A crucial role of neutrophil extracellular traps in pulmonary infectious diseases.

Neutrophil extracellular traps (NETs), extrusions of intracellular DNA with attached granular material that exert an antibacterial effect through entangling, isolating, and immobilizing microorganisms, have been extensively studied in recent decades. The primary role of NETs is to entrap and facilitate the killing of bacteria, fungi, viruses, and parasites, preventing bacterial and fungal dissemination. NET formation has been described in many pulmonary diseases, including both infectious and non-infectious. NETs are considered a double-edged sword. As innate immune cells, neutrophils release NETs to kill pathogens and remove cellular debris. However, the deleterious effects of excessive NET release in lung disease are particularly important because NETs and by-products of NETosis can directly induce epithelial and endothelial cell death while simultaneously inducing inflammatory cytokine secretion and immune-mediated thrombosis. Thus, NET formation must be tightly regulated to preserve the anti-microbial capability of NETs while minimizing damage to the host. In this review, we summarized the recent updates on the mechanism of NETs formation and pathophysiology associated with excessive NETs, aiming to provide insights for research and treatment of pulmonary infectious diseases.

AI-based epidemic and pandemic early warning systems: A systematic scoping review.

Background: Timely detection of disease outbreaks is critical in public health. Artificial Intelligence (AI) can identify patterns in data that signal the onset of epidemics and pandemics. This scoping review examines the effectiveness of AI in epidemic and pandemic early warning systems (EWS). Objective: To assess the capability of AI-based systems in predicting epidemics and pandemics and to identify challenges and strategies for improvement. Methods: A systematic scoping review was conducted. The review included studies from the last 5 years, focusing on AI and machine learning applications in EWS. After screening 1087 articles, 33 were selected for thematic analysis. Results: The review found that AI-based EWS have been effectively implemented in various contexts, using a range of algorithms. Key challenges identified include data quality, model explainability, bias, data volume, velocity, variety, availability, and granularity. Strategies for mitigating AI bias and improving system adaptability were also discussed. Conclusion: AI has shown promise in enhancing the speed and accuracy of epidemic detection. However, challenges related to data quality, bias, and model transparency need to be addressed to improve the reliability and generalizability of AI-based EWS. Continuous monitoring and improvement, as well as incorporating social and environmental data, are essential for future development.

Systematic review of knowledge, attitudes, and practices of dairy farmers and consumers towards bovine tuberculosis in low- and middle-income countries.

Bovine Tuberculosis (bTB), caused by Mycobacterium bovis, is a neglected zoonotic disease primarily associated with cattle. The incidence of bTB is highest in low-income settings with high cattle density and unpasteurised dairy consumption. Smallholder dairy farming has steadily grown in low- and middle-income countries (LMICs) with limited professional support for adequate bTB surveillance and risk mitigation. Several studies have explored the knowledge, attitudes, and practices (KAP) of milk value chain stakeholders towards bTB in LMICs, but this evidence has not been collated and synthesised. We conducted a systematic review to determine what is known, believed, and done in relation to bTB among dairy producers and consumers in LMICs. We performed a systematic search of studies in OVID Medline, Scopus and CABI on 11 September 2023. KAP data were summarised using narrative synthesis and forest plots. We retrieved 2763 articles, retaining 51 for the review. Only studies from Africa (n = 38) and Asia (n = 13) met the eligibility criteria. Most populations reported awareness of human tuberculosis and knew it could be treated, but there was limited awareness of bTB and its zoonotic potential. Knowledge of bTB transmission routes and bTB mitigation varied across populations, and risky practices were also variable. Inconsistencies in study design and survey tools suggest some results may have a mid- to high-risk of bias. Awareness of bTB is surprisingly low among African and Asian populations with high bTB exposure risk, possibly due to the long-standing divide between animal and human health messages that has obscured the One Health implications of bTB. Addressing bTB in LMICs requires a structural One Health approach and standard KAP survey tools to adequately explore the socio-cultural, political, and economic processes and drivers favouring bTB spread and persistence.

Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of developing serious infections (SIs) vs. individuals without RA; efforts to predict SIs in this patient group are ongoing. We assessed the ability of different machine learning modeling approaches to predict SIs using baseline data from the tofacitinib RA clinical trials program. METHODS: This analysis included data from 19 clinical trials (phase 2, n = 10; phase 3, n = 6; phase 3b/4, n = 3). Patients with RA receiving tofacitinib 5 or 10 mg twice daily (BID) were included in the analysis; patients receiving tofacitinib 11 mg once daily were considered as tofacitinib 5 mg BID. All available patient-level baseline variables were extracted. Statistical and machine learning methods (logistic regression, support vector machines with linear kernel, random forest, extreme gradient boosting trees, and boosted trees) were implemented to assess the association of baseline variables with SI (logistic regression only), and to predict SI using selected baseline variables using 5-fold cross-validation. Missing values were handled individually per prediction model. RESULTS: A total of 8404 patients with RA treated with tofacitinib were eligible for inclusion (15,310 patient-years of total follow-up) of which 473 patients reported SIs. Amongst other baseline factors, age, previous infection, and corticosteroid use were significantly associated with SI. When applying prediction modeling for SI across data from all studies, the area under the receiver operating characteristic (AUROC) curve ranged from 0.656 to 0.739. AUROC values ranged from 0.599 to 0.730 in data from phase 3 and 3b/4 studies, and from 0.563 to 0.643 in data from ORAL Surveillance only. CONCLUSIONS: Baseline factors associated with SIs in the tofacitinib RA clinical trial program were similar to established SI risk factors associated with advanced treatments for RA. Furthermore, while model performance in predicting SI was similar to other published models, this did not meet the threshold for accurate prediction (AUROC > 0.85). Thus, predicting the occurrence of SIs at baseline remains challenging and may be complicated by the changing disease course of RA over time. Inclusion of other patient-associated and healthcare delivery-related factors and harmonization of the duration of studies included in the models may be required to improve prediction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT02831855; NCT02092467.

Bat humoral immunity and its role in viral pathogenesis, transmission, and zoonosis.

Bats harbor viruses that can cause severe disease and death in humans including filoviruses (e.g., Ebola virus), henipaviruses (e.g., Hendra virus), and coronaviruses (e.g., SARS-CoV). Bats often tolerate these viruses without noticeable adverse immunological effects or succumbing to disease. Previous studies have largely focused on the role of the bat's innate immune response to control viral pathogenesis, but little is known about bat adaptive immunity. A key component of adaptive immunity is the humoral response, comprised of antibodies that can specifically recognize viral antigens with high affinity. The antibody genes within the 1,400 known bat species are highly diverse, and these genetic differences help shape fundamental aspects of the antibody repertoire, including starting diversity and viral antigen recognition. Whether antibodies in bats protect, mediate viral clearance, and prevent transmission within bat populations is poorly defined. Furthermore, it is unclear how neutralizing activity and Fc-mediated effector functions contribute to bat immunity. Although bats have canonical Fc genes (e.g., mu, gamma, alpha, and epsilon), the copy number and sequences of their Fc genes differ from those of humans and mice. The function of bat antibodies targeting viral antigens has been speculated based on sequencing data and polyclonal sera, but functional and biochemical data of monoclonal antibodies are lacking. In this review, we summarize current knowledge of bat humoral immunity, including variation between species, their potential protective role(s) against viral transmission and replication, and address how these antibodies may contribute to population dynamics within bats communities. A deeper understanding of bat adaptive immunity will provide insight into immune control of transmission and replication for emerging viruses with the potential for zoonotic spillover.

Influence of HIV status on outcomes of children admitted with sepsis at a paediatric hospital in Zambia: protocol for a prospective longitudinal study.

INTRODUCTION: Sepsis, a condition of global public health concern, is a major cause of morbidity and mortality, especially in patients with underlying HIV infection. This study aims to determine outcomes, aetiology and antibiotic resistance patterns among children with HIV exposure or infection admitted with a clinical presentation suggestive of sepsis who have confirmed bloodstream infections at Arthur Davison Children's Hospital (ADCH) in Ndola, Zambia. METHODS AND ANALYSIS: This will be a prospective longitudinal study of 200 children aged <2 years admitted with sepsis at ADCH with two of the following conditions: temperature of 38.0°C, respiratory rate ≥20 breaths per minute and pulse rate ≥90 beats per minute. About 2-5 mL of blood collected from each participant will be inoculated into BACTEC culture bottles and incubated for 5-7 days. Positive cultures will be inoculated onto culture media for subculture followed by species identification followed by antibiotic susceptibility testing. Time-to-event outcomes such as hospital readmission and mortality will be analysed using Kaplan-Meier and Cox proportional hazards. Predictors will be identified using regression methods. All statistical tests will use a 5% significance level with a 95% confidence level. STATA V.16 will be used for statistical analysis. ETHICS AND DISSEMINATION: Ethical clearance and approval have been granted by the Tropical Diseases Research Centre Ethics Committee (TDRC-EC 092/07/23). Caregiver consent will be obtained verbally for participants presenting as medical emergencies, and written informed consent will be obtained once stable. Findings from this study will be shared with the Ministry of Health Zambia and will be disseminated to the scientific community through peer-reviewed scientific journals.

