gcPathogen: a comprehensive genomic resource of human pathogens for public health.

Here, we present the manually curated Global Catalogue of Pathogens (gcPathogen), an extensive genomic resource designed to facilitate rapid and accurate pathogen analysis, epidemiological exploration and monitoring of antibiotic resistance features and virulence factors. The catalogue seamlessly integrates and analyzes genomic data and associated metadata for human pathogens isolated from infected patients, animal hosts, food and the environment. The pathogen list is supported by evidence from medical or government pathogenic lists and publications. The current version of gcPathogen boasts an impressive collection of 1 164 974 assemblies comprising 986 044 strains from 497 bacterial taxa, 4794 assemblies encompassing 4319 strains from 265 fungal taxa, 89 965 assemblies featuring 13 687 strains from 222 viral taxa, and 646 assemblies including 387 strains from 159 parasitic taxa. Through this database, researchers gain access to a comprehensive 'one-stop shop' that facilitates global, long-term public health surveillance while enabling in-depth analysis of genomes, sequence types, antibiotic resistance genes, virulence factors and mobile genetic elements across different countries, diseases and hosts. To access and explore the data and statistics, an interactive web interface has been developed, which can be accessed at https://nmdc.cn/gcpathogen/. This user-friendly platform allows seamless querying and exploration of the extensive information housed within the gcPathogen database.

Burdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status.

The Post-Acute Sequelae of SARS-CoV-2 infection (PASC) have been characterized; however, the burden of PASC remains unknown. Here we used the healthcare databases of the US Department of Veterans Affairs to build a cohort of 181,384 people with COVID-19 and 4,397,509 non-infected controls and estimated that burden of PASC-defined as the presence of at least one sequela in excess of non-infected controls-was 73.43 (72.10, 74.72) per 1000 persons at 6 months. Burdens of individual sequelae varied by demographic groups (age, race, and sex) but were consistently higher in people with poorer baseline health and in those with more severe acute infection. In sum, the burden of PASC is substantial; PASC is non-monolithic with sequelae that are differentially expressed in various population groups. Collectively, our results may be useful in informing health systems capacity planning and care strategies of people with PASC.

Neutrophil Extracellular Traps Affecting Cardiovascular Health in Infectious and Inflammatory Diseases.

Neutrophil extracellular traps (NETs) are web-like structures of decondensed extracellular chromatin fibers and neutrophil granule proteins released by neutrophils. NETs participate in host immune defense by entrapping pathogens. They are pro-inflammatory in function, and they act as an initiator of vascular coagulopathies by providing a platform for the attachment of various coagulatory proteins. NETs are diverse in their ability to alter physiological and pathological processes including infection and inflammation. In this review, we will summarize recent findings on the role of NETs in bacterial/viral infections associated with vascular inflammation, thrombosis, atherosclerosis and autoimmune disorders. Understanding the complex role of NETs in bridging infection and chronic inflammation as well as discussing important questions related to their contribution to pathologies outlined above may pave the way for future research on therapeutic targeting of NETs applicable to specific infections and inflammatory disorders.

Miller Fisher Syndrome Triggered by Infections: A Review of the Literature and a Case Report.

AIM: We reported a case of Miller Fisher syndrome following a breakthrough varicella zoster virus infection in an otherwise healthy 6-year-old male. The objective of this review was to summarize the infectious etiologic agents known to trigger Miller Fisher syndrome. METHODS: Review of the literature on infections associated with Miller Fisher syndrome. RESULTS: We identified 762 studies after duplicates were removed. Titles, abstracts, and full texts were screened. Finally, 37 studies were included in qualitative synthesis after citations and reference list were checked. The age range of cases reported was 0-78 years, and male sex was predominant in studies where these parameters were reported. The most common causative agent was Campylobacter jejuni followed by Haemophilus influenzae. CONCLUSIONS: Our review highlights the importance of recognizing the infections triggering Miller Fisher syndrome. We also present a unique case of Miller Fisher syndrome associated with breakthrough varicella zoster virus infection. Preventive policies may consider population immunization for certain causative agents.

Sample size calculation for phylogenetic case linkage.

Sample size calculations are an essential component of the design and evaluation of scientific studies. However, there is a lack of clear guidance for determining the sample size needed for phylogenetic studies, which are becoming an essential part of studying pathogen transmission. We introduce a statistical framework for determining the number of true infector-infectee transmission pairs identified by a phylogenetic study, given the size and population coverage of that study. We then show how characteristics of the criteria used to determine linkage and aspects of the study design can influence our ability to correctly identify transmission links, in sometimes counterintuitive ways. We test the overall approach using outbreak simulations and provide guidance for calculating the sensitivity and specificity of the linkage criteria, the key inputs to our approach. The framework is freely available as the R package phylosamp, and is broadly applicable to designing and evaluating a wide array of pathogen phylogenetic studies.

Complex Roles of Neutrophils during Arboviral Infections.

