Outbreak Of Respiratory Disease Research Articles

Respiratory tract bacteria distribution and transmission patterns among individuals in close contact.

Respiratory disease outbreaks frequently occur in settings where individuals are in close contact, for example, schools and factories. However, the transmission patterns of oropharyngeal microbiota among healthy individuals living in clusters are unclear. Therefore, we aimed to investigate the respiratory tract bacteria distribution and transmission patterns among individuals in close contact. A total of 36 freshmen from Peking University Medical School participated in the study. We collected pharyngeal swabs on the first day of enrollment, 15, 30, and 60 days after cohabitation. DNA was extracted from the swabs and subjected to high-throughput sequencing to profile the microbial composition. Statistical analyses were performed to assess diversity and significance. Neisseriaceae, Prevotellaceae, and Streptococcaceae were the most abundant bacterial families detected. Over time, changes were observed in the bacterial communities, with a tendency for increased similarity between dormitory room members. By day 60 of cohabitation, the bacterial communities appeared to be more similar compared to the baseline (prior to cohabitation). The transmission patterns included spreading with colonization, spreading without colonization, and non-spreading. Bacteria belonging to the core genera are most likely to spread and colonize easily. The risk of healthy cohabitants acquiring respiratory pathogens through close contact may be overestimated in epidemiological studies. Therefore, monitoring the spread of core genera that are easily transmitted and colonized is crucial for effective prevention of respiratory pathogen transmission.

Temporal Trends of Early COVID-19 Infections in New York City Transit Workers and Residents: March 01, 2020-May 02, 2020.

The continuity of public transportation was necessary during the COVID-19 pandemic so that essential workers could report for duty. Therefore, it is important to consider COVID-19's impact on transit workers themselves. We described COVID-19 incidence rates over time in New York City (NYC) transit workers and the NYC general population during March-May, 2020. NYC transit COVID-19 cases were abstracted from occupational injury and illness logs, and health department data was used to ascertain NYC resident cases. COVID-19 rates among transit workers peaked during the week of March 22-28 (429.8 cases/100,000 workers). The peak in transit workers occurred 1-2weeks before the general public's peak (March 29-April 4: 368.8 cases/100,000 people; April 5-11: 357.8 cases/100,000 people). These data suggest that NYC transit workers may have been impacted by COVID-19 earlier than the general public. Thus, improving early detection and response of respiratory disease outbreaks may be vital to protecting transit workers.

Perforated plate ventilation system and dynamics of infectious respiratory particle transmission

AbstractWith the removal of indoor pollutants and the assurance of air quality emerging as critical research topics, the optimization of the internal environment in offices, where people stay for extended periods, is essential for controlling the spread of infectious respiratory particles. Frequent movements of personnel and the operation of doors and windows within offices significantly impact the mechanisms of droplet transmission, warranting further investigation. This study employs computational fluid dynamics simulations to explore the droplet dispersion characteristics and pollutant removal efficiency of the simplified model of perforated plate ventilation system (PPVS) (the diameter of the air supply openings has been reasonably simplified and uniformly set to 0.02 m) in office settings, as well as the impact of dynamic door operation scenarios on droplet spread and concentrations in breathing zones. To optimize the ventilation system's pollutant removal efficiency, airflow velocities (2.86, 3.18, and 5.00 m/s) are varied, with simulations conducted at the optimal velocity of 3.18 m/s. The effects of continuous door operations, door‐opening directions (towards the office and towards the isolation room), and opening speeds (π/4, π/6, π/8, and π/10 rad/s) are also examined, revealing significant impacts on droplet spread. Results indicate that PPVS effectively reduces indoor pollutant concentrations at all tested airflow velocities, with the optimal speed identified as 3.18 m/s. Additionally, door‐opening direction and speed can significantly influence droplet spread. Opening doors towards isolation rooms at smaller angles (less than 30°) effectively reduces droplet concentrations in personnel breathing zones, thereby mitigating the risk of droplet transmission. Faster door‐opening speeds also contribute to lower droplet concentrations in these zones. This innovative study explores the impacts of PPVS and dynamic door operation dynamics on droplet transmission during respiratory disease outbreaks, providing valuable theoretical insights and technical support for disease prevention and indoor air quality improvement.

