Identification of Early Warning Signals of Infectious Diseases in Hospitals by Integrating Clinical Treatment and Disease Prevention.

The global incidence of infectious diseases has increased in recent years, posing a significant threat to human health. Hospitals typically serve as frontline institutions for detecting infectious diseases. However, accurately identifying warning signals of infectious diseases in a timely manner, especially emerging infectious diseases, can be challenging. Consequently, there is a pressing need to integrate treatment and disease prevention data to conduct comprehensive analyses aimed at preventing and controlling infectious diseases within hospitals. This paper examines the role of medical data in the early identification of infectious diseases, explores early warning technologies for infectious disease recognition, and assesses monitoring and early warning mechanisms for infectious diseases. We propose that hospitals adopt novel multidimensional early warning technologies to mine and analyze medical data from various systems, in compliance with national strategies to integrate clinical treatment and disease prevention. Furthermore, hospitals should establish institution-specific, clinical-based early warning models for infectious diseases to actively monitor early signals and enhance preparedness for infectious disease prevention and control.

Effectiveness of metagenomic next-generation sequencing in the diagnosis of infectious diseases: A systematic review and meta-analysis.

OBJECTIVES: Early diagnosis of infectious diseases remains a challenge. This study assessed the diagnostic value of mNGS in infections and explored the effect of various factors on the accuracy of mNGS. METHODS: An electronic article search of PubMed, Cochrane Library, and Embase was performed. A total of 85 papers were eligible for inclusion and analysis. Stata 12.0 was used for statistical calculation to evaluate the efficacy of mNGS for the diagnosis of infectious diseases. RESULTS: The AUC of 85 studies was 0.88 (95%CI, 0.85-0.90). The AUC of the clinical comprehensive diagnosis and conventional test groups was 0.92 (95%CI, 0.89-0.94) and 0.82 (95%CI, 0.78-0.85), respectively. The results of subgroup analysis indicated that the PLR and NLR were 12.67 (95%CI, 6.01-26.70) and 0.05 (95%CI, 0.03-0.10), respectively, in arthrosis infections. The PLR was 24.41 (95%CI, 5.70-104.58) in central system infections and the NLR of immunocompromised patients was 0.08 (95%CI, 0.01-0.62). CONCLUSION: mNGS demonstrated satisfactory diagnostic performance for infections, especially for bone and joint infections and central system infections. Moreover, mNGS also has a high value in the exclusion of infection in immunocompromised patients.

Enhancing Clinical Utility: Utilization of International Standards and Guidelines for Metagenomic Sequencing in Infectious Disease Diagnosis.

Metagenomic sequencing has emerged as a transformative tool in infectious disease diagnosis, offering a comprehensive and unbiased approach to pathogen detection. Leveraging international standards and guidelines is essential for ensuring the quality and reliability of metagenomic sequencing in clinical practice. This review explores the implications of international standards and guidelines for the application of metagenomic sequencing in infectious disease diagnosis. By adhering to established standards, such as those outlined by regulatory bodies and expert consensus, healthcare providers can enhance the accuracy and clinical utility of metagenomic sequencing. The integration of international standards and guidelines into metagenomic sequencing workflows can streamline diagnostic processes, improve pathogen identification, and optimize patient care. Strategies in implementing these standards for infectious disease diagnosis using metagenomic sequencing are discussed, highlighting the importance of standardized approaches in advancing precision infectious disease diagnosis initiatives.

CRISPR-Cas12/Cas13: Bibliometric analysis and systematic review of its application in infectious disease detection.