Arboviruses are known to cause large-scale epidemics in many parts of the world. These arthropod-borne viruses are a large group consisting of viruses from a wide range of families. The ability of their vector to enhance viral pathogenesis and transmission makes the development of treatments against these viruses challenging. Neutrophils are generally the first leukocytes to be recruited to a site of infection, playing a major role in regulating inflammation and, as a result, viral replication and dissemination. However, the underlying mechanisms through which neutrophils control the progression of inflammation and disease remain to be fully understood. In this review, we highlight the major findings from recent years regarding the role of neutrophils during arboviral infections. We discuss the complex nature of neutrophils in mediating not only protection, but also augmenting disease pathology. Better understanding of neutrophil pathways involved in effective protection against arboviral infections can help identify potential targets for therapeutics.

Expresión de infección por SARS-CoV-2 en niños: infección aguda sintomática y síndrome inflamatorio multisistémico.

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In vitro three-dimensional organotypic culture models of the oral mucosa.

Three-dimensional, organotypic models of the oral mucosa have been developed to study a wide variety of phenomena occurring in the oral cavity. Although a number of models have been developed in academic research labs, only a few models have been commercialized. Models from academic groups offer a broader range of phenotypes while the commercial models are more focused on the oral and gingival mucosa. The commercialized models are manufactured under highly controlled conditions and meet the requirements of quality standards, which leads to high levels of reproducibility. These in vitro models have been used to evaluate the irritancy of oral care products such as toothpastes, mouthwashes, and mucoadhesives. The effects of cigarette smoke on oral cavity tissues have been studied and compared to those of e-cigarettes. Oral tissue models have facilitated investigation of the mechanisms of oral mucositis and oral candidiasis and have been used to examine transbuccal drug delivery rates and the absorption of nanoparticles. Infection studies have investigated the effects of HIV-1 along with the effects of commensal and pathogenic bacteria. More recently, a differentiated oral tissue model has been shown to express the ACE2 receptor, which is known to be important for the receptor-mediated entry of the SARS-CoV-2 coronavirus into human cells and tissues. Hence, oral mucosal models may find application in determining whether viral infection of the oral mucosa is possible and whether such infection has implications vis-a-vis the current COVID-19 pandemic. As is apparent, these models are used in a broad variety of applications and often offer advantages versus animal models in terms of reproducibility, avoiding species extrapolation, and the ethical concerns related to human and animal experimentation. The goals of this paper are to review commercially available models of the human buccal and gingival mucosa and highlight their use to gain a better understanding of a broad range of phenomena affecting tissues in the oral cavity.

PANoptosis in microbial infection.

The immune system has evolved multiple mechanisms to restrict microbial infections and regulate inflammatory responses. Without appropriate regulation, infection-induced inflammatory pathology can be deadly. The innate immune system recognizes the microbial molecules conserved in many pathogens and engages a rapid response by producing inflammatory mediators and activating programmed cell death pathways, including pyroptosis, apoptosis, and necroptosis. Activation of pattern recognition receptors, in combination with inflammatory cytokine-induced signaling through death domain-containing receptors, initiates a highly interconnected cell death process called PANoptosis (pyroptosis, apoptosis, necroptosis). Broadly speaking, PANoptosis is critical for restricting a wide range of pathogens (including bacteria, viruses, fungi, and parasites), which we describe in this review. We propose that re-examining the role of cell death and inflammatory cytokines through the lens of PANoptosis will advance our understanding of host-pathogen evolution and may reveal new treatment strategies for controlling a wide range of infectious diseases.

Infectious and non-infectious diseases burden among Haitian immigrants in Chile: a cross-sectional study.

Chile has become a popular destination for migrants from South America and the Caribbean (low- and middle-income countries migration). Close to 200.000 Haitian migrants have arrived in Chile. Infectious and non-infectious disease burden among the Haitian adult population living in Chile is unknown. This study aimed to acquire the basic health information (selected transmissible and non-transmissible conditions) of the Haitian adult population living in Chile. A cross-sectional survey was performed, inviting Haitian-born residents in Chile older than 18 years old. Common conditions and risk factors for disease were assessed, as well as selected transmissible conditions (HIV, HBV, and HCV). 498 participants (60.4% female) from 10 communities in two regions of Chile were surveyed. Most subjects had never smoked (91.5%), and 80% drank less than one alcohol unit per month. The mean BMI was 25.6, with 45% of participants having a normal BMI (20-25). Hypertension was present in 31.5% (33% in the 25-44 age group). Prevalence of HIV was 2.4% (95 CI 1.3-4.2%), hepatitis B (HBsAg positive) was 3.4% (95 CI 2.1-5.5%), and hepatitis C was 0% (95 CI 0.0-0.9%). Quality of life showed a significant prevalence of depression and anxiety markers, particularly in those arriving in Chile less than 1 year ago. Low prevalence of obesity, diabetes, smoking, and drinking and estimated cardiovascular risk were found. Nonetheless, hypertension at a younger age, disproportionately higher prevalence of HIV and HBV infection and frequent markers of anxiety and depression were also found. Public policies for detecting and treating hypertension, HIV, and HBV screening, offering HBV vaccination, and organizing mental health programs for Haitian immigrants, are urgently needed.

