Featured
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Article
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Ultrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device
The recent monkeypox outbreak highlighted the need for rapid and accurate diagnosis of this disease. Here, authors develop an ultrasensitive and streamlined CRISPR assay using miniaturized device, which can detect monkeypox virus in rash fluid swab, oral swab, saliva, and urine within 15 minutes.
- Yunxiang Wang
- , Hong Chen
- & Shengqi Wang
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Article
| Open Access
Accurate and rapid antibiotic susceptibility testing using a machine learning-assisted nanomotion technology platform
Sturm et. al developed a 2 to 4 h antibiotic susceptibility test based on bacterial vibrations. This diagnostic test applies to the most frequently found gram-negative bacteria in bloodstream infections and demonstrates its potential in contributing to faster treatment decisions.
- Alexander Sturm
- , Grzegorz Jóźwiak
- & Danuta Cichocka
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Rapid deep learning-assisted predictive diagnostics for point-of-care testing
A key aim in the development of diagnostic assays is improving diagnostic speed while maintaining sensitivity. Here the authors report an approach for the rapid and accurate analysis of lateral flow tests, which integrates time-series deep learning and AI verification, achieving a diagnostic time of 1-2 minutes.
- Seungmin Lee
- , Jeong Soo Park
- & Jeong Hoon Lee
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Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach
Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.
- Ivan Barilar
- , Simone Battaglia
- & Baoli Zhu
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Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies
Bacterial infections and sepsis are a major cause of mortality in preterm babies. Here Das and colleagues assess the paediatric immune response to bacterial infection in very preterm babies and identify blood immune markers that could improve accuracy of diagnostics to rule-out sepsis and guide antibiotic treatment.
- A. Das
- , G. Ariyakumar
- & D. L. Gibbons
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ANCA: artificial nucleic acid circuit with argonaute protein for one-step isothermal detection of antibiotic-resistant bacteria
Antibiotic-resistant bacteria pose a growing threat to global health. Here, the authors present an artificial nucleic acid circuit with argonaute protein (ANCA) for one-step, amplification-free, and isothermal detection of carbapenemase-producing Klebsiella pneumoniae.
- Hyowon Jang
- , Jayeon Song
- & Taejoon Kang
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Estimating the potential impact and diagnostic requirements for SARS-CoV-2 test-and-treat programs
Antivirals are now available for treating COVID-19 but must be used early in the course of infection to be effective. Here, the authors use mathematical modelling to assess the potential public health impacts of antiviral use considering different levels of testing and country sociodemographic characteristics.
- Alvin X. Han
- , Emma Hannay
- & Colin A. Russell
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Article
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Interrogating ligand-receptor interactions using highly sensitive cellular biosensors
The interaction of membrane-resident proteins plays an essential role in biological processes. Here the authors describe cellular biosensors based on chimeric receptors, as a tool to study the interaction of receptor-ligand pairs such as immune checkpoint molecules or virus attachment proteins and their receptors.
- Maximilian A. Funk
- , Judith Leitner
- & Peter Steinberger
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Article
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Multiplexed detection of viral antigen and RNA using nanopore sensing and encoded molecular probes
Fast discrimination of SARS-CoV-2 variants in clinical samples remains a challenge. Here, authors report on single molecule nanopore sensing combined with DNA molecular probes to simultaneously detect various antigens and RNA mutations of SARS-CoV-2 variants in patient samples.
- Ren Ren
- , Shenglin Cai
- & Joshua B. Edel
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Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals
In this work, Otter et al. compared the humoral immune responses induced by MPXV infection and Smallpox vaccination. Although comparable responses were observed, infection- or vaccination specific serological markers were identified enabling discrimination between vaccinated and infected individuals.
- Ashley D. Otter
- , Scott Jones
- & Bassam Hallis
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Article
| Open Access
Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine
Although diagnosis of urinary tract infections has improved through the use of point-of-care molecular technologies, they are however limited by poor specificity and / or sensitivity, and requirement of laboratory resources. In this work, the authors develop a bacteriophage-based diagnostic assay for the detection of prevalent uropathogens.
