An update on the human and animal enteric pathogen Clostridium perfringens

Clostridium perfringens, a rapid-growing pathogen known to secrete an arsenal of >20 virulent toxins, has been associated with intestinal diseases in both animals and humans throughout the past century. Recent advances in genomic analysis and experimental systems make it timely to re-visit this clinically and veterinary important pathogen. This Review will summarise our understanding of the genomics and virulence-linked factors, including antimicrobial potentials and secreted toxins of this gut pathogen, and then its up-to-date clinical epidemiology and biological role in the pathogenesis of several important human and animal-associated intestinal diseases, including pre-term necrotising enterocolitis. Finally, we highlight some of the important unresolved questions in relation to C. perfringens-mediated infections, and implications for future research directions

Quantifying Excess Deaths Related to Heatwaves under Climate Change Scenarios: A multicountry time series modelling study

Background: Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of climate change on heatwave-related mortality at a global scale is limited. Methods and findings: We collected historical daily time series of mean temperature and mortality for all causes or nonexternal causes, in periods ranging from January 1, 1984, to December 31, 2015, in 412 communities within 20 countries/regions. We estimated heatwave–mortality associations through a two-stage time series design. Current and future daily mean temperature series were projected under four scenarios of greenhouse gas emissions from 1971–2099, with five general circulation models. We projected excess mortality in relation to heatwaves in the future under each scenario of greenhouse gas emissions, with two assumptions for adaptation (no adaptation and hypothetical adaptation) and three scenarios of population change (high variant, median variant, and low variant). Results show that, if there is no adaptation, heatwave-related excess mortality is expected to increase the most in tropical and subtropical countries/regions (close to the equator), while European countries and the United States will have smaller percent increases in heatwave-related excess mortality. The higher the population variant and the greenhouse gas emissions, the higher the increase of heatwave-related excess mortality in the future. The changes in 2031–2080 compared with 1971–2020 range from approximately 2,000% in Colombia to 150% in Moldova under the highest emission scenario and high-variant population scenario, without any adaptation. If we considered hypothetical adaptation to future climate, under high-variant population scenario and all scenarios of greenhouse gas emissions, the heatwave-related excess mortality is expected to still increase across all the countries/regions except Moldova and Japan. However, the increase would be much smaller than the no adaptation scenario. The simple assumptions with respect to adaptation as follows: no adaptation and hypothetical adaptation results in some uncertainties of projections. Conclusions: This study provides a comprehensive characterisation of future heatwave-related excess mortality across various regions and under alternative scenarios of greenhouse gas emissions, different assumptions of adaptation, and different scenarios of population change. The projections can help decision makers in planning adaptation and mitigation strategies for climate change. © 2018 Guo et al. http://creativecommons.org/licenses/by/4.0/

Effect modification of greenness on the association between heat and mortality: A multi-city multi-country study