How many human pathogens are there in Laos? An estimate of national human pathogen diversity and analysis of historical trends.

OBJECTIVE: The emergence of infectious diseases pose major global health threats. Estimates of total in-country human pathogen diversity, and insights as to how and when species were described through history, could be used to estimate the probability of new pathogen discoveries. Data from the Lao People's Democratic Republic (Laos) were used in this proof-of-concept study to estimate national human pathogen diversity and to examine historical discovery rate drivers. METHODS: A systematic survey of the French and English scientific and grey literature of pathogen description in Laos between 1874 and 2017 was conducted. The first descriptions of each known human pathogen in Laos were coded according to the diagnostic evidence available. Cumulative frequency of discovery across time informed the rate of discovery. Four distinct periods of health systems development in Laos were identified prospectively and juxtaposed to the unmodelled rate of discovery. A model with a time-varying rate of discovery was fitted to these data using a Markov-Chain- Monte-Carlo technique. RESULTS: From 6456 pathogen descriptions, 245 discoveries of known human pathogens in Laos, including repeat discoveries using different grades of evidence, were identified. The models estimate that the Laos human pathogen species diversity in 2017 is between 169 and 206. During the last decade, there has been a 33-fold increase in the discovery rate coinciding with the strengthening of medical research and microbiology. CONCLUSION: Discovery curves can be used to model and estimate country-level human pathogen diversity present in a territory. Combining this with historical assessment improves the understanding of the factors affecting local pathogen discovery. PROSPERO REGISTRATION NUMBER: A protocol of this work was registered on PROSPERO (ID:CRD42016046728).

Autophagy and Inflammatory Diseases.

Autophagy is an essential biological process for cells to maintain their homeostasis. It is a complex regulatory system that integrates innate and adaptive immunity. The role of autophagy in immune diseases has been paid more and more attention with the deepening of the mutual regulation and mechanism of autophagy and immunity. It is found that the aberrant autophagy is closely related to inflammatory diseases, including infections, adaptive immune-associated inflammation and inflammatory bowel disease. Autophagy plays critical roles in the activation of NLRP3 inflammasome, the clearance of bacterial and viral infections and what is more, the function of adaptive immune cells.

LRCH1 deficiency enhances LAT signalosome formation and CD8+ T cell responses against tumors and pathogens.

CD8+ T cells play pivotal roles in eradicating pathogens and tumor cells. T cell receptor (TCR) signaling is vital for the optimal activation of CD8+ T cells. Upon TCR engagement, the transmembrane adapter protein LAT (linker for activation of T cells) recruits other key signaling molecules and forms the "LAT signalosome" for downstream signal transduction. However, little is known about which functional partners could restrain the formation of the LAT signalosome and inhibit CD8+ cytotoxic T lymphocyte (CTL)-mediated cytotoxicity. Here we have demonstrated that LRCH1 (leucine-rich repeats and calponin homology domain containing 1) directly binds LAT, reduces LAT phosphorylation and interaction with GRB2, and also promotes the endocytosis of LAT. Lrch1-/- mice display better protection against influenza virus and Listeria infection, with enhanced CD8+ T cell proliferation and cytotoxicity. Adoptive transfer of Lrch1-/- CD8+ CTLs leads to increased B16-MO5 tumor clearance in vivo. Furthermore, knockout of LRCH1 in human chimeric antigen receptor (CAR) T cells that recognize the liver tumor-associated antigen glypican-3 could improve CAR T cell migration and proliferation in vitro. These findings suggest LRCH1 as a potential translational target to improve T cell immunotherapy against infection and tumors.

Infection within 2 weeks before liver transplantation closely related to prognosis of posttransplant infection: A single-center retrospective observational study in China.

BACKGROUND: Infections still represent the main factors influencing morbidity and mortality following liver transplantation. This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation. METHODS: We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital. Clinical manifestations and results of pathogen detection test were used to define infection. We analyzed the prevalence, risk factors and prognosis of patients with infection. RESULTS: The median follow-up was 214 days; the incidence of infection after liver transplantation was 46.7% (n = 98) which included pneumonia (43.4%), biliary tract infection (21.9%), peritonitis (21.4%) and bloodstream infection (7.6%). Among the pathogens in pneumonia, the most frequently isolated was Acinetobacter baumanii (23.5%) and Klebsiella pneumoniae (21.2%). Model for end-stage liver disease (MELD) score (OR = 1.083, 95% CI: 1.045-1.123; P < 0.001), biliary complication (OR = 4.725, 95% CI: 1.119-19.947; P = 0.035) and duration of drainage tube (OR = 1.040, 95% CI: 1.007-1.074; P = 0.017) were independent risk factors for posttransplant infection. All-cause mortality was 11.0% (n = 23). The prognostic factors for postoperative infection in liver recipients were prior-transplant infection, especially pneumonia within 2 weeks before transplantation. Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection (65.2% vs. 90.0%; hazard ratio: 4.480; P < 0.001). CONCLUSIONS: Infection, especially pneumonia within 2 weeks before transplantation, complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients.