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.

Integrating gated recurrent unit in graph neural network to improve infectious disease prediction: an attempt.

Objective: This study focuses on enhancing the precision of epidemic time series data prediction by integrating Gated Recurrent Unit (GRU) into a Graph Neural Network (GNN), forming the GRGNN. The accuracy of the GNN (Graph Neural Network) network with introduced GRU (Gated Recurrent Units) is validated by comparing it with seven commonly used prediction methods. Method: The GRGNN methodology involves multivariate time series prediction using a GNN (Graph Neural Network) network improved by the integration of GRU (Gated Recurrent Units). Additionally, Graphical Fourier Transform (GFT) and Discrete Fourier Transform (DFT) are introduced. GFT captures inter-sequence correlations in the spectral domain, while DFT transforms data from the time domain to the frequency domain, revealing temporal node correlations. Following GFT and DFT, outbreak data are predicted through one-dimensional convolution and gated linear regression in the frequency domain, graph convolution in the spectral domain, and GRU (Gated Recurrent Units) in the time domain. The inverse transformation of GFT and DFT is employed, and final predictions are obtained after passing through a fully connected layer. Evaluation is conducted on three datasets: the COVID-19 datasets of 38 African countries and 42 European countries from worldometers, and the chickenpox dataset of 20 Hungarian regions from Kaggle. Metrics include Average Root Mean Square Error (ARMSE) and Average Mean Absolute Error (AMAE). Result: For African COVID-19 dataset and Hungarian Chickenpox dataset, GRGNN consistently outperforms other methods in ARMSE and AMAE across various prediction step lengths. Optimal results are achieved even at extended prediction steps, highlighting the model's robustness. Conclusion: GRGNN proves effective in predicting epidemic time series data with high accuracy, demonstrating its potential in epidemic surveillance and early warning applications. However, further discussions and studies are warranted to refine its application and judgment methods, emphasizing the ongoing need for exploration and research in this domain.

Nota técnica sobre la aceleración de la eliminación de P. falciparum en las Américas

Esta nota técnica busca guiar a los programas nacionales de malaria y a las organizaciones implicadas en el apoyo de los esfuerzos para la eliminación de la malaria en la Región de las Américas, a fin de que intensifiquen las acciones políticas/estratégicas e implementen los cambios operativos necesarios para acelerar la eliminación de P. falciparum como parte de las estrategias nacionales para la eliminación de la malaria. Con tal finalidad, orienta las acciones que deben llevarse a cabo para acelerar la eliminación de P. falciparum en zonas próximas a su eliminación, sin comprometer los esfuerzos unificados de eliminación del paludismo (P. vivax - P. falciparum) y contribuyendo al objetivo final del país de eliminar el paludismo en su conjunto. La aceleración de la eliminación de P. falciparum procura mitigar el riesgo de aparición y propagación de la resistencia a la artemisinina y de la resistencia a los fármacos asociados; acelerar la reducción del número total de casos de paludismo en zonas con una proporción importante de P falciparum; acelerar la eliminación de la malaria (P. vivax y P. falciparum) teniendo en cuenta que P. falciparum es uno de los desencadenantes de las recaídas de P. vivax; desarrollar capacidades en intervenciones para acelerar la eliminación de la malaria a partir de la experiencia de eliminación de P. falciparum, reduciendo el tiempo para alcanzar la eliminación de la malaria; y empoderar a diferentes actores, autoridades de alto nivel, donantes, municipios y otras entidades para la eliminación de la malaria con inspiración en los logros de la eliminación del P. falciparum.

Appendice. Pour une meilleure immunité : l’approche du parcours de vie pour une longévité en bonne santé

