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1.
J Clin Microbiol ; 59(6)2021 05 19.
Article in English | MEDLINE | ID: covidwho-1511414

ABSTRACT

The threat posed by novel pandemics in the future remains active. Equipping our routine laboratory with clinical metagenomics to detect unknown threats early on offers a considerable advantage and may be feasible and scalable with the ability to identify complicated infectious diseases in routine care. Though several technical and regulatory challenges still exist, clinical metagenomics may improve individual patient outcomes and provide earlier warning signs to improve pandemic preparedness.


Subject(s)
Communicable Diseases , Influenza, Human , Communicable Diseases/diagnosis , Communicable Diseases/epidemiology , Humans , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Metagenomics , Pandemics
2.
J Clin Microbiol ; 59(10): e0236020, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1486498

ABSTRACT

Efforts to control transmissible infectious diseases rely on the ability to screen large populations, ideally in community settings. These efforts can be limited by the requirement for invasive or logistically difficult collection of patient samples, such as blood, urine, stool, sputum, and nasopharyngeal swabs. Oral sampling is an appealing, noninvasive alternative that could greatly facilitate high-throughput sampling in community settings. Oral sampling has been described for the detection of dozens of human pathogens, including pathogens whose primary sites of infection are outside of the oral cavity, such as the respiratory pathogens Mycobacterium tuberculosis and SARS-CoV-2. Oral sampling can demonstrate active infections as well as resolving or previous infections, the latter through the detection of antibodies. Its potential applications are diverse, including improved diagnosis in special populations (e.g., children), population surveillance, and infectious disease screening. In this minireview, we address the use of oral samples for the detection of diseases that primarily manifest outside the oral cavity. Focusing on well-supported examples, we describe applications for such methods and highlight their potential advantages and limitations in medicine, public health, and research.


Subject(s)
COVID-19 , Communicable Diseases , Child , Communicable Diseases/diagnosis , Humans , SARS-CoV-2 , Specimen Handling , Sputum
3.
PLoS One ; 16(6): e0252803, 2021.
Article in English | MEDLINE | ID: covidwho-1453123

ABSTRACT

A variety of infectious diseases occur in mainland China every year. Cyclic oscillation is a widespread attribute of most viral human infections. Understanding the outbreak cycle of infectious diseases can be conducive for public health management and disease surveillance. In this study, we collected time-series data for 23 class B notifiable infectious diseases from 2004 to 2020 using public datasets from the National Health Commission of China. Oscillatory properties were explored using power spectrum analysis. We found that the 23 class B diseases from the dataset have obvious oscillatory patterns (seasonal or sporadic), which could be divided into three categories according to their oscillatory power in different frequencies each year. These diseases were found to have different preferred outbreak months and infection selectivity. Diseases that break out in autumn and winter are more selective. Furthermore, we calculated the oscillation power and the average number of infected cases of all 23 diseases in the first eight years (2004 to 2012) and the next eight years (2012 to 2020) since the update of the surveillance system. A strong positive correlation was found between the change of oscillation power and the change in the number of infected cases, which was consistent with the simulation results using a conceptual hybrid model. The establishment of reliable and effective analytical methods contributes to a better understanding of infectious diseases' oscillation cycle characteristics. Our research has certain guiding significance for the effective prevention and control of class B infectious diseases.


Subject(s)
Algorithms , Communicable Diseases/epidemiology , Disease Outbreaks , Models, Theoretical , Seasons , China/epidemiology , Communicable Diseases/classification , Communicable Diseases/diagnosis , Humans , Incidence , Infection Control/methods , Infection Control/statistics & numerical data , Population Surveillance/methods , Public Health/methods , Public Health/statistics & numerical data
4.
BMJ Mil Health ; 166(1): 37-41, 2020 Feb.
Article in English | MEDLINE | ID: covidwho-1452951

ABSTRACT

Major disease outbreaks continue to be a significant risk to public health, with pandemic influenza or an emerging infectious disease outbreak at the top of the UK National Risk Register. The risk of deliberate release of a biological agent is lower but remains possible and may only be recognised after casualties seek medical attention. In this context the emergency preparedness, resilience and response (EPRR) process protects the public from high consequence infectious diseases, other infectious disease outbreaks and biological agent release. The core elements of the EPRR response are recognition of an outbreak, isolation of patients, appropriate personal protective equipment for medical staff and actions to minimise further disease spread. The paper discusses how high-threat agents may be recognised by clinicians, the initial actions to be taken on presentation and how the public health system is notified and responds. It draws on the national pandemic influenza plans to describe the wider response to a major disease outbreak and discusses training requirements and the potential role of the military.


