A Systematic Review of Methodology: Time Series Regression Analysis for Environmental Factors and Infectious Diseases

Background: Time series analysis is suitable for investigations of relatively direct and short-term effects of exposures on outcomes. In environmental epidemiology studies, this method has been one of the standard approaches to assess impacts of environmental factors on acute non-infectious diseases (e.g.cardiovascular deaths), with conventionally generalized linear or additive models (GLM and GAM). However, the same analysis practices are often observed with infectious diseases despite of the substantial differences from non-infectious diseases that may result in analytical challenges. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, systematic review was conducted to elucidate important issues in assessing the associations between environmental factors and infectious diseases using time series analysis with GLM and GAM. Published studies on the associations between weather factors and malaria, cholera, dengue, and influenza were targeted. Findings: Our review raised issues regarding the estimation of susceptible population and exposure lag times, the adequacy of seasonal adjustments, the presence of strong autocorrelations, and the lack of a smaller observation time unit of outcomes (i.e. daily data). These concerns may be attributable to features specific to infectious diseases, such as transmission among individuals and complicated causal mechanisms. Conclusion: The consequence of not taking adequate measures to address these issues is distortion of the appropriate risk quantifications of exposures factors. Future studies should pay careful attention to details and examine alternative models or methods that improve studies using time series regression analysis for environmental determinants of infectious diseases

mcr-Colistin resistance genes mobilized by IncX4, IncHI2, and IncI2 plasmids in Escherichia coli of pigs and white stork in Spain

Colistin has become the last-line antimicrobial for the treatment of multidrug resistant (MDR) Enterobacterales in human medicine. To date, several colistin resistance genes have been described. Of them mcr-1 is disseminated worldwide in Escherichia coli of human and animal origin. The aim of this study was to characterize mcr-mediated resistance plasmids from E. coli of animal origin in Spain. From our strain collection, 70 E. coli of pig origin collected between 2005 and 2014 (10 per year, except for years 2009-2010-2013) were randomly selected and screened for the presence of mcr-genes. Additionally, 20 E. coli isolated in 2011 from white storks (Ciconia ciconia) from the same urban household waste landfill associated colony were also included. Whole genome sequencing of mcr-positive isolates was carried out on a MiSeq (Illumina). Hybrid whole genome sequencing strategy combining nanopore and Illumina technologies were performed in a selection of isolates to close the genomes and plasmids and identify the presence of antimicrobial resistance genes. Minimum inhibitory concentration (MIC) was used to assess the susceptibility to colistin. Mating experiments were carried out to evaluate transferability of the mcr-genes. A total of 19 mcr-1 and one mcr-4 positive isolates were detected, 15 from pigs distributed during the study period, and five from storks collected in 2011. No other mcr-variants were found. The MICs for colistin ranged between 4 and >4 mg/L. High diversity of STs were detected among the mcr-1 positive E. coli isolates, with only ST-10 shared between pigs and white storks. Except for one isolate, all were genotypic and phenotypically MDR, and five of them also harbored cephalosporin resistance genes (bla CTX-M- 14, bla SHV- 12, and three bla CMY- 2). mcr-1 genes were mobilizable by conjugation, associated with IncX4, IncHI2, and IncI2 plasmids. In our study, mcr-1 genes have been circulating in pig farms since 2005 harbored by a variety of E. coli clones. Its persistence may be driven by co-selection since plasmids containing mcr-1 also exhibit resistance to multiple drugs used in veterinary medicine. Furthermore, this is the first report of the presence of mcr-1 gene in isolates from white storks in Spain. This finding highlights the potential importance of wildlife that forage at urban household waste landfills in the transmission and spread of colistin resistance genes.info:eu-repo/semantics/publishedVersio

mcr -Colistin Resistance Genes Mobilized by IncX4, IncHI2, and IncI2 Plasmids in Escherichia coli of Pigs and White Stork in Spain