Cette publication est une annexe au document technique "Building better immunity : Une approche du parcours de vie pour une longévité en bonne santé", avec les contributions de plusieurs experts en la matière au sein et en dehors de l'Organisation panaméricaine de la santé (OPS). Cette annexe fournit des exemples d'activités au sein du programme national de vaccination qui peuvent améliorer les taux de couverture et réduire les occasions manquées pour quatre groupes de population : les femmes enceintes, les adolescents, les travailleurs de la santé et les personnes âgées. Ces exemples traduisent les principes et les concepts de l'approche fondée sur le parcours de vie en activités concrètes, qui peuvent être utilisées par les responsables des programmes nationaux de vaccination et par les vaccinateurs, respectivement, pour améliorer les taux de couverture vaccinale. Ces quatre groupes représentent des étapes de la vie pour lesquelles il existe des vaccins très efficaces et qui peuvent grandement influencer leurs capacités sanitaires. L'application des séries primaires, des rappels et des doses de vaccin de rattrapage dans ces groupes est essentielle pour combler les déficits d'immunité émergents. Les activités sont regroupées en huit composantes : (i) gestion et plaidoyer, (ii) équité, (iii) ressources humaines et financement, (iv) organisation et prestation de services, (v) génération de la demande et engagement communautaire, (vi) systèmes d'information, (vii) formation et (viii) évaluation et recherche. Les exemples doivent être évalués, adaptés, mis en œuvre et éventuellement élargis par les États membres pour s'aligner sur les contextes nationaux et locaux. Ce document s'inscrit dans le cadre des efforts déployés par l'OPS pour promouvoir l'application d'une approche de la vaccination fondée sur le parcours de vie dans les pays et territoires des Amériques et pour aider les ministères de la santé à mettre en place des stratégies de santé publique aux niveaux infranational et local afin de préserver la santé et le bien-être des personnes de tous âges.

Apéndice. Lograr una mejor inmunidad: El enfoque del curso de vida para una longevidad saludable

Esta publicación es un apéndice del documento técnico "Lograr una mejor inmunidad: el enfoque de curso de vida para una longevidad saludable", con las contribuciones de varios expertos en la materia dentro y fuera de la Organización Panamericana de la Salud (OPS). Este apéndice proporciona ejemplos de actividades dentro del programa nacional de inmunización que pueden mejorar las tasas de cobertura y reducir las oportunidades perdidas para cuatro grupos de población: mujeres embarazadas, adolescentes, trabajadores sanitarios y adultos mayores. Estos ejemplos traducen los principios y conceptos del Enfoque del Ciclo Vital en actividades concretas, que pueden ser utilizadas por los gestores de los programas nacionales de inmunización y por los vacunadores, respectivamente, para reforzar las tasas de cobertura de vacunación. Estos cuatro grupos representan etapas de la vida para las que existen vacunas muy eficaces y que pueden influir enormemente en sus capacidades sanitarias. La aplicación de dosis de vacunas de la serie primaria, de refuerzo y de recuperación en estos grupos es fundamental para cerrar las brechas de inmunidad emergentes. Las actividades se agrupan en ocho componentes (i) administración y promoción, (ii) equidad, (iii) recursos humanos y financiación, (iv) organización y prestación de servicios, (v) generación de demanda y participación de la comunidad, (vi) sistemas de información, (vii) formación y (viii) evaluación e investigación. Los ejemplos deben ser evaluados, adaptados, implementados y posiblemente ampliados por los Estados Miembros para alinearlos con los contextos nacionales y locales. Este documento forma parte de los esfuerzos de la OPS para promover la aplicación de un enfoque de inmunización a lo largo de la vida por parte de los países y territorios de las Américas y para apoyar a los Ministerios de Salud a establecer estrategias de salud pública a nivel subnacional y local para salvaguardar la salud y el bienestar de las personas de todas las edades.

Why We Need to Change How We Talk About Infectious Disease.

This article builds a case for raising occupational consciousness by critically questioning ahistorical and apolitical uses of battle language, especially when referring to infectious diseases. Words such as invasion, colonization, and resistance are particularly ethically troubling, and this article considers why the social practices our language brings about matter in health care. Dynamic relationships among humans and microbes, as well as metaphor, are considered here in historical context and through the lens of Derrida's portmanteau hostipitality, which invites reconsideration of an infectious disease notion of host and how conceptions of hospitality have been institutionalized and commodified. This article argues that language used in infectious disease care settings should be informed by coexistence as a guiding value of clinical and ethical relevance.

Diagnostic stewardship in infectious diseases: a scoping review.