FASTER AND COST-EFFECTIVE EXTRACTION FREE METHOD FOR SARS-COV2 DETECTION BY RT-PCR

Background: The World Health Organization (WHO) declared an outbreak of febrile respiratory illness caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) in Wuhan City, China in December 2019. Within the immediate outbreak of three months, the global community was challenged with a devastating pandemic that caused heavy morbidities and mortalities around the globe. The expeditious spread of the virus, challenged the diagnostic laboratories to rapidly develop the accurate molecular diagnostic methods. As SARS CoV-2 assays became available for testing on existing molecular platforms, laboratories devoted unprecedented energy and resources to evaluating the analytical performance of the new tests and in some cases developed their diagnostic assays under FDA-EUA guidance. Aim: This study aims to compare the diagnostic efficacy of the extraction-free method of COVID-19 PCR and the conventional RT-PCR with extraction. Method: To get an accurate view of how an omission of RNA extraction step would perform in a real-world setting, a comparative study was performed using TATA MD CHECK RT-PCR DIRECT (Direct PCR) and LabGun Genomics for Conventional RT-PCR method. Result: From this study, direct RT-PCR correctly identified 92.3% of samples (n = 50) identified positive for SARS-CoV-2 RNA by conventional RT-PCR featuring an RNA extraction. Conclusion: Direct methods may represent a reasonable alternative to meet higher testing demands with low turnaround time as reverse transcription PCR includes traditionally time-consuming RNA extraction and purification procedures.

MERS-CoV-nsp5 expression in human epithelial BEAS 2b cells attenuates type I interferon production by inhibiting IRF3 nuclear translocation

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an enveloped, positive-sense RNA virus that emerged in 2012, causing sporadic cases and localized outbreaks of severe respiratory illness with high fatality rates. A characteristic feature of the immune response to MERS-CoV infection is low type I IFN induction, despite its importance in viral clearance. The non-structural proteins (nsps) of other coronaviruses have been shown to block IFN production. However, the role of nsp5 from MERS-CoV in IFN induction of human respiratory cells is unclear. In this study, we elucidated the role of MERS-CoV-nsp5, the viral main protease, in modulating the host’s antiviral responses in human bronchial epithelial BEAS 2b cells. We found that overexpression of MERS-CoV-nsp5 had a dose-dependent inhibitory effect on IFN-β promoter activation and cytokine production induced by HMW-poly(I:C). It also suppressed IFN-β promoter activation triggered by overexpression of key components in the RIG-I-like receptor (RLR) pathway, including RIG-I, MAVS, IKK-ε and IRF3. Moreover, the overexpression of MERS-CoV-nsp5 did not impair expression or phosphorylation of IRF3, but suppressed the nuclear translocation of IRF3. Further investigation revealed that MERS-CoV-nsp5 specifically interacted with IRF3. Using docking and molecular dynamic (MD) simulations, we also found that amino acids on MERS-CoV-nsp5, IRF3, and KPNA4 may participate in protein-protein interactions. Additionally, we uncovered protein conformations that mask the nuclear localization signal (NLS) regions of IRF3 and KPNA4 when interacting with MERS-CoV-nsp5, suggesting a mechanism by which this viral protein blocks IRF3 nuclear translocation. Of note, the IFN-β expression was restored after administration of protease inhibitors targeting nsp5, indicating this suppression of IFN-β production was dependent on the enzyme activity of nsp5. Collectively, our findings elucidate a mechanism by which MERS-CoV-nsp5 disrupts the host’s innate antiviral immunity and thus provides insights into viral pathogenesis.

A tentative exploration for the association between influenza virus infection and SARS-CoV-2 infection in Shihezi, China: A test-negative study

The outbreak of respiratory diseases, such as COVID-19 and influenza, has drawn global attention. However, it remains unclear whether the risk of influenza A infection may be affected by the history of SARS-CoV-2 infection. In this study, we conducted a test-negative case-control study, and utilized a logistic regression model to analyze the relationship between SARS-CoV-2 and influenza A infections. Among 258 eligible patient samples with influenza-like illness (ILI), we did not detect a statistically significant association between the history of SARS-CoV-2 infection and the risk of influenza A infection. These findings might indicate that antibodies against COVID-19 acquired through vaccination or natural immunity have not protected against influenza.