Subject(s)
Biohazard Release , Civil Defense , Influenza, Human/prevention & control , Military Personnel , Pandemics/prevention & control , Public Health Practice , Biohazard Release/prevention & control , Civil Defense/education , Communicable Disease Control , Communicable Diseases/diagnosis , Disaster Planning , Disease Notification , Humans , Influenza, Human/therapy , Interinstitutional Relations , Patient Isolation , Personal Protective Equipment , United Kingdom
5.
Front Public Health ; 9: 659695, 2021.
Article in English | MEDLINE | ID: covidwho-1441153

ABSTRACT

The current COVID-19 pandemic demonstrates the need for urgent and on-demand solutions to provide diagnostics, treatment and preventative measures for infectious disease outbreaks. Once solutions are developed, meeting capacities depends on the ability to mitigate technical, logistical and production issues. While it is difficult to predict the next outbreak, augmenting investments in preparedness, such as infectious disease surveillance, is far more effective than mustering last-minute response funds. Bringing research outputs into practice sooner rather than later is part of an agile approach to pivot and deliver solutions. Cooperative multi- country research programs, especially those funded by global biosecurity programs, develop capacity that can be applied to infectious disease surveillance and research that enhances detection, identification, and response to emerging and re-emerging pathogens with epidemic or pandemic potential. Moreover, these programs enhance trust building among partners, which is essential because setting expectation and commitment are required for successful research and training. Measuring research outputs, evaluating outcomes and justifying continual investments are essential but not straightforward. Lessons learned include those related to reducing biological threats and maturing capabilities for national laboratory diagnostics strategy and related health systems. Challenges, such as growing networks, promoting scientific transparency, data and material sharing, sustaining funds and developing research strategies remain to be fully resolved. Here, experiences from several programs highlight successful partnerships that provide ways forward to address the next outbreak.


Subject(s)
COVID-19 , Communicable Diseases , Communicable Diseases/diagnosis , Disease Outbreaks/prevention & control , Humans , Pandemics , SARS-CoV-2
7.
Molecules ; 26(18)2021 Sep 18.
Article in English | MEDLINE | ID: covidwho-1430926

ABSTRACT

Sample preparation is an essential step for nearly every type of biochemical analysis in use today. Among the most important of these analyses is the diagnosis of diseases, since their treatment may rely greatly on time and, in the case of infectious diseases, containing their spread within a population to prevent outbreaks. To address this, many different methods have been developed for use in the wide variety of settings for which they are needed. In this work, we have reviewed the literature and report on a broad range of methods that have been developed in recent years and their applications to point-of-care (POC), high-throughput screening, and low-resource and traditional clinical settings for diagnosis, including some of those that were developed in response to the coronavirus disease 2019 (COVID-19) pandemic. In addition to covering alternative approaches and improvements to traditional sample preparation techniques such as extractions and separations, techniques that have been developed with focuses on integration with smart devices, laboratory automation, and biosensors are also discussed.


Subject(s)
High-Throughput Screening Assays/methods , Specimen Handling/methods , Biosensing Techniques/methods , COVID-19 , Communicable Diseases/diagnosis , High-Throughput Screening Assays/trends , Humans , Pandemics/prevention & control , Point-of-Care Systems/trends , Point-of-Care Testing/trends , SARS-CoV-2
8.
J Med Internet Res ; 23(10): e32328, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1430628

