Exploring the role of secretory proteins in the human infectious diseases diagnosis and therapeutics.

Secretory proteins are playing important role during the host-pathogen interaction to develop the infection or protection into the cell. Pathogens developing infectious disease to human being are taken up by host macrophages or number of immune cells, play an important role in physiological, developmental and immunological function. At the same time, infectious agents are also secreting various proteins to neutralize the resistance caused by host cells and also helping the pathogens to develop the infection. Secretory proteins (secretome) are only developed at the time of host-pathogen interaction, therefore they become very important to develop the targeted and potential therapeutic strategies. Pathogen specific secretory proteins released during interaction with host cell provide opportunity to develop point of care and rapid diagnostic kits. Proteins secreted by pathogens at the time of interaction with host cell have also been found as immunogenic in nature and numbers of vaccines have been developed to control the spread of human infectious diseases. This chapter highlights the importance of secretory proteins in the development of diagnostic and therapeutic strategies to fight against human infectious diseases.

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Public health emergency preparedness for infectious disease emergencies: a scoping review of recent evidence.

BACKGROUND: The COVID-19 pandemic continues to demonstrate the risks and profound health impacts that result from infectious disease emergencies. Emergency preparedness has been defined as the knowledge, capacity and organizational systems that governments, response and recovery organizations, communities and individuals develop to anticipate, respond to, or recover from emergencies. This scoping review explored recent literature on priority areas and indicators for public health emergency preparedness (PHEP) with a focus on infectious disease emergencies. METHODS: Using scoping review methodology, a comprehensive search was conducted for indexed and grey literature with a focus on records published from 2017 to 2020 onward, respectively. Records were included if they: (a) described PHEP, (b) focused on an infectious emergency, and (c) were published in an Organization for Economic Co-operation and Development country. An evidence-based all-hazards Resilience Framework for PHEP consisting of 11 elements was used as a reference point to identify additional areas of preparedness that have emerged in recent publications. The findings were analyzed deductively and summarized thematically. RESULTS: The included publications largely aligned with the 11 elements of the all-hazards Resilience Framework for PHEP. In particular, the elements related to collaborative networks, community engagement, risk analysis and communication were frequently observed across the publications included in this review. Ten emergent themes were identified that expand on the Resilience Framework for PHEP specific to infectious diseases. Planning to mitigate inequities was a key finding of this review, it was the most frequently identified emergent theme. Additional emergent themes were: research and evidence-informed decision making, building vaccination capacity, building laboratory and diagnostic system capacity, building infection prevention and control capacity, financial investment in infrastructure, health system capacity, climate and environmental health, public health legislation and phases of preparedness. CONCLUSION: The themes from this review contribute to the evolving understanding of critical public health emergency preparedness actions. The themes expand on the 11 elements outlined in the Resilience Framework for PHEP, specifically relevant to pandemics and infectious disease emergencies. Further research will be important to validate these findings, and expand understanding of how refinements to PHEP frameworks and indicators can support public health practice.

Therapeutic roles of CAR T cells in infectious diseases: Clinical lessons learnt from cancer.

Cancer immunotherapy has made improvements due to the advances in chimaeric antigen receptor (CAR) T cell development, offering a promising treatment option for patients who have failed to respond to traditional treatments. In light of the successful use of adoptive CAR T cell therapy for cancer, researchers have been inspired to develop CARs for the treatment of other diseases beyond cancers such as viral infectious diseases. Nonetheless, various obstacles limit the efficacy of CAR T cell therapies and prevent their widespread usage. Severe toxicities, poor in vivo persistence, antigen escape, and heterogeneity, as well as off-target effect, are key challenges that must all be addressed to broaden the application of CAR T cells to a wider spectrum of diseases. The key advances in CAR T cell treatment for cancer and viral infections are reviewed in this article. We will also discuss revolutionary CAR T cell products developed to improve and enhance the therapeutic advantages of these treatments.

Prevention and treatment of infectious diseases in migrants in Europe in the era of universal health coverage.