Optimization of Bangladesh and Malaysian genotype recombinant reporter Nipah viruses for in vitro antiviral screening and in vivo disease modeling

Nipah virus (NiV) causes near-annual outbreaks of fatal encephalitis and respiratory disease in South Asia with a high mortality rate (∼70%). Since there are no approved therapeutics for NiV disease in humans, the WHO has designated NiV and henipaviral diseases priority pathogens for research and development. We generated a new recombinant green fluorescent reporter NiV of the circulating Bangladesh genotype (rNiV-B-ZsG) and optimized it alongside our previously generated Malaysian genotype reporter counterpart (rNiV-M-ZsG) for antiviral screening in primary-like human respiratory cell types. Validating our platform for rNiV-B-ZsG with a synthetic compound library directed against viral RNA-dependent RNA polymerases, we identified a hit compound and confirmed its sub-micromolar activity against wild-type NiV, green fluorescent reporter, and the newly constructed bioluminescent red fluorescent double reporter (rNiV-B-BREP) NiV. We furthermore demonstrated that rNiV-B-ZsG and rNiV-B-BREP viruses showed pathogenicity comparable to wild-type NiV-B in the Syrian golden hamster model of disease, supporting additional use of these tools for both pathogenesis and advanced pre-clinical studies in vivo.

Detection and subtyping of influenza A virus in porcine clinical samples from Spain in 2020

A total of 1019 samples collected on 726 Spanish swine farms suffering from outbreaks of respiratory disease were screened for influenza A viruses (IAVs) using a RT-qPCR method. A subset of positive samples was further analyzed using a subtype-specific RT-qPCR method (n: 142) and Sanger sequencing (n: 64). A total of 19.4% samples from 23% farms tested positive, with infection being most common in suckling (53.6%) and weaning pigs (30.2%). Viruses belonging to four HA subtypes (H1av, H1hu, H1pdm, H3) were detected, with subtypes H1avN2, H1huN2 and H1avN1 accounting for over half of the specimens. An optimized protocol with newly designed primers allowed the detection of H3 viruses in a significant number of samples (21%). A comparison of antigenic positions revealed that circulating strains exhibited mutations with vaccine strains in a significant percentage of amino acid residues, both in the NA protein (27.8–43.3%) and particularly in the HA protein (51–75.3%).

Lifting COVID-19-associated non-pharmaceutical interventions: potential impact on notifications of infectious diseases transmitted from person to person in 2022 in Bavaria, Germany.

The COVID-19 pandemic and associated non-pharmaceutical interventions (NPIs) have led to substantial decreases in case numbers of infectious diseases in several countries worldwide. As NPIs were gradually lifted, intense or out-of-season outbreaks of respiratory and gastrointestinal diseases were reported, raising the hypothesis of a potential catch-up effect of infections. By analysing surveillance data from the federal reporting system for notifiable infectious diseases, we aimed to assess the potential impact of lifting COVID-19 associated NPIs on notifications of selected infectious diseases in Bavaria, 2022. We compared influenza, chickenpox, norovirus gastroenteritis, rotavirus gastroenteritis weekly case numbers in a pre-pandemic period (2016-2019) and 2022 using two time series analyses approaches: (i) a predictive model forecasting weekly case numbers for the pandemic years 2020-2022, based on 2016-2019 data, (ii) interrupted time series model, based on 2016-2022 data, including a term per pandemic period. In 2022, incidence rates were higher compared to pre-pandemic period for influenza (IRR = 3.47, 95%CI: 1.49-7.94) and rotavirus gastroenteritis (IRR = 1.36, 95%CI: 0.95-1.93), though not significant for rotavirus gastroenteritis. Conversely, case numbers remained significantly below pre-pandemic levels for chickenpox (IRR = 0.52, 95%CI: 0.41-0.65) and norovirus gastroenteritis (IRR = 0.59, 95%CI: 0.42-0.82). Seasonality changed notably for influenza, showing an earlier influenza wave compared to pre-pandemic periods. The lifting of NPIs was associated with heterogenic epidemiological patterns depending on the selected disease. The full impact of NPIs and their discontinuation may only become clear with continued monitoring and assessment of potential additional contributing factors.

Biosecurity perceptions among Ontario horse owners during the COVID-19 pandemic.