ABSTRACT

BACKGROUND: The COVID-19 pandemic has increased the importance of the deployment of digital detection surveillance systems to support early warning and monitoring of infectious diseases. These opportunities create a "double-edge sword," as the ethical governance of such approaches often lags behind technological achievements. OBJECTIVE: The aim was to investigate ethical issues identified from utilizing artificial intelligence-augmented surveillance or early warning systems to monitor and detect common or novel infectious disease outbreaks. METHODS: In a number of databases, we searched relevant articles that addressed ethical issues of using artificial intelligence, digital surveillance systems, early warning systems, and/or big data analytics technology for detecting, monitoring, or tracing infectious diseases according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and further identified and analyzed them with a theoretical framework. RESULTS: This systematic review identified 29 articles presented in 6 major themes clustered under individual, organizational, and societal levels, including awareness of implementing digital surveillance, digital integrity, trust, privacy and confidentiality, civil rights, and governance. While these measures were understandable during a pandemic, the public had concerns about receiving inadequate information; unclear governance frameworks; and lack of privacy protection, data integrity, and autonomy when utilizing infectious disease digital surveillance. The barriers to engagement could widen existing health care disparities or digital divides by underrepresenting vulnerable and at-risk populations, and patients' highly sensitive data, such as their movements and contacts, could be exposed to outside sources, impinging significantly upon basic human and civil rights. CONCLUSIONS: Our findings inform ethical considerations for service delivery models for medical practitioners and policymakers involved in the use of digital surveillance for infectious disease spread, and provide a basis for a global governance structure. TRIAL REGISTRATION: PROSPERO CRD42021259180; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259180.


Subject(s)
COVID-19 , Communicable Diseases , Artificial Intelligence , Communicable Diseases/diagnosis , Communicable Diseases/epidemiology , Humans , Pandemics , SARS-CoV-2
9.
Theranostics ; 11(18): 9133-9161, 2021.
Article in English | MEDLINE | ID: covidwho-1410987

ABSTRACT

During an epidemic or pandemic, the primary task is to rapidly develop precise diagnostic approaches and effective therapeutics. Oligonucleotide aptamer-based pathogen detection assays and control therapeutics are promising, as aptamers that specifically recognize and block pathogens can be quickly developed and produced through simple chemical synthesis. This work reviews common aptamer-based diagnostic techniques for communicable diseases and summarizes currently available aptamers that target various pathogens, including the SARS-CoV-2 virus. Moreover, this review discusses how oligonucleotide aptamers might be leveraged to control pathogen propagation and improve host immune system responses. This review offers a comprehensive data source to the further develop aptamer-based diagnostics and therapeutics specific for infectious diseases.


Subject(s)
Aptamers, Nucleotide , Bacteria/genetics , Communicable Diseases/diagnosis , Molecular Diagnostic Techniques/methods , Viruses/genetics , Aptamers, Nucleotide/pharmacology , Biosensing Techniques , COVID-19 Testing/methods , Communicable Disease Control , Communicable Diseases/microbiology , Communicable Diseases/virology , Enzyme-Linked Immunosorbent Assay/methods , Host-Pathogen Interactions/immunology , Humans , SELEX Aptamer Technique , Virus Internalization
10.
ACS Biomater Sci Eng ; 7(5): 1722-1724, 2021 05 10.
Article in English | MEDLINE | ID: covidwho-1408220
11.
Sci Rep ; 11(1): 18108, 2021 09 13.
Article in English | MEDLINE | ID: covidwho-1406409

ABSTRACT

The progress of the SARS-CoV-2 pandemic requires the design of large-scale, cost-effective testing programs. Pooling samples provides a solution if the tests are sensitive enough. In this regard, the use of the gold standard, RT-qPCR, raises some concerns. Recently, droplet digital PCR (ddPCR) was shown to be 10-100 times more sensitive than RT-qPCR, making it more suitable for pooling. Furthermore, ddPCR quantifies the RNA content directly, a feature that, as we show, can be used to identify nonviable samples in pools. Cost-effective strategies require the definition of efficient deconvolution and re-testing procedures. In this paper we analyze the practical implementation of an efficient hierarchical pooling strategy for which we have recently derived the optimal, determining the best ways to proceed when there are impediments for the use of the absolute optimum or when multiple pools are tested simultaneously and there are restrictions on the throughput time. We also show how the ddPCR RNA quantification and the nested nature of the strategy can be combined to perform self-consistency tests for a better identification of infected individuals and nonviable samples. The studies are useful to those considering pool testing for the identification of infected individuals.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Diagnostic Tests, Routine/methods , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , Algorithms , COVID-19/epidemiology , COVID-19/virology , Communicable Diseases/diagnosis , Communicable Diseases/virology , Humans , Models, Genetic , Pandemics , RNA, Viral/genetics , Reproducibility of Results , SARS-CoV-2/physiology , Sensitivity and Specificity , Specimen Handling/methods
13.
Infection ; 49(3): 377-385, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1384709

