Unravelling the impact of El Niño on waterborne diseases in South America

Lead Research Organisation: University of Bath
Department Name: Biology and Biochemistry

Abstract

Vibrio species are a diverse genus of Gram-negative bacteria found in marine habitats. In addition to playing a critical ecological role in many marine ecosystems, this genus also includes key pathogens of humans. V. cholerae and V. parahaemolyticus, are amongst the most significant human pathogenic bacteria originating from the marine environment. Cholera alone affects an estimated 3-5 million people worldwide; V. parahaemolyticus is the leading cause of seafood borne bacterial gastroenteritis in the world. Infections caused by Vibrio cholerae and V. parahaemolyticus have shown a steady expansion over the last decades associated with the emergence of pandemic clones. The seventh cholera pandemic began in Indonesia in 1961 and was confined to Asia until 1970 when it reached Africa and Europe. After a long time without any new evidence of dissemination, it re-emerged in northern Peru in 1991 causing more than 1,000,000 cases of cholera in just three years. Likewise, V. parahaemolyticus infections were almost confined to Asia until the emergence of cases associated with a single clone in Calcutta in 1996. We report the first incursion of this clone outside Asia in 1997 causing infections along the coast of Peru. The advent of V. cholerae and V. parahaemolyticus infections on the West coast of South America in 1991 and 1997 represented the two only reported evidences of an eastward drift of Asian variants of these pathogens and both processes were concurrent with the arrival of warm equatorial waters displaced by El Niño.

El Niño is a climate pattern that describes the unusual warming of surface waters along the tropical west coast of South America causing a notable impact on the ocean and weather at global scale. El Niño events occur irregularly and are not strictly predictable and one of the most major manifestations is the zonal displacement of the Indo-Pacific Warm Pool, a body of water which holds the warmest oceanic seawaters in the world. This body of water is subjected to strong east migrations to Ecuador in phase with the movement of El Niño waters. In the Pacific coast of South America, the incoming of El Niño equatorial waters to the American coasts originate the incursion of warm waters of lower salinity moving southward along the coast, which has been shown to transport foreign zooplankton populations into Peru and Chile. As the survival and spread of vibrios in the marine environment under adverse conditions has been linked to the ability of these bacteria to attach to plankton, we hypothesize that zooplankton provide nutrients and protection to enable vibrios to travel across oceans.

We have been working in Peru over the last 10 years isolating and characterizing Vibrio strains obtained from environmental and clinical sources with the aim of identifying new evidence of the link between populations in Asia and the Pacific coast of South America. As result of these investigations, we have identified in environmental sources in Peru the presence of four genetic variants of Vibrio which had been uniquely previously reported in Asia and, strikingly, all of these variants emerged both in time and space with significant El Niño events. According to these observations, the incursion of invasive plankton populations into the coasts of Peru trapped in the El Niño waters may provide a unique source of novel pathogenic variants of Vibrio.

After more than ten years waiting for a new El Niño episode, the active event provides a unique opportunity to test the hypothesis of the existence of an effective trans-Pacific transference of Vibrio populations in phase with the zonal displacement of El Niño waters. All these aspects will address key aspects of the ecology of zooplankton and Vibrio, and specifically the role of zooplankton in driving the global dispersal of Vibrio through major oceanic corridors, which will be particularly useful protection of populations and prevention of future epidemics.

Planned Impact

This proposal aims to deliver substantial and lasting impact by providing mechanistic understanding of one of the more elusive yet fundamental aspects regarding the mechanisms of spreading of Vibrio diseases. Results of the project will address key aspects regarding the ecology of zooplankton and Vibrio, and specifically the role of zooplankton in driving the global dispersal of Vibrio through major oceanic corridors, which will be particularly useful protection of populations and prevention of future major epidemics. As this research is multidisciplinary in nature, research will be of relevance to a wide variety of stakeholders with interests in microbial ecology, bacterial genomics, food safety, epidemiology and oceanography, among others. In addition to diverse scientific communities, the research will therefore have a wider impact in relation to understanding of the long-distant routes of migration of marine organisms through the open ocean and how the introduction of new populations through this mechanisms can impact the ecological equilibrium of local communities.

Although we will engage directly with a variety of stakeholders (in academic, industry and policy areas), a key goal of the proposed research is to build pathways to enable the connection of basic scientific knowledge with policy and decision makers with a clear aim of applying the results of this research proposal to design intervention strategies to anticipate risks associated with the arrival of El Niño waters to Peru.

The economic and societal impacts of the research are broad as the results may affect many aspects of society that rely on marine ecosystems. In Peru, the implementation of surveillance programs resulting from the proposed research would contribute to an early detection of the arrival of pathogens to coastal areas, which provides to the local authorities of an effective tool to design strategies and implement measures directed to minimize the potential impacts of the introduction of new pathogens on health. These measures may be particularly useful to provide protection to coastal populations and low income groups with a diet primarily based on seafood consumption, mainly raw and undercooked seafood, and main target of previous Vibrio epidemics. Fishing industry in Peru. Peru has a coastal belt of over 3,000 km fishing more than 50 species of commercial interest. Secondly, due to importance of fish activities in Peru (154 millions of tons in 2011 and more than 120,000 jobs), results of the present research would help to competent authorities for the seafood safety to implement measures for an early detection of potentially pathogenic Vibrio arriving to coastal areas of Peru, which will contribute to minimise further risks associated with the commercialization of contaminated seafood and infection of consumers. These measures will be instrumental in preventing the dramatic impacts that have occurred during previous epidemics, such as the closure of the borders for exportation and affecting local coastal populations with a primary economic sector based on small-scale fisheries.

Outside Peru, non-academic stakeholders include policy forming bodies such as Governmental Health and Environment Departments (e.g. the European Union, UK Government Departments, US Food and Drug Administration, NOAA). All of these groups have a potential interest in human marine pathogens and the impact climate and ocean dynamics on human health. Results from the proposed research will not affect to our understanding of the role of the El Niño in the dissemination of pathogenic bacteria in the Pacific, but also will built up a new framework for the study of the ocean dynamics as major driver for microbial communities and pathogenic bacteria with consequences for ecology and epidemiology on a global scale.

Publications

10 25 50
 
Description The central hypothesis of the project was to assess the role of El Niño in the introduction of new genetic variants of pathogenic bacteria into Peru and the consequences for public health in the country, resulting in large outbreaks of illness and epidemics. As result of the different activities has been possible to identify new genetic variants of pathogenic Vibrio associated with the recent event of El Niño in 2015-2016. Moreover, the sudden arrival of an exceptional and anomalous El Niño event over the austral summer of 2017, termed "coastal El Niño", provided us a unique opportunity to test our hypothesis in the course of an ongoing event. The coastal El Niño caused severe flooding event and major disruptions all along the coast of Peru with dramatic consequences for the population, with deceases, shortage of food and water availably and increase of food and waterborne infections. The extension of the length of the project and sampling activities allowed us the collections of samples over the course of these events.

Due to the fact that many of the project activities have finished by the end of February, results of several samples are still subjected to analysis. However, as a primary finding of the project, we have been able to find definitive evidences linking the arrival of new genetic strains of Vibrio and the emergence of infections in Peru with the El Niño event. Although the ultimate mechanisms driving the arrival of these strains will remain unconcluded until completing the ongoing analysis, we have confirmed that the origin of most of these new genetics variants in Southeast Asia. These foreign strains have been introduced in the coastal water of Peru at different point in the pass and the warming of the water typically associated with the arrival of El Niño has operated a contributing factor causing the ignition of infections and epidemics. We are currently applying a new generation of genomic tools developed over the course of the project to track the dispersal of these pathogens and identify links between populations from both sides of the Pacific Ocean. New results from the analyses have been incorporated as part of new manuscripts which are currently under review in different journals.

The activities carried out over the course of the project in collaboration with the two major institutions in Peru responsible for the food safety in the country (the National Institution for Seafood Safety - SANIPES, Ministry of Fisheries, and of the National Institute of Health - INS, Ministry of Health) has covered a broad number of aspects from training and public engagement to academic and technical collaborations. All these activities have contributed to strength the existing programs for food safety and epidemiology associated with extreme weather events -such as El Niño- in Peru. As result of this work, a regular monitoring program to assess the biological and environmental risks associated with flooding events is now active in Peru covering all the coastal areas of the country. As part of the program, samples of water from rivers and sea are collecting in a regular basis to identify any change in the composition of Vibrio communities in the aquatic systems as a preliminary signal of risk.

A second impact of the project activities has been the implementation of a new generation of tools to apply in a regular basis for the surveillance of food and waterborne diseases in the region. A new scheme for strain typing using whole genome sequences has been developed in collaboration with one of the partner (US-FDA), published (J. Clin. Microbiol. June 2017 vol. 55 no. 6 1682-1697) and it is now publically available (https://pubmlst.org/vparahaemolyticus/). This new tool will contribute to a quicker and enhanced analysis of strains with a higher resolution which will be critical for an effective tracking the dispersal of strains. Furthermore, the generation of global repositories of genomes for the two major pathogens, V. parahaemolyticus and V. cholerae, in this project has been used to identify connections between populations identified in different regions of the world and draw the potential routes of dispersal. In the course of this project, more than 600 genomes of V. parahaemolyticus have been sequenced and the global database, initially composed by 600 genomes, comprises today mored than 1300 genomes for this bacteria. Additional, 150 genomes of V. cholerae and 100 genomes of Salmonella Infantis have been also sequenced and incorporated to the global databases for these pathogenic bacteria. The global phylogeny of V. parahaemolyticus and the new tools for typing are now available on specific web developed in the project and publically accessible (http://www.vibrioviewer.org). Additionally, the website also contains a tool to visualise the environmental suitability for Vibrio in coastal regions based on remote sensing data. This tool, with global coverage, provides an estimate of the risk of presence pathogenic Vibrio in coastal areas as a proxy of the risk of infections. We are now finishing a new version of the tool with an enhanced resolution for coastal areas of Peru. The partner institutions in Peru will be using these new tools in regular basis as a complement of the field work and surveillance programs.

The close collaboration with the local partner have contributed to a rapid and effective dissemination of the benefits of the project. Additionally, the participation in public events with representation of the industry has been essential for a broader diffusion of the major findings of the project and also for the dissemination of the new tools among non-institutional partners.
Exploitation Route As result of the collaboration over the course of this project, the National Institute of Health (INS) in Peru has implement a regular monitoring program to assess the biological and environmental risks associated with extreme weather events. Applying the new genomic tools developed in the project and according the level of risk identified using the map of risk, the INS is collecting samples in different regions of the country which are subjected to sequencing and analysis to identify the presence of new variants of pathogenic Vibrio. The new identified strains will be deposited into the global database generated in the project and analysed in a global context to identify potential sources and origins of the new populations.

As extension of the project, partners working on the project are exploring different sources of funding for expanding the sampling strategy and analyse samples of zooplankton. Due to the fact that zooplankton represent the major reservoir for Vibrio in oceanic waters, we want to analyse samples deposited in the different collections in Peru along with newly collected samples to identify the impact of El Niño on the Vibrio communities associated with zooplankton over the last decades.
Sectors Agriculture, Food and Drink,Education,Environment,Healthcare

URL http://www.vibrioviewer.org/
 
Description As mentioned in previous sections, the first results of the project activities have been incorporated to the current projects of two different international organisations: FAO and ECDC. The ongoing activities on the impact of climate and food trade on the dispersal of Vibrio pathogens are providing novel insights on the epidemic dynamics of these diseases and the mechanisms of spreading of pathogens and diseases which have been incorporated into the revision of the risk of Vibrio diseases undertaken by these two institutions over the last months. The National Instituto of Health and Sanipes (two of the partners of this project) have implemented a new monitoring program based on the results of the project activities and they are using the genomic and environmental tools developed in the project to identify the potential risk of infections (map of risk) and introduction of new genetic variants (phylogeny). The National Institute of Health has also implemented a new surveillance program to identify pathogenic vibrios environmental setting in remote areas of the country as part of a new sentinel program to detect the presence of pathogens over periods of heavy rain.
First Year Of Impact 2016
Sector Agriculture, Food and Drink,Education,Environment,Healthcare,Government, Democracy and Justice
Impact Types Societal,Policy & public services

 
Description FAO Update risk assessment on Vibrio diseases
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact Results of the present project are providing a new vision on the epidemic dynamics of Vibrio diseases at global scales, including aspects of pathogen dispersal, risk factors, exposition to disease and risk managing. All these factors have been discussed as part of the activities of the panel for the update of the risk assessment of Vibrio diseases at the Food and Agriculture Organization of the United Nations (FAO) and several of the outcomes of the project have been incorporated in the updated version of the document. The FAO Risk Assessments are applied at global scale to introduce or modify the existing regulations at national level on aspect related to food production and food safety.
 