Disease outbreaks present a significant challenge to horse health and welfare and the economic stability of horse industries internationally. This is a particular concern in Ontario, Canada, where there have been frequent outbreaks of respiratory infectious diseases among horses. Despite these risks, there has been limited research on whether Ontario horse owners engage in biosecurity measures sufficient to mitigate risk of equine diseases, and whether current events such as the COVID-19 pandemic influence attitudes towards equine biosecurity practices. To explore Ontario horse owners' perceptions, attitudes and experiences relating to on-farm biosecurity during the COVID-19 pandemic. Qualitative study using virtual semi-structured interviews. Participants (horse owners, frequent horse riders and part boarders) were recruited using social media snowball sampling where advertisements were shared by equine and veterinary organisations. Interviews were conducted virtually between June and September 2022 and were analysed using reflexive thematic analysis. Three key themes relating to biosecurity perceptions among the 14 participants were identified. Participants relied on minimal preventative measures (such as vaccines) where perceived risk of disease was low, but implemented additional measures including quarantine and handwashing when perceived risk of disease was high. Participants' choice of biosecurity practices often mirrored those recommended by the barn manager. Moreover, participants felt that responsibility for biosecurity was not shared equally across horse owners, with more emphasis placed on those engaging in high-risk situations for disease spread. Despite experiencing biosecurity during the COVID-19 pandemic, horse owners were not consistently applying these practices to their horse care routines. The perspectives reported here are from a small sample of horse owners and may not be generalisable to all populations. Our findings indicate that horse owners need improved access to and engagement with educational initiatives that emphasise the importance and purpose of all biosecurity measures.

Bovine Rhinitis B Virus Variant as the Putative Cause of Bronchitis in Goat Kids.

A diagnostic investigation into an outbreak of fatal respiratory disease among young goats in Iowa, USA revealed bronchitis lesions of unknown etiology and secondary bacterial bronchopneumonia. Hypothesis-free metagenomics identified a previously unreported picornavirus (USA/IA26017/2023), and further phylogenetic analysis classified USA/IA26017/2023 as an aphthovirus related to bovine rhinitis B virus. Viral nucleic acid was localized to lesions of bronchitis using in situ hybridization. This marks the first report of a picornavirus putatively causing respiratory disease in goats and highlights the potential for cross-species transmission of aphthoviruses.

Analyzing evolutionary game theory in epidemic management: A study on social distancing and mask-wearing strategies.

When combating a respiratory disease outbreak, the effectiveness of protective measures hinges on spontaneous shifts in human behavior driven by risk perception and careful cost-benefit analysis. In this study, a novel concept has been introduced, integrating social distancing and mask-wearing strategies into a unified framework that combines evolutionary game theory with an extended classical epidemic model. To yield deeper insights into human decision-making during COVID-19, we integrate both the prevalent dilemma faced at the epidemic's onset regarding mask-wearing and social distancing practices, along with a comprehensive cost-benefit analysis. We explore the often-overlooked aspect of effective mask adoption among undetected infectious individuals to evaluate the significance of source control. Both undetected and detected infectious individuals can significantly reduce the risk of infection for non-masked individuals by wearing effective facemasks. When the economical burden of mask usage becomes unsustainable in the community, promoting affordable and safe social distancing becomes vital in slowing the epidemic's progress, allowing crucial time for public health preparedness. In contrast, as the indirect expenses associated with safe social distancing escalate, affordable and effective facemask usage could be a feasible option. In our analysis, it was observed that during periods of heightened infection risk, there is a noticeable surge in public interest and dedication to complying with social distancing measures. However, its impact diminishes beyond a certain disease transmission threshold, as this strategy cannot completely eliminate the disease burden in the community. Maximum public compliance with social distancing and mask-wearing strategies can be achieved when they are affordable for the community. While implementing both strategies together could ultimately reduce the epidemic's effective reproduction number ([Formula: see text]) to below one, countries still have the flexibility to prioritize either of them, easing strictness on the other based on their socio-economic conditions.

Pharmacological activation of TLR7 exerts inhibition on the replication of EV-D68 in respiratory cells.

