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

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.

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

Acta Tropica ◽

10.1016/j.actatropica.2016.02.007 ◽

2016 ◽

Vol 157 ◽

pp. 158-161 ◽

Cited By ~ 6

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

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Role ofPfmdr1inIn VitroPlasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03494-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7032-7040 ◽

Cited By ~ 41

Author(s):

Nathalie Wurtz ◽

Bécaye Fall ◽

Aurélie Pascual ◽

Mansour Fall ◽

Eric Baret ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Antimalarial Drug ◽

Antimalarial Drugs ◽

Wild Type ◽

Antimalarial Drug Resistance ◽

Content Type ◽

Increased Susceptibility

ABSTRACTThe involvement ofPfmdr1(Plasmodium falciparummultidrug resistance 1) polymorphisms in antimalarial drug resistance is still debated. Here, we evaluate the association between polymorphisms inPfmdr1(N86Y, Y184F, S1034C, N1042D, and D1246Y) andPfcrt(K76T) andin vitroresponses to chloroquine (CQ), mefloquine (MQ), lumefantrine (LMF), quinine (QN), monodesethylamodiaquine (MDAQ), and dihydroartemisinin (DHA) in 174Plasmodium falciparumisolates from Dakar, Senegal. ThePfmdr186Y mutation was identified in 14.9% of the samples, and the 184F mutation was identified in 71.8% of the isolates. No 1034C, 1042N, or 1246Y mutations were detected. ThePfmdr186Y mutation was significantly associated with increased susceptibility to MDAQ (P= 0.0023), LMF (P= 0.0001), DHA (P= 0.0387), and MQ (P= 0.00002). The N86Y mutation was not associated with CQ (P= 0.214) or QN (P= 0.287) responses. ThePfmdr1184F mutation was not associated with various susceptibility responses to the 6 antimalarial drugs (P= 0.168 for CQ, 0.778 for MDAQ, 0.324 for LMF, 0.961 for DHA, 0.084 for QN, and 0.298 for MQ). ThePfmdr186Y-Y184 haplotype was significantly associated with increased susceptibility to MDAQ (P= 0.0136), LMF (P= 0.0019), and MQ (P= 0.0001). The additionalPfmdr186Y mutation increased significantly thein vitrosusceptibility to MDAQ (P< 0.0001), LMF (P< 0.0001), MQ (P< 0.0001), and QN (P= 0.0026) in wild-typePfcrtK76 parasites. The additionalPfmdr186Y mutation significantly increased thein vitrosusceptibility to CQ (P= 0.0179) inPfcrt76T CQ-resistant parasites.

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In Vitroand Molecular Surveillance for Antimalarial Drug Resistance in Plasmodium falciparum Parasites in Western Kenya Reveals Sustained Artemisinin Sensitivity and Increased Chloroquine Sensitivity

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01894-15 ◽

2015 ◽

Vol 59 (12) ◽

pp. 7540-7547 ◽

Cited By ~ 16

Author(s):

Naomi W. Lucchi ◽

Franklin Komino ◽

Sheila Akinyi Okoth ◽

Ira Goldman ◽

Philip Onyona ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Antimalarial Drug ◽

Mutant Allele ◽

Surveillance Program ◽

Wild Type ◽

Antimalarial Drug Resistance ◽

Western Kenya ◽

Content Type

ABSTRACTMalaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials, including current artemisinin-based combination therapies. An antimalarial drug resistance surveillance study involving 203Plasmodium falciparummalaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzedin vitrofor sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine, and artemisinin derivatives (artesunate and dihydroartemisinin) and for drug resistance allele polymorphisms inP. falciparum crt(Pfcrt),Pfmdr-1, and the K13 propeller domain (K13). We observed a significant increase in the proportion of samples with thePfcrtwild-type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (P< 0.0001), and higher proportions of parasites with elevated sensitivity to CQin vitro. The majority of isolates harbored the wild-type N allele inPfmdr-1codon 86 (93.5%), with only 7 (3.50%) samples with the N86Ymutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-typePfmdr-1D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246Ymutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of thePfmdr-1gene (mean of 0.907 ± 0.141 copies). None of the sequenced parasites had mutations in K13. Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya.

