scholarly journals Genomic surveillance of Plasmodium falciparum and Plasmodium vivax cases at the University Hospital in Tegucigalpa, Honduras

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hugo O. Valdivia ◽  
Fredy E. Villena ◽  
Stephen E. Lizewski ◽  
Jorge Garcia ◽  
Jackeline Alger ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Population Structure ◽  
Plasmodium Vivax ◽  
Artemisinin Resistance ◽  
Population Diversity ◽  
University Hospital ◽  
Parasite Diversity ◽  
Sequencing Data ◽  
Local Case ◽  
Imported Cases

AbstractMalaria continues to be an important health problem in Honduras despite major progress achieved reducing its incidence in the last two decades. In a context of case reduction, continuing surveillance of parasite diversity and drug resistance is an important component to assist effective malaria control strategies and support risk assessments. In this study, we employed next generation sequencing on collected Plasmodium vivax and P. falciparum samples from the Hospital Escuela (University Hospital) in Honduras between 2005 and 2017. Hospital Escuela is the main public health hospital in Honduras and receives suspected malaria cases from endemic regions within the country. The resulting sequencing data was used to assess complexity of infections, parasite population structure, parasite diversity and drug resistance profiling. All P. vivax samples and all autochtonous P. falciparum samples were monoclonal and presented a low intra population diversity (π = 0.25 and 0.07, respectively). Genotyping of drug resistance markers showed that three P. falciparum samples presented the chloroquine resistant haplotype SVMNT on pfcrtr (positions 72–76). Epidemiological data suggested that two of these samples were imported cases from Africa whereas the third one was a local case. Three suspected imported cases (two of which were also pfcrt mutants) presented the pfmdr1 86Y mutation that further enhances the CQ resistant genotype. No evidence was found for kelch13 artemisinin resistance associated mutations nor parasite genetic background mutations. Discriminant analysis of principal components and phylogenetic analysis showed two P. vivax and two P. falciparum parasite sub-populations with limited recombination between them. It also confirmed the closer relationship of the three imported cases with African strains. Our findings showed that local Honduras P. falciparum strains do not hold CQ resistance polymorphisms which aligns with clinical data reported by the country and supports the continuity of CQ based treatment in Honduras. In addition, our findings highlight the need of using genomic approaches to provide key information about parasite biology including drug resistance, population structure and HRP2/HRP3 deletions which are becoming relevant as the country move towards elimination.

scholarly journals Multi-locus genotyping reveals established endemicity of a geographically distinct Plasmodium vivax population in Mauritania, West Africa

2020 ◽  
Author(s):  
Hampate Ba ◽  
Sarah Auburn ◽  
Christopher G. Jacob ◽  
Sonia Goncalves ◽  
Craig W. Duffy ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Population Structure ◽  
Linkage Disequilibrium ◽  
West Africa ◽  
Plasmodium Vivax ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
Endemic Transmission