Routine Infectious Diseases Consultations on a Pediatric Cardiac Unit to Improve Positive Blood Culture Management.

Bacteremia can be life-threatening, and highly medicalized patients, such as those with complex congenital heart disease, are at high risk. Infectious diseases (ID) consultation is associated with improved outcomes in bacteremia. We noted an opportunity for improvement in management of positive blood cultures in our cardiac care unit (CCU). We completed a quality improvement project that included a single plan-do-study-act cycle consisting of a policy of routine ID consultation for all positive blood cultures events in the CCU. Our outcome measure of interest was percentage of appropriately managed blood culture events, the process measure was percentage of blood culture events for which the ID service was formally consulted, and the balancing measure was number of individual patients for whom the ID service was formally consulted. Appropriate antimicrobial management was determined via chart review by an ID physician. Data were analyzed via run chart and simple statistics. Following the intervention, the rate of appropriately managed positive blood culture events increased from a baseline of 86% to 98%, and the rate of ID consultation for these events increased from 75% to 98%. A shift was noted in run charts for both the outcome and process measures. There was an increase in patients for whom the ID service was consulted throughout the entire study period. We successfully implemented mandatory ID consultations in a CCU to increase proportion of appropriately managed blood cultures. While this intervention cannot be universally applied, others may find it useful in selected scenarios.

Developing a Research Network of Early Warning Systems for Infectious Diseases Transmission Between China and Australia.

This article offers a thorough review of current early warning systems (EWS) and advocates for establishing a unified research network for EWS in infectious diseases between China and Australia. We propose that future research should focus on improving infectious disease surveillance by integrating data from both countries to enhance predictive models and intervention strategies. The article highlights the need for standardized data formats and terminologies, improved surveillance capabilities, and the development of robust spatiotemporal predictive models. It concludes by examining the potential benefits and challenges of this collaborative approach and its implications for global infectious disease surveillance. This is particularly relevant to the ongoing project, early warning systems for Infectious Diseases between China and Australia (NetEWAC), which aims to use seasonal influenza as a case study to analyze influenza trends, peak activities, and potential inter-hemispheric transmission patterns. The project seeks to integrate data from both hemispheres to improve outbreak predictions and develop a spatiotemporal predictive modeling system for seasonal influenza transmission based on socio-environmental factors.

The Burden and Risk Factors Associated with Infectious Diseases among Refugees in a Camp for Migrants in Porto Alegre: A Cross-Sectional Survey.

Refugees usually face a disproportionate burden of infectious diseases. Recently, Brazil has experienced an influx of refugees which demands the need for scaling up public health efforts to address the challenges. The research sought to study the burden and risk factors associated with infectious diseases among refugees received in the city of Porto Alegre. This was a cross-sectional study of 261 newly arrived refugees. The study sample was predominantly composed of Venezuelans (50.6%) and Haitians (44%), male (146: 56.7%), single (30.7%), with an average age of 33.38 (± 7.30) years. The average schooling was 10.42 (± 2.09) years. Diseases with the highest prevalence were influenza, whooping cough, diphtheria, and tuberculosis. There was significant association between the country of origin and presence of symptoms for infectious and contagious diseases, which warrants targeted interventions for reducing the incidence of these diseases among refugees in Brazil.

Parvimonas micra orbital cellulitis complicated with cerebral venous thrombosis and mycotic aneurysm.

Parvimonas micra is a gram-positive anaerobic coccus typically found in the human oral cavity, upper respiratory tract and gastrointestinal system. It occasionally causes intra-abdominal abscesses, spondylodiscitis and other infections. There are very few case reports on mycotic aneurysm related to P. micra We describe a rare case of P. micra orbital cellulitis complicated with meningitis, cerebral venous thrombosis and internal carotid artery mycotic aneurysm, which was successfully treated with the combination of endovascular therapy and antibiotics. Additionally, the patient received 6 months of anticoagulation therapy for cerebral venous thrombosis.

Diagnostic prediction models for bacterial meningitis in children with a suspected central nervous system infection: a systematic review and prospective validation study.

