Genome sequencing sheds light on emerging drug resistance in malaria parasites

2013 ◽  
Vol 45 (6) ◽  
pp. 589-590 ◽  
Author(s):  
Daniel E Neafsey
Keyword(s):  
Drug Resistance ◽  
Genome Sequencing ◽  
Malaria Parasites

Within Host Evolution of Malaria Parasites Revealed by Single Genome Sequencing

2020 ◽  
Author(s):  
Aliou Dia ◽  
Catherine Jett ◽  
Simon G. Trevino ◽  
Cindy S. Chu ◽  
Kanlaya Sriprawat ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Malaria Parasites ◽  
Single Genome ◽  
Host Evolution

scholarly journals Assessment of the Drug Susceptibility of Plasmodium falciparum Clinical Isolates from Africa by Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-Percent Inhibitory Concentration

2006 ◽  
Vol 50 (10) ◽  
pp. 3343-3349 ◽  
Author(s):  
Halima Kaddouri ◽  
Serge Nakache ◽  
Sandrine Houzé ◽  
France Mentré ◽  
Jacques Le Bras
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Active Metabolite ◽  
Inhibitory Concentration ◽  
Drug Susceptibility ◽  
Maximum Effect ◽  
Malaria Parasites ◽  
Effect Model

ABSTRACT The extension of drug resistance among malaria-causing Plasmodium falciparum parasites in Africa necessitates implementation of new combined therapeutic strategies. Drug susceptibility phenotyping requires precise measurements. Until recently, schizont maturation and isotopic in vitro assays were the only methods available, but their use was limited by technical constraints. This explains the revived interest in the development of replacement methods, such as the Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA-Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug susceptibility in a standard in vitro assay using fairly basic laboratory equipment to study the in vitro resistance of malaria parasites to major antimalarials. Five Plasmodium falciparum clones and 121 clinical African isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8-3H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC50) and its confidence intervals. The two methods were observed to have similar reproducibilities, but the pLDH ELISA demonstrated a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic agreement (κ = 0.88) between the two methods allowed comparison by determination of the IC50s. Recently collected Plasmodium falciparum African isolates were tested by pLDH ELISA and showed drug resistance or decreased susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite of artemisinin was detected. The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites.

scholarly journals Pooled Sequencing and Rare Variant Association Tests for Identifying the Determinants of Emerging Drug Resistance in Malaria Parasites

2015 ◽  
Vol 32 (4) ◽  
pp. 1080-1090 ◽  
Author(s):  
Ian H. Cheeseman ◽  
Marina McDew-White ◽  
Aung Pyae Phyo ◽  
Kanlaya Sriprawat ◽  
François Nosten ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Rare Variant ◽  
Malaria Parasites ◽  
Rare Variant Association ◽  
Association Tests ◽  
Pooled Sequencing

scholarly journals Adaptive Drug Resistance in Malaria Parasite: A Threat to Malaria Elimination Agenda?

2021 ◽  
Author(s):  
Moses Okpeku
Keyword(s):  
Drug Resistance ◽  
Malaria Elimination ◽  
Malaria Parasite ◽  
Disease Burden ◽  
Drug Application ◽  
African Region ◽  
Malaria Parasites ◽  
Sub Saharan ◽  
Host Development

Malaria is a global disease of importance, especially in the sub-Saharan African region, where malaria accounts for great losses economically and to life. Fight to eliminate this disease has resulted in reduced disease burden in many places where the diseases is endemic. Elimination strategies in most places is focus on the use of treated nets and drug application. Exposure of malaria parasites to anti-malaria drugs have led to the evolution of drug resistance in both parasites and host. Development of drug resistance vary but, studies on adaptive drug resistance has implications and consequences. Our knowledge of this consequences are limited but important for the pursuit of an uninterrupted malaria elimination agenda. This chapter draws our attention to this risks and recommends interventions.

scholarly journals Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State

2017 ◽  
Vol 55 (6) ◽  
pp. 1871-1882 ◽  
Author(s):  
Joseph Shea ◽  
Tanya A. Halse ◽  
Pascal Lapierre ◽  
Matthew Shudt ◽  
Donna Kohlerschmidt ◽  
...  
Keyword(s):  
New York ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Predictive Value ◽  
New York State ◽  
Whole Genome ◽  
Content Type ◽  
York State

ABSTRACTWhole-genome sequencing (WGS) is a newer alternative for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles while performing species identification and capturing the data necessary for genotyping. Our laboratory developed and validated a comprehensive and sensitive WGS assay to characterizeMycobacterium tuberculosisand otherM. tuberculosiscomplex (MTBC) strains, composed of a novel DNA extraction, optimized library preparation, paired-end WGS, and an in-house-developed bioinformatics pipeline. This new assay was assessed using 608 MTBC isolates, with 146 isolates during the validation portion of this study and 462 samples received prospectively. In February 2016, this assay was implemented to test all clinical cases of MTBC in New York State, including isolates and early positive Bactec mycobacterial growth indicator tube (MGIT) 960 cultures from primary specimens. Since the inception of the assay, we have assessed the accuracy of identification of MTBC strains to the species level, concordance with culture-based drug susceptibility testing (DST), and turnaround time. Species identification by WGS was determined to be 99% accurate. Concordance between drug resistance profiles generated by WGS and culture-based DST methods was 96% for eight drugs, with an average resistance-predictive value of 93% and susceptible-predictive value of 96%. This single comprehensive WGS assay has replaced seven molecular assays and has resulted in resistance profiles being reported to physicians an average of 9 days sooner than with culture-based DST for first-line drugs and 32 days sooner for second-line drugs.