AbstractBackgroundPlasmodium vivax has been recently discovered as a significant cause of malaria in Mauritania, although very rare elsewhere in West Africa. It has not been known if this is a recently introduced or locally remnant parasite population, nor whether the genetic structure reflects epidemic or endemic transmission.Methodology / Principal FindingsTo investigate the P. vivax population genetic structure in Mauritania and compare with populations previously analysed elsewhere, multi-locus genotyping was undertaken on 100 clinical isolates, using a genome-wide panel of 38 single nucleotide polymorphisms (SNPs), plus seven SNPs in drug resistance genes. The Mauritanian P. vivax population is shown to be genetically diverse and divergent from populations elsewhere, indicated consistently by genetic distance matrix analysis, principal components analyses, and fixation indices. Only one isolate had a genotype clearly indicating recent importation, from a southeast Asian source. There was no linkage disequilibrium in the local parasite population, and only a small number of infections appeared to be closely genetically related, indicating that there is ongoing genetic recombination consistent with endemic transmission. The P. vivax diversity in a remote mining town was similar to that in the capital Nouakchott, with no indication of local substructure or of epidemic population structure. Drug resistance alleles were virtually absent in Mauritania, in contrast with P. vivax in other areas of the world.Conclusions / SignificanceThe molecular epidemiology indicates that there is long-standing endemic transmission that will be very challenging to eliminate. The virtual absence of drug resistance alleles suggests that most infections have been untreated, and that this endemic infection has been more neglected in comparison to P. falciparum locally or to P. vivax elsewhere.Author SummaryPlasmodium vivax is a widespread cause of malaria in Mauritania, in contrast to its rarity elsewhere throughout West Africa. To investigate whether the parasite may be recently introduced or epidemic, multi-locus genotyping was performed on 100 Mauritanian P. vivax malaria cases. Analysis of a genome-wide panel of single nucleotide polymorphisms showed the P. vivax population to be genetically diverse and divergent from populations elsewhere, indicating that there has been long-standing endemic transmission. Almost all infections appear to be locally acquired, with the exception of one that was presumably imported with a genotype similar to infections seen in Southeast Asia. The Mauritanian P. vivax population shows no linkage disequilibrium, and very few infections have closely related genotypes, indicating ongoing recombination. The parasite showed no indication of local substructure or epidemic population structure. Drug resistance alleles were virtually absent, suggesting that most infections have been untreated historically. The molecular epidemiology indicates that there has been long-standing endemic transmission of this neglected parasite that requires special attention for control.

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.

scholarly journals Genetic diversity and population structure of Plasmodium falciparum in Nigeria: insights from microsatellite loci analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fehintola V. Ajogbasile ◽  
Adeyemi T. Kayode ◽  
Paul E. Oluniyi ◽  
Kazeem O. Akano ◽  
Jessica N. Uwanibe ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Population Structure ◽  
Microsatellite Loci ◽  
Control Strategies ◽  
Population Diversity ◽  
Parasite Population ◽  
Nested Polymerase Chain Reaction ◽  
Public Health Burden ◽  
Genetic Diversity And Structure

Abstract Background Malaria remains a public health burden especially in Nigeria. To develop new malaria control and elimination strategies or refine existing ones, understanding parasite population diversity and transmission patterns is crucial. Methods In this study, characterization of the parasite diversity and structure of Plasmodium falciparum isolates from 633 dried blood spot samples in Nigeria was carried out using 12 microsatellite loci of P. falciparum. These microsatellite loci were amplified via semi-nested polymerase chain reaction (PCR) and fragments were analysed using population genetic tools. Results Estimates of parasite genetic diversity, such as mean number of different alleles (13.52), effective alleles (7.13), allelic richness (11.15) and expected heterozygosity (0.804), were high. Overall linkage disequilibrium was weak (0.006, P < 0.001). Parasite population structure was low (Fst: 0.008–0.105, AMOVA: 0.039). Conclusion The high level of parasite genetic diversity and low population structuring in this study suggests that parasite populations circulating in Nigeria are homogenous. However, higher resolution methods, such as the 24 SNP barcode and whole genome sequencing, may capture more specific parasite genetic signatures circulating in the country. The results obtained can be used as a baseline for parasite genetic diversity and structure, aiding in the formulation of appropriate therapeutic and control strategies in Nigeria.

scholarly journals Prevalence of molecular markers associated with drug resistance of Plasmodium vivax isolates in Western Yunnan Province, China

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoxiao Wang ◽  
Wei Ruan ◽  
Shuisen Zhou ◽  
Xinyu Feng ◽  
He Yan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Molecular Markers ◽  
Plasmodium Vivax ◽  
Yunnan Province ◽  
Western Yunnan

scholarly journals Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax

2012 ◽  
Vol 11 (1) ◽  
pp. 68 ◽  
Author(s):  
Stella M Chenet ◽  
Lorena L Tapia ◽  
Ananias A Escalante ◽  
Salomon Durand ◽  
Carmen Lucas ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Population Structure ◽  
Plasmodium Vivax ◽  
Vaccine Candidate ◽  
Genes Encoding

scholarly journals Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon

2010 ◽  
Vol 9 (1) ◽  
Author(s):  
Peter Van den Eede ◽  
Gert Van der Auwera ◽  
Christopher Delgado ◽  
Tine Huyse ◽  
Veronica E Soto-Calle ◽  
...  
Keyword(s):  
Population Structure ◽  
Plasmodium Vivax ◽  
Local Population ◽  
Peruvian Amazon ◽  
Multilocus Genotyping ◽  
Vivax Population