BACKGROUND: Infectious diseases impose a significant burden on the global public health and economy, resulting in an estimated 15 million deaths out of 57 million annually worldwide. This study examines the current state of CRISPR-Cas12/Cas13 research, focusing on its applications in infectious disease detection and its evolutionary trajectory. METHODS: A bibliometric analysis and systematic review were conducted by retrieving CRISPR-Cas12/Cas13-related articles published between January 1, 2015 to December 31, 2022, from the Web of Science database. The research protocol was registered with International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202380062). RESULTS: Our search identified 1987 articles, of which, 1856 were included in the bibliometric analysis and 445 were used in qualitative analysis. The study reveals a substantial increase in scientific production on CRISPR-Cas12/Cas13, with an annual growth rate of 104.5%. The United States leads in the number of published articles. The systematic review identified 580 different diagnostic assays targeting 170 pathogens, with SARS-CoV-2 dominating with 158 assays. Recombinase polymerase amplification (RPA)/reverse transcription-RPA (RT-RPA) emerged as the predominant amplification method, while lateral flow assay was the most common readout method. Approximately 72% of the diagnostic assays developed are suitable for point-of-care testing. CONCLUSION: The rapid increase in research on CRISPR-Cas12/Cas13 between 2015 and 2022 suggests promising potential for advancements in infectious disease diagnosis. Given the numerous advantages of CRISPR-Cas technology for disease detection over other methods, and the dedicated efforts of scientists from around the world, it is reasonable to anticipate that CRISPR-Cas technology may emerge as a formidable alternative, offering the possibility of expedited point-of-care testing in the not-too-distant future.

Infectious Diseases in a Changing Climate.

This JAMA Insights in the Climate Change and Health series discusses the importance of clinicians having awareness of changes in the geographic range, seasonality, and intensity of transmission of infectious diseases to help them diagnose, treat, and prevent these diseases.

Nanotechnology's frontier in combatting infectious and inflammatory diseases: prevention and treatment.

Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases, which continuously pose one of the most serious threats to human health, attributed to factors such as the emergence of new pathogens, increasing drug resistance, changes in living environments and lifestyles, and the aging population. Despite rapid advancements in mechanistic research and drug development for these diseases, current treatments often have limited efficacy and notable side effects, necessitating the development of more effective and targeted anti-inflammatory therapies. In recent years, the rapid development of nanotechnology has provided crucial technological support for the prevention, treatment, and detection of inflammation-associated diseases. Various types of nanoparticles (NPs) play significant roles, serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability. NPs can also directly combat pathogens and inflammation. In addition, nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases. This review categorizes and characterizes different types of NPs, summarizes their applications in the prevention, treatment, and detection of infectious and inflammatory diseases. It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects. In conclusion, nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.

[Interests of clinical metagenomic in infectious diseases]. / Intérêts de la métagénomique clinique en infectiologie.

INTERESTS OF CLINICAL METAGENOMICS IN INFECTIOUS DISEASES. Clinical metagenomics (CM) is a cutting-edge molecular biology technique that is now a valuable diagnostic tool for microbiologists. It enables the detection of all microorganisms present in a sample, without any prior assumption or bias. The CM approach can be applied to various types of samples and involves multiple steps, such as extraction, library preparation, Next Generation Sequencing, and bioinformatics analysis. CM has been implemented in the diagnosis of various conditions, including infections of the central nervous system, respiratory, digestive, ocular, skin infection, and sepsis. Moreover, CM provides a comprehensive analysis of the microbiome present in the sample, microbial transcripts, and the host response in a single analysis. However, further studies are necessary to determine its place in the diagnostic algorithm. Besides diagnosis, CM has proven useful in identifying resistance to antimicrobial treatments and in epidemiology. Although the cost of CM is still higher than conventional methods, the emergence of more affordable sequencers and commercial tests will enable its implementation in a larger number of laboratories in the future.