Colistin has become the last-line antimicrobial for the treatment of multidrug resistant (MDR) Enterobacterales in human medicine. To date, several colistin resistance genes have been described. Of them mcr -1 is disseminated worldwide in Escherichia coli of human and animal origin. The aim of this study was to characterize mcr -mediated resistance plasmids from E. coli of animal origin in Spain. From our strain collection, 70 E. coli of pig origin collected between 2005 and 2014 (10 per year, except for years 2009-2010-2013) were randomly selected and screened for the presence of mcr -genes. Additionally, 20 E. coli isolated in 2011 from white storks (Ciconia ciconia) from the same urban household waste landfill associated colony were also included. Whole genome sequencing of mcr -positive isolates was carried out on a MiSeq (Illumina). Hybrid whole genome sequencing strategy combining nanopore and Illumina technologies were performed in a selection of isolates to close the genomes and plasmids and identify the presence of antimicrobial resistance genes. Minimum inhibitory concentration (MIC) was used to assess the susceptibility to colistin. Mating experiments were carried out to evaluate transferability of the mcr -genes. A total of 19 mcr -1 and one mcr -4 positive isolates were detected, 15 from pigs distributed during the study period, and five from storks collected in 2011. No other mcr -variants were found. The MICs for colistin ranged between 4 and >4 mg/L. High diversity of STs were detected among the mcr-1 positive E. coli isolates, with only ST-10 shared between pigs and white storks. Except for one isolate, all were genotypic and phenotypically MDR, and five of them also harbored cephalosporin resistance genes (bla , bla , and three bla ). mcr -1 genes were mobilizable by conjugation, associated with IncX4, IncHI2, and IncI2 plasmids. In our study, mcr -1 genes have been circulating in pig farms since 2005 harbored by a variety of E. coli clones. Its persistence may be driven by co-selection since plasmids containing mcr -1 also exhibit resistance to multiple drugs used in veterinary medicine. Furthermore, this is the first report of the presence of mcr -1 gene in isolates from white storks in Spain. This finding highlights the potential importance of wildlife that forage at urban household waste landfills in the transmission and spread of colistin resistance genes

Complete Genome Sequence of <em>Vibrio parahaemolyticus</em> Environmental Strain UCM-V493

Vibrio parahaemolyticus is the leading bacterial cause of seafood-related gastroenteritis in the world. Here, we report the complete genome sequence and annotation of an environmental strain of V. parahaemolyticus, UCM-V493, with the aim of understanding the differences between the clinical and environmental isolates of the bacteria. We also make some preliminary sequence comparisons with the clinical strain RIMD2210633

Acquired Type III Secretion System Determines Environmental Fitness of Epidemic Vibrio parahaemolyticus in the Interaction with Bacterivorous Protists

Genome analyses of marine microbial communities have revealed the widespread occurrence of genomic islands (GIs), many of which encode for protein secretion machineries described in the context of bacteria-eukaryote interactions. Yet experimental support for the specific roles of such GIs in aquatic community interactions remains scarce. Here, we test for the contribution of type III secretion systems (T3SS) to the environmental fitness of epidemic Vibrio parahaemolyticus. Comparisons of V. parahaemolyticus wild types and T3SS-defective mutants demonstrate that the T3SS encoded on genome island VPaI-7 (T3SS-2) promotes survival of V. parahaemolyticus in the interaction with diverse protist taxa. Enhanced persistence was found to be due to T3SS-2 mediated cytotoxicity and facultative parasitism of V. parahaemolyticus on coexisting protists. Growth in the presence of bacterivorous protists and the T3SS-2 genotype showed a strong correlation across environmental and clinical isolates of V. parahaemolyticus. Short-term microcosm experiments provide evidence that protistan hosts facilitate the invasion of T3SS-2 positive V. parahaemolyticus into a coastal plankton community, and that water temperature and productivity further promote enhanced survival of T3SS-2 positive V. parahaemolyticus. This study is the first to describe the fitness advantage of GI-encoded functions in a microbial food web, which may provide a mechanistic explanation for the global spread and the seasonal dynamics of V. parahaemolyticus pathotypes, including the pandemic serotype cluster O3:K6, in aquatic environments