Some subpopulations of migrants to Europe are generally healthier than the population of the country of settlement, but are at increased risk of key infectious diseases, including tuberculosis, HIV, and viral hepatitis, as well as under- immunisation. Infection screening programmes across Europe work in disease silos with a focus on individual diseases at the time of arrival. We argue that European health-care practitioners and policy makers would benefit from developing a framework of universal health care for migrants, which proactively offers early testing and vaccinations by delivering multi-disease testing and catch-up vaccination programmes integrated within existing health systems. Such interventions should be codeveloped with migrant populations to overcome barriers faced in accessing services. Aligning policies with the European Centre for Disease Prevention and Control guidance for health care for migrants, community-based preventive health-care programmes should be delivered as part of universal health care. However, effective implementation needs appropriate funding, and to be underpinned by high-quality evidence.

The Case for Integrating Health Systems to Manage Noncommunicable and Infectious Diseases in Low- and Middle-Income Countries: Lessons Learned From Zambia.

Noncommunicable diseases (NCDs) are the leading cause of death in the world, and 80% of all NCD deaths occur in low- and middle-income countries (LMICs). The COVID-19 pandemic has demonstrated that patients with NCDs are at increased risk of becoming severely ill from the virus. Disproportionate investment in vertical health programs can result in health systems vulnerable to collapse when resources are strained, such as during pandemics. Although NCDs are largely preventable, globally there is underinvestment in efforts to address them. Integrating health systems to collectively address NCDs and infectious diseases through a wide range of services in a comprehensive manner reduces the economic burden of healthcare and strengthens the healthcare system. Health system resiliency is essential for health security. In this article, we provide an economically sound approach to incorporating NCDs into routine healthcare services in LMICs through improved alignment of institutions that support prevention and control of both NCDs and infectious diseases. Examples from Zambia's multisector interventions to develop and support a national NCD action plan can inform and encourage LMIC countries to invest in systems integration to reduce the social and economic burden of NCDs and infectious diseases.

Radioimmunotherapy for the treatment of infectious diseases: a comprehensive update.

INTRODUCTION: Corona Virus Disease of 2019 (COVID-19) pandemic has renewed interest in monoclonal antibodies for treating infectious diseases. During last two decades experimental data has been accumulated showing the potential of radioimmunotherapy (RIT) of infectious diseases. In addition, COVID-19 pandemic has created a novel landscape for opportunistic fungal infections in post-COVID-19 patients resulting from severe immune suppression. AREAS COVERED: We analyze recent results on targeting "pan-antigens" shared by fungal pathogens in mouse models and in healthy dogs; on developing RIT of prosthetic joint infections (PJI); examine RIT as potential human immunodeficiency virus (HIV) cure strategy and analyze its mechanisms and safety. Literature review was performed using PubMed and Google Scholar and includes relevant articles from 2000 to 2022. EXPERT OPINION: Some of the RIT of infection applications can, hopefully, be moved into the clinic earlier than others after preclinical development: (1) RIT of opportunistic fungal infections might contribute to saving lives as current antifungal drugs do not work in severely immunocompromised patients; (2) RIT of patients with PJI. Success of RIT in these patients will allow to expand the application of RIT to other similarly vulnerable patients' populations such as cancer patients with weakened immune system and organ transplant recipients.

Ten Years of Medical Informatics and Standards Support for Clinical Research in an Infectious Diseases Network.

BACKGROUND: It is 30 years since evidence-based medicine became a great support for individual clinical expertise in daily practice and scientific research. Electronic systems can be used to achieve the goal of collecting data from heterogeneous datasets and to support multicenter clinical trials. The Ligurian Infectious Diseases Network (LIDN) is a web-based platform for data collection and reuse originating from a regional effort and involving many professionals from different fields. OBJECTIVES: The objective of this work is to present an integrated system of ad hoc interfaces and tools that we use to perform pseudonymous clinical data collection, both manually and automatically, to support clinical trials. METHODS: The project comprehends different scenarios of data collection systems, according to the degree of information technology of the involved centers. To be compliant with national regulations, the last developed connection is based on the standard Clinical Document Architecture Release 2 by Health Level 7 guidelines, interoperability is supported by the involvement of a terminology service. RESULTS: Since 2011, the LIDN platform has involved more than 8,000 patients from eight different hospitals, treated or under treatment for at least one infectious disease among human immunodeficiency virus (HIV), hepatitis C virus, severe acute respiratory syndrome coronavirus 2, and tuberculosis. Since 2013, systems for the automatic transfer of laboratory data have been updating patients' information for three centers, daily. Direct communication was set up between the LIDN architecture and three of the main national cohorts of HIV-infected patients. CONCLUSION: The LIDN was originally developed to support clinicians involved in the project in the management of data from HIV-infected patients through a web-based tool that could be easily used in primary-care units. Then, the developed system grew modularly to respond to the specific needs that arose over a time span of more than 10 years.