INTÉRÊTS DE LA MÉTAGÉNOMIQUE CLINIQUE EN INFECTIOLOGIE. La métagénomique clinique (MgC) est un nouvel outil de biologie moléculaire dans l'arsenal diagnostique des microbiologistes. Elle permet de détecter sans a priori tous les micro-organismes présents. Utilisable sur tous types de prélèvements, elle nécessite plusieurs étapes (extraction, préparation des banques, séquençage par next generation sequencing, analyses bio-informatiques). Son utilisation en diagnostic a été décrite dans différentes pathologies (infections du système nerveux central, infections respiratoires, digestives, oculaires, cutanées et en cas de sepsis). En une seule analyse, la MgC permet également d'étudier le microbiome présent dans le prélèvement, d'analyser les transcrits microbiens et d'étudier la réponse de l'hôte. Sa place dans l'algorithme diagnostique doit faire l'objet d'études supplémentaires. En sus du diagnostic, la MgC a démontré son utilité dans la recherche de résistance aux traitements antimicrobiens, mais également en épidémiologie. Malgré les progrès visant à réduire les coûts, la MgC reste encore à l'heure actuelle plus coûteuse que les méthodes conventionnelles. La mise sur le marché de séquenceurs plus accessibles ainsi que le développement de tests commerciaux permettront l'utilisation de la MgC dans un plus grand nombre de laboratoires dans les années futures.

External Validation of the 2023 Duke-International Society for Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis.

BACKGROUND: The 2023 Duke-International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) were introduced to improve classification of IE for research and clinical purposes. External validation studies are required. METHODS: We studied consecutive patients with suspected IE referred to the IE team of Amsterdam University Medical Center (from October 2016 to March 2021). An international expert panel independently reviewed case summaries and assigned a final diagnosis of "IE" or "not IE," which served as the reference standard, to which the "definite" Duke-ISCVID classifications were compared. We also evaluated accuracy when excluding cardiac surgical and pathologic data ("clinical" criteria). Finally, we compared the 2023 Duke-ISCVID with the 2000 modified Duke criteria and the 2015 and 2023 European Society of Cardiology (ESC) criteria. RESULTS: A total of 595 consecutive patients with suspected IE were included: 399 (67%) were adjudicated as having IE; 111 (19%) had prosthetic valve IE, and 48 (8%) had a cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than either the modified Duke or 2015 ESC criteria (84.2% vs 74.9% and 80%, respectively; P < .001) without significant loss of specificity. The 2023 Duke-ISCVID criteria were similarly sensitive but more specific than the 2023 ESC criteria (94% vs 82%; P < .001). The same pattern was seen for the clinical criteria (excluding surgical/pathologic results). New modifications in the 2023 Duke-ISCVID criteria related to "major microbiological" and "imaging" criteria had the most impact. CONCLUSIONS: The 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients with suspected IE.

Microfluidics as diagnostic tools.

The challenges in the management of human diseases are largely determined by the precision, speed and ease of diagnostic procedures available. Developments in biomedical engineering technologies have greatly helped in transforming human health care, especially for disease diagnosis which in turn lead to better patient outcomes. One such development is in the form of microfluidic chip technology which has transformed various aspects of human health care. We present in this review, a comprehensive account on the utility of microfluidic chip technologies for the diagnosis of autoimmune disorders, cardiovascular diseases (CVDs), infectious diseases, and neurodegenerative conditions. We have included the diseases posing global threat such as rheumatoid arthritis, diabetes, pernicious anemia, tuberculosis, COVID-19, influenza, alzheimer's, multiple sclerosis, and epilepsy. Apart from discussing the ways of microfluidic chip in diagnosis, we included a section presenting electrochemical, electrical, optical, and acoustic detection technologies for the precise diagnosis of CVDs. Microfluidics platforms have thus revolutionized novel capabilities in addressing the requirements of point-of-care diagnostics enabling miniaturization by integrating multiple laboratory functions into a single chip resulting in "one flow - one solution" systems. Hence, the precision and early diagnoses of diseases are now possible due to the advancements of microfluidics-based technology.

The development of droplet-based microfluidic virus detection technology for human infectious diseases.