ABSTRACT

PURPOSE: CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases. METHODS: We searched Pubmed and Google Scholar for CRISPR-based strategies in the diagnosis and treatment of infectious diseases. Reference lists were reviewed and synthesized for narrative review. RESULTS: CRISPR-based strategies represent a novel approach to many challenging infectious diseases. CRISPR technologies can be harnessed to create rapid, low-cost diagnostic systems, as well as to identify drug-resistance genes. Therapeutic strategies, such as CRISPR systems that cleave integrated viral genomes or that target resistant bacteria, are in development. CRISPR-based therapies for emerging viruses, such as SARS-CoV-2, have also been proposed. Finally, CRISPR systems can be used to reprogram human B cells to produce neutralizing antibodies. The risks of CRISPR-based therapies include off-target and on-target modifications. Strategies to control these risks are being developed and a phase 1 clinical trials of CRISPR-based therapies for cancer and monogenic diseases are already underway. CONCLUSIONS: CRISPR systems have broad applicability in the field of infectious diseases and may offer solutions to many of the most challenging human infections.


Subject(s)
CRISPR-Cas Systems , Communicable Diseases/diagnosis , Communicable Diseases/therapy , Animals , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/pathogenicity , Gene Editing , Humans , Molecular Diagnostic Techniques , Molecular Targeted Therapy , Viruses/genetics , Viruses/isolation & purification , Viruses/pathogenicity
14.
J Mater Chem B ; 9(38): 7878-7908, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1373457

ABSTRACT

Infectious diseases caused by bacteria, viruses, and fungi and their global spread pose a great threat to human health. The 2019 World Health Organization report predicted that infection-related mortality will be similar to cancer mortality by 2050. Particularly, the global cumulative numbers of the recent outbreak of coronavirus disease (COVID-19) have reached 110.7 million cases and over 2.4 million deaths as of February 23, 2021. Moreover, the crisis of these infectious diseases exposes the many problems of traditional diagnosis, treatment, and prevention, such as time-consuming and unselective detection methods, the emergence of drug-resistant bacteria, serious side effects, and poor drug delivery. There is an urgent need for rapid and sensitive diagnosis as well as high efficacy and low toxicity treatments. The emergence of nanomedicine has provided a promising strategy to greatly enhance detection methods and drug treatment efficacy. Owing to their unique optical, magnetic, and electrical properties, nanoparticles (NPs) have great potential for the fast and selective detection of bacteria, viruses, and fungi. NPs exhibit remarkable antibacterial activity by releasing reactive oxygen species and metal ions, exerting photothermal effects, and causing destruction of the cell membrane. Nano-based delivery systems can further improve drug permeability, reduce the side effects of drugs, and prolong systemic circulation time and drug half-life. Moreover, effective drugs against COVID-19 are still lacking. Recently, nanomedicine has shown great potential to accelerate the development of safe and novel anti-COVID-19 drugs. This article reviews the fundamental mechanisms and the latest developments in the treatment and diagnosis of bacteria, viruses, and fungi and discusses the challenges and perspectives in the application of nanomedicine.


Subject(s)
Anti-Infective Agents/therapeutic use , Communicable Diseases/drug therapy , Nanomedicine , Anti-Infective Agents/chemistry , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Communicable Diseases/diagnosis , Communicable Diseases/microbiology , Communicable Diseases/virology , Drug Carriers/chemistry , Humans , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification
15.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Article in English | MEDLINE | ID: covidwho-1371647

ABSTRACT

Epidemic preparedness depends on our ability to predict the trajectory of an epidemic and the human behavior that drives spread in the event of an outbreak. Changes to behavior during an outbreak limit the reliability of syndromic surveillance using large-scale data sources, such as online social media or search behavior, which could otherwise supplement healthcare-based outbreak-prediction methods. Here, we measure behavior change reflected in mobile-phone call-detail records (CDRs), a source of passively collected real-time behavioral information, using an anonymously linked dataset of cell-phone users and their date of influenza-like illness diagnosis during the 2009 H1N1v pandemic. We demonstrate that mobile-phone use during illness differs measurably from routine behavior: Diagnosed individuals exhibit less movement than normal (1.1 to 1.4 fewer unique tower locations; [Formula: see text]), on average, in the 2 to 4 d around diagnosis and place fewer calls (2.3 to 3.3 fewer calls; [Formula: see text]) while spending longer on the phone (41- to 66-s average increase; [Formula: see text]) than usual on the day following diagnosis. The results suggest that anonymously linked CDRs and health data may be sufficiently granular to augment epidemic surveillance efforts and that infectious disease-modeling efforts lacking explicit behavior-change mechanisms need to be revisited.


