniques were employed to genotype point mutations in the P. falciparum bifunctional dihydrofolate reductase-thymidylate synthase (Pfdhfr, PF3D7_0417200), dihydropteorate synthase (Pfdhps, PF3D7_0810800) and kelch 13 (PfK13, PF3D7_1343700) genes. Results: Eight of nineteen (42%) of the dried blood spot samples were successful for PCR-amplification. Data analyses of the PCR-positive isolates revealed the following point mutations: Pfdhfr N51I in four isolates, C59R in one isolate, S108N in four isolates, a rare non-synonymous substitution V45A in four isolates and Pfdhps K540E in four isolates. No PfK13 point mutations were reported. Conclusions: Pfdhfr C59R and Pfdhps K540E point mutations are reliable markers for the sulfadoxine-pyrimethamine quintuple mutant haplotype combination. These findings highlight first reports in Eritrea, which verify the underlying genetic mechanism of antifolate resistance. Continuous monitoring of the PfK13 marker is recommended.

scholarly journals Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Mónica Guerra ◽  
Rita Neres ◽  
Patrícia Salgueiro ◽  
Cristina Mendes ◽  
Nicolas Ndong-Mabale ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Microsatellite Loci ◽  
Point Mutations ◽  
Artemisinin Resistance ◽  
Equatorial Guinea ◽  
Content Type ◽  
Before And After

ABSTRACT Efforts to control malaria may affect malaria parasite genetic variability and drug resistance, the latter of which is associated with genetic events that promote mechanisms to escape drug action. The worldwide spread of drug resistance has been a major obstacle to controlling Plasmodium falciparum malaria, and thus the study of the origin and spread of associated mutations may provide some insights into the prevention of its emergence. This study reports an analysis of P. falciparum genetic diversity, focusing on antimalarial resistance-associated molecular markers in two socioeconomically different villages in mainland Equatorial Guinea. The present study took place 8 years after a previous one, allowing the analysis of results before and after the introduction of an artemisinin-based combination therapy (ACT), i.e., artesunate plus amodiaquine. Genetic diversity was assessed by analysis of the Pfmsp2 gene and neutral microsatellite loci. Pfdhps and Pfdhfr alleles associated with sulfadoxine-pyrimethamine (SP) resistance and flanking microsatellite loci were investigated, and the prevalences of drug resistance-associated point mutations of the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes were estimated. Further, to monitor the use of ACT, we provide the baseline prevalences of K13 propeller mutations and Pfmdr1 copy numbers. After 8 years, noticeable differences occurred in the distribution of genotypes conferring resistance to chloroquine and SP, and the spread of mutated genotypes differed according to the setting. Regarding artemisinin resistance, although mutations reported as being linked to artemisinin resistance were not present at the time, several single nucleotide polymorphisms (SNPs) were observed in the K13 gene, suggesting that closer monitoring should be maintained to prevent the possible spread of artemisinin resistance in Africa.

Short Communication: HIV Type 1 Tropism Determination in a Novel Dried Blood Spot Membrane and the Use of a Mixture of Outer Nested Polymerase Chain Reaction Primers

2014 ◽  
Vol 30 (2) ◽  
pp. 147-150 ◽  
Author(s):  
Shirlene Lavigne ◽  
Carlos Santos ◽  
Muhammad Shoaib Arif ◽  
Alexanda Reis ◽  
Sadia Samer ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Short Communication ◽  
Dried Blood Spot ◽  
Chain Reaction ◽  
Nested Polymerase Chain Reaction ◽  
Polymerase Chain ◽  
Hiv Type 1 ◽  
Polymerase Chain Reaction Primers ◽  
Blood Spot

Antimalarial Drug Susceptibility and Point Mutations Associated with Drug Resistance in 248 Plasmodium falciparum Isolates Imported from Comoros to Marseille, France in 2004–2006

2007 ◽  
Vol 77 (3) ◽  
pp. 431-437 ◽  
Author(s):  
Philippe Parola ◽  
Philippe Brouqui ◽  
Sékéné Badiaga ◽  
Lionel Bertaux ◽  
Daniel Parzy ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Point Mutations ◽  
Drug Susceptibility

scholarly journals Surveillance of Artemisinin Resistance in Plasmodium falciparum in India Using the kelch13 Molecular Marker

