scholarly journals Metagenomic sequencing as a clinical diagnostic tool for infectious diseases: a systematic review and meta-analysis

Author(s):  
Kumeren N. Govender ◽  
Teresa L. Street ◽  
Nicholas D. Sanderson ◽  
David W. Eyre

SummaryBackgroundMetagenomics has the potential to revolutionise infectious diseases diagnostics, from rapid species and antimicrobial resistance prediction, to finding unrecognised and sometimes untreated infections. Our aim was to summarise all literature on culture-independent metagenomic sequencing to describe the accuracy of species and antimicrobial resistance prediction and, describe the challenges and progress in the field.MethodsWe conducted a systematic review with meta-analysis from eligible studies retrieved from PubMed, Google Scholar and bioRxiv and, assessed risk of bias and quality using the QUADAS-2 tool. This study is registered with PROSPERO, number CRD42020163777.FindingsWe identified 36 studies, 22 of which used a species-agnostic approach to identify all possible pathogens. In these studies, the overall sensitivity and specificity of pathogen species detection were 88% (95%CI 81-92%) and 86% (95%CI 70-94%) respectively. Antimicrobial resistance prediction and comparison to phenotypic results was undertaken in six studies. Categorical agreement was 83% (95%CI 68-92%), very major (prediction sensitive, phenotype resistant) and major error (prediction resistant, phenotype sensitive) rates were 9% (95%CI 2-27%) and 1% (95%CI 0-20%) respectively. We report limited use of negative controls in studies 61% (22/36) which contribute to a major challenge of discriminating true pathogens from contamination, where there is no convergence on methodology. More efficient human DNA depletion methods are required as a median of 79% (IQR 62-96) [Range 7-98] of sequences were classified as human despite laboratory depletion techniques. The median time from sample to result was 23·5 hours (7-31) [4-144], with sequencing time accounting 10 hours (4·8-16) [1-16]. The average reported consumables cost per sample ranged from $128 to $685.InterpretationThe science and regulatory environment are rapidly developing, and its role as a routine test or test of last resort still needs to be determined, however it is likely that clinical metagenomics will be an increasing part of the clinician’s armamentarium to diagnose infectious diseases in the near future.FundingNone.

2021 ◽  
Vol 9 (4) ◽  
pp. 707
Author(s):  
J. Christopher Noone ◽  
Fabienne Antunes Ferreira ◽  
Hege Vangstein Aamot

Our culture-independent nanopore shotgun metagenomic sequencing protocol on biopsies has the potential for same-day diagnostics of orthopaedic implant-associated infections (OIAI). As OIAI are frequently caused by Staphylococcus aureus, we included S. aureus genotyping and virulence gene detection to exploit the protocol to its fullest. The aim was to evaluate S. aureus genotyping, virulence and antimicrobial resistance genes detection using the shotgun metagenomic sequencing protocol. This proof of concept study included six patients with S. aureus-associated OIAI at Akershus University Hospital, Norway. Five tissue biopsies from each patient were divided in two: (1) conventional microbiological diagnostics and genotyping, and whole genome sequencing (WGS) of S. aureus isolates; (2) shotgun metagenomic sequencing of DNA from the biopsies. Consensus sequences were analysed using spaTyper, MLST, VirulenceFinder, and ResFinder from the Center for Genomic Epidemiology (CGE). MLST was also compared using krocus. All spa-types, one CGE and four krocus MLST results matched Sanger sequencing results. Virulence gene detection matched between WGS and shotgun metagenomic sequencing. ResFinder results corresponded to resistance phenotype. S. aureus spa-typing, and identification of virulence and antimicrobial resistance genes are possible using our shotgun metagenomics protocol. MLST requires further optimization. The protocol has potential application to other species and infection types.


One Health ◽  
2021 ◽  
pp. 100286
Author(s):  
Biruk Alemu Gemeda ◽  
Ayalew Assefa ◽  
Megarsa Bedasa Jaleta ◽  
Kebede Amenu ◽  
Barbara Wieland

Author(s):  
Sharanagouda S. Patil ◽  
Rajamani Shinduja ◽  
Kuralayanapalya Puttahonnappa Suresh ◽  
Sulekha Phukan ◽  
Sachin Kumar ◽  
...  

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Yemataw Gelaw ◽  
Zegeye Getaneh ◽  
Mulugeta Melku