Subject(s)
Behavior , Cell Phone , Communicable Diseases/epidemiology , Cell Phone Use , Communicable Diseases/diagnosis , Geography , Humans , Iceland/epidemiology , Information Dissemination , Movement , Privacy
18.
Clin Lab Med ; 41(2): 185-202, 2021 06.
Article in English | MEDLINE | ID: covidwho-1232935

ABSTRACT

Various analytical methods can be applied to concentrate, separate, and examine trace volatile organic metabolites in the breath, with the potential for noninvasive, rapid, real-time identification of various disease processes, including an array of microbial infections. Although biomarker discovery and validation in microbial infections can be technically challenging, it is an approach that has shown great promise, especially for infections that are particularly difficult to identify with standard culture and molecular amplification-based approaches. This article discusses the current state of breath analysis for the diagnosis of infectious diseases.


Subject(s)
Communicable Diseases , Volatile Organic Compounds , Breath Tests , Communicable Diseases/diagnosis , Humans
19.
Nat Biomed Eng ; 5(7): 643-656, 2021 07.
Article in English | MEDLINE | ID: covidwho-1324420

ABSTRACT

The accurate and timely diagnosis of disease is a prerequisite for efficient therapeutic intervention and epidemiological surveillance. Diagnostics based on the detection of nucleic acids are among the most sensitive and specific, yet most such assays require costly equipment and trained personnel. Recent developments in diagnostic technologies, in particular those leveraging clustered regularly interspaced short palindromic repeats (CRISPR), aim to enable accurate testing at home, at the point of care and in the field. In this Review, we provide a rundown of the rapidly expanding toolbox for CRISPR-based diagnostics, in particular the various assays, preamplification strategies and readouts, and highlight their main applications in the sensing of a wide range of molecular targets relevant to human health.


Subject(s)
CRISPR-Cas Systems/genetics , Communicable Diseases/diagnosis , Nucleic Acid Amplification Techniques/methods , Nucleic Acids/analysis , Communicable Diseases/microbiology , Communicable Diseases/virology , Genetic Diseases, Inborn/diagnosis , Humans , Nucleic Acid Amplification Techniques/economics , Nucleic Acids/metabolism , Point-of-Care Systems , Polymorphism, Single Nucleotide , Sequence Analysis, DNA
20.
Front Cell Infect Microbiol ; 11: 697876, 2021.
Article in English | MEDLINE | ID: covidwho-1325516

ABSTRACT

Antibodies are essential molecules for diagnosis and treatment of diseases caused by pathogens and their toxins. Antibodies were integrated in our medical repertoire against infectious diseases more than hundred years ago by using animal sera to treat tetanus and diphtheria. In these days, most developed therapeutic antibodies target cancer or autoimmune diseases. The COVID-19 pandemic was a reminder about the importance of antibodies for therapy against infectious diseases. While monoclonal antibodies could be generated by hybridoma technology since the 70ies of the former century, nowadays antibody phage display, among other display technologies, is robustly established to discover new human monoclonal antibodies. Phage display is an in vitro technology which confers the potential for generating antibodies from universal libraries against any conceivable molecule of sufficient size and omits the limitations of the immune systems. If convalescent patients or immunized/infected animals are available, it is possible to construct immune phage display libraries to select in vivo affinity-matured antibodies. A further advantage is the availability of the DNA sequence encoding the phage displayed antibody fragment, which is packaged in the phage particles. Therefore, the selected antibody fragments can be rapidly further engineered in any needed antibody format according to the requirements of the final application. In this review, we present an overview of phage display derived recombinant antibodies against bacterial, viral and eukaryotic pathogens, as well as microbial toxins, intended for diagnostic and therapeutic applications.


Subject(s)
Bacteriophages , COVID-19 , Communicable Diseases , Animals , Antibodies, Monoclonal , Communicable Diseases/diagnosis , Communicable Diseases/therapy , Humans , Pandemics , SARS-CoV-2
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