- Susanne Meile
- , Jiemin Du
- & Samuel Kilcher
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Article
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Genome-wide tiled detection of circulating Mycobacterium tuberculosis cell-free DNA using Cas13
In this work, the authors developed a multiplexed, minimally invasive, CRISPR-Cas13-based approach to detect Mycobacterium tuberculosis cell-free DNA in the plasma of active pulmonary tuberculosis patients.
- Sri Gowtham Thakku
- , Jackson Lirette
- & Deborah T. Hung
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Emergence and spread of two SARS-CoV-2 variants of interest in Nigeria
Data on geographically restricted SARS-CoV-2 variants is lacking in some regions. In this nationwide effort including 18 public health labs, the authors used genomic epidemiology and travel data to understand the origin and spread of 2 variants of interest that predominated during the second wave of the pandemic in Nigeria.
- Idowu B. Olawoye
- , Paul E. Oluniyi
- & Christian T. Happi
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Sequence-specific capture and concentration of viral RNA by type III CRISPR system enhances diagnostic
Many viral diagnostic approaches require nucleic acid extraction and amplification prior to detection. Here, the authors develop a method based on type III CRISPR systems which allows sequence specific capture, concentration, and detection of viral RNA directly from patient samples.
- Anna Nemudraia
- , Artem Nemudryi
- & Blake Wiedenheft
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A Mycobacterium tuberculosis fingerprint in human breath allows tuberculosis detection
Most conventional tuberculosis diagnostic tests rely on difficult to obtain sputum samples. In this proof-of-concept study, authors analyse whether pulmonary tuberculosis can be detected using exhaled breath condensate samples.
- Sergio Fabián Mosquera-Restrepo
- , Sophie Zuberogoïtia
- & Jérôme Nigou
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High-throughput screening of caterpillars as a platform to study host–microbe interactions and enteric immunity
Here, combining diagnostic imaging modalities and in vivo assays, Windfelder and colleagues established tobacco hornworm larvae Manduca sexta as an alternative high-throughput platform to study the innate immunity of the gut and host-pathogen interactions. Using the platform, the authors identify mediators of gut inflammation, differentiate pathogens from gut mutualist bacteria, and demonstrate pharmacological interventions.
- Anton G. Windfelder
- , Frank H. H. Müller
- & Ulrich Flögel
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The prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria
Malaria diagnosis by microscopy provides valuable rapid diagnostic and prognostic information, which is critical to clinical management. In this work, authors carry out a meta-analysis on the prognostic and diagnostic value of polymorphonuclear leukocytes and monocytes containing malaria pigment in peripheral blood film counts taken from patients with severe malaria.
- Ketsanee Srinamon
- , James A. Watson
- & Nicholas J. White
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Microfluidic space coding for multiplexed nucleic acid detection via CRISPR-Cas12a and recombinase polymerase amplification
Fast, low-cost and multiplexed nucleic acid detection is challenging. Here the authors report a strategy that couples microfluidic space coding, CRISPRCas12a, and multiplex RPA for the rapid detection of up to 30 targets with only one fluorescent probe.
- Zhichen Xu
- , Dongjuan Chen
- & Maili Liu
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Article
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Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants
Increasing reliance on antigen tests for SARS-CoV-2 screening may risk selection for variants not detected by these tests. Here, the authors identify a variant of this type circulating in Italy, estimate the potential impact of failure to detect the variant, and model testing strategies to mitigate the risk.
- Claudia Del Vecchio
- , Bethan Cracknell Daniels
- & Andrea Crisanti
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Mitigation of SARS-CoV-2 transmission at a large public university
Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.