Introduction. The term 'diagnostic stewardship' is relatively new, with a recent surge in its use within the literature. Despite its increasing popularity, a precise definition remains elusive. Various attempts have been made to define it, with some viewing it as an integral part of antimicrobial stewardship. The World Health Organization offers a broad definition, emphasizing the importance of timely, accurate diagnostics. However, inconsistencies in the use of this term still persist, necessitating further clarification.Gap Statement. There are currently inconsistencies in the definition of diagnostic stewardship used within the academic literature.Aim. This scoping review aims to categorize the use of diagnostic stewardship approaches and define this approach by identifying common characteristics and factors of its use within the literature.Methodology. This scoping review undertook a multi-database search from date of inception until October 2022. Any observational or experimental study where the authors define the intervention to be diagnostic stewardship from any clinical area was included. Screening of all papers was undertaken by a single reviewer with 10% verification by a second reviewer. Data extraction was undertaken by a single reviewer using a pre-piloted form. Given the wide variation in study design and intervention outcomes, a narrative synthesis approach was applied. Studies were clustered around common diagnostic stewardship interventions where appropriate.Results. After duplicate removal, a total of 1310 citations were identified, of which, after full-paper screening, 105 studies were included in this scoping review. The classification of an intervention as taking a diagnostic stewardship approach is a relatively recent development, with the first publication in this field dating back to 2017. The majority of research in this area has been conducted within the USA, with very few studies undertaken outside this region. Visual inspection of the citation map reveals that the current evidence base is interconnected, with frequent references to each other's work. The interventions commonly adopt a restrictive approach, utilizing hard and soft stops within the pre-analytical phase to restrict access to testing. Upon closer examination of the outcomes, it becomes evident that there is a predominant focus on reducing the number of tests rather than enhancing the current test protocol. This is further reflected in the limited number of studies that report on test performance (including protocol improvements, specificity and sensitivity).Conclusion. Diagnostic stewardship seems to have deviated from its intended course, morphing into a rather rudimentary instrument wielded not to enhance but to constrict the scope of testing. Despite the World Health Organization's advocacy for an ideology that promotes a more comprehensive approach to quality improvement, it may be more appropriate to consider alternative regional narratives when categorizing these types of quality improvement interventions.

Modelling the impact of precaution on disease dynamics and its evolution.

In this paper, we introduce the notion of practically susceptible population, which is a fraction of the biologically susceptible population. Assuming that the fraction depends on the severity of the epidemic and the public's level of precaution (as a response of the public to the epidemic), we propose a general framework model with the response level evolving with the epidemic. We firstly verify the well-posedness and confirm the disease's eventual vanishing for the framework model under the assumption that the basic reproduction number R 0 < 1 . For R 0 > 1 , we study how the behavioural response evolves with epidemics and how such an evolution impacts the disease dynamics. More specifically, when the precaution level is taken to be the instantaneous best response function in literature, we show that the endemic dynamic is convergence to the endemic equilibrium; while when the precaution level is the delayed best response, the endemic dynamic can be either convergence to the endemic equilibrium, or convergence to a positive periodic solution. Our derivation offers a justification/explanation for the best response used in some literature. By replacing "adopting the best response" with "adapting toward the best response", we also explore the adaptive long-term dynamics.

A risk-induced dispersal strategy of the infected population for a disease-free state in the SIS epidemic model.

This article proposes a dispersal strategy for infected individuals in a spatial susceptible-infected-susceptible (SIS) epidemic model. The presence of spatial heterogeneity and the movement of individuals play crucial roles in determining the persistence and eradication of infectious diseases. To capture these dynamics, we introduce a moving strategy called risk-induced dispersal (RID) for infected individuals in a continuous-time patch model of the SIS epidemic. First, we establish a continuous-time n-patch model and verify that the RID strategy is an effective approach for attaining a disease-free state. This is substantiated through simulations conducted on 7-patch models and analytical results derived from 2-patch models. Second, we extend our analysis by adapting the patch model into a diffusive epidemic model. This extension allows us to explore further the impact of the RID movement strategy on disease transmission and control. We validate our results through simulations, which provide the effects of the RID dispersal strategy.