Governance structure affects transboundary disease management under alternative objectives.

BACKGROUND: The development of public health policy is inextricably linked with governance structure. In our increasingly globalized world, human migration and infectious diseases often span multiple administrative jurisdictions that might have different systems of government and divergent management objectives. However, few studies have considered how the allocation of regulatory authority among jurisdictions can affect disease management outcomes. METHODS: Here we evaluate the relative merits of decentralized and centralized management by developing and numerically analyzing a two-jurisdiction SIRS model that explicitly incorporates migration. In our model, managers choose between vaccination, isolation, medication, border closure, and a travel ban on infected individuals while aiming to minimize either the number of cases or the number of deaths. RESULTS: We consider a variety of scenarios and show how optimal strategies differ for decentralized and centralized management levels. We demonstrate that policies formed in the best interest of individual jurisdictions may not achieve global objectives, and identify situations where locally applied interventions can lead to an overall increase in the numbers of cases and deaths. CONCLUSIONS: Our approach underscores the importance of tailoring disease management plans to existing regulatory structures as part of an evidence-based decision framework. Most importantly, we demonstrate that there needs to be a greater consideration of the degree to which governance structure impacts disease outcomes.

How sex and gender matter in infectious diseases - outcomes of the first Polish conference "A woman in an infectious diseases circle".

Occurrence of infectious disease in a woman is an interdisciplinary area of medicine. The common problem of lower recruitment of women to clinical trials leads to the necessity to rely in clinical practice on the exchange of practical experiences, specialist consultations and individualization of treatment. As the COVID-19 pandemic shows, there is a close relationship between infectious diseases and civilization diseases. People suffering from chronic diseases are both more susceptible to infection and the more severe course of an infectious disease. On the other hand, infection may accelerate or initiate the onset of a noncommunicable disease. Women, especially those living with HIV, are a group with an underestimated risk of high blood pressure or some cancers. Therefore, one of the main goals of the conference is to break the stereotypes of thinking about health, in which gender is the main determinant of some screening tests. Late presentation of women to medical care is a significant problem that is of great importance in the diagnosis and treatment of both communicable and non-communicable diseases. Women put family and professional responsibilities in the first place, and they are known to downplay their own health problems. It leads to the diagnosis of cardiovascular diseases or cancer at the stage of advanced changes, limiting the possibilities of effective therapy. Understanding gender attributed differences in the etiology and epidemiology of diseases allows for the improvement of patient care, as well as determines the right direction of reforms in the area of healthcare. It is essential to build models of care based on an interdisciplinary and patient-centered approach, with broad support from both stakeholders and NGOs. Each contact of the patient with the health care system should be seen as an opportunity for screening both in the area of civilization diseases, women's health, and infectious diseases corresponding to her lifestyle.

#SoMe the Money! Value, Strategy, and Implementation of Social Media Engagement for Infectious Diseases Trainees, Clinicians, and Divisions.

Social media platforms have revolutionized how we consume information, along with how to effectively present communication, education, and advocacy efforts. There is profound value in leveraging social media within these aspects for the field of infectious diseases, for divisions and individual clinicians. Herein, we provide the rationale to incorporate social media as a key competency for infectious diseases training and specific guidance on aspects of education and strategic development of new accounts critical for success.

Preparing for patients with high-consequence infectious diseases: Example of a high-level isolation unit.