- Diana Rose E. Ranoa
- , Robin L. Holland
- & Martin D. Burke
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Rapid, adaptable and sensitive Cas13-based COVID-19 diagnostics using ADESSO
SARS-CoV-2 antigen tests are commonly used point-of-care tests and provide rapid results but lack sensitivity. Here, the authors present a new point-of-care approach for COVID-19 diagnosis, “ADESSO”, which outperforms antigen tests on clinical samples and can be quickly adapted for different variants.
- Beatrice Casati
- , Joseph Peter Verdi
- & Riccardo Pecori
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Co-infection with SARS-CoV-2 Omicron and Delta variants revealed by genomic surveillance
Here, using genomic approaches, Rockett et al. identify Omicron and Delta SARS-CoV-2 co-infections in two adults, highlighting the usefulness of genomic surveillance for the timely recognition of co-infections in situations when different variants of the virus are circulating in the community.
- Rebecca J. Rockett
- , Jenny Draper
- & Vitali Sintchenko
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Metabolic preference assay for rapid diagnosis of bloodstream infections
It is currently slow to identify bloodstream infection pathogens. Here the authors report a rapid metabolic preference assay that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles.
- Thomas Rydzak
- , Ryan A. Groves
- & Ian A. Lewis
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In vivo imaging of invasive aspergillosis with 18F-fluorodeoxysorbitol positron emission tomography
Current diagnostic methods for invasive aspergillosis are time-consuming and poorly sensitive. Here, the authors show that positron emission tomography with 2-deoxy-2-18F-fluorosorbitol can visualize Aspergillus fumigatus infection of the lungs, brain and muscles in mouse models, and can distinguish pulmonary aspergillosis from other diseases such as Staphylococcus aureus infection and lung cancer.
- Dong-Yeon Kim
- , Ayoung Pyo
- & Jung-Joon Min
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Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics
Tuberculous meningitis is difficult to differentiate from meningitis caused by other pathogens. Here, the authors combine metagenomics-based pathogen detection in cerebrospinal fluid with a host gene expression-based machine learning classifier for diagnosis.
- P. S. Ramachandran
- , A. Ramesh
- & M. R. Wilson
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Rescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing data
Tracking low frequency intra-host variants has helped understanding within-host viral population dynamics and transmission. Precise tracking, however, depends partially on the error rate of the sequencing platforms used. Here, Liu et al. present Variabel, a method to rescue low frequency intra-host variants from Oxford Nanopore Technologies (ONT) platforms and validate their approach on Ebola virus, norovirus, and SARS-CoV-2 datasets.
- Yunxi Liu
- , Joshua Kearney
- & Todd J. Treangen
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Article
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Rapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections
It remains unclear how rapid antibiotic switching affects the evolution of antibiotic resistance in individual patients. Here, Chung et al. combine short- and long-read sequencing and resistance phenotyping of 420 serial isolates of Pseudomonas aeruginosa collected from the onset of respiratory infection, and show that rare resistance mutations can increase by nearly 40-fold over 5–12 days in response to antibiotic changes, while mutations conferring resistance to antibiotics not administered diminish and even go to extinction.
- Hattie Chung
- , Christina Merakou
- & Gregory P. Priebe
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Distinct kinetics of antibodies to 111 Plasmodium falciparum proteins identifies markers of recent malaria exposure
Serological markers of recent Plasmodium falciparum infection could be useful to estimate incidence. Here, the authors identify a combination of five serological markers to detect exposure to infection within the previous three months with >80% sensitivity and specificity.
- Victor Yman
- , James Tuju
- & Anna Färnert
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Article
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Paper microfluidic implementation of loop mediated isothermal amplification for early diagnosis of hepatitis C virus
Current HCV nucleic acid-based diagnosis is largely performed in centralised laboratories. Here, the authors present a pan-genotypic RNA assay, based on reverse transcriptase loop mediated isothermal amplification and develop a low-cost prototype paper-based lateral flow device for point-of-care use, providing a visually read result within 40 min.