Virus-based human infectious diseases have a significant negative impact on people's health and social development. The need for quick, accurate, and early viral infection detection in preventive medicine is expanding. A microfluidic control is particularly suitable for point-of-care-testing virus diagnosis due to its advantages of low sample consumption, quick detection speed, simple operation, multi-functional integration, small size, and easy portability. It is also thought to have significant development potential and a wide range of application prospects in the research on virus detection technology. In an effort to aid researchers in creating novel microfluidic tools for virus detection, this review highlights recent developments of droplet-based microfluidics in virus detection research and also discusses the challenges and opportunities for rapid virus detection.

[Emergencies in infectious diseases]. / Infektiologische Notfälle.

This article aims to provide an overview of common and high-impact medical emergencies that require prompt and effective infectious diseases management. In the described clinical scenarios of malaria, sepsis, necrotizing fasciitis, and meningitis the authors have emphasized the crucial importance of rapid and accurate diagnosis, as well as appropriate treatment from the perspective of infectious diseases. All of these emergencies demand a high degree of clinical suspicion for accurate diagnosis. Some of them also necessitate the involvement of other medical disciplines, such as neurology in the case of meningitis or surgery for necrotizing fasciitis. Additionally, implementing the right empiric antibiotic regimen or, in the case of malaria, antiparasitic treatment is crucial for improving patient outcomes. As patients with these diagnoses may present at any outpatient department, and efficient and quick management is essential, a deep understanding of diagnostic algorithms and potential pitfalls is of the utmost importance.

Systematic Review of Scales for Measuring Infectious Disease-Related Stigma.

Infectious disease outbreaks are associated with substantial stigma, which can have negative effects on affected persons and communities and on outbreak control. Thus, measuring stigma in a standardized and validated manner early in an outbreak is critical to disease control. We reviewed existing scales used to assess stigma during outbreaks. Our findings show that many different scales have been developed, but few have been used more than once, have been adequately validated, or have been tested in different disease and geographic contexts. We found that scales were usually developed too slowly to be informative early during an outbreak and were published a median of 2 years after the first case of an outbreak. A rigorously developed, transferable stigma scale is needed to assess and direct responses to stigma during infectious disease outbreaks.

Improving diagnostic accuracy of blood culture-positive cases in a cancer center via an antimicrobial stewardship program and infectious disease consultations.

The direct impact of antimicrobial stewardship programs (ASP) and infectious disease (ID) consultations on patients' clinical diagnoses remains unknown. We assessed their influence on improving the diagnostic accuracy of blood culture-positive inpatients at a Japanese cancer center. Our single-center, retrospective observational study was conducted from April 1, 2018 to March 31, 2022 to evaluate two phases: pre-intervention (notification of antimicrobials by the infection control team) and post-intervention (ASP implementation and ID consultation service establishment). There were 42,514 inpatients: 22,096 during the pre-intervention and 20,418 during the intervention periods. A total of 939 blood culture-positive episodes (pre-intervention, n = 434; post-intervention, n = 505) were analyzed. During the pre-intervention period, 28.1% of the patients had an unknown diagnosis, which decreased significantly to 1.2% post-intervention. Furthermore, hepatobiliary tract and other infections increased significantly post-intervention, and the mortality rate due to Staphylococcus aureus infection decreased from 28.6% pre-intervention to 10.4% post-intervention. The trend and level of the total number of culture specimens submitted per 1000 patient days for all culture specimens increased significantly post-intervention. Notably, the two-set rate of monthly blood cultures increased significantly. In conclusion, improving the overall diagnostic process with ASP and ID consultations at cancer centers could lead to the optimization of patient care.

[Diagnostic stewardship in outpatient and hospital medicine with focus on microbiological urinary and bloodstream diagnostics]. / Diagnostic Stewardship in Klinik und Praxis mit Fokus auf die mikrobiologische Harnwegs- und Blutstromdiagnostik.

