scholarly journals Ten-Year Molecular Surveillance of Drug-Resistant Plasmodium spp. Isolated From the China–Myanmar Border

2021 ◽  
Vol 11 ◽  
Author(s):  
Tongke Tang ◽  
Yanchun Xu ◽  
Long Cao ◽  
Penghai Tian ◽  
Jiang Shao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Low Frequency ◽  
Artemisinin Resistance ◽  
Border Region ◽  
Chloroquine Resistance ◽  
Antimalarial Drug Resistance ◽  
Molecular Surveillance ◽  
First Choice ◽  
Greater Mekong Subregion ◽  
C580y Mutation

Antimalarial drug resistance has emerged as a major threat to global malaria control efforts, particularly in the Greater Mekong Subregion (GMS). In this study, we analyzed the polymorphism and prevalence of molecular markers associated with resistance to first-line antimalarial drugs, such as artemisinin, chloroquine, and pyrimethamine, using blood samples collected from malaria patients in the China–Myanmar border region of the GMS from 2008 to 2017, including 225 cases of Plasmodium falciparum and 194 cases of Plasmodium vivax. In artemisinin resistance, only the C580Y mutation with low frequency was detected in pfk13, and no highly frequent stable mutation was found in pvk12. In chloroquine resistance, the frequency of K76T mutation in pfcrt was always high, and the frequency of double mutations in pvmdr1 of P. vivax has been steadily increasing every year. In pyrimidine resistance, pfdhfr and pvdhfr had relatively more complex mutant types associated with drug resistance sites, and the overall mutation rate was still high. Therefore, artemisinin-based combination therapies are still suitable for use as the first choice of antimalarial strategy in the China–Myanmar border region in the future.

scholarly journals Bibliometric Analysis of Worldwide Publications on Antimalarial Drug Resistance (2006–2015)

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Waleed M. Sweileh ◽  
Samah W. Al-Jabi ◽  
Ansam F. Sawalha ◽  
Adham S. AbuTaha ◽  
Sa’ed H. Zyoud
Keyword(s):  
Drug Resistance ◽  
Antimalarial Drug ◽  
Relevant Literature ◽  
International Health ◽  
Artemisinin Resistance ◽  
Chloroquine Resistance ◽  
Research Activity ◽  
Antimalarial Drug Resistance ◽  
Noticeable Increase ◽  
The Usa

Background. In response to international efforts to control and eradicate malaria, we designed this study to give a bibliometric overview of research productivity in antimalarial drug resistance (AMDR). Methods. Keywords related to AMDR were used to retrieve relevant literature using Scopus database. Results. A total of 976 publications with an h-index of 63 were retrieved. The number of publications showed a noticeable increase starting in the early 1990s. The USA was the most productive country with 337 publications equivalent to one-third of worldwide publications in this field. More than two-thirds of publications by the USA (236, 70.03%) were made by international collaboration. Of the top ten productive countries, two countries were from Mekong subregion, particularly Thailand and Cambodia. The Malaria Journal was the most productive journal (136, 13.93%) in this field. Mahidol University (80, 8.20%) in Thailand was the most productive institution. Seven articles in the top-ten list were about artemisinin resistance in Plasmodium falciparum, one was about chloroquine resistance, one was about sulfadoxine-pyrimethamine resistance, and the remaining one was about general multidrug resistance. Conclusion. Eradication and control of AMDR require continuing research activity to help international health organizations identify spots that require an immediate action to implement appropriate measures.

scholarly journals Next-Generation Sequencing and Bioinformatics Protocol for Malaria Drug Resistance Marker Surveillance

2018 ◽  
Vol 62 (4) ◽  
pp. e02474-17 ◽  
Author(s):  
Eldin Talundzic ◽  
Shashidhar Ravishankar ◽  
Julia Kelley ◽  
Dhruviben Patel ◽  
Mateusz Plucinski ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Next Generation Sequencing ◽  
Deep Sequencing ◽  
Artemisinin Resistance ◽  
The United States ◽  
Imported Malaria ◽  
Chloroquine Resistance ◽  
Next Generation ◽  
Content Type ◽  
Generation Sequencing

ABSTRACT The recent advances in next-generation sequencing technologies provide a new and effective way of tracking malaria drug-resistant parasites. To take advantage of this technology, an end-to-end Illumina targeted amplicon deep sequencing (TADS) and bioinformatics pipeline for molecular surveillance of drug resistance in P. falciparum, called malaria resistance surveillance (MaRS), was developed. TADS relies on PCR enriching genomic regions, specifically target genes of interest, prior to deep sequencing. MaRS enables researchers to simultaneously collect data on allele frequencies of multiple full-length P. falciparum drug resistance genes (crt, mdr1, k13, dhfr, dhps, and the cytochrome b gene), as well as the mitochondrial genome. Information is captured at the individual patient level for both known and potential new single nucleotide polymorphisms associated with drug resistance. The MaRS pipeline was validated using 245 imported malaria cases that were reported to the Centers for Disease Control and Prevention (CDC). The chloroquine resistance crt CVIET genotype (mutations underlined) was observed in 42% of samples, the highly pyrimethamine-resistant dhps IRN triple mutant in 92% of samples, and the sulfadoxine resistance dhps mutation SGEAA in 26% of samples. The mdr1 NFSND genotype was found in 40% of samples. With the exception of two cases imported from Cambodia, no artemisinin resistance k13 alleles were identified, and 99% of patients carried parasites susceptible to atovaquone-proguanil. Our goal is to implement MaRS at the CDC for routine surveillance of imported malaria cases in the United States and to aid in the adoption of this system at participating state public health laboratories, as well as by global partners.

