Single domain antibodies from camelids in the treatment of microbial infections.

Infectious diseases continue to pose significant global health challenges. In addition to the enduring burdens of ailments like malaria and HIV, the emergence of nosocomial outbreaks driven by antibiotic-resistant pathogens underscores the ongoing threats. Furthermore, recent infectious disease crises, exemplified by the Ebola and SARS-CoV-2 outbreaks, have intensified the pursuit of more effective and efficient diagnostic and therapeutic solutions. Among the promising options, antibodies have garnered significant attention due to their favorable structural characteristics and versatile applications. Notably, nanobodies (Nbs), the smallest functional single-domain antibodies of heavy-chain only antibodies produced by camelids, exhibit remarkable capabilities in stable antigen binding. They offer unique advantages such as ease of expression and modification and enhanced stability, as well as improved hydrophilicity compared to conventional antibody fragments (antigen-binding fragments (Fab) or single-chain variable fragments (scFv)) that can aggregate due to their low solubility. Nanobodies directly target antigen epitopes or can be engineered into multivalent Nbs and Nb-fusion proteins, expanding their therapeutic potential. This review is dedicated to charting the progress in Nb research, particularly those derived from camelids, and highlighting their diverse applications in treating infectious diseases, spanning both human and animal contexts.

Nanobodies in the fight against infectious diseases: repurposing nature's tiny weapons.

Nanobodies are the smallest known antigen-binding molecules to date. Their small size, good tissue penetration, high stability and solubility, ease of expression, refolding ability, and negligible immunogenicity in the human body have granted them excellence over conventional antibodies. Those exceptional attributes of nanobodies make them promising candidates for various applications in biotechnology, medicine, protein engineering, structural biology, food, and agriculture. This review presents an overview of their structure, development methods, advantages, possible challenges, and applications with special emphasis on infectious diseases-related ones. A showcase of how nanobodies can be harnessed for applications including neutralization of viruses and combating antibiotic-resistant bacteria is detailed. Overall, the impact of nanobodies in vaccine design, rapid diagnostics, and targeted therapies, besides exploring their role in deciphering microbial structures and virulence mechanisms are highlighted. Indeed, nanobodies are reshaping the future of infectious disease prevention and treatment.

Unmasking the NLRP3 inflammasome in dendritic cells as a potential therapeutic target for autoimmunity, cancer, and infectious conditions.

Proper and functional immune response requires a complex interaction between innate and adaptive immune cells, which dendritic cells (DCs) are the primary actors in this coordination as professional antigen-presenting cells. DCs are armed with numerous pattern recognition receptors (PRRs) such as nucleotide-binding and oligomerization domain-like receptors (NLRs) like NLRP3, which influence the development of their activation state upon sensation of ligands. NLRP3 is a crucial component of the immune system for protection against tumors and infectious agents, because its activation leads to the assembly of inflammasomes that cause the formation of active caspase-1 and stimulate the maturation and release of proinflammatory cytokines. But, when NLRP3 becomes overactivated, it plays a pathogenic role in the progression of several autoimmune disorders. So, NLRP3 activation is strictly regulated by diverse signaling pathways that are mentioned in detail in this review. Furthermore, the role of NLRP3 in all of the diverse immune cells' subsets is briefly mentioned in this study because NLRP3 plays a pivotal role in modulating other immune cells which are accompanied by DCs' responses and subsequently influence differentiation of T cells to diverse T helper subsets and even impact on cytotoxic CD8+ T cells' responses. This review sheds light on the functional and therapeutic role of NLRP3 in DCs and its contribution to the occurrence and progression of autoimmune disorders, prevention of diverse tumors' development, and recognition and annihilation of various infectious agents. Furthermore, we highlight NLRP3 targeting potential for improving DC-based immunotherapeutic approaches, to be used for the benefit of patients suffering from these disorders.

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.

The Intersection of Substance Use Disorders and Infectious Diseases in the Emergency Department.