Targeted infection diagnosis supports decision-making in the rational use of antibiotics usually encompassed as Antibiotic Stewardship (ABS). Similar to ABS, the term "Diagnostic Stewardship" (DGS) is suggested, whereas DGS includes, beneath general, predominantly microbiological infection diagnostics - with specific pathogen detection, conventional via culture or immunology, increasingly also using molecular biological methods. Especially in microbiology, pre-analytics, analytics and post-analytics play an essential role. Pathogen characterization is accompanied by an antimicrobial susceptibility test (with S-I-R classification), which deserves special attention, especially in the context of ABS. All of these aspects are dealt with in this work and represented using two practical examples of urinary and bloodstream diagnostics that are relevant for outpatients and inpatients.

Microfluidic systems for infectious disease diagnostics.

Microorganisms, encompassing both uni- and multicellular entities, exhibit remarkable diversity as omnipresent life forms in nature. They play a pivotal role by supplying essential components for sustaining biological processes across diverse ecosystems, including higher host organisms. The complex interactions within the human gut microbiota are crucial for metabolic functions, immune responses, and biochemical signalling, particularly through the gut-brain axis. Viruses also play important roles in biological processes, for example by increasing genetic diversity through horizontal gene transfer when replicating inside living cells. On the other hand, infection of the human body by microbiological agents may lead to severe physiological disorders and diseases. Infectious diseases pose a significant burden on global healthcare systems, characterized by substantial variations in the epidemiological landscape. Fast spreading antibiotic resistance or uncontrolled outbreaks of communicable diseases are major challenges at present. Furthermore, delivering field-proven point-of-care diagnostic tools to the most severely affected populations in low-resource settings is particularly important and challenging. New paradigms and technological approaches enabling rapid and informed disease management need to be implemented. In this respect, infectious disease diagnostics taking advantage of microfluidic systems combined with integrated biosensor-based pathogen detection offers a host of innovative and promising solutions. In this review, we aim to outline recent activities and progress in the development of microfluidic diagnostic tools. Our literature research mainly covers the last 5 years. We will follow a classification scheme based on the human body systems primarily involved at the clinical level or on specific pathogen transmission modes. Important diseases, such as tuberculosis and malaria, will be addressed more extensively.

The impact of inaccurate assumptions about antibody test accuracy on the parametrisation and results of infectious disease models of epidemics.

The parametrisation of infectious disease models is often done based on epidemiological studies that use diagnostic and serology tests to establish disease prevalence or seroprevalence in the population being modelled. During outbreaks of an emerging infectious disease, tests are often used, both for disease control and epidemiological studies, before studies evaluating their accuracy in the population have concluded, with assumptions made about accuracy parameters like sensitivity and specificity. In this simulation study, we simulated such an outbreak, based on the case study of COVID-19, and found that inaccurate parametrisation of infectious disease models due to assumptions about antibody test accuracy in a seroprevalence study can cause modelling results that inform public health decisions to be inaccurate; for example, in our simulation setup, assuming that antibody test specificity was 0.99 instead of 0.90 when it was in fact 0.90 led to an average relative difference of 0.78 in model-projected peak hospitalisations, even when test sensitivity and all other parameters were accurately characterised. We therefore suggest that methods to speed up test evaluation studies are vitally important in the public health response to an emerging outbreak.

Present and Future Non-Culture-Based Diagnostics: Stewardship Potentials and Considerations.

The medical microbiologist plays a key role in the transition from culture-based to molecular test methods for diagnosis of infectious diseases. They must understand the scientific and technical bases underlying these tests along with their associated benefits and limitations and be able to educate administrators and patient providers on their proper use. Coordination of testing practices between clinical departments and the spectrum of public health and research laboratories is essential to optimize health care delivery.

Home and Clinical Laboratory Improvement Amendments-Waived Testing for Infectious Diseases-How Do These Fit in the Testing Landscape?

Though testing for infectious diseases has long been performed in traditional clincial laboratory settings, more widespread availability of waived testing is expanding accessibility of patients to rapid test results. This is being further expanded to home testing. Nevertheless, with this greater democratization and availability of clinical testing there are important limitations that need to be balanced. In this article, we review the current test landscape for infectious diseases waived testing and opportunities for assuring optimal quality testing.