The globally reemerging respiratory pathogen enterovirus D68 (EV-D68) is implicated in outbreaks of severe respiratory illness and associated with acute flaccid myelitis. However, there remains a lack of effective treatments for EV-D68 infection. In this work, we found that the host Toll-like receptor 7 (TLR7) proteins, which function as powerful innate immune sensors, were selectively elevated in expression in response to EV-D68 infection. Subsequently, we investigated the impact of Vesatolimod (GS-9620), a Toll-like receptor 7 agonist, on EV-D68 replication. Our findings revealed that EV-D68 infection resulted in increased mRNA levels of TLR7. Treatment with Vesatolimod significantly inhibited EV-D68 replication [half maximal effective concentration (EC50) = 0.1427 µM] without inducing significant cytotoxicity at virucidal concentrations. Although Vesatolimod exhibited limited impact on EV-D68 attachment, it suppressed RNA replication and viral protein synthesis after virus entry. Vesatolimod broadly inhibited the replication of circulating isolated strains of EV-D68. Furthermore, our findings demonstrated that treatment with Vesatolimod conferred resistance to both respiratory and neural cells against EV-D68 infection. Overall, these results present a promising strategy for drug development by pharmacologically activating TLR7 to initiate an antiviral state in EV-D68-infected cells selectively.IMPORTANCEConventional strategies for antiviral drug development primarily focus on directly targeting viral proteases or key components, as well as host proteins involved in viral replication. In this study, based on our intriguing discovery that enterovirus D68 (EV-D68) infection specifically upregulates the expression of immune sensor Toll-like receptor 7 (TLR7) protein, which is either absent or expressed at low levels in respiratory cells, we propose a potential antiviral approach utilizing TLR7 agonists to activate EV-D68-infected cells into an anti-viral defense state. Notably, our findings demonstrate that pharmacological activation of TLR7 effectively suppresses EV-D68 replication in respiratory tract cells through a TLR7/MyD88-dependent mechanism. This study not only presents a promising drug candidate and target against EV-D68 dissemination but also highlights the potential to exploit unique alterations in cellular innate immune responses induced by viral infections, selectively inducing a defensive state in infected cells while safeguarding uninfected normal cells from potential adverse effects associated with therapeutic interventions.

One-hit kill: On the inactivation of RNA viruses by ultraviolet (UV)-C-induced genomic damage

Large scale outbreaks of infectious respiratory disease have repeatedly plagued the globe over the last 100 years. The scope and strength of the outbreaks are getting worse as pathogenic RNA viruses are rapidly evolving and highly evasive to vaccines and anti-viral drugs. Germicidal UV-C is considered as a robust agent to disinfect RNA viruses regardless of their evolution. While genomic damage by UV-C has been known to be associated with viral inactivation, the precise relationship between the damage and inactivation remains unsettled as genomic damage has been analyzed in small areas, typically under 0.5 kb. In this study, we assessed genomic damage by the reduced efficiency of reverse transcription of regions of up to 7.2 kb. Our data seem to indicate that genomic damage was directly proportional to the size of the genome, and a single hit of damage was sufficient for inactivation of RNA viruses. The high efficacy of UV-C is already effectively adopted to inactivate airborne RNA viruses.

Changes in public interest in sudden cardiac arrest: a big data analysis

Abstract Background Search engine queries (SEQ) are considered a surrogate for public interest, with the most popular global search engine processing ~ 1.2 trillion online queries annually and >1 billion health-related queries daily.1 Big data from SEQ trends have been used for disease surveillance and may be able to offer insights for public health interventions, such as detecting respiratory illness outbreaks and understanding cardiac disease patterns.2-4 Sudden cardiac arrest (SCA) occurs in ~5 million people annually worldwide; October is internationally designated for SCA awareness, with public health campaigns aimed to improve early recognition of and early defibrillation for SCA. Use of big data from SEQ as a public health tool to assess changes in public interest surrounding SCA campaigns has not been explored. Purpose To characterize changes in public interest in SCA via analysis of internet SEQ trends. Methods Google Trends was queried for the terms "cardiac arrest", "cardiopulmonary resuscitation" (CPR), "automated external defibrillation" (AED) and "myocardial infarction" (MI) worldwide for the past 5 years (11/2018 – 11/2023). Relative search volumes (RSV, expressed in scale from 0-100) and related queries were analyzed. Baseline RSV for each term was defined as 2 weeks pre-peak. Numerical percentage and Chi square tests were used for statistical comparison. Results Compared to baseline, RSV for "cardiac arrest" significantly increased in correlation with the SCA of 2 professional athletes: Christian Eriksen (football, Denmark) on 6/12/2021 (+321%, p<0.001), Damar Hamlin (American football, United States) on 1/2/2023 (+653%, p<0.001) and collegiate athlete Bronny James (basketball, United States) on 7/24/2023 (+164%, p<0.001). (Figure) RSV significantly increased for "cardiopulmonary resuscitation" (+61% and +170% respectively, p<0.001 for both) and "Automated external defibrillator" (+141% and +192% p<0.001 and p=0.003, respectively) during the same period for pro-athletes but not for the college athlete (p=1.0 and p= 0.84 respectively). While none of the athletes had MI, RSV for "myocardial infarction" also had correlating increases over baseline for all 3 athletes (+35%, p<0.001 +30%, p<0.001 and +22%, p=0.027, respectively). RSV did not significantly change for any search terms during October SCA awareness months during the study period (all p>0.05). Conclusions Public interest in SCA, CPR and AED surge when SCA occurs in well-known individuals such as athletes, rather than with scheduled public health campaigns; co-surge in MI interest likely indicates on-going public confusion between SCA and MI. Analyses of big data from SEQ could assist cardiovascular societies in planning targeted SCA educational campaigns by building upon periodic natural surges in public interest in SCA, CPR and AED; this should include continued education on the differences in recognition and treatment of SCA and MI.