2015 ◽  
Vol 59 (5) ◽  
pp. 2548-2553 ◽  
Author(s):  
Neelima Mishra ◽  
Surendra Kumar Prajapati ◽  
Kamlesh Kaitholia ◽  
Ram Suresh Bharti ◽  
Bina Srivastava ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Marker ◽  
Association Studies ◽  
Point Mutations ◽  
Artemisinin Resistance ◽  
Content Type ◽  
Combination Treatments ◽  
The Status ◽  
Genome Association ◽  
Efficacy Studies

ABSTRACTMalaria treatment in Southeast Asia is threatened with the emergence of artemisinin-resistantPlasmodium falciparum. Genome association studies have strongly linked a locus onP. falciparumchromosome 13 to artemisinin resistance, and recently, mutations in the kelch13 propeller region (Pfk-13) were strongly linked to resistance. To date, this information has not been shown in Indian samples.Pfk-13mutations were assessed in samples from efficacy studies of artemisinin combination treatments in India. Samples were PCR amplified and sequenced from codon 427 to 727. Out of 384 samples, nonsynonymous mutations in the propeller region were found in four patients from the northeastern states, but their presence did not correlate with ACT treatment failures. This is the first report ofPfk-13point mutations from India. Further phenotyping and genotyping studies are required to assess the status of artemisinin resistance in this region.

scholarly journals Attenuation of Plasmodium falciparum in vitro drug resistance phenotype following culture adaptation compared to fresh clinical isolates in Cambodia

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Suwanna Chaorattanakawee ◽  
Charlotte A. Lanteri ◽  
Siratchana Sundrakes ◽  
Kritsanai Yingyuen ◽  
Panita Gosi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Clinical Isolates ◽  
Resistance Phenotype ◽  
Culture Adaptation

scholarly journals Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
Eldin Talundzic ◽  
Yaye D. Ndiaye ◽  
Awa B. Deme ◽  
Christian Olsen ◽  
Dhruviben S. Patel ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Deep Sequencing ◽  
Artemisinin Resistance ◽  
Potential Drug ◽  
Drug Pressure ◽  
Low Frequencies ◽  
Content Type ◽  
Public Health Activity ◽  
Codon Positions

ABSTRACT The emergence of Plasmodium falciparum resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the P. falciparum kelch gene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms. The results were compared to previously reported Pfk13 polymorphisms from around the world. A total of 22 Pfk13 propeller domain polymorphisms were identified in this study, of which 12 have previously not been reported. Interestingly, of the 10 polymorphisms identified in the present study that were also previously reported, all had a different amino acid substitution at these codon positions. Most of the polymorphisms were present at low frequencies and were confined to single isolates, suggesting they are likely transient polymorphisms that are part of naturally evolving parasite populations. The results of this study underscore the need to identify potential drug resistance loci existing within a population, which may emerge under increasing drug pressure.

scholarly journals Surveillance of Transmitted HIV Drug Resistance Using Matched Plasma and Dried Blood Spot Specimens From Voluntary Counseling and Testing Sites in Ho Chi Minh City, Vietnam, 2007–2008

2012 ◽  
Vol 54 (suppl_4) ◽  
pp. S343-S347 ◽  
Author(s):  
Nguyen Bui Duc ◽  
Bui Thu Hien ◽  
Nick Wagar ◽  
Tran Hong Tram ◽  
Le Truong Giang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dried Blood Spot ◽  
Ho Chi Minh City ◽  
Voluntary Counseling ◽  
Hiv Drug Resistance ◽  
Voluntary Counseling And Testing ◽  
Counseling And Testing ◽  
Blood Spot

scholarly journals Use of Dried-Blood-Spot Samples and In-House Assays To Identify Antiretroviral Drug Resistance in HIV-Infected Children in Resource-Constrained Settings

2011 ◽  
Vol 49 (12) ◽  
pp. 4077-4082 ◽  
Author(s):  
C. Ziemniak ◽  
Y. Mengistu ◽  
A. Ruff ◽  
Y.-H. Chen ◽  
L. Khaki ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dried Blood Spot ◽  
Resource Constrained ◽  
Antiretroviral Drug Resistance ◽  
Antiretroviral Drug ◽  
Blood Spot
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