Ophthalmic and immunopathological characterization of systemic infectious diseases in cats.

Ocular involvement in systemic diseases is frequent in cats; however, without concurrent clinical and ophthalmic examinations with gross and/or histologic analysis of the eye, these findings can be underdiagnosed. This article aims to provide gross, histologic, and immunohistochemical characteristics of ocular lesions from cats submitted to necropsy, focusing on those caused by systemic infectious agents. Cats that died due to a systemic infectious disease were selected based on necropsy diagnosis and presence of ocular lesions. Gross, histologic, and immunohistochemical findings were recorded. From April 2018 to September 2019, 849 eyes of 428 cats were evaluated. Histologic abnormalities were seen in 29% of cases, which were classified as inflammatory (41%), neoplastic (32%), degenerative (19%), and metabolic/vascular (8%). Macroscopic changes were present in one-third of eyes with histologic lesions. Of these, 40% were attributed to inflammatory or neoplastic diseases associated with infectious agents. The most important infectious agents causing ocular disease in this study were feline leukemia virus, feline infectious peritonitis virus, and Cryptococcus sp. The most common ocular abnormalities associated with infectious agents were uveitis (anterior, posterior, or panuveitis), optic neuritis, and meningitis of the optic nerve. Ocular lesions secondary to systemic infections in cats are frequent; however, these are not always diagnosed because gross lesions are less common than histologic lesions. Therefore, both gross and histologic evaluation of the eyes of cats is recommended, mainly for cases in which the clinical suspicion or necropsy diagnosis suggests that an infectious agent might be related to the cause of death.

A four-part guide to lung immunology: Invasion, inflammation, immunity, and intervention.

Lungs are important respiratory organs primarily involved in gas exchange. Lungs interact directly with the environment and their primary function is affected by several inflammatory responses caused by allergens, inflammatory mediators, and pathogens, eventually leading to disease. The immune architecture of the lung consists of an extensive network of innate immune cells, which induce adaptive immune responses based on the nature of the pathogen(s). The balance of immune responses is critical for maintaining immune homeostasis in the lung. Infection by pathogens and physical or genetic dysregulation of immune homeostasis result in inflammatory diseases. These responses culminate in the production of a plethora of cytokines such as TSLP, IL-9, IL-25, and IL-33, which have been implicated in the pathogenesis of several inflammatory and autoimmune diseases. Shifting the balance of Th1, Th2, Th9, and Th17 responses have been the targets of therapeutic interventions in the treatment of these diseases. Here, we have briefly reviewed the innate and adaptive i3mmune responses in the lung. Genetic and environmental factors, and infection are the major causes of dysregulation of various functions of the lung. We have elaborated on the impact of inflammatory and infectious diseases, advances in therapies, and drug delivery devices on this critical organ. Finally, we have provided a comprehensive compilation of different inflammatory and infectious diseases of the lungs and commented on the pros and cons of different inhalation devices for the management of lung diseases. The review is intended to provide a summary of the immunology of the lung, with an emphasis on drug and device development.

The differential expression of toll like receptors and RIG-1 correlates to the severity of infectious diseases.

The toll like receptors (TLRs) and RIG-1 are proteins involved in the initial reaction of the innate immune system to infectious diseases and, thus, can provide much information to the surgical pathologist in terms of the molecular dynamics of the infection. The TLRs (TLR1, 2, 3, 4, 7, 8) and RIG-1 distribution as determined by immunohistochemistry was examined in the following diseases: human papillomavirus (n = 30 including 15 squamous intraepithelial lesions (SIL), 5 cancers, and 10 controls); molluscum contagiosum (n = 8 including 4 controls), SARS-CoV2 (n = 52 including 20 mild, 5 fatal, and 27 controls) and reovirus infection as oncolytic therapy. Mild, regressing infection (molluscum contagiosum, mild SARS-CoV2 and low grade SIL) each showed the same pattern: marked up regulation of at least three of the TLRs/RIG-1 with decreased expression of none compared to the controls. Severe infection (fatal SARS-CoV2, and cervical cancer) each showed marked decrease expression in at least three of the TLRs/RIG-1. We recently documented an equivalent marked decrease expression of the TLRs/RIG-1 in the placenta in fatal in utero infections. The reoviral infected tissues showed an overall pattern of marked increase expression of TLRs/RIG-1, consistent with a strong anti-viral response. Thus, the in situ testing of infectious diseases by a panel of these early infectious disease recognition proteins may allow the surgical pathologist to predict the outcome of the disease which, in turn, may assist in the understanding of the role of the TLRs/RIG-1 in determining the fate of a given infectious process.