Cost-effectiveness of mask mandates on subways to prevent SARS-CoV-2 transmission in the United States.

Community-based mask wearing has been shown to reduce the transmission of SARS-CoV-2. However, few studies have conducted an economic evaluation of mask mandates, specifically in public transportation settings. This study evaluated the cost-effectiveness of implementing mask mandates for subway passengers in the United States by evaluating its potential to reduce COVID-19 transmission during subway travel. We assessed the health impacts and costs of subway mask mandates compared to mask recommendations based on the number of infections that would occur during subway travel in the U.S. Using a combined box and Wells-Riley infection model, we estimated monthly infections, hospitalizations, and deaths averted under a mask mandate scenario as compared to a mask recommendation scenario. The analysis included costs of implementing mask mandates and COVID-19 treatment from a limited societal perspective. The cost-effectiveness (net cost per averted death) of mandates was estimated for three different periods based on dominant SARS-CoV-2 variants: Alpha, Beta, and Gamma (November 2020 to February 2021); Delta (July to October 2021); and early Omicron (January to March 2022). Compared with mask recommendations only, mask mandates were cost-effective across all periods, with costs per averted death less than a threshold of $11.4 million (ranging from cost-saving to $3 million per averted death). Additionally, mask mandates were more cost-effective during the early Omicron period than the other two periods and were cost saving in January 2022. Our findings showed that mandates remained cost-effective when accounting for uncertainties in input parameters (e.g., even if mandates only resulted in small increases in mask usage by subway ridership). The findings highlight the economic value of mask mandates on subways, particularly during high virus transmissibility periods, during the COVID-19 pandemic. This study may inform stakeholders on mask mandate decisions during future outbreaks of novel viral respiratory diseases.

Dynamic contact networks of residents of an urban jail in the era of SARS-CoV-2

BackgroundIn custodial settings such as jails and prisons, infectious disease transmission is heightened by factors such as overcrowding and limited healthcare access. Specific features of social contact networks within these settings have not been sufficiently characterized, especially in the context of a large-scale respiratory infectious disease outbreak. The study aims to quantify contact network dynamics within the Fulton County Jail in Atlanta, Georgia. MethodsJail roster data were utilized to construct social contact networks. Rosters included resident details, cell locations, and demographic information. This analysis involved 6702 male residents over 140,901 person days. Network statistics, including degree, mixing, and dissolution (movement within and out of the jail) rates, were assessed. We compared outcomes for two distinct periods (January 2022 and April 2022) to understand potential responses in network structures during and after the SARS-CoV-2 Omicron variant peak. ResultsWe found high cross-sectional network degree at both cell and block levels. While mean degree increased with age, older residents exhibited lower degree during the Omicron peak. Block-level networks demonstrated higher mean degrees than cell-level networks. Cumulative degree distributions increased from January to April, indicating heightened contacts after the outbreak. Assortative age mixing was strong, especially for younger residents. Dynamic network statistics illustrated increased degrees over time, emphasizing the potential for disease spread. ConclusionsDespite some reduction in network characteristics during the Omicron peak, the contact networks within the Fulton County Jail presented ideal conditions for infectious disease transmission. Age-specific mixing patterns suggested unintentional age segregation, potentially limiting disease spread to older residents. This study underscores the necessity for ongoing monitoring of contact networks in carceral settings and provides valuable insights for epidemic modeling and intervention strategies, including quarantine, depopulation, and vaccination, laying a foundation for understanding disease dynamics in such environments.Top of Form

Enhancing infectious diseases early warning: A deep learning approach for influenza surveillance in China