Climate warming and increasing Vibrio vulnificus infections in North America

Vibrio vulnificus is an opportunistic bacterial pathogen, occurring in warm low-salinity waters. V. vulnificus wound infections due to seawater exposure are infrequent but mortality rates are high (~ 18%). Seawater bacterial concentrations are increasing but changing disease pattern assessments or climate change projections are rare. Here, using a 30-year database of V. vulnificus cases for the Eastern USA, changing disease distribution was assessed. An ecological niche model was developed, trained and validated to identify links to oceanographic and climate data. This model was used to predict future disease distribution using data simulated by seven Global Climate Models (GCMs) which belong to the newest Coupled Model Intercomparison Project (CMIP6). Risk was estimated by calculating the total population within 200 km of the disease distribution. Predictions were generated for different “pathways” of global socioeconomic development which incorporate projections of greenhouse gas emissions and demographic change. In Eastern USA between 1988 and 2018, V. vulnificus wound infections increased eightfold (10–80 cases p.a.) and the northern case limit shifted northwards 48 km p.a. By 2041–2060, V. vulnificus infections may expand their current range to encompass major population centres around New York (40.7°N). Combined with a growing and increasingly elderly population, annual case numbers may double. By 2081–2100 V. vulnificus infections may be present in every Eastern USA State under medium-to-high future emissions and warming. The projected expansion of V. vulnificus wound infections stresses the need for increased individual and public health awareness in these areas

Tracking the impacts of climate change on human health via indicators: lessons from the Lancet Countdown

Background: In the past decades, climate change has been impacting human lives and health via extreme weather and climate events and alterations in labour capacity, food security, and the prevalence and geographical distribution of infectious diseases across the globe. Climate change and health indicators (CCHIs) are workable tools designed to capture the complex set of interdependent interactions through which climate change is affecting human health. Since 2015, a novel sub-set of CCHIs, focusing on climate change impacts, exposures, and vulnerability indicators (CCIEVIs) has been developed, refined, and integrated by Working Group 1 of the “Lancet Countdown: Tracking Progress on Health and Climate Change”, an international collaboration across disciplines that include climate, geography, epidemiology, occupation health, and economics. / Discussion: This research in practice article is a reflective narrative documenting how we have developed CCIEVIs as a discrete set of quantifiable indicators that are updated annually to provide the most recent picture of climate change’s impacts on human health. In our experience, the main challenge was to define globally relevant indicators that also have local relevance and as such can support decision making across multiple spatial scales. We found a hazard, exposure, and vulnerability framework to be effective in this regard. We here describe how we used such a framework to define CCIEVIs based on both data availability and the indicators’ relevance to climate change and human health. We also report on how CCIEVIs have been improved and added to, detailing the underlying data and methods, and in doing so provide the defining quality criteria for Lancet Countdown CCIEVIs. / Conclusions: Our experience shows that CCIEVIs can effectively contribute to a world-wide monitoring system that aims to track, communicate, and harness evidence on climate-induced health impacts towards effective intervention strategies. An ongoing challenge is how to improve CCIEVIs so that the description of the linkages between climate change and human health can become more and more comprehensive

Tracking the impacts of climate change on human health via indicators: lessons from the Lancet Countdown

Background: In the past decades, climate change has been impacting human lives and health via extreme weather and climate events and alterations in labour capacity, food security, and the prevalence and geographical distribution of infectious diseases across the globe. Climate change and health indicators (CCHIs) are workable tools designed to capture the complex set of interdependent interactions through which climate change is affecting human health. Since 2015, a novel sub-set of CCHIs, focusing on climate change impacts, exposures, and vulnerability indicators (CCIEVIs) has been developed, refined, and integrated by Working Group 1 of the “Lancet Countdown: Tracking Progress on Health and Climate Change”, an international collaboration across disciplines that include climate, geography, epidemiology, occupation health, and economics. Discussion: This research in practice article is a reflective narrative documenting how we have developed CCIEVIs as a discrete set of quantifiable indicators that are updated annually to provide the most recent picture of climate change’s impacts on human health. In our experience, the main challenge was to define globally relevant indicators that also have local relevance and as such can support decision making across multiple spatial scales. We found a hazard, exposure, and vulnerability framework to be effective in this regard. We here describe how we used such a framework to define CCIEVIs based on both data availability and the indicators’ relevance to climate change and human health. We also report on how CCIEVIs have been improved and added to, detailing the underlying data and methods, and in doing so provide the defining quality criteria for Lancet Countdown CCIEVIs. Conclusions: Our experience shows that CCIEVIs can effectively contribute to a world-wide monitoring system that aims to track, communicate, and harness evidence on climate-induced health impacts towards effective intervention strategies. An ongoing challenge is how to improve CCIEVIs so that the description of the linkages between climate change and human health can become more and more comprehensive