Temporal shifts in 24 notifiable infectious diseases in China before and during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic, along with the implementation of public health and social measures (PHSMs), have markedly reshaped infectious disease transmission dynamics. We analysed the impact of PHSMs on 24 notifiable infectious diseases (NIDs) in the Chinese mainland, using time series models to forecast transmission trends without PHSMs or pandemic. Our findings revealed distinct seasonal patterns in NID incidence, with respiratory diseases showing the greatest response to PHSMs, while bloodborne and sexually transmitted diseases responded more moderately. 8 NIDs were identified as susceptible to PHSMs, including hand, foot, and mouth disease, dengue fever, rubella, scarlet fever, pertussis, mumps, malaria, and Japanese encephalitis. The termination of PHSMs did not cause NIDs resurgence immediately, except for pertussis, which experienced its highest peak in December 2023 since January 2008. Our findings highlight the varied impact of PHSMs on different NIDs and the importance of sustainable, long-term strategies, like vaccine development.

Social contacts patterns relevant to the transmission of infectious diseases in Suzhou, China following the COVID-19 epidemic.

BACKGROUND: The COVID-19 pandemic has profoundly affected human social contact patterns, but there is limited understanding regarding the post-pandemic social contact patterns. Our objective is to quantitatively assess social contact patterns in Suzhou post-COVID-19. METHODS: We employed a diary design and conducted social contact surveys from June to October 2023, utilizing paper questionnaires. A generalized linear model was utilized to analyze the relationship between individual contacts and covariates. We examined the proportions of contact type, location, duration, and frequency. Additionally, age-related mixed matrices were established. RESULTS: The participants reported an average of 11.51 (SD 5.96) contact numbers and a total of 19.78 (SD 20.94) contact numbers per day, respectively. The number of contacts was significantly associated with age, household size, and the type of week. Compared to the 0-9 age group, those in the 10-19 age group reported a higher number of contacts (IRR = 1.12, CI: 1.01-1.24), while participants aged 20 and older reported fewer (IRR range: 0.54-0.67). Larger households (5 or more) reported more contacts (IRR = 1.09, CI: 1.01-1.18) and fewer contacts were reported on weekends (IRR = 0.95, CI: 0.90-0.99). School had the highest proportion of contact durations exceeding 4 h (49.5%) and daily frequencies (90.4%), followed by home and workplace. The contact patterns exhibited clear age-assortative mixing, with Q indices of 0.27 and 0.28. CONCLUSIONS: We assessed the characteristics of social contact patterns in Suzhou, which are essential for parameterizing models of infectious disease transmission. The high frequency and intensity of contacts among school-aged children should be given special attention, making school intervention policies a crucial component in controlling infectious disease transmission.

Mortality Associated with Priority Diseases in Flood-Affected Areas Using District Health Information System (DHIS2) During September-December 2022: Pakistan Experience.

OBJECTIVES: To quantify the burden of communicable diseases and characterize the most reported infections during public health emergency of floods in Pakistan. METHODS: The study's design is a descriptive trend analysis. The study utilized the disease data reported to District Health Information System (DHIS2) for the 12 most frequently reported priority diseases under the Integrated Disease Surveillance and Response (IDSR) system in Pakistan. RESULTS: In total, there were 1,532,963 suspected cases during August to December 2022 in flood-affected districts (n = 75) across Pakistan; Sindh Province reported the highest number of cases (n = 692,673) from 23 districts, followed by Khyber Pakhtunkhwa (KP) (n = 568,682) from 17 districts, Balochistan (n = 167,215) from 32 districts, and Punjab (n = 104,393) from 3 districts. High positivity was reported for malaria (79,622/201,901; 39.4%), followed by acute diarrhea (non-cholera) (23/62; 37.1%), hepatitis A and E (47/252; 18.7%), and dengue (603/3245; 18.6%). The crude mortality rate was 11.9 per 10 000 population (1824/1,532,963 [deaths/cases]). CONCLUSION: The study identified acute respiratory infection, acute diarrhea, malaria, and skin diseases as the most prevalent diseases. This suggests that preparedness efforts and interventions targeting these diseases should be prioritized in future flood response plans. The study highlights the importance of strengthening the IDSR as a Disease Early Warning System through the implementation of the DHIS2.

Contagion dynamics in time-varying metapopulation networks with node's activity and attractiveness.