ObjectiveThis study aimed to develop a universally applicable, feedback-informed Self-Excitation Attention Residual Network (SEAR) model. This model dynamically adapts to evolving disease trends and surveillance system changes, accommodating various scenarios. Thereby enhancing the effectiveness of early warning systems. MethodsSurveillance data on influenza-like illness (ILI) was collected from various regions including Northern China, Southern China, Beijing, and Yunnan. The reproduction number (Rt) was estimated to determine the threshold for issuing warnings. The Self-Excitation Attention Residual Network (SEAR) was devised employing deep learning algorithms and was trained, validated, and tested. The SEAR model's efficacy was assessed based on five metrics: accuracy rate, recall rate, F1 score, confusion matrix, and the receiver operating characteristic curve. ResultsWith an advance warning set at three days, the SEAR model outperformed five primary models − logistic regression, support vector machine, random forest, Extreme Gradient Boosting, and Long Short-Term Memory model − in all five evaluation metrics. Notably, the model's warning performance declined with an increase in the early warning value and the number of warning days, albeit maintaining a ROC value over 0.7 in all scenarios. ConclusionThe SEAR model demonstrated robust early warning performance for influenza in diverse Chinese regions with high accuracy and specificity. This novel model, augmenting traditional systems, supports widespread application for respiratory disease outbreak monitoring. Future evaluations could incorporate alternative indicators, with the model continuously updating through data feedback, thus enhancing its universal applicability. Ongoing optimization, using iterative feedback and expert judgment, heralds a transformative approach to surveillance-based early warning strategies.

Equine herpesvirus type 1 (EHV-1) replication at the upper respiratory entry site is inhibited by neutralizing EHV-1-specific IgG1 and IgG4/7 mucosal antibodies.

Equine herpesvirus type 1 (EHV-1) is a contagious respiratory pathogen that infects the mucosa of the upper respiratory tract (URT). Mucosal immune responses at the URT provide the first line of defense against EHV-1 and are crucial for orchestrating immunity. To define host-pathogen interactions, we characterized B-cell responses, antibody isotype functions, and EHV-1 replication of susceptible (non-immune) and clinically protected (immune) horses after experimental EHV-1 infection. Nasal secretion and nasal wash samples were collected and used for the isolation of DNA, RNA, and mucosal antibodies. Shedding of infectious virus, EHV-1 copy numbers, viral RNA expression, and host B-cell activation in the URT were compared based on host immune status. Mucosal EHV-1-specific antibody responses were associated with EHV-1 shedding and viral RNA transcription. Finally, mucosal immunoglobulin G (IgG) and IgA isotypes were purified and tested for neutralizing capabilities. IgG1 and IgG4/7 neutralized EHV-1, while IgG3/5, IgG6, and IgA did not. Immune horses secreted high amounts of mucosal EHV-1-specific IgG4/7 antibodies and quickly upregulated B-cell pathway genes, while EHV-1 was undetected by virus isolation and PCR. RNA transcription analysis reinforced incomplete viral replication in immune horses. In contrast, complete viral replication with high viral copy numbers and shedding of infectious viruses was characteristic for non-immune horses, together with low or absent EHV-1-specific neutralizing antibodies during viral replication. These data confirm that pre-existing mucosal IgG1 and IgG4/7 and rapid B-cell activation upon EHV-1 infection are essential for virus neutralization, regulation of viral replication, and mucosal immunity against EHV-1.IMPORTANCEEquine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion storms, and neurologic outbreaks known as equine herpes myeloencephalopathy (EHM). EHV-1 is transmitted with respiratory secretions by nose-to-nose contact or via fomites. The virus initially infects the epithelium of the upper respiratory tract (URT). Host-pathogen interactions and mucosal immunity at the viral entry site provide the first line of defense against the EHV-1. Robust mucosal immunity can be essential in protecting against EHV-1 and to reduce EHM outbreaks. It has previously been shown that immune horses do not establish cell-associated viremia, the prerequisite for EHM. Here, we demonstrate how mucosal antibodies can prevent the replication of EHV-1 at the epithelium of the URT and, thereby, the progression of the virus to the peripheral blood. The findings improve the mechanistic understanding of mucosal immunity against EHV-1 and can support the development of enhanced diagnostic tools, vaccines against EHM, and the management of EHV-1 outbreaks.

Common cold viruses circulating in children threaten wild chimpanzees through asymptomatic adult carriers

Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as “common cold” paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3–11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020–2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.