scholarly journals The Silent Partners

Author(s):  
Gal Almogy

Despite great advances in understanding the dynamics of viral epidemics, the emergence of rapidly spreading, highly pathogenic viruses remains a realistic and catastrophic possibility, which current health systems may not be able to fully contain. An intriguing feature in many recent zoonotic viral outbreaks is the presence of ‘superspreaders’, which are infected individuals that cause dramatically more new cases than the average. Here I study the effect of superspreaders on the early dynamics of emerging viruses that have not gained the capacity for efficient human-to-human transmission, i.e viruses with R0 < 1. I show that superspreaders have a higher chance of rapid extinction, but under ‘crowded’ conditions can lead to ‘outbreaks’, causing far more cases than regular viruses. Hence I suggest that outbreaks of highly pathogenic superspreaders are more likely when they coincide in time and space with an unrelated outbreak leading to increased hospital admission rates. These superspreader outbreaks may be difficult to detect, especially in the context of a different epidemic in progress, and can significantly affect mortality patterns observed in affected areas.

Author(s):  
Gal Almogy

Despite great advances in understanding the dynamics of viral epidemics, the emergence of rapidly spreading, highly pathogenic viruses remains a realistic and catastrophic possibility, which current health systems may not be able to fully contain. An intriguing feature in many recent zoonotic viral outbreaks is the presence of superspreaders, which are infected individuals that cause dramatically more new cases than the average. Here I study the effect of superspreaders on the early dynamics of emerging viruses that have not gained the capacity for efficient human-to-human transmission, i.e viruses with R0 < 1. I show that superspreaders have a higher chance of rapid extinction, but under crowded conditions can lead to outbreaks, causing far more cases than regular viruses. I suggest that outbreaks of highly pathogenic superspreaders are more likely when they coincide in time and space with an unrelated outbreak leading to increased hospital admission rates. These superspreader outbreaks may be difficult to detect, especially in the context of a different epidemic in progress, and can significantly affect mortality patterns observed in affected areas.


Membranes ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Jordana Muñoz-Basagoiti ◽  
Daniel Perez-Zsolt ◽  
Jorge Carrillo ◽  
Julià Blanco ◽  
Bonaventura Clotet ◽  
...  

Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.


Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 369
Author(s):  
Karl M. Valerdi ◽  
Adam Hage ◽  
Sarah van van Tol ◽  
Ricardo Rajsbaum ◽  
Maria I. Giraldo

Ubiquitination of proteins is a post-translational modification process with many different cellular functions, including protein stability, immune signaling, antiviral functions and virus replication. While ubiquitination of viral proteins can be used by the host as a defense mechanism by destroying the incoming pathogen, viruses have adapted to take advantage of this cellular process. The ubiquitin system can be hijacked by viruses to enhance various steps of the replication cycle and increase pathogenesis. Emerging viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), flaviviruses like Zika and dengue, as well as highly pathogenic viruses like Ebola and Nipah, have the ability to directly use the ubiquitination process to enhance their viral-replication cycle, and evade immune responses. Some of these mechanisms are conserved among different virus families, especially early during virus entry, providing an opportunity to develop broad-spectrum antivirals. Here, we discuss the mechanisms used by emergent viruses to exploit the host ubiquitin system, with the main focus on the role of ubiquitin in enhancing virus replication.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S825-S826
Author(s):  
Thomas Lodise ◽  
Teena Chopra ◽  
Brian Nathanson ◽  
Katherine Sulham