Transmission and drug-resistance of tuberculosis in Luodian revealed by whole genome sequencing based molecular epidemiology study

2020 ◽  
Author(s):  
Mei Liu ◽  
Peng Xu ◽  
Xingwei Liao ◽  
Qing Li ◽  
Wei Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Interquartile Range ◽  
Beijing Genotype ◽  
Limited Area ◽  
Whole Genome ◽  
Effective Prevention ◽  
Lineage 2 ◽  
Cluster Rate

Abstract BACKGROUND Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB), remains a severe public health problem globally. Guizhou has the fourth highest TB report rate of pulmonary TB around China. Uncovering the current status of TB epidemic, and distinguishing disease caused by recent or remote infections are the key issue to formulate effective prevention and control strategy. However, these data are limited in Guizhou. In this study, we aimed to investigate the transmission and drug-resistance profiles of TB in Luodian, a highest TB incidence and resources limited area in Guizhou, China. METHODS During 22 May 2018 to 21 April 2019, individuals with positive MTB culture were enrolled, all of them accepted the standardized interview. MTB isolates were performed whole genome sequencing. The prevalence of MTB genotypes, the genomic cluster rate and drug-resistance conferring mutations were analyzed based on the sequencing data. RESULTS A total of 107 cases were enrolled, of which 64.5% were male, and the median age of the patients was 51 years old (interquartile range, 40–65 years old). 84% patient were new case while 16% were retreated cases. All cases excepted three came from nine towns, and 55.1% of cases were from Longping and Bianyang. The phylogeny tree showed that 53.3% of strains were Lineage 2 (Beijing genotype), while 46.7% were Lineage 4 (Euro-American genotype). Among Lineage 2 strains, 66.7% were modern Beijing. Seven clusters with genomic distance within 12 SNVs were identified. The clusters included 14 strains, accounting for a cluster rate of 13.1%. The distance of clustered cases was between 2.1 to 71 kilometers (Km), with a media distance of 14 Km (interquartile range, 2.8–38 Km). Cases of two clusters came from the same town. Based on the gene mutations associated to drug-resistance, we predicted that 4.8% was resistant to isoniazid, 3.7% to rifampicin, 3.7% to streptomycin, and only one strain (0.9%) was multidrug resistance (MDR). CONLUSIONS: The study found high transmission and low drug-resistance rate in Luodian, and sublineages of modern Beijing branch had recent expansion in Luodian. this work also may serve as a genomic baseline to study the evolution and spread of MTB in Guizhou.

scholarly journals Nanopore sequencing of drug-resistance-associated genes in malaria parasites, Plasmodium falciparum

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Lucky R. Runtuwene ◽  
Josef S. B. Tuda ◽  
Arthur E. Mongan ◽  
Wojciech Makalowski ◽  
Martin C. Frith ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Nanopore Sequencing ◽  
Malaria Parasites

scholarly journals Independent Microevolution Mediated by Mobile Genetic Elements of IndividualClostridium difficileIsolates from Clade 4 Revealed by Whole-Genome Sequencing

mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Yuan Wu ◽  
Chen Liu ◽  
Wen-Ge Li ◽  
Jun-Li Xu ◽  
Wen-Zhu Zhang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clostridium Difficile ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Mobile Genetic Elements ◽  
High Rate ◽  
Whole Genome ◽  
Content Type ◽  
Genetic Elements ◽  
Sequence Types

ABSTRACTHorizontal gene transfer of mobile genetic elements (MGEs) accounts for the mosaic genome ofClostridium difficile, leading to acquisition of new phenotypes, including drug resistance and reconstruction of the genomes. MGEs were analyzed according to the whole-genome sequences of 37C. difficileisolates with a variety of sequence types (STs) within clade 4 from China. Great diversity was found in each transposon even within isolates with the same ST. Two novel transposons were identified in isolates ZR9 and ZR18, of which approximately one third to half of the genes showed heterogenous origins compared with the usual intestinal bacterial genes. Most importantly,catD, known to be harbored by Tn4453a/b, was replaced byaac(6′) aph(2′′)in isolates 2, 7, and 28. This phenomenon illustrated the frequent occurrence of gene exchanges betweenC. difficileand other enterobacteria with individual heterogeneity. Numerous prophages and CRISPR arrays were identified inC. difficileisolates of clade 4. Approximately 20% of spacers were located in prophage-carried CRISPR arrays, providing a new method for typing and tracing the origins of closely related isolates, as well as in-depth studies of the mechanism underlying genome remodeling. The rates of drug resistance were obviously higher than those reported previously around the world, although all isolates retained high sensitivity to vancomycin and metronidazole. The increasing number ofC. difficileisolates resistant to all antibiotics tested here suggests the ease with which resistance is acquiredin vivo. This study gives insights into the genetic mechanism of microevolution within clade 4.IMPORTANCEMobile genetic elements play a key role in the continuing evolution ofClostridium difficile, resulting in the emergence of new phenotypes for individual isolates. On the basis of whole-genome sequencing analysis, we comprehensively explored transposons, CRISPR, prophage, and genetic sites for drug resistance within clade 4C. difficileisolates with different sequence types. Great diversity in MGEs and a high rate of multidrug resistance were found within this clade, including new transposons, Tn4453a/bwithaac(6′) aph(2′′)instead ofcatD, and a relatively high rate of prophage-carried CRISPR arrays. These findings provide important new insights into the mechanism of genome remodeling within clade 4 and offer a new method for typing and tracing the origins of closely related isolates.

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