Description Vibrio Risk Map-European Centre for Disease Prevention and Control (ECDC)
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact We have been regularly updating the exiting tool that we created in 2014 to assess the risk of Vibrio illness at global scale using remote sensing data. The tool is hosted on the European Centre for Disease Prevention and Control (ECDC) website as part of the activities of the European Environment and Epidemiology (E3) Network. Results of the present project has been used to improve the resolution of the models applied to generated the risk fields on the map in coordination with the ECDC (Prof. Jan Semenza). This tool is used to assess the risk of Vibrio infections at almost real time based on associations between risk of illness and seawater temperature and salinity.
URL https://e3geoportal.ecdc.europa.eu/SitePages/Vibrio%20Map%20Viewer.aspx
 
Title Core Genome Multilocus Sequence Typing Scheme for the Global Epidemiology of Vibrio parahaemolyticus 
Description To establish this universal V. parahaemolyticus core genome cgMLST scheme. We created the new V. parahaemolyticus cgMLST scheme able to distinguish related and unrelated strains, including those with the same Sequence Type using the classical MLST scheme (which only uses 7 genes). This new method clearly shows an enhanced resolution over conventional MLST analysis. e have created a standardized cgMLST scheme that allows for fast typing of V. parahaemolyticus from WGS data in a publicly available database. This cgMLST scheme was tested with a diverse set of strains belonging to the same or unrelated outbreaks and was able to differentiate them accordingly, therefore showing a great potential for use in outbreak investigations. Application of this cgMLST scheme to V. parahaemolyticus strains collected by different laboratories around the world will help define the global picture of the epidemiology, spread, and evolution of this pathogen. All of this information will be critical in its application to outbreak investigations, providing a unique repository of genomes that can be used for unambiguous comparisons of data generated worldwide. Finally, since V. parahaemolyticus is a bacterium highly intertwined with environmental changes, it is our goal to develop a tool that would be able to integrate the results obtained from the cgMLST scheme analysis of the entire database, as it continues to grow, into a geographical visualization that together with environmental variables (e.g., salinity and temperature) would help to determine worldwide dispersal rates of this pathogen and help in modifying risk assessments for this bacterium in different regions. 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact Application of this cgMLST scheme to V. parahaemolyticus strains collected by different laboratories around the world will help define the global picture of the epidemiology, spread, and evolution of this pathogen. All of this information will be critical in its application to outbreak investigations, providing a unique repository of genomes that can be used for unambiguous comparisons of data generated worldwide. Finally, since V. parahaemolyticus is a bacterium highly intertwined with environmental changes, it is our goal to develop a tool that would be able to integrate the results obtained from the cgMLST scheme analysis of the entire database, as it continues to grow, into a geographical visualization that together with environmental variables (e.g., salinity and temperature) would help to determine worldwide dispersal rates of this pathogen and help in modifying risk assessments for this bacterium in different regions. 
URL https://pubmlst.org/vparahaemolyticus/
 
Title Vibrio parahaemolyticus Disease Tool Genomics and Climate Analysis for Risk Assessment 
Description As part of the aims of the project, we have developed a new online tool for the visualisation of genomic data and risk of infections associated with Vibrio. The genomic tool shows the global phylogeny of Vibrio parahaemolyticus using the repository of genomes collected over the course of the project. This section displays data using two different analytical approaches: single nucleotide polymorphisms and the new method for whole-genome multi-locus sequence typing developed in this project, allowing of the selection of the strains isolated in each country. The second component of the tool provides a measure of the risk of infections associated with non-cholera Vibrio (vibriosis) a global scale, showing the risk of infections at global scale as result of the ecological suitability for these organisms. 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact This tool provides basic information about two of the major aspects associated with Vibrio infections: environmental conditions and risk of infections, and genetic diversity of strains from infections and the environment. This website, currently in process of improvement, will provide basic information for public health officers and policy makers to make decision about the risk of infections associated with this pathogen, in a single site, epidemiologist and public health expert will. be able to find all the available information about different genetic variants of V. parahaemolyticus and the connections between populations identified in different regions of the world associated with infections, as well as the level of risk of infections in the local waters at almost real time inferred from remote-sensing data. 
URL http://www.vibrioviewer.org/
 
Title Global database of Vibrio parahaemolyticus genomes 
Description As part of the activities of the project, we have created a repository of all the available genomes of Vibrio parahaemolyticus with global coverage. In addition to the publicly available genomes, we have generated new 300 genomes of strains deposited in our collection and new strains collected in the course of the present project. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact This database has been used to identify connections between Vibrio parahaemolyticus populations from different regions of the world and, in particular, to assess potential links between strains from Asia and South America in relation to the major El Niño events. Additionally, this database has been also applied to other ongoing studies on the investigation of outbreaks of illness or epidemiological patterns of Vibrio diseases in region of Europe, USA and South America. 
 