Abstract Background There is an increase in hospital admissions for cUTI in the US despite apparent reductions in the severity of admissions. However, there are scant data on cUTI hospital admission rates from the emergency department (ED) stratified by age, infection severity, and presence of comorbidities. This study described US hospitalization patterns among adults who present to the ED with a cUTI. We sought to quantify the proportion of admissions that were potentially avoidable based on presence of sepsis and associated symtpoms as well as Charlston Comorbidity Index (CCI) scores. Methods A retrospective multi-center study using data from the Premier Healthcare Database (2013-18) was performed. Inclusion criteria: (1) age ≥ 18 years, (2) primary cUTI ED/inpatient discharge diagnosis, (3) positive blood or urine culture between index ED service days -5 to +2. Transfers from acute care facilities were excluded. Based on ICD-9/10 diagnosis codes present on admission, incidence of hospital admissions were stratified by age (≥ 65 years vs. < 65 years), presence of sepsis (S), sepsis symptoms but no sepsis codes (SS) (e.g., fever, tachycardia, tachypnea, leukocytosis, etc.), and CCI. Results 187,789 patients met inclusion criteria. The mean (SD) age was 59.7 (21.9), 40.4% were male, 29.4% had sepsis, 16.7% had at least 1 SS symptom (but no S), and 53.9% had no evidence of S or SS. The median [IQR] CCI was 1 [0, 3]. 119,668 out of 187,789 (63.7%) were admitted to hospital. Among inpatients, median [IQR] length of stay (LOS) and total costs were 5 [3, 7] days and $7,956 [$4,834, $13,960] USD. Incidence of hospital admissions by age, presence of S/SS, and CCI score are shown in the Table. 18.9% of admissions (22,644/119,668) occurred in patients with no S/SS and a CCI ≤ 2. Their median [IQR] LOS and total costs were 3 [2, 5] days and $5,575 [$3,607, $9,133]. Incidence of Hospital Admission by Age, Charlson comorbidity index (CCI), Presence of Sepsis (S), and Presence of Sepsis Symptoms (SS) Conclusion Nearly 1 in 5 cUTI hospital admissions may be avoidable. Given the resources associated with the management of inpatients with cUTIs, these findings highlight the critical need for healthcare systems to develop well-defined criteria for hospital admission based on presence of comorbid conditions and infection severity. Preventing avoidable hospital admissions has the potential to save the healthcare system substantial costs. Disclosures Thomas Lodise, PharmD, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Teena Chopra, MD, MPH, Spero Therapeutics (Consultant, Advisor or Review Panel member) Brian Nathanson, PhD, Spero Therapeutics (Independent Contractor) Katherine Sulham, MPH, Spero Therapeutics (Independent Contractor)


2021 ◽  
pp. 135581962110127
Author(s):  
Irina Lut ◽  
Kate Lewis ◽  
Linda Wijlaars ◽  
Ruth Gilbert ◽  
Tiffany Fitzpatrick ◽  
...  

Objectives To demonstrate the challenges of interpreting cross-country comparisons of paediatric asthma hospital admission rates as an indicator of primary care quality. Methods We used hospital administrative data from >10 million children aged 6–15 years, resident in Austria, England, Finland, Iceland, Ontario (Canada), Sweden or Victoria (Australia) between 2008 and 2015. Asthma hospital admission and emergency department (ED) attendance rates were compared between countries using Poisson regression models, adjusted for age and sex. Results Hospital admission rates for asthma per 1000 child-years varied eight-fold across jurisdictions. Admission rates were 3.5 times higher when admissions with asthma recorded as any diagnosis were considered, compared with admissions with asthma as the primary diagnosis. Iceland had the lowest asthma admission rates; however, when ED attendance rates were considered, Sweden had the lowest rate of asthma hospital contacts. Conclusions The large variations in childhood hospital admission rates for asthma based on the whole child population reflect differing definitions, admission thresholds and underlying disease prevalence rather than primary care quality. Asthma hospital admissions among children diagnosed with asthma is a more meaningful indicator for inter-country comparisons of primary care quality.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040610
Author(s):  
Renée O'Donnell ◽  
Melissa Savaglio ◽  
Debra Fast ◽  
Ash Vincent ◽  
Dave Vicary ◽  
...  