OBJECTIVES: Diagnostic prediction models exist to assess the probability of bacterial meningitis (BM) in paediatric patients with suspected meningitis. To evaluate the diagnostic accuracy of these models in a broad population of children suspected of a central nervous system (CNS) infection, we performed external validation. METHODS: We performed a systematic literature review in Medline to identify articles on the development, refinement or validation of a prediction model for BM, and validated these models in a prospective cohort of children aged 0-18 years old suspected of a CNS infection. PRIMARY AND SECONDARY OUTCOME MEASURES: We calculated sensitivity, specificity, predictive values, the area under the receiver operating characteristic curve (AUC) and evaluated calibration of the models for diagnosis of BM. RESULTS: In total, 23 prediction models were validated in a cohort of 450 patients suspected of a CNS infection included between 2012 and 2015. In 75 patients (17%), the final diagnosis was a CNS infection including 30 with BM (7%). AUCs ranged from 0.69 to 0.94 (median 0.83, interquartile range [IQR] 0.79-0.87) overall, from 0.74 to 0.96 (median 0.89, IQR 0.82-0.92) in children aged ≥28 days and from 0.58 to 0.91 (median 0.79, IQR 0.75-0.82) in neonates. CONCLUSIONS: Prediction models show good to excellent test characteristics for excluding BM in children and can be of help in the diagnostic workup of paediatric patients with a suspected CNS infection, but cannot replace a thorough history, physical examination and ancillary testing.

Demographic and zoological drivers of infectome diversity in companion cats with ascites.

Cats (Felidae) have become an integral part of many households. However, our understanding of the full spectrum of pathogens affecting cats (referred to as the infectome) is limited, mainly due to the inadequacy of commonly used diagnostic tools in capturing the complete diversity of potential pathogens and the prevalence of pathogen co-infections. In this study, we employed a meta-transcriptomic approach to simultaneously characterize the infectome contributing to different disease syndromes and to investigate spatial, demographic, and ecological factors influencing pathogen diversity and community composition in a cohort of 27 hospitalized cats and seven stray cats. We identified 15 species of pathogens, with Candidatus Rickettsia tarasevichiae and Tritrichomonas foetus representing potential spillover risks. Importantly, although most cases of ascites hyperplasia were explained by coinfection with multiple pathogens, we identified the potential novel clinical outcomes of M. aubagnense infection among cats. We demonstrated that the increase in infectome diversity can be explained by a variety of predictors including age growth, temperature increase, and a higher proportion of females, with age growth presenting the strongest effect. Fine-scale analysis indicated that a higher diversity of infectomes were harbored in young cats rather than adult ones. Our results demonstrated that most feline diseases are better explained by the presence of virus-bacteria or virus-virus coinfection. This study serves as a timely endorsement for clinical diagnosis by vets to consider the cause of a disease based on a panel of cryptical co-infecting pathogens rather than on individual infectious agents. IMPORTANCE: Frequent studies reported the risks of cats as an intermediate host of zoonotic pathogens (e.g., SARS-CoV-2). Cats have a physically close interaction with their owners through activities like petting, kissing, and being licked on the cheek and hands. However, there are still limited studies that systematically investigate the infectome structure of cats. In this study, we employed a meta-transcriptomics approach to characterize 15 species of pathogens in cats, with Candidatus Rickettsia tarasevichiae first characterizing infection in diseased cats. Most feline diseases were better explained by the presence of virus-bacteria or virus-virus coinfection. The increase in infectome diversity could be influenced by a variety of predictors including age growth, temperature increase, and a higher proportion of females. A higher diversity of pathogens was harbored in young cats rather than adults. Importantly, we showed the value of linking the modern influx of meta-transcriptomics with comparative ecology and demography and of utilizing it to affirm that ecological and demographic variations impact the total infectome.

Assessing vaccine efficacy for infectious diseases with variable immunity using a mathematical model.

This study introduces an SIRS compartmental mathematical model encompassing vaccination and variable immunity periods for infectious diseases. I derive a basic reproduction number formula and assess the local and global stability of disease-free and the local stability of the endemic equilibria. I demonstrate that the basic reproduction number in the presence of a vaccine is highly sensitive to the rate of immunity loss, and even a slight reduction in this rate can significantly contribute to disease control. Additionally, I have derived a formula to calculate the critical efficacy period required for a vaccine to effectively manage and control the disease.The analysis conducted for the model suggests that increasing the vaccine's immunity duration (efficacy) decelerates disease dynamics, leading to reduced rates of reinfection and less severe disease outcomes. Furthermore, this delay contributes to a decrease in the basic reproduction number ( R 0 ), thus facilitating more rapid disease control efforts.