Precision-cut lung slices: A powerful ex vivo model to investigate respiratory infectious diseases.

Respiratory infections are a leading cause of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid, or surrogate animal models. Although these provide important insights, they have limitations. Cell culture models fail to recapitulate cellular interactions in the lung and animal models often do not permit high-throughput analysis of drugs or pathogen isolates; hence, there is a need for improved, scalable models. Precision-cut lung slices (PCLS), small, uniform tissue slices generated from animal or human lungs are increasingly recognized and employed as an ex vivo organotypic model. PCLS retain remarkable cellular complexity and the architecture of the lung, providing a platform to investigate respiratory pathogens in a near-native environment. Here, we review the generation and features of PCLS, their use to investigate the pathogenesis of viral and bacterial pathogens, and highlight their potential to advance respiratory infection research in the future.

Simple epidemic models with segmentation can be better than complex ones.

Given a sequence of epidemic events, can a single epidemic model capture its dynamics during the entire period? How should we divide the sequence into segments to better capture the dynamics? Throughout human history, infectious diseases (e.g., the Black Death and COVID-19) have been serious threats. Consequently, understanding and forecasting the evolving patterns of epidemic events are critical for prevention and decision making. To this end, epidemic models based on ordinary differential equations (ODEs), which effectively describe dynamic systems in many fields, have been employed. However, a single epidemic model is not enough to capture long-term dynamics of epidemic events especially when the dynamics heavily depend on external factors (e.g., lockdown and the capability to perform tests). In this work, we demonstrate that properly dividing the event sequence regarding COVID-19 (specifically, the numbers of active cases, recoveries, and deaths) into multiple segments and fitting a simple epidemic model to each segment leads to a better fit with fewer parameters than fitting a complex model to the entire sequence. Moreover, we propose a methodology for balancing the number of segments and the complexity of epidemic models, based on the Minimum Description Length principle. Our methodology is (a) Automatic: not requiring any user-defined parameters, (b) Model-agnostic: applicable to any ODE-based epidemic models, and (c) Effective: effectively describing and forecasting the spread of COVID-19 in 70 countries.

Using fiction to engage audiences with infectious disease: the effect of the coronavirus pandemic on participation in the Bad Bugs Bookclub.

During Bad Bugs Bookclub meetings, scientists and non-scientists discuss novels in which infectious disease forms part of the plot in order to encourage public understanding of, and engagement with, microbiology. The website presents meeting reports and reading guides for over 70 novels. The aim of this work was to raise awareness of the bookclub and increase website engagement. In 2019, events designed to reach new audiences maintained an increase in page views from the end of 2018 (around 200 per month). In 2020, the coronavirus pandemic forced bookclub meetings online (Zoom). These, with podcasts and some Twitter discussion, increased page views with a peak of 400 per month. Membership increased, and global 'attendance' was facilitated. Feelings and observations related to each book and the pandemic were noted in meeting reports. A survey of current and previous bookclub members carried out early in lockdown with the aim of determining the future direction of the bookclub revealed the continuing value of both literary and scientific experiences to members. The bookclub has engaged scientists and non-scientists in meaningful discussion about infectious disease. Reach is modest, but the resource is significant, with potential impact in education and engagement.

COVID-19 Toes and Other Skin Lesions During the Pandemic: Emerging Entities?

There is accumulating evidence to indicate an association between coronavirus infectious disease 2019 (COVID-19) and clusters of incident cutaneous eruptions. Of these, chilblains-like perniosis have received widespread medical and media attention. These typically affect the toes, and have been called "COVID-toes." Other acral lesions such as large bullae have also been reported. However, a definitive causal relationship with the severe acute respiratory syndrome coronavirus 2 has not yet been definitively proven, nor has a pathogenic mechanism been established. These episodes are self-limiting, but we need to know whether long-term sequelae exist.

Online respondent-driven detection for enhanced contact tracing of close-contact infectious diseases: benefits and barriers for public health practice.

BACKGROUND: Online respondent-driven detection (RDD) is a novel method of case finding that can enhance contact tracing (CT). However, the advantages and challenges of RDD for CT have not yet been investigated from the perspective of public health professionals (PHPs). Therefore, it remains unclear if, and under what circumstances, PHPs are willing to apply RDD for CT. METHODS: Between March and April 2019, we conducted semi-structured interviews with Dutch PHPs responsible for CT in practice. Questions were derived from the 'diffusion of innovations' theory. Between May and June 2019, we distributed an online questionnaire among 260 Dutch PHPs to quantify the main qualitative findings. Using different hypothetical scenarios, we assessed anticipated advantages and challenges of RDD, and PHPs' intention to apply RDD for CT. RESULTS: Twelve interviews were held, and 70 PHPs completed the online questionnaire. A majority of questionnaire respondents (71%) had a positive intention towards using RDD for CT. Anticipated advantages of RDD were 'accommodating easy and autonomous participation in CT of index cases and contact persons', and 'reaching contact persons more efficiently'. Anticipated challenges were 'limited opportunities for PHPs to support, motivate, and coordinate the execution of CT', 'not being able to adequately convey measures to index cases and contact persons', and 'anticipated unrest among index cases and contact persons'. Circumstances under which PHPs anticipated RDD applicable for CT included index cases and contact persons being reluctant to share information directly with PHPs, digitally skilled and literate persons being involved, and large scale CT. Circumstances under which PHPs anticipated RDD less applicable for CT included severe consequences of missing information or contact persons for individual or public health, involvement of complex or impactful measures for index cases and contact persons, and a disease being perceived as severe or sensitive by index cases and their contact persons. CONCLUSIONS: PHPs generally perceived RDD as a potentially beneficial method for public health practice, that may help overcome challenges present in traditional CT, and could be used during outbreaks of infectious diseases that spread via close contact. The circumstances under which CT is performed, appear to strongly influence PHPs' intention to use RDD for CT.

Eliciting B cell immunity against infectious diseases using nanovaccines.

Infectious diseases, including the coronavirus disease 2019 (COVID-19) pandemic that has brought the world to a standstill, are emerging at an unprecedented rate with a substantial impact on public health and global economies. For many life-threatening global infectious diseases, such as human immunodeficiency virus (HIV) infection, malaria and influenza, effective vaccinations are still lacking. There are numerous roadblocks to developing new vaccines, including a limited understanding of immune correlates of protection to these global infections. To induce a reproducible, strong immune response against difficult pathogens, sophisticated nanovaccine technologies are under investigation. In contrast to conventional vaccines, nanovaccines provide improved access to lymph nodes, optimal packing and presentation of antigens, and induction of a persistent immune response. This Review provides a perspective on the global trends in emerging nanoscale vaccines for infectious diseases and describes the biological, experimental and logistical problems associated with their development, and how immunoengineering can be leveraged to overcome these challenges.

Preserve a Voucher Specimen! The Critical Need for Integrating Natural History Collections in Infectious Disease Studies.

Despite being nearly 10 months into the COVID-19 (coronavirus disease 2019) pandemic, the definitive animal host for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19, remains unknown. Unfortunately, similar problems exist for other betacoronaviruses, and no vouchered specimens exist to corroborate host species identification for most of these pathogens. This most basic information is critical to the full understanding and mitigation of emerging zoonotic diseases. To overcome this hurdle, we recommend that host-pathogen researchers adopt vouchering practices and collaborate with natural history collections to permanently archive microbiological samples and host specimens. Vouchered specimens and associated samples provide both repeatability and extension to host-pathogen studies, and using them mobilizes a large workforce (i.e., biodiversity scientists) to assist in pandemic preparedness. We review several well-known examples that successfully integrate host-pathogen research with natural history collections (e.g., yellow fever, hantaviruses, helminths). However, vouchering remains an underutilized practice in such studies. Using an online survey, we assessed vouchering practices used by microbiologists (e.g., bacteriologists, parasitologists, virologists) in host-pathogen research. A much greater number of respondents permanently archive microbiological samples than archive host specimens, and less than half of respondents voucher host specimens from which microbiological samples were lethally collected. To foster collaborations between microbiologists and natural history collections, we provide recommendations for integrating vouchering techniques and archiving of microbiological samples into host-pathogen studies. This integrative approach exemplifies the premise underlying One Health initiatives, providing critical infrastructure for addressing related issues ranging from public health to global climate change and the biodiversity crisis.