The metapopulation network model is a mathematical framework used to study the spatial spread of epidemics with individuals' mobility. In this paper, we develop a time-varying network model in which the activity of a population is correlated with its attractiveness in mobility. By studying the spreading dynamics of the SIR (susceptible-infectious-recovered)-type disease in different correlated networks based on the proposed model, we theoretically derive the mobility threshold and numerically observe that increasing the correction between activity and attractiveness results in a reduced mobility threshold but suppresses the fraction of infected subpopulations. It also introduces greater heterogeneity in the spatial distribution of infected individuals. Additionally, we investigate the impact of nonpharmaceutical interventions on the spread of epidemics in different correlation networks. Our results show that the simultaneous implementation of self-isolation and self-protection is more effective in negatively correlated networks than that in positively correlated or non-correlated networks. Both self-isolation and self-protection strategies enhance the mobility threshold and, thus, slow down the spread of the epidemic. However, the effectiveness of each strategy in reducing the fraction of infected subpopulations varies in different correlated networks. Self-protection is more effective in positively correlated networks, whereas self-isolation is more effective in negatively correlated networks. Our study will provide insights into epidemic prevention and control in large-scale time-varying metapopulation networks.

The burden of infectious diseases throughout and after the COVID-19 pandemic (2020-2023) and Russo-Ukrainian war migration.

Understanding how the infectious disease burden was affected throughout the COVID-19 pandemic is pivotal to identifying potential hot spots and guiding future mitigation measures. Therefore, our study aimed to analyze the changes in the rate of new cases of Poland's most frequent infectious diseases during the entire COVID-19 pandemic and after the influx of war refugees from Ukraine. We performed a registry-based population-wide study in Poland to analyze the changes in the rate of 24 infectious disease cases from 2020 to 2023 and compared them to the prepandemic period (2016-2019). Data were collected from publicly archived datasets of the Epimeld database published by national epidemiological authority institutions. The rate of most of the studied diseases (66.6%) revealed significantly negative correlations with the rate of SARS-CoV-2 infections. For the majority of infectious diseases, it substantially decreased in 2020 (in case of 83%) and 2021 (63%), following which it mostly rebounded to the prepandemic levels and, in some cases, exceeded them in 2023 when the exceptionally high annual rates of new cases of scarlet fever, Streptococcus pneumoniae infections, HIV infections, syphilis, gonococcal infections, and tick-borne encephalitis were noted. The rate of Clostridioides difficile enterocolitis was two-fold higher than before the pandemic from 2021 onward. The rate of Legionnaires' disease in 2023 also exceeded the prepandemic threshold, although this was due to a local outbreak unrelated to lifted COVID-19 pandemic restrictions or migration of war refugees. The influx of war migrants from Ukraine could impact the epidemiology of sexually transmitted diseases. The present analysis indicates that continued efforts are needed to prevent COVID-19 from overwhelming healthcare systems again and decreasing the control over the burden of other infectious diseases. It also identifies the potential tipping points that require additional mitigation measures, which are also discussed in the paper, to avoid escalation in the future.

Obesity is a communicable disease.

Obesity has multiple causes and correlates. Usually studied as a metabolic and endocrine disease, with mechanical and musculoskeletal comorbidities, obesity also has a communicable angle to it. Obesity can be considered a communicable disease from the conventional point of view, as it is associated with viral etiology in animal and human models. It is also associated with increased prevalence and worse prognosis of infectious diseases. Not only that, obesity is a 'socially communicable' disease, as it 'spreads' amongst people living in similar environments.

Vitamin D and viral infections: Infectious diseases, autoimmune diseases, and cancers.

Viruses can cause many human diseases. Three types of human diseases caused by viruses are discussed in this chapter: infectious diseases, autoimmune diseases, and cancers. The infectious diseases included in this chapter include three respiratory tract diseases: influenza, COVID-19, and respiratory syncytial virus. In addition, the mosquito-borne dengue virus diseases are discussed. Vitamin D can reduce risk, severity, and mortality of the respiratory tract diseases and possibly for dengue virus. Many autoimmune diseases are initiated by the body's reaction to a viral infection. The protective role of vitamin D in Epstein-Barr virus-related diseases such as multiple sclerosis is discussed. There are a few cancers linked to viral infections. Such cancers include cervical cancer, head and neck cancers, Hodgkin's and non-Hodgkin's lymphoma, and liver cancer. Vitamin D plays an important role in reducing risk of cancer incidence and mortality, although not as strongly for viral-linked cancers as for other types of cancer.