scholarly journals Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Ruimin Zhou ◽  
Chengyun Yang ◽  
Suhua Li ◽  
Yuling Zhao ◽  
Ying Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Henan Province ◽  
Nucleotide Polymorphisms ◽  
Combination Therapies ◽  
Antimalarial Drug Resistance ◽  
Single Nucleotide ◽  
Molecular Surveillance ◽  
Content Type

ABSTRACT Angola was the main origin country for the imported malaria in Henan Province, China. Antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance, such as pfcrt, pfmdr1, pfdhfr, pfdhps, and K13. This study evaluated the drug resistance of the 180 imported Plasmodium falciparum isolates from Angola via nested PCR using Sanger sequencing. The prevalences of pfcrt C72V73M74N75K76, pfmdr1 N86Y184S1034N1042D1246, pfdhfr A16N51C59S108D139I164, and pfdhps S436A437A476K540A581 were 69.4%, 59.9%, 1.3% and 6.3%, respectively. Three nonsynonymous (A578S, M579I, and Q613E) and one synonymous (R471R) mutation of K13 were found, the prevalences of which were 2.5% and 1.3%, respectively. The single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, and pfdhps were generally shown as multiple mutations. The mutant prevalence of pfcrt reduced gradually, but pfdhfr and pfdhps still showed high mutant prevalence, while pfmdr1 was relatively low. The mutation of the K13 gene was rare. Molecular surveillance of artemisinin (ART) resistance will be used as a tool to evaluate the real-time efficacy of the artemisinin-based combination therapies (ACTs) and the ART resistance situation.

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.

Molecular surveillance of antimalarial drug resistance related genes in Plasmodium falciparum isolates from Eritrea

Acta Tropica ◽  
2016 ◽  
Vol 157 ◽  
pp. 158-161 ◽  
Author(s):  
Michela Menegon ◽  
Abduselam M. Nurahmed ◽  
Albadawi A. Talha ◽  
Bakri Y.M. Nour ◽  
Carlo Severini
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Antimalarial Drug Resistance ◽  
Molecular Surveillance

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 Plasmodium Species and Drug Resistance

2021 ◽  
Author(s):  
Sintayehu Tsegaye Tseha
Keyword(s):  
Drug Resistance ◽  
Artemisinin Resistance ◽  
Plasmodium Species ◽  
Public Health Problem ◽  
Antimalarial Drugs ◽  
Chloroquine Resistance ◽  
Resistance Pattern ◽  
Malaria Parasites ◽  
Human Malaria ◽  
The World

Malaria is a leading public health problem in tropical and subtropical countries of the world. In 2019, there were an estimated 229 million malaria cases and 409, 000 deaths due malaria in the world. The objective of this chapter is to discuss about the different Plasmodium parasites that cause human malaria. In addition, the chapter discusses about antimalarial drugs resistance. Human malaria is caused by five Plasmodium species, namely P. falciparum, P. malariae, P. vivax, P. ovale and P. knowlesi. In addition to these parasites, malaria in humans may also arise from zoonotic malaria parasites, which includes P. inui and P. cynomolgi. The plasmodium life cycle involves vertebrate host and a mosquito vector. The malaria parasites differ in their epidemiology, virulence and drug resistance pattern. P. falciparum is the deadliest malaria parasite that causes human malaria. P. falciparum accounted for nearly all malarial deaths in 2018. One of the major challenges to control malaria is the emergence and spread of antimalarial drug-resistant Plasmodium parasites. The P. vivax and P. falciparum have already developed resistance against convectional antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine, and atovaquone. Chloroquine-resistance is connected with mutations in pfcr. Resistance to Sulfadoxine and pyrimethamine is associated with multiple mutations in pfdhps and pfdhfr genes. In response to the evolution of drug resistance Plasmodium parasites, artemisinin-based combination therapies (ACTs) have been used for the treatment of uncomplicated falciparum malaria since the beginning of 21th century. However, artemisinin resistant P. falciparum strains have been recently observed in different parts of the world, which indicates the possibility of the spread of artemisinin resistance to all over the world. Therefore, novel antimalarial drugs have to be searched so as to replace the ACTs if Plasmodium parasites develop resistance to ACTs in the future.

scholarly journals A comprehensive analysis of drug resistance molecular markers and Plasmodium falciparum genetic diversity in two malaria endemic sites in Mali