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Antimalarial Drug Resistance Profiling of Plasmodium falciparum Infections in Ghana Using Molecular Inversion Probes and Next-Generation Sequencing

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01423-19 ◽

2020 ◽

Vol 64 (4) ◽

Cited By ~ 4

Author(s):

Benedicta A. Mensah ◽

Ozkan Aydemir ◽

James L. Myers-Hansen ◽

Millicent Opoku ◽

Nicholas J. Hathaway ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Next Generation Sequencing ◽

Antimalarial Drug ◽

Next Generation ◽

Cape Coast ◽

Antimalarial Drug Resistance ◽

Content Type ◽

Molecular Inversion Probes ◽

Generation Sequencing

ABSTRACT A key drawback to monitoring the emergence and spread of antimalarial drug resistance in sub-Saharan Africa is early detection and containment. Next-generation sequencing methods offer the resolution, sensitivity, and scale required to fill this gap by surveilling for molecular markers of drug resistance. We performed targeted sequencing using molecular inversion probes to interrogate five Plasmodium falciparum genes (pfcrt, pfmdr1, pfdhps, pfdhfr, and pfk13) implicated in chloroquine, sulfadoxine-pyrimethamine (SP), and artemisinin resistance in two sites in Ghana. A total of 803 dried blood spots from children aged between 6 months and 14 years presenting with uncomplicated P. falciparum malaria at the Begoro District Hospital in Begoro and the Ewim Polyclinic in Cape Coast, Ghana, from 2014 to 2017 were prepared on filter paper. Thirteen years after the removal of drug pressure, chloroquine-sensitive parasite strains with pfcrt K76 have increased nearly to fixation in Begoro, in the forest area (prevalence = 95%), but at a lower rate in Cape Coast, in the coastal region (prevalence = 71%, Z = −3.5, P < 0.001). In addition, pfmdr1 184F-bearing parasites are under strong selection. The pfdhfr/pfdhps quadruple genotype (IRNGK), associated with SP resistance, is near saturation. Our study identified at a 2 to 10% prevalence pfdhps 581G, which is a sulfadoxine resistance marker that correlates with the failure of SP prophylaxis in pregnancy and which has not been observed in Ghana. The differences in the reexpansion of chloroquine-sensitive strains observed at the two study sites, the stronger SP resistance, and the high prevalence of pfmdr1 184F should be further monitored to inform malaria control strategies in Ghana.

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Association between Polymorphisms in the Pfmdr6 Gene and Ex Vivo Susceptibility to Quinine in Plasmodium falciparum Parasites from Dakar, Senegal

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01183-16 ◽

2017 ◽

Vol 61 (3) ◽

Cited By ~ 6

Author(s):

Mathieu Gendrot ◽

Silman Diawara ◽

Marylin Madamet ◽

Mame Bou Kounta ◽

Sébastien Briolant ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Antimalarial Drug ◽

Ex Vivo ◽

Atp Binding ◽

Antimalarial Drug Resistance ◽

Content Type ◽

Polymorphic Microsatellite ◽

Atp Binding Cassette

ABSTRACT Polymorphisms and the overexpression of transporter genes, especially of the ATP-binding cassette superfamily, have been involved in antimalarial drug resistance. The objective of this study was to use 77 Senegalese Plasmodium falciparum isolates to evaluate the association between the number of Asn residues in the polymorphic microsatellite region of the Plasmodium falciparum multidrug resistance 6 gene (Pfmdr6) and the ex vivo susceptibility to antimalarials. A significant association was observed between the presence of 7 or 9 Asn repeats and reduced susceptibility to quinine.

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Diagnostic accuracy of molecular methods for detecting markers of antimalarial drug resistance in clinical samples of Plasmodium falciparum: protocol for an update to a systematic review and meta-analysis

Systematic Reviews ◽

10.1186/s13643-018-0891-6 ◽

2018 ◽

Vol 7 (1) ◽

Cited By ~ 1

Author(s):

Rebekah Burrow ◽

Thomas R. Fanshawe ◽

Georgina S. Humphreys

Keyword(s):

Systematic Review ◽

Drug Resistance ◽

Plasmodium Falciparum ◽

Diagnostic Accuracy ◽

Antimalarial Drug ◽

Meta Analysis ◽

Molecular Methods ◽

Clinical Samples ◽

Antimalarial Drug Resistance

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History and current status of Plasmodium falciparum antimalarial drug resistance in Madagascar

Scandinavian Journal of Infectious Diseases ◽

10.3109/00365540903289670 ◽

2010 ◽

Vol 42 (1) ◽

pp. 22-32 ◽

Cited By ~ 9

Author(s):

Valérie Andriantsoanirina ◽

Didier Ménard ◽

Luciano Tuseo ◽

Rémy Durand

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Antimalarial Drug ◽

Current Status ◽

Antimalarial Drug Resistance

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

BMC Research Notes ◽

10.1186/s13104-020-05334-5 ◽

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.

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