Substance use disorders (SUDs) intersect clinically with many infectious diseases, leading to significant morbidity and mortality if either condition is inadequately treated. In this article, we will describe commonly seen SUDs in the emergency department (ED) as well as their associated infectious diseases, discuss social drivers of patient outcomes, and introduce novel ED-based interventions for co-occurring conditions. Clinicians should come away from this article with prescriptions for both antimicrobial medications and pharmacotherapy for SUDs, as well as an appreciation for social barriers, to care for these patients.

[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.

Interferon-γ and infectious diseases: Lessons and prospects.

Infectious diseases continue to claim many lives. Prevention of morbidity and mortality from these diseases would benefit not just from new medicines and vaccines but also from a better understanding of what constitutes protective immunity. Among the major immune signals that mobilize host defense against infection is interferon-γ (IFN-γ), a protein secreted by lymphocytes. Forty years ago, IFN-γ was identified as a macrophage-activating factor, and, in recent years, there has been a resurgent interest in IFN-γ biology and its role in human defense. Here we assess the current understanding of IFN-γ, revisit its designation as an "interferon," and weigh its prospects as a therapeutic against globally pervasive microbial pathogens.

[Infectious Diseases - a new specialty for postgraduate training in Germany]. / Infektiologie ­ eine neue Facharztdisziplin in Deutschland.

Medicine in Germany is currently facing major structural and economic challenges. Infectious Diseases, with the recent introduction of a new specialty in "Internal Medicine and Infectious Diseases" and with the existing additional training for almost all specializations, will make an important contribution to overcoming these challenges. Expertise in infectious diseases has to be very broad and requires high interdisciplinarity, which makes infectious diseases an attractive and demanding specialty. The complex fundamentals of infectious diseases must now be quickly conveyed to as many physicians as possible in a short period of time, as part of their specialization or as additional training. Until this is achieved, transitional solutions will be necessary for some time. The adaptation of the current billing and reimbursement system for infectious diseases services and improved intersectoral cooperation are of the utmost importance for the further development of the specialty.

The Global Framework for the Progressive Control of Transboundary Animal Diseases - Strengthening Infectious Disease Management and Veterinary Systems Across the Continents: Origins and Testimony.

Transboundary animal diseases are defined by the Food and Agriculture Organization (FAO) of the United Nation's Emergency Prevention System as those diseases that are of significant economic, trade and/or food security importance, which can easily spread to other countries and reach epidemic proportions, and where control/management including exclusion requires cooperation among several countries. The Global Framework for the Progressive Control of Transboundary Animal Diseases represents a platform of the FAO and World Organisation for Animal Health to engage regional sub-regional organizations and national veterinary authorities in developing and monitoring progress in animal disease management efforts.

RNA therapeutics for infectious diseases.

Ribonucleic acids (RNAs), including the messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), play important roles in living organisms and viruses. In recent years, the RNA-based technologies including the RNAs inhibiting other RNA activities, the RNAs targeting proteins, the RNAs reprograming genetic information, and the RNAs encoding therapeutical proteins, are useful methods to apply in prophylactic and therapeutic vaccines. In this review, we summarize and highlight the current application of the RNA therapeutics, especially on mRNA vaccines which have potential for prevention and treatment against human and animal infectious diseases.

CAR Immunotherapy for the treatment of infectious diseases: a systematic review.

Immunotherapy treatments aim to modulate the host's immune response to either mitigate it in inflammatory/autoimmune disease or enhance it against infection or cancer. Among different immunotherapies reaching clinical application during the last years, chimeric antigen receptor (CAR) immunotherapy has emerged as an effective treatment for cancer where different CAR T cells have already been approved. Yet their use against infectious diseases is an area still relatively poorly explored, albeit with tremendous potential for research and clinical application. Infectious diseases represent a global health challenge, with the escalating threat of antimicrobial resistance underscoring the need for alternative therapeutic approaches. This review aims to systematically evaluate the current applications of CAR immunotherapy in infectious diseases and discuss its potential for future applications. Notably, CAR cell therapies, initially developed for cancer treatment, are gaining recognition as potential remedies for infectious diseases. The review sheds light on significant progress in CAR T cell therapy directed at viral and opportunistic fungal infections.

Child Health Needs and the Pediatric Infectious Diseases Workforce: 2020-2040.