Mathematical modeling and cellular automata simulation of infectious disease dynamics: Applications to the understanding of herd immunity.

The complexity associated with an epidemic defies any quantitatively reliable predictive theoretical scheme. Here, we pursue a generalized mathematical model and cellular automata simulations to study the dynamics of infectious diseases and apply it in the context of the COVID-19 spread. Our model is inspired by the theory of coupled chemical reactions to treat multiple parallel reaction pathways. We essentially ask the question: how hard could the time evolution toward the desired herd immunity (HI) be on the lives of people? We demonstrate that the answer to this question requires the study of two implicit functions, which are determined by several rate constants, which are time-dependent themselves. Implementation of different strategies to counter the spread of the disease requires a certain degree of a quantitative understanding of the time-dependence of the outcome. Here, we compartmentalize the susceptible population into two categories, (i) vulnerables and (ii) resilients (including asymptomatic carriers), and study the dynamical evolution of the disease progression. We obtain the relative fatality of these two sub-categories as a function of the percentages of the vulnerable and resilient population and the complex dependence on the rate of attainment of herd immunity. We attempt to study and quantify possible adverse effects of the progression rate of the epidemic on the recovery rates of vulnerables, in the course of attaining HI. We find the important result that slower attainment of the HI is relatively less fatal. However, slower progress toward HI could be complicated by many intervening factors.

Evaluating approaches to designing effective Co-Created hand-hygiene interventions for children in India, Sierra Leone and the UK.

Effective and culturally appropriate hand-hygiene education is essential to promote health-related practices to control and prevent diseases such as Diarrhoea, Ebola and COVID-19. In this paper we outline and evaluate the Co-Creation processes underpinning a handwashing intervention for young children (A Germ's Journey) developed and delivered in India, Sierra Leone and the UK, and consider the implications surrounding Imperialist/Colonial discourse and the White Saviour Complex. The paper focuses both on the ways Co-Creation was conceptualised by our collaborators in all three countries and the catalysts and challenges encountered. Qualitative data have been drawn from in-depth interviews with five key stakeholders, focus group data from 37 teachers in Sierra Leone and responses to open-ended questionnaires completed by teachers in India (N = 66) and UK (N = 63). Data were analysed using thematic analysis and three themes, each with three constituent subthemes are presented. In the theme 'Representations of and Unique Approaches to Co-Creation' we explore the ways in which Co-Creation was constructed in relation to teamwork, innovative practice and more continuous models of evaluation. In 'Advantages of Co-Creation' we consider issues around shared ownership, improved outcomes and more meaningful insights alongside the mitigation of risks and short-circuiting of problems. In 'Challenges of Co-Creation' we discuss issues around timing and organisation, attracting and working with appropriate partners and understanding the importance of local context with inherent social, economic and structural barriers, especially in low-and-middle-income countries. We consider how theoretical elements of Co-Creation can inform effective international public health interventions; crucial during a global pandemic in which handwashing is the most effective method to control the transmission of COVID-19. Finally we reflect on some of the methodological challenges of our own work and in managing the potentially conflicting goals of the ethical and participatory values of Co-Creation with pragmatic considerations about ensuring an effective final 'product'.

Universal Precautions Provide Appropriate Protection during Autopsies of Patients with Infectious Diseases.

The current coronavirus disease 2019 (COVID-19) pandemic has raised concerns about the safety of laboratory personnel who handle tissue samples that harbor pathogens, including those performing autopsies. While pathologists have performed autopsies on infected decedents for centuries, universal precaution protocols for limiting exposure to pathogens were not developed until the 20th century. This article reviews the history and effectiveness of universal precautions, with an emphasis on performing autopsies on COVID-19 decedents.