- Weronika Witkowska McConnell
- , Chris Davis
- & Jonathan M. Cooper
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Quantifying previous SARS-CoV-2 infection through mixture modelling of antibody levels
The proportion of a population that has previously been infected by a pathogen is typically estimated using antibody thresholds adjusted for sensitivity and specificity. Here, the authors present a model-based alternative to threshold methods which accounts for antibody waning and other sources of spectrum bias.
- C. Bottomley
- , M. Otiende
- & J. A. G. Scott
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Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth
Here, the authors apply DESI-MS, a sample preparation-free, direct on-swab mass spectrometry analytical tool, to profile the cervicovaginal metabolome of two independent cohorts of pregnant women and, combined with matched metataxonomic and immuno-profiling data, show that DESI-MS predicts vaginal microbiota composition and local inflammatory status associated with preterm birth and clinical interventions used during pregnancy.
- Pamela Pruski
- , Gonçalo D. S. Correia
- & David A. MacIntyre
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Article
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SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation
Type III CRISPR-Cas systems recognize and cleave target RNAs and produce signalling molecules. Here the authors discover that both processes are governed by a flexible seed region, ultimately resulting in SCOPE, a SARSCoV-2 diagnostic assay with atto-molar sensitivity.
- Jurre A. Steens
- , Yifan Zhu
- & Raymond H. J. Staals
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Oil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2
Bottlenecks in qPCR-based COVID-19 diagnostics include the lengthy multistep process and reagent shortages. Here the authors report OIL-TAS which integrates RNA extraction and detection into a single device.
- Duane S. Juang
- , Terry D. Juang
- & David J. Beebe
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Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma
Respiratory syncytial virus (RSV) bronchiolitis during infancy is a major risk factor for asthma development. Here, Raita et al. integrate clinical data with airway microbiome, transcriptome, and metabolome data and identity four endotypes with differential risks for developing asthma.
- Yoshihiko Raita
- , Marcos Pérez-Losada
- & Kohei Hasegawa
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Distinct clinical and immunological profiles of patients with evidence of SARS-CoV-2 infection in sub-Saharan Africa
Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.
- Ben Morton
- , Kayla G. Barnes
- & Kondwani C. Jambo
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Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens
It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.
- Nicholas D. Walter
- , Sarah E. M. Born
- & Martin I. Voskuil
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| Open Access
Dysregulated transcriptional responses to SARS-CoV-2 in the periphery
The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate dysregulated immune responses in COVID-19 with both heterogeneous and conserved components.
- Micah T. McClain
- , Florica J. Constantine
- & Christopher W. Woods
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Article
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Magneto-optical diagnosis of symptomatic malaria in Papua New Guinea
Here Arndt et al. establish rotating-crystal magneto-optical detection (RMOD) as a near-point-of-care diagnostic tool for malaria detection and report a sensitivity and specificity of 82% and 84%, respectively, as validated by analyzing a clinical population in a high transmission setting in Papua New Guinea.
- L. Arndt
- , T. Koleala
- & S. Karl
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Article
| Open Access
Artificial intelligence in sepsis early prediction and diagnosis using unstructured data in healthcare
Early prediction and diagnosis of sepsis, which is critical in reducing mortality, is challenging as many of its signs and symptoms are similar to other less critical conditions. Here, the authors develop an artificial intelligence algorithm which uses both structured data and unstructured clinical notes to predict sepsis.
- Kim Huat Goh
- , Le Wang
- & Gamaliel Yu Heng Tan
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Article
| Open Access
Remote near infrared identification of pathogens with multiplexed nanosensors
Fast and specific detection of pathogenic bacteria is needed to combat infections. Here the authors generate an array of near-infrared biosensors based on carbon nanotubes to detect released metabolites and virulence factors and use them to distinguish pathogens such as S. aureus and P. aeruginosa.
