The Immune Response to Herpes Simplex Virus Type 1 Infection in Susceptible Mice is a Major Cause of CNS Pathology Resulting in Fatal Encephalitis

This study was undertaken to investigate possible immune mechanisms in fatal HSV-1 encephalitis (HSE) after HSV-1 corneal inoculation. Susceptible 129S6 (129) but not resistant C57BL/6 (B6) mice developed intense focal inflammatory brainstem lesions of primarily F4/80+ macrophages and Gr-1+ neutrophils detectable by MRI as early as day 6 post infection (PI). Depletion of macrophages and neutrophils significantly enhanced survival of infected 129 mice. Immunodeficient B6 (IL-7R-/-Kitw41/w41) mice lacking adaptive cells (B6-E mice) transplanted with 129 bone marrow showed significantly accelerated fatal HSE compared to B6-E mice transplanted with B6 marrow or control non-transplanted B6-E mice. In contrast, there was no difference in ocular viral shedding in B6-E mice transplanted with 129 bone marrow or B6 bone marrow. Acyclovir treatment of 129 mice beginning day 4 PI (24 h after HSV-1 first reaches the brain stem) reduced nervous system viral titers to undetectable levels but did not alter brainstem inflammation or mortality. We conclude that fatal HSE in 129 mice results from widespread damage in the brainstem caused by destructive inflammatory responses initiated early in infection by massive infiltration of innate cells

The etiological role of common respiratory viruses in acute respiratory infections in older adults::A systematic review and meta-analysis

Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 [95% CI, 3.9-18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4-15.9]; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 [95% CI, 2.3-41.0]; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 [95% CI, 3.7-13.6]; AFE, 86%) and CoV (OR, 2.8 [95% CI, 2.0-4.1]; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report

Global Disease Burden Estimates of Respiratory Syncytial Virus–Associated Acute Respiratory Infection in Older Adults in 2015::A Systematic Review and Meta-Analysis

Respiratory syncytial virus associated acute respiratory infection (RSV-ARI)constitutes a substantial disease burden in older adults≥65 years. We aimed to identify all studies worldwide investigating the disease burden ofRSV-ARIin this population. We estimated thecommunityincidence, hospitalisationrate and in-hospital case fatality ratio (hCFR) of RSV-ARI in older adults stratified by industrialized anddeveloping regions, with data from a systematic review ofstudies published between January 1996 and April 2018, and from 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015, to calculate the global and regional burdenin older adults with RSV-ARIin community and in hospital duringthat year. We estimated thenumber ofin-hospital RSV-ARIdeaths by combining hCFR with hospital admission estimates from hospital-based studies. In 2015, there were about 1.5million(95% CI 0.3-6.9) episodes of RSV-ARIin older adults in41industrialised countries (data missing in developing countries), and of these 214,000 (~14.5%; 95% CI 100,000-459,000) were admitted to hospitals. The global number of hospital admissionsforRSV-ARI in older adults was estimated at 336,000 (UR 186,000-614,000).We further estimated about 14,000 (UR 5,000-50,000) in-hospital deaths related to RSV-ARIglobally.The hospital admission rate and hCFR were higher for those ≥65 years than those aged 50-64 years. The disease burden of RSV-ARIamong older adults is substantialwith limited data from developing countries; appropriate prevention and management strategiesare needed to reduce this burden

Exploring the sensitivity of coastal inundation modelling to DEM vertical error

© 2018 Informa UK Limited, trading as Taylor & Francis Group. As sea level is projected to rise throughout the twenty-first century due to climate change, there is a need to ensure that sea level rise (SLR) models accurately and defensibly represent future flood inundation levels to allow for effective coastal zone management. Digital elevation models (DEMs) are integral to SLR modelling, but are subject to error, including in their vertical resolution. Error in DEMs leads to uncertainty in the output of SLR inundation models, which if not considered, may result in poor coastal management decisions. However, DEM error is not usually described in detail by DEM suppliers; commonly only the RMSE is reported. This research explores the impact of stated vertical error in delineating zones of inundation in two locations along the Devon, United Kingdom, coastline (Exe and Otter Estuaries). We explore the consequences of needing to make assumptions about the distribution of error in the absence of detailed error data using a 1 m, publically available composite DEM with a maximum RMSE of 0.15 m, typical of recent LiDAR-derived DEMs. We compare uncertainty using two methods (i) the NOAA inundation uncertainty mapping method which assumes a normal distribution of error and (ii) a hydrologically correct bathtub method where the DEM is uniformly perturbed between the upper and lower bounds of a 95% linear error in 500 Monte Carlo Simulations (HBM+MCS). The NOAA method produced a broader zone of uncertainty (an increase of 134.9% on the HBM+MCS method), which is particularly evident in the flatter topography of the upper estuaries. The HBM+MCS method generates a narrower band of uncertainty for these flatter areas, but very similar extents where shorelines are steeper. The differences in inundation extents produced by the methods relate to a number of underpinning assumptions, and particularly, how the stated RMSE is interpreted and used to represent error in a practical sense. Unlike the NOAA method, the HBM+MCS model is computationally intensive, depending on the areas under consideration and the number of iterations. We therefore used the HBM+ MCS method to derive a regression relationship between elevation and inundation probability for the Exe Estuary. We then apply this to the adjacent Otter Estuary and show that it can defensibly reproduce zones of inundation uncertainty, avoiding the computationally intensive step of the HBM+MCS. The equation-derived zone of uncertainty was 112.1% larger than the HBM+MCS method, compared to the NOAA method which produced an uncertain area 423.9% larger. Each approach has advantages and disadvantages and requires value judgements to be made. Their use underscores the need for transparency in assumptions and communications of outputs. We urge DEM publishers to move beyond provision of a generalised RMSE and provide more detailed estimates of spatial error and complete metadata, including locations of ground control points and associated land cover