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Seidina A. S. Diakité ◽  
Karim Traoré ◽  
Ibrahim Sanogo ◽  
Taane G. Clark ◽  
Susana Campino ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Malaria Transmission ◽  
Resistance Gene ◽  
Artemisinin Resistance ◽  
Chloroquine Resistance ◽  
Malaria Control Programme ◽  
Codon Substitution

Abstract Background Drug resistance is one of the greatest challenges of malaria control programme in Mali. Recent advances in next-generation sequencing (NGS) technologies provide new and effective ways of tracking drug-resistant malaria parasites in Africa. The diversity and the prevalence of Plasmodium falciparum drug-resistance molecular markers were assessed in Dangassa and Nioro-du-Sahel in Mali, two sites with distinct malaria transmission patterns. Dangassa has an intense seasonal malaria transmission, whereas Nioro-du-Sahel has an unstable and short seasonal malaria transmission. Methods Up to 270 dried blood spot samples (214 in Dangassa and 56 in Nioro-du-Sahel) were collected from P. falciparum positive patients in 2016. Samples were analysed on the Agena MassARRAY® iPLEX platform. Specific codons were targeted in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps, Pfarps10, Pfferredoxin, Pfexonuclease and Pfmdr2 genes. The Sanger’s 101-SNPs-barcode method was used to assess the genetic diversity of P. falciparum and to determine the parasite species. Results The Pfcrt_76T chloroquine-resistance genotype was found at a rate of 64.4% in Dangassa and 45.2% in Nioro-du-Sahel (p = 0.025). The Pfdhfr_51I-59R-108N pyrimethamine-resistance genotype was 14.1% and 19.6%, respectively in Dangassa and Nioro-du-Sahel. Mutations in the Pfdhps_S436-A437-K540-A581-613A sulfadoxine-resistance gene was significantly more prevalent in Dangassa as compared to Nioro-du-Sahel (p = 0.035). Up to 17.8% of the isolates from Dangassa vs 7% from Nioro-du-Sahel harboured at least two codon substitutions in this haplotype. The amodiaquine-resistance Pfmdr1_N86Y mutation was identified in only three samples (two in Dangassa and one in Nioro-du-Sahel). The lumefantrine-reduced susceptibility Pfmdr1_Y184F mutation was found in 39.9% and 48.2% of samples in Dangassa and Nioro-du-Sahel, respectively. One piperaquine-resistance Exo_E415G mutation was found in Dangassa, while no artemisinin resistance genetic-background were identified. A high P. falciparum diversity was observed, but no clear genetic aggregation was found at either study sites. Higher multiplicity of infection was observed in Dangassa with both COIL (p = 0.04) and Real McCOIL (p = 0.02) methods relative to Nioro-du-Sahel. Conclusions This study reveals high prevalence of chloroquine and pyrimethamine-resistance markers as well as high codon substitution rate in the sulfadoxine-resistance gene. High genetic diversity of P. falciparum was observed. These observations suggest that the use of artemisinins is relevant in both Dangassa and Nioro-du-Sahel.

scholarly journals Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Najia Karim Ghanchi ◽  
Bushra Qurashi ◽  
Hadiqa Raees ◽  
Mohammad Asim Beg
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Single Nucleotide Polymorphisms ◽  
Low Frequency ◽  
Artemisinin Resistance ◽  
University Hospital ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Low Frequencies

Abstract Background K13 propeller (k13) polymorphism are useful molecular markers for tracking the emergence and spread of artemisinin resistance in Plasmodium falciparum. Polymorphisms are reported from Cambodia with rapid invasion of the population and almost near fixation in south East Asia. The study describes single nucleotide polymorphisms in Kelch protein propeller domain of P. falciparum associated with artemisinin resistance from Southern Pakistan. Methods Two hundred and forty-nine samples were collected from patients with microscopy confirmed P. falciparum malaria attending Aga Khan University Hospital during September 2015-April 2018. DNA was isolated using the whole blood protocol for the QIAmp DNA Blood Kit. The k13 propeller gene (k13) was amplified using nested PCR. Double-strand sequencing of PCR products was performed using Sanger sequencing methodology. Sequences were analysed with MEGA 6 and Bio edit software to identify specific SNP combinations. Results All isolates analysed for k13 propeller allele were observed as wild-type in samples collected post implementation of ACT in Pakistan. C580Y, A675V, Y493H and R539T variants associated with reduced susceptibility to artemisinin-based combination therapy (ACT) were not found. Low frequency of M476I and C469Y polymorphisms was found, which is significantly associated with artemisinin resistance. Conclusion Low frequencies of both nonsynonymous and synonymous polymorphisms were observed in P. falciparum isolates circulating in Southern Pakistan. The absence of known molecular markers of artemisinin resistance in this region is favourable for anti-malarial efficacy of ACT. Surveillance of anti-malarial drug resistance to detect its emergence and spread need to be strengthened in Pakistan.

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