- Robert Nißler
- , Oliver Bader
- & Sebastian Kruss
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Article
| Open Access
Streamlined inactivation, amplification, and Cas13-based detection of SARS-CoV-2
The COVID-19 pandemic has highlighted the need for user-friendly diagnostic techniques. Here, the authors present SHINE, a streamlined and optimised Cas13-based method with accompanying smartphone app for visual diagnosis.
- Jon Arizti-Sanz
- , Catherine A. Freije
- & Cameron Myhrvold
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| Open Access
Low SARS-CoV-2 seroprevalence in blood donors in the early COVID-19 epidemic in the Netherlands
The Netherlands is a country highly affected by the COVID-19 pandemic. In this study, Slot, Hogema and colleagues report a low SARS-CoV-2 seroprevalence one month into the outbreak and provide insights into virus exposure by region and age group when widespread non-pharmaceutical interventions are in place.
- Ed Slot
- , Boris M. Hogema
- & Hans L. Zaaijer
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A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation
Neutralizing antibody titers in SARS-CoV-2 infected or vaccinated people are an important measure for vaccine development and public health decision-making. Here, the authors develop a fluorescence based SARS-CoV-2 assay to determine neutralizing antibody titers in COVID-19 patient sera in a high throughput set-up.
- Antonio E. Muruato
- , Camila R. Fontes-Garfias
- & Pei-Yong Shi
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Article
| Open Access
Development of CRISPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria
CRISPR technology is emerging as a potential antimicrobial against antimicrobial-resistant bacteria. Here the authors develop a bacteriophage delivered Cas13a system for killing target bacteria and detecting bacterial genes.
- Kotaro Kiga
- , Xin-Ee Tan
- & Longzhu Cui
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Article
| Open Access
Plasmid-mediated metronidazole resistance in Clostridioides difficile
Cases of C. difficile (CD) resistant to metronidazole have been reported but the mechanism remains enigmatic. Here the authors identify a plasmid, which correlates with metronidazole resistance status in a large international collection of CD isolates, and demonstrate that the plasmid can confer metronidazole resistance.
- Ilse M. Boekhoud
- , Bastian V. H. Hornung
- & Wiep Klaas Smits
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Article
| Open Access
Sensitive detection of a bacterial pathogen using allosteric probe-initiated catalysis and CRISPR-Cas13a amplification reaction
The detection of pathogens in food and clinical samples remains a challenge. Here, Shen et al. present a detection system, involving a combination of nucleic acid-based allosteric probes and CRISPR-Cas13a components, that can detect very low numbers of a bacterial pathogen in milk and serum samples without isolation.
- Jinjin Shen
- , Xiaoming Zhou
- & Da Xing
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Article
| Open Access
Molecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections
Necrotizing soft tissue infections (NSTIs) are caused by a single pathogen such as Streptococcus pyogenes or by multiple bacterial species. Here, the authors integrate microbial community profiling with host and pathogen transcriptional analysis in patient biopsies, and identify an interferon-related signature specific to S. pyogenes NSTIs.
- Robert Thänert
- , Andreas Itzek
- & Dietmar H. Pieper
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Article
| Open Access
Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection
Identification of host factors associated with severe influenza infection could provide insights into treatment options. Here, the authors provide transcriptomic analyses of blood from >100 influenza infected patients and show that changes in circulating neutrophils are associated with severe influenza infection.
- Benjamin M. Tang
- , Maryam Shojaei
- & Klaus Schughart
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Article
| Open Access
FDA-ARGOS is a database with public quality-controlled reference genomes for diagnostic use and regulatory science
To be able to use infectious disease next generation sequencing as a diagnostic tool, appropriate reference datasets are required. Here, Sichtig et al. describe FDA-ARGOS, a reference database for high-quality microbial reference genomes, and demonstrate its utility on the example of two use cases.
- Heike Sichtig
- , Timothy Minogue
- & Uwe Scherf
Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children