Antimalarial drug resistance markers in human immunodeficiency virus (HIV)-positive and HIV-negative adults with asymptomatic malaria infections in Port Harcourt, Nigeria

2021 ◽  
Author(s):  
Ifeyinwa Chijioke-Nwauche ◽  
Mary C Oguike ◽  
Chijioke A Nwauche ◽  
Khalid B Beshir ◽  
Colin J Sutherland
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Drug Susceptibility ◽  
Blood Film ◽  
University Hospital ◽  
Hiv Positive ◽  
Asymptomatic Malaria ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Hiv Negative

Abstract Background In Nigeria, indiscriminate use of antimalarial drugs may contribute to the threat of drug resistance, but this has not been evaluated among people living with human immunodeficiency virus (HIV). Methods HIV-positive adults attending a university hospital HIV clinic and HIV-negative adult volunteers from the university hospital community with a positive blood film were treated with artemether–lumefantrine. Parasite DNA from before and after treatment was polymerase chain reaction amplified to identify molecular markers of drug susceptibility. Results The pfcrt76T genotype was prevalent among both HIV-positive and HIV-negative participants (78.6% and 68.2%, respectively). Three new mutations in the pfmdr1 gene—F73S, S97L and G165R—and the uncommon pfdhps S436F variant were detected, whereas pfdhps K540E and pfdhfr I164L were absent. The A437G allele of pfdhps predominated (62/66 [94%]). The I431 V mutation was found in 19 of 66 pretreatment pfdhps sequences (28.8%). The pfmdr1 86N allele was significantly more common at day 3 post-treatment than at baseline (odds ratio 8.77 [95% confidence interval 1.21 to 380]). Conclusions We found evidence of continued chloroquine use among HIV-positive individuals. Selection for the pfmdr1 86N after artemether–lumefantrine treatment was observed, indicating a possible threat to antimalarial efficacy in the study area. The complexity of pfdhps haplotypes emphasises the need for careful monitoring of anti-folate susceptibility in Nigeria.

Population-specific genome graphs improve high-throughput sequencing data analysis: A case study on the Pan-African genome

2021 ◽  
Author(s):  
H. Serhat Tetikol ◽  
Kubra Narci ◽  
Deniz Turgut ◽  
Gungor Budak ◽  
Ozem Kalay ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Information Overload ◽  
African Ancestry ◽  
Sample Selection ◽  
Variant Calling ◽  
Population Diversity ◽  
Human Populations ◽  
Sequencing Data ◽  
Bioinformatics Pipeline ◽  
Graph Augmentation

ABSTRACTGraph-based genome reference representations have seen significant development, motivated by the inadequacy of the current human genome reference for capturing the diverse genetic information from different human populations and its inability to maintain the same level of accuracy for non-European ancestries. While there have been many efforts to develop computationally efficient graph-based bioinformatics toolkits, how to curate genomic variants and subsequently construct genome graphs remains an understudied problem that inevitably determines the effectiveness of the end-to-end bioinformatics pipeline. In this study, we discuss major obstacles encountered during graph construction and propose methods for sample selection based on population diversity, graph augmentation with structural variants and resolution of graph reference ambiguity caused by information overload. Moreover, we present the case for iteratively augmenting tailored genome graphs for targeted populations and test the proposed approach on the whole-genome samples of African ancestry. Our results show that, as more representative alternatives to linear or generic graph references, population-specific graphs can achieve significantly lower read mapping errors, increased variant calling sensitivity and provide the improvements of joint variant calling without the need of computationally intensive post-processing steps.

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