IntroductionPeople with serious mental illness (SMI) often fail to receive adequate treatment. To provide a higher level of support, mental health systems have been reformed substantially to integrate mental healthcare into the community. MyCare is one such community-based mental health model of care. This paper describes the study protocol of a controlled trial examining the effect of MyCare on psychosocial and clinical outcomes and hospital admission and duration rates for adults with SMI.Methods and analysisThis is a multisite non-randomised controlled trial with a 3, 6 and 12-month follow-up period. The study participants will be adults (18–64 years of age) with SMI recruited from Hobart, Launceston and the North-West of Tasmania. The treatment group will include adults who receive both the MyCare intervention and standard mental health support; the control group will include adults who receive only standard mental health support. The primary outcome includes psychosocial and clinical functioning and the secondary outcome will examine hospital admission rates and duration of stay. Mixed-effects models will be used to examine outcome improvements between intake and follow-up. This trial will generate the evidence needed to evaluate the effect of a community mental health support programme delivered in Tasmania, Australia. If MyCare results in sustained positive outcomes for adults with SMI, it could potentially be scaled up more broadly across Australia, addressing the inequity and lack of comprehensive treatment that many individuals with SMI experience.Ethics and disseminationThis study has been approved by the Tasmanian Health and Medical Human Research Ethics Committee. The findings will be disseminated to participants and staff who delivered the intervention, submitted for publication in a peer-reviewed journal and shared at academic conferences.Trial registration numberACTRN12620000673943.


BMJ ◽  
2020 ◽  
pp. m4571 ◽  
Author(s):  
Caroline Fyfe ◽  
Lucy Telfar ◽  
Barnard ◽  
Philippa Howden-Chapman ◽  
Jeroen Douwes

Abstract Objectives To investigate whether retrofitting insulation into homes can reduce cold associated hospital admission rates among residents and to identify whether the effect varies between different groups within the population and by type of insulation. Design A quasi-experimental retrospective cohort study using linked datasets to evaluate a national intervention programme. Participants 994 317 residents of 204 405 houses who received an insulation subsidy through the Energy Efficiency and Conservation Authority Warm-up New Zealand: Heat Smart retrofit programme between July 2009 and June 2014. Main outcome measure A difference-in-difference approach was used to compare the change in hospital admissions of the study population post-insulation with the change in hospital admissions of the control population that did not receive the intervention over the same two timeframes. Relative rate ratios were used to compare the two groups. Results 234 873 hospital admissions occurred during the study period. Hospital admission rates after the intervention increased in the intervention and control groups for all population categories and conditions with the exception of acute hospital admissions among Pacific Peoples (rate ratio 0.94, 95% confidence interval 0.90 to 0.98), asthma (0.92, 0.86 to 0.99), cardiovascular disease (0.90, 0.88 to 0.93), and ischaemic heart disease for adults older than 65 years (0.79, 0.74 to 0.84). Post-intervention increases were, however, significantly lower (11%) in the intervention group compared with the control group (relative rate ratio 0.89, 95% confidence interval 0.88 to 0.90), representing 9.26 (95% confidence interval 9.05 to 9.47) fewer hospital admissions per 1000 in the intervention population. Effects were more pronounced for respiratory disease (0.85, 0.81 to 0.90), asthma in all age groups (0.80, 0.70 to 0.90), and ischaemic heart disease in those older than 65 years (0.75, 0.66 to 0.83). Conclusion This study showed that a national home insulation intervention was associated with reduced hospital admissions, supporting previous research, which found an improvement in self-reported health.


Cell ◽  
2021 ◽  
Vol 184 (6) ◽  
pp. 1604-1620
Author(s):  
Lu Lu ◽  
Shan Su ◽  
Haitao Yang ◽  
Shibo Jiang

2017 ◽  
Vol 52 (6) ◽  
pp. 720-728 ◽  
Author(s):  
Cem Hasan Razi ◽  
Nazlı Cörüt ◽  
Nesibe Andıran

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