INTRODUCTION: Patients with high-consequence infectious diseases (HCID) are rare in Western Europe. However, high-level isolation units (HLIU) must always be prepared for patient admission. Case fatality rates of HCID can be reduced by providing optimal intensive care management. We here describe a single centre's preparation, its embedding in the national context and the challenges we faced during the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. METHODS: Ten team leaders organize monthly whole day trainings for a team of doctors and nurses from the HLIU focusing on intensive care medicine. Impact and relevance of training are assessed by a questionnaire and a perception survey, respectively. Furthermore, yearly exercises with several partner institutions are performed to cover different real-life scenarios. Exercises are evaluated by internal and external observers. Both training sessions and exercises are accompanied by intense feedback. RESULTS: From May 2017 monthly training sessions were held with a two-month and a seven-month break due to the first and second wave of the SARS-CoV-2 pandemic, respectively. Agreement with the statements of the questionnaire was higher after training compared to before training indicating a positive effect of training sessions on competence. Participants rated joint trainings for nurses and doctors at regular intervals as important. Numerous issues with potential for improvement were identified during post processing of exercises. Action plans for their improvement were drafted and as of now mostly implemented. The network of the permanent working group of competence and treatment centres for HCID (Ständiger Arbeitskreis der Kompetenz- und Behandlungszentren für Krankheiten durch hochpathogene Erreger (STAKOB)) at the Robert Koch-Institute (RKI) was strengthened throughout the SARS-CoV-2 pandemic. DISCUSSION: Adequate preparation for the admission of patients with HCID is challenging. We show that joint regular trainings of doctors and nurses are appreciated and that training sessions may improve perceived skills. We also show that real-life scenario exercises may reveal additional deficits, which cannot be easily disclosed in training sessions. Although the SARS-CoV-2 pandemic interfered with our activities the enhanced cooperation among German HLIU during the pandemic ensured constant readiness for the admission of HCID patients to our or to collaborating HLIU. This is a single centre's experience, which may not be generalized to other centres. However, we believe that our work may address aspects that should be considered when preparing a unit for the admission of patients with HCID. These may then be adapted to the local situations.

Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment.

Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future. Systematic Review Registration.

[Infectious diseases: Achievements, new Developments and Perspectives in 2021]. / Maladies infectieuses - Acquis, nouveautés et perspectives en 2021.

The substantial progresses during the last decades in the field of infectious diseases have significantly improved their prevention, diagnosis and treatment. Basic and medical sciences have efficiently dealt with the challenges of emerging infections, infectious complications related to the increasing complexity of medical practices and marked slow-down in the development of new antimicrobial agents. During the worldwide crisis related to the COVID-19 pandemic, the « medical normality ¼ has been put in stand-by, but medical advances have fortunately continued. In the present article we present new knowledge in the field of bacterial, viral and fungal infections, which may modify hospital and ambulatory practices. Significant achievements in the field of COVID-19 will be presented in a future article.

Les progrès spectaculaires des dernières décennies dans le domaine des maladies infectieuses ont sensiblement amélioré leurs prévention, diagnostic et traitement. Les sciences de base et cliniques ont répondu présent face à de multiples défis: infections émergentes, complications infectieuses de pratiques médicales de plus en plus complexes, ralentissement préoccupant du développement de nouveaux agents antimicrobiens. Pendant la crise mondiale liée à la pandémie de Covid-19, la « normalité médicale ¼ a dû être mise entre parenthèses, mais les progrès médicaux se sont ­ fort heureusement ­ poursuivis. Dans cet article, nous vous présentons de nouvelles connaissances en matière d'infections bactériennes, virales ou fongiques qui pourraient faire évoluer nos pratiques hospitalières et ambulatoires. Les acquis marquants dans le domaine du Covid-19 feront l'objet d'un article à venir.

Lipid Nanoparticle-mRNA Formulations for Therapeutic Applications.