Pediatric infectious diseases (PID) physicians prevent and treat childhood infections through clinical care, research, public health, education, antimicrobial stewardship, and infection prevention. This article is part of an American Board of Pediatrics Foundation-sponsored supplement investigating the future of the pediatric subspecialty workforce. The article offers context to findings from a modeling analysis estimating the supply of PID subspecialists in the United States between 2020 and 2040. It provides an overview of children cared for by PID subspecialists, reviews the current state of the PID workforce, and discusses the projected headcount and clinical workforce equivalents of PID subspecialists at the national, census region, and census division levels over this 2-decade period. The article concludes by discussing the education and training, clinical practice, policy, and research implications of the data presented. Adjusting for population growth, the PID workforce is projected to grow more slowly than most other pediatric subspecialties and geographic disparities in access to PID care are expected to worsen. In models considering alternative scenarios, decreases in the number of fellows and time spent in clinical care significantly affect the PID workforce. Notably, model assumptions may not adequately account for potential threats to the PID workforce, including a declining number of fellows entering training and the unknown impact of the COVID-19 pandemic and future emerging infections on workforce attrition. Changes to education and training, clinical care, and policy are needed to ensure the PID workforce can meet the future needs of US children.

Complexity of patients with or without infectious disease consultation in tertiary-care hospitals in Germany.

PURPOSE: Patients seen by infectious disease (ID) specialists are more complex compared to patients treated by other subspecialities according to Tonelli et al. (2018). However, larger studies on the complexity of patients related to the involvement of ID consultation services are missing. METHODS: Data of patients being treated in 2015 and 2019 in four different German university hospitals was retrospectively collected. Data were collected from the hospitals' software system and included whether the patients received an ID consultation as well as patient clinical complexity level (PCCL), case mix index (CMI) and length of stay (LOS) as a measurement for the patients' complexity. Furthermore, a comparison of patients with distinct infectious diseases treated with or without an ID consultation was initiated. RESULTS: In total, 215.915 patients were included in the study, 3% (n = 6311) of those were seen by an ID consultant. Patients receiving ID consultations had a significantly (p < 0.05) higher PCCL (median 4 vs. 0), CMI (median 3,8 vs. 1,1) and deviation of the expected mean LOS (median 7 days vs. 0 days) than patients in the control group. No differences among hospitals or between years were observed. Comparing patients with distinct infectious diseases treated with or without an ID consultation, the differences were confirmed throughout the groups. CONCLUSION: Patients receiving ID consultations are highly complex, frequently need further treatment after discharge and have a high economic impact. Thus, ID specialists should be clinically trained in a broad spectrum of diseases and treating these complex patients should be sufficiently remunerated.

Update on Cardiovascular Implantable Electronic Device Infections and Their Prevention, Diagnosis, and Management: A Scientific Statement From the American Heart Association: Endorsed by the International Society for Cardiovascular Infectious Diseases.

The American Heart Association sponsored the first iteration of a scientific statement that addressed all aspects of cardiovascular implantable electronic device infection in 2010. Major advances in the prevention, diagnosis, and management of these infections have occurred since then, necessitating a scientific statement update. An 11-member writing group was identified and included recognized experts in cardiology and infectious diseases, with a career focus on cardiovascular infections. The group initially met in October 2022 to develop a scientific statement that was drafted with front-line clinicians in mind and focused on providing updated clinical information to enhance outcomes of patients with cardiovascular implantable electronic device infection. The current scientific statement highlights recent advances in prevention, diagnosis, and management, and how they may be incorporated in the complex care of patients with cardiovascular implantable electronic device infection.

mSphere of Influence: How host genetics impact microbial pathogenesis and treatment of infectious disease.

Emily Rosowski works in the field of host-pathogen interactions, studying how host innate immune mechanisms control pathogens. In this mSphere of Influence article, she reflects on how "Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections" by D. M. Tobin, F. J. Roca, S. F. Oh, R. McFarland, et al. (Cell 148:434-446, 2012, https://doi.org/10.1016/j.cell.2011.12.023) made an impact on her by investigating how differences in host genetics can affect modes of microbial pathogenesis and inform treatments for infectious disease.