Background: Identifying how greenspace impacts the temperature-mortality relationship in urban environments is crucial, especially given climate change and rapid urbanization. However, the effect modification of greenspace on heat-related mortality has been typically focused on a localized area or single country. This study examined the heat-mortality relationship among different greenspace levels in a global setting. Methods: We collected daily ambient temperature and mortality data for 452 locations in 24 countries and used Enhanced Vegetation Index (EVI) as the greenspace measurement. We used distributed lag non-linear model to estimate the heat-mortality relationship in each city and the estimates were pooled adjusting for city-specific average temperature, city-specific temperature range, city-specific population density, and gross domestic product (GDP). The effect modification of greenspace was evaluated by comparing the heat-related mortality risk for different greenspace groups (low, medium, and high), which were divided into terciles among 452 locations. Findings: Cities with high greenspace value had the lowest heat-mortality relative risk of 1·19 (95% CI: 1·13, 1·25), while the heat-related relative risk was 1·46 (95% CI: 1·31, 1·62) for cities with low greenspace when comparing the 99th temperature and the minimum mortality temperature. A 20% increase of greenspace is associated with a 9·02% (95% CI: 8·88, 9·16) decrease in the heat-related attributable fraction, and if this association is causal (which is not within the scope of this study to assess), such a reduction could save approximately 933 excess deaths per year in 24 countries. Interpretation: Our findings can inform communities on the potential health benefits of greenspaces in the urban environment and mitigation measures regarding the impacts of climate change.Research in context - I-Evidence before this study: Urbanization and climate change have resulted in changes to the urban environment, including the urban heat island effect and contributions to other extreme weather events. Recently, as metropolitan areas have become denser due to rapid urbanization, environmental problems such as high temperatures are also worsening. Many studies showed that high temperatures increase health risks, including mortality. Therefore, identifying factors that could mitigate the high-temperature conditions in urban environments are a crucial part of climate change mitigation strategies. Many studies found that urban green spaces may play an important role in mitigating heat. Specifically, large green spaces have shown a significant and positive cooling effect. Vegetation can promote air convection through shading and evapotranspiration, which indicates that dense vegetation can lower air temperature. Therefore, more greenspace could result in lower temperatures during the warm season, which would lower exposure to high temperatures that impact human health. Importantly, while greenspace can lower exposure to heat, this study examined how greenspace modifies the heat-health relationship. Some studies have investigated this issue. For example, studies found that heat-related mortality and ambulance calls are negatively correlated with the amount of greenspace coverage. However, most previous work on how greenspace modifies the heat-health relationship was based on one country or region. Research is needed on a global scale to understand how greenspace in urban areas among different countries, with different populations, levels of urbanization, and types of greenspace, can modify the relationship between extreme temperatures and health. As climate change is anticipated to increase temperatures and the associated health consequences worldwide, greenspace may be a plausible mitigation strategy for cities in order to address heat-related health impacts at present and in the future. II-Added value of this study: In this study, we explored the effect modification of greenspace on the heat-mortality relationship on a global scale. With a dataset of 452 locations from 24 countries located in various climate zones and continents, this study incorporated variability in greenspace, temperature, and population characteristics. We found that, based on 452 locations, the heat-mortality risks differed with greenspace category and the cities with higher greenspace values had lower heat-mortality risk than those with lower greenspace values. III-Implications of all the available evidence: Our findings provide evidence that higher greenspace reduces the heat-related mortality, which is similar to other previous smaller studies, and our study results were consistent in different countries around various climate zones. These findings indicate that disparate greenspace levels, temperature, and environment settings should be considered when developing policies and strategies in climate change mitigation and public health adaptation. This study adds to the existing literature that greenspace can reduce the urban heat island effect, by providing evidence for the theory that greenspace can also lower the heat-mortality association, and documents such impacts on a global scale.This publication was developed under Assistance Agreement No. RD83587101 awarded by the U.S. Environmental Protection Agency to Yale University. Research reported in this publication was also supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD012769. Also, this work has been supported by the National Research Foundation of Korea (2021R1A6A3A03038675), Medical Research Council-UK (MR/V034162/1 and MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/R009384/1), Academy of Finland (Grant ID: 310372), European Union's Horizon 2020 Project Exhaustion (Grant ID: 820655 and 874990), Czech Science Foundation (22-24920S), Emory University's NIEHS-funded HERCULES Center (Grant ID: P30ES019776), and Grant CEX2018-000794-S funded by MCIN/AEI/ 10.13039/501100011033.info:eu-repo/semantics/publishedVersio

How urban characteristics affect vulnerability to heat and cold: a multi-country analysis.

BACKGROUND: The health burden associated with temperature is expected to increase due to a warming climate. Populations living in cities are likely to be particularly at risk, but the role of urban characteristics in modifying the direct effects of temperature on health is still unclear. In this contribution, we used a multi-country dataset to study effect modification of temperature-mortality relationships by a range of city-specific indicators. METHODS: We collected ambient temperature and mortality daily time-series data for 340 cities in 22 countries, in periods between 1985 and 2014. Standardized measures of demographic, socio-economic, infrastructural and environmental indicators were derived from the Organisation for Economic Co-operation and Development (OECD) Regional and Metropolitan Database. We used distributed lag non-linear and multivariate meta-regression models to estimate fractions of mortality attributable to heat and cold (AF%) in each city, and to evaluate the effect modification of each indicator across cities. RESULTS: Heat- and cold-related deaths amounted to 0.54% (95% confidence interval: 0.49 to 0.58%) and 6.05% (5.59 to 6.36%) of total deaths, respectively. Several city indicators modify the effect of heat, with a higher mortality impact associated with increases in population density, fine particles (PM2.5), gross domestic product (GDP) and Gini index (a measure of income inequality), whereas higher levels of green spaces were linked with a decreased effect of heat. CONCLUSIONS: This represents the largest study to date assessing the effect modification of temperature-mortality relationships. Evidence from this study can inform public-health interventions and urban planning under various climate-change and urban-development scenarios

Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries.