After decades of extensive fundamental studies and clinical trials, lipid nanoparticles (LNPs) have demonstrated effective mRNA delivery such as the Moderna and Pfizer-BioNTech vaccines fighting against COVID-19. Moreover, researchers and clinicians have been investigating mRNA therapeutics for a variety of therapeutic indications including protein replacement therapy, genome editing, and cancer immunotherapy. To realize these therapeutics in the clinic, there are many formidable challenges. First, novel delivery systems such as LNPs with high delivery efficiency and low toxicity need to be developed for different cell types. Second, mRNA molecules need to be engineered for improved pharmaceutical properties. Lastly, the LNP-mRNA nanoparticle formulations need to match their therapeutic applications.In this Account, we summarize our recent advances in the design and development of various classes of lipids and lipid derivatives, which can be formulated with multiple types of mRNA molecules to treat diverse diseases. For example, we conceived a series of ionizable lipid-like molecules based on the structures of a benzene core, an amide linker, and hydrophobic tails. We identified N1,N3,N5-tris(3-(didodecylamino)propyl)benzene-1,3,5-tricarboxamide (TT3) as a lead compound for mRNA delivery both in vitro and in vivo. Moreover, we tuned the biodegradability of these lipid-like molecules by introducing branched ester or linear ester chains. Meanwhile, inspired by biomimetic compounds, we synthesized vitamin-derived lipids, chemotherapeutic conjugated lipids, phospholipids, and glycolipids. These scaffolds greatly broaden the chemical space of ionizable lipids for mRNA delivery. In another section, we highlight our efforts on the research direction of mRNA engineering. We previously optimized mRNA chemistry using chemically-modified nucleotides to increase the protein expression, such as pseudouridine (ψ), 5-methoxyuridine (5moU), and N1-methylpseudouridine (me1ψ). Also, we engineered the sequences of mRNA 5' untranslated regions (5'-UTRs) and 3' untranslated regions (3'-UTRs), which dramatically enhanced protein expression. With the progress of LNP development and mRNA engineering, we consolidate these technologies and apply them to treat diseases such as genetic disorders, infectious diseases, and cancers. For instance, TT3 and its analog-derived lipid-like nanoparticles can effectively deliver factor IX or VIII mRNA and recover the clotting activity in hemophilia mouse models. Engineered mRNAs encoding SARS-CoV-2 antigens serve well as vaccine candidates against COVID-19. Vitamin-derived lipid nanoparticles loaded with antimicrobial peptide-cathepsin B mRNA enable adoptive macrophage transfer to treat multidrug resistant bacterial sepsis. Biomimetic lipids such as phospholipids formulated with mRNAs encoding costimulatory receptors lead to enhanced cancer immunotherapy.Overall, lipid-mRNA nanoparticle formulations have considerably benefited public health in the COVID-19 pandemic. To expand their applications in clinical use, research work from many disciplines such as chemistry, engineering, materials, pharmaceutical sciences, and medicine need to be integrated. With these collaborative efforts, we believe that more and more lipid-mRNA nanoparticle formulations will enter the clinic in the near future and benefit human health.

The Infectious Disease Ontology in the age of COVID-19.

BACKGROUND: Effective response to public health emergencies, such as we are now experiencing with COVID-19, requires data sharing across multiple disciplines and data systems. Ontologies offer a powerful data sharing tool, and this holds especially for those ontologies built on the design principles of the Open Biomedical Ontologies Foundry. These principles are exemplified by the Infectious Disease Ontology (IDO), a suite of interoperable ontology modules aiming to provide coverage of all aspects of the infectious disease domain. At its center is IDO Core, a disease- and pathogen-neutral ontology covering just those types of entities and relations that are relevant to infectious diseases generally. IDO Core is extended by disease and pathogen-specific ontology modules. RESULTS: To assist the integration and analysis of COVID-19 data, and viral infectious disease data more generally, we have recently developed three new IDO extensions: IDO Virus (VIDO); the Coronavirus Infectious Disease Ontology (CIDO); and an extension of CIDO focusing on COVID-19 (IDO-COVID-19). Reflecting the fact that viruses lack cellular parts, we have introduced into IDO Core the term acellular structure to cover viruses and other acellular entities studied by virologists. We now distinguish between infectious agents - organisms with an infectious disposition - and infectious structures - acellular structures with an infectious disposition. This in turn has led to various updates and refinements of IDO Core's content. We believe that our work on VIDO, CIDO, and IDO-COVID-19 can serve as a model for yielding greater conformance with ontology building best practices. CONCLUSIONS: IDO provides a simple recipe for building new pathogen-specific ontologies in a way that allows data about novel diseases to be easily compared, along multiple dimensions, with data represented by existing disease ontologies. The IDO strategy, moreover, supports ontology coordination, providing a powerful method of data integration and sharing that allows physicians, researchers, and public health organizations to respond rapidly and efficiently to current and future public health crises.

[Discussion on prevention and treatment of infectious diseases by using moxibustion for warming yang and strengthening body resistance to eliminate pathogenic cold and qi in ancient and mo-dern literature].

Moxibustion therapy has a good therapeutic effect in warming yang, strengthening body resistance to dispel pathogenic cold and qi, thus being able to prevent and treat infectious diseases. There are many records about clinical application of moxibustion to infectious diseases in ancient and modern literature. In the present paper, we expound the specific methods of moxibustion for strengthening the body resistance and preventing infectious diseases and its application in the treatment of miasma, bone steaming disease, cholera, pestis, epidemic hemorrhagic fever and so on, in the records of ancient and modern times, and expound its effectiveness. On this basis, we also proposed the feasibility of moxibustion in the prevention and treatment of COVID-19, a new type of infectious disease currently.

CRISPR-based strategies in infectious disease diagnosis and therapy.

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.