Abstract Background Tuberculosis is a major public health problem caused by Mycobacterium tuberculosis, occurring predominantly in population with low socioeconomic status. It is the second most common cause of death from infectious diseases. Tuberculosis becomes a double burden among anemic patients. Anemia increases an individual’s susceptibility to infectious diseases including tuberculosis by reducing the immunity level. Therefore, the purpose of this study was to determine whether anemia is a risk factor for tuberculosis. Method Relevant published articles were searched in electronic databases like PubMed, Google Scholar, EMBASE, and Cochrane Library using the following MeSH terms: risk factor, predictors, tuberculosis, TB, Anaemia, Anemia, hemoglobin, Hgb, and Hb. Articles written in the English, observational studies conducted on the incidence/prevalence of tuberculosis among anemic patients, or papers examined anemia as risk factors for tuberculosis were included. From those studies meeting eligibility criteria, the first author’s name, publication year, study area, sample size and age of participants, study design, and effect measure of anemia for tuberculosis were extracted. The data were entered using Microsoft Excel and exported to Stata version 11 for analysis. The random-effects model was applied to estimate the pooled OR and HR, and 95% CI. The sources of heterogeneity were tested by Cochrane I-squared statistics. The publication bias was assessed using Egger’s test statistics. Results A total of 17 articles with a 215,294 study participants were included in the analysis. The odd of tuberculosis among anemic patients was 3.56 (95% CI 2.53–5.01) times higher than non-anemic patients. The cohort studies showed that the HR of tuberculosis was 2.01 (95% CI 1.70–2.37) times higher among anemic patients than non-anemic patients. The hazard of tuberculosis also increased with anemia severity (HR 1.37 (95% CI 0.92–2.05), 2.08 (95% CI 1.14–3.79), and 2.66 (95% CI 1.71–4.13) for mild, moderate, and severe anemia, respectively). Conclusion According to the current systematic review and meta-analysis, we can conclude that anemia was a risk factor for tuberculosis. Therefore, anemia screening, early diagnose, and treatment should be provoked in the community to reduce the burden of tuberculosis.


2019 ◽  
Vol 95 (5) ◽  
pp. 328-335 ◽  
Author(s):  
Manuel Cina ◽  
Lukas Baumann ◽  
Dianne Egli-Gany ◽  
Florian S Halbeisen ◽  
Hammad Ali ◽  
...  

BackgroundMycoplasma genitalium is increasingly seen as an emerging sexually transmitted pathogen, and has been likened to Chlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determine M. genitalium incidence, persistence, concordance between sexual partners and the risk of pelvic inflammatory disease (PID).MethodsWe searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies.ResultsWe screened 4634 records and included 18 studies; six (4201 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI 0.61 to 1.53, I2 0%). Median persistence of M. genitalium was estimated from one to three months in four studies but 15 months in one study. In 10 studies measuring M. genitalium infection status in couples, 39%–50% of male or female sexual partners of infected participants also had M. genitalium detected. In prospective studies, PID incidence was higher in women with M. genitalium than those without (risk ratio 1.73, 95% CI 0.92 to 3.28, I2 0%, two studies).DiscussionIncidence of M. genitalium in very highly developed countries is similar to that for C. trachomatis, but concordance might be lower. Taken together with other evidence about age distribution and antimicrobial resistance in the two infections, M. genitalium is not the new chlamydia. Synthesised data about prevalence, incidence and persistence of M. genitalium infection are inconsistent. These findings can be used for mathematical modelling to investigate the dynamics of M. genitalium.Registration numbersCRD42015020420, CRD42015020405


Author(s):  
Daniel Diaz ◽  
Pavel Eduardo Hernandez-Carreño ◽  
Diana Zuleika Velazquez ◽  
Miguel Angel Chaidez-Ibarra ◽  
Arnulfo Montero-Pardo ◽  
...  

Poultry and poultry-derived products such as meat and eggs are among the main sources of non-typhoidal Salmonella (NTS) transmission to the human. Therefore, we performed a systematic review and used random-effects meta-analyses to 1) estimate the prevalence of NTS in poultry samples from birds, products and subproducts, and environmental samples, 2) examine the diversity and frequency of their serovars, and 3) estimate the prevalence and profiles of antimicrobial resistance (AMR) in NTS isolates reported in studies from the Americas. We included 157 studies from 15 countries comprising 261,408 poultry samples and estimated an overall pooled prevalence of 17.9% (95% CI: 10.8–26.3) in birds, 21.8% (17.7–26.1) in products and subproducts, and 29.5% (24.2–35.1) in environmental samples. At the national level, the prevalence of NTS was heterogenous across countries with the highest values in Mexico, the USA, and Canada. In total, 131 serovars were identified from 13,388 isolates, Heidelberg, Kentucky, Enteritidis, and Typhimurium were the most prevalent in the overall top 10 ranking (range 6.5–20.8%). At the national level, Enteritidis and Typhimurium were identified in most of the countries, though with national differences in their ranks. The prevalence of AMR increased from 24.1% for 1 antibiotic, to 36.2% for 2-3 antibiotics, and 49.6% for ≥ 4 antibiotics. Kentucky, Heidelberg, Typhimurium, and Enteritidis were the serovars with the highest prevalence of AMR and tetracycline, ampicillin, streptomycin, ceftiofur, and amoxicillin-clavulanic acid were the top five antibiotics to which NTS isolates were resistant. In conclusion, NTS was distributed through the avian production chain with high and heterogenous values of prevalence in poultry samples. Besides, there were distinctive patterns of serovars distribution across countries and an alarming prevalence of AMR among zoonotic serovars.


2017 ◽  
Vol 50 (5) ◽  
pp. 629-639 ◽  
Author(s):  
Kerlly J. Bernabé ◽  
Céline Langendorf ◽  
Nathan Ford ◽  
Jean-Baptiste Ronat ◽  
Richard A. Murphy

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