BACKGROUND Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. METHODS We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. RESULTS The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively. CONCLUSIONS Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate

Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries

Background: Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. Methods: We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. Results: The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1–2.3) and 9.1 (95% eCI, 8.9–9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4–2.8) and 12.8 (95% eCI, 12.2–13.1) for every 1000 heart failure deaths, respectively. Conclusions: Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day—and especially under a changing climate.Clinical Perspective_ What Is New?: This study provided evidence from what we believe is the largest multinational dataset ever assembled on cardiovascular outcomes and environmental exposures; Extreme hot and cold temperatures were associated with increased risk of death from any cardiovascular cause, ischemic heart disease, stroke, and heart failure; For every 1000 cardiovascular deaths, 2 and 9 excess deaths were attributed to extreme hot and cold days, respectively. _ What Are the Clinical Implications?: Extreme temperatures from a warming planet may become emerging priorities for public health and preventative cardiology; The findings of this study should prompt professional cardiology societies to commission scientific statements on the intersections of extreme temperature exposure and cardiovascular health.This study was supported by the Kuwait Foundation for the Advancement of Science (CB21-63BO-01); the US Environmental Protection Agency (RD-835872); Harvard Chan National Institute of Environmental Health Sciences Center for Environmental Health (P01ES009825); the UK Medical Research Council (MR/R013349/1); the UK Natural Environment Research Council (NE/R009384/1); the European Union’s Horizon 2020 Project Exhaustion (820655); the Australian National Health and Medical Research Council (APP 2000581, APP 1109193, APP 1163693); the National Institute of Environmental Health Sciences–funded HERCULES Center (P30ES019776); the MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S); the Taiwanese Ministry of Science and Technology (MOST 109–2621-M-002–021); the Environmental Restoration and Conservation Agency, Environment Research and Technology Development Fund (JPMEERF15S11412); the São Paulo Research Foundation; and Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016)info:eu-repo/semantics/publishedVersio

Ambient Particulate Air Pollution and Daily Mortality in 652 Cities.

BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived. RESULTS: On average, an increase of 10 μg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.)

Temperature-Related Mortality Impacts Under and Beyond Paris Agreement Climate Change Scenarios

The Paris Agreement binds all nations to undertake ambitious efforts to combat climate change, with the commitment to Bhold warming well below 2 °C in global mean temperature (GMT), relative to pre-industrial levels, and to pursue efforts to limit warming to 1.5 °C^. The 1.5 °C limit constitutes an ambitious goal for which greater evidence on its benefits for health would help guide policy and potentially increase the motivation for action. Here we contribute to this gap with an assessment on the potential health benefits, in terms of reductions in temperature-related mortality, derived from the compliance to the agreed temperature targets, compared to more extreme warming scenarios. We performed a multi-region analysis in 451 locations in 23 countries with different climate zones, and evaluated changes in heat and coldrelated mortality under scenarios consistent with the Paris Agreement targets (1.5 and 2 °C) and more extreme GMT increases (3 and 4 °C), and under the assumption of no changes in demographic distribution and vulnerability. Our results suggest that limiting warming below 2 °C could prevent large increases in temperature-related mortality in most regions worldwide. The comparison between 1.5 and 2 °C is more complex and characterized by higher uncertainty, with geographical differences that indicate potential benefits limited to areas located in warmer climates, where direct climate change impacts will be more discernible

Projections of Excess Mortality Related to Diurnal Temperature Range Under Climate Change Scenarios: a multi-country modelling study

Various retrospective studies have reported on the increase of mortality risk due to higher diurnal temperature range (DTR). This study projects the effect of DTR on future mortality across 445 communities in 20 countries and regions

Temperature-Related Mortality Impacts Under and Beyond Paris Agreement Climate Change Scenarios

The Paris Agreement binds all nations to undertake ambitious efforts to combat climate change, with the commitment to Bhold warming well below 2 °C in global mean temperature (GMT), relative to pre-industrial levels, and to pursue efforts to limit warming to 1.5 °C^. The 1.5 °C limit constitutes an ambitious goal for which greater evidence on its benefits for health would help guide policy and potentially increase the motivation for action. Here we contribute to this gap with an assessment on the potential health benefits, in terms of reductions in temperature-related mortality, derived from the compliance to the agreed temperature targets, compared to more extreme warming scenarios. We performed a multi-region analysis in 451 locations in 23 countries with different climate zones, and evaluated changes in heat and coldrelated mortality under scenarios consistent with the Paris Agreement targets (1.5 and 2 °C) and more extreme GMT increases (3 and 4 °C), and under the assumption of no changes in demographic distribution and vulnerability. Our results suggest that limiting warming below 2 °C could prevent large increases in temperature-related mortality in most regions worldwide. The comparison between 1.5 and 2 °C is more complex and characterized by higher uncertainty, with geographical differences that indicate potential benefits limited to areas located in warmer climates, where direct climate change impacts will be more discernible