Description Chinese Center for Disease Control and Prevention (China CDC) 
Organisation Chinese Center for Disease Control and Prevention (China CDC)
Country China 
Sector Public 
PI Contribution Our team has been leading the genomic analysis of the strains collected in China and Peru with the aim of identifying new epidemiological evidences connecting the pathogens involved in foodborne infections in Asia and South America associated with different El Niño events.
Collaborator Contribution Chinese Center for Disease Control and Prevention (China CDC) has been providing us new strains of Vibrio parahaemolyticus isolated from infections in China to be compared with our collection from Peru in order to assess possible connections between both populations driven by El Niño events.
Impact No outputs yet, but we expect to publish an article describing the genomic analysis of strains collected on both side of the Pacific Ocean to assess possible connection between populations.
Start Year 2016
 
Description Collaboration with the Universidad de la Frontera, Temuco, Chile 
Organisation University of La Frontera
Country Chile 
Sector Academic/University 
PI Contribution The former postdoc working on the project (Michel Abanto) left the University of Bath in July 2017 to work as academic in the University de la Frontera (Chile). Since he started in the new position, we have been working closely on several activities of the project, from data analysis to expanding our area of study to Chile. As result of this collaboration, we have organised a workshop in the University de la Frontera on the analysis of genomic data in epidemiology and ecology to provide basic skills on bioinformatic analyses to the postgraduate students in this university. As second important aspect of this collaboration was the organisation of a final meeting for the project in Santiago (Chile) with contributions from Peruvian and Chilean scientists and public health experts working on food and waterborne disease where all the major findings of the research carried out in the course of this project were presented. This meeting in Santiago was also the first foundational meeting for a new network on Vibrio research in South America as platform where all the active scientists and public health experts working on this area in Chile and Peru will work together sharing information on Vibrio infections.
Collaborator Contribution The main contribution of the partner was to provide support in all the activities associated with the analysis of genomic data. A second important aspect of this collaboration was also the expansion of the area of study to Chile (initially limited to Peru).
Impact Network of Vibrio in South America: "Towards a collaborative network on Vibrio research in South America" 25 - 26 de enero 2018. Universidad Autónoma de Chile
Start Year 2017
 
Description Instituto del Mar del Perú - IMARPE 
Organisation Institute of the Sea of Peru
Country Peru 
Sector Public 
PI Contribution We are providing our expertise in genomic analysis of bacteria to the study of the microbial communities living associated with zooplankton. The final aim of this collaboration is to assess the potential role of the migration of zooplankton in the introduction of new variants of pathogenic Vibrio into the coasts of Peru in phase with the arrival of El Niño waters.
Collaborator Contribution IMARPE will be providing us samples of zooplankton collected from different locations along the coast of Peru before, during and after El Niño events. Additionally, IMARPE will contribute to the project providing the knowledge on physical and biological oceanography of the coasts of Peru to analyse and decipher results and findings from the study.
Impact No outputs yet since the collaboration is still ongoing.
Start Year 2017
 
Description IV Conferencia Internacional Sanidad e Inocuidad de la Pesca y la Acuicultura 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact The "IV CONFERENCIA INTERNACIONAL SANIDAD E INOCUIDAD DE LA PESCA Y LA ACUICULTURA" is the most influential event in Peru on food safety for fishing activities and aquaculture. Organised by the Peruvian government, this forum is one of most important International meeting on this field with participation of international expert from all the continent. The PI of the project presented in the meeting the main outcomes of the project, the impact on food safety in the regions, the tools available for risk mitigation, and the work carried out with local authorities to implement controls and action to minimise the impacts of El Niño on food-related infection in Peru and Chile.
Year(s) Of Engagement Activity 2017
URL http://www.sanipes.gob.pe/CISIPA/
 
Description Towards a collaborative network on Vibrio research in South America 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Foundational meeting for the creation of a new network on Vibrio research in South America as platform where all the active scientists and public health experts working on this area in Chile and Peru will work together sharing information on Vibrio infections.
Year(s) Of Engagement Activity 2008
URL http://somich.cl/simposio-internacional-vibrio-chile-2018/
 
Description Workshop on the use of new sequencing technologies for environmental samples in the UNAM 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact In July 2017, some of the participants in the project organised a workshop at the Instituto de Ecología, UNAM (Mexico) on the use of the Nanopore sequencing technologies to analyse environmental samples. In this workshop, a group of PhD students and postdoctoral researchers were trained in the use of these technologies in samples collected in the Gulf of Calfornia over different periods to identify possibles links between microbial composition and El Niño events. Over this visit, several samples were collected and subjected to analysis and we are currently waiting for the first results of these analyses to write a manuscript with the outcomes of this work. As second product of these activity, we are considering to apply for a new project to investigate the impact of El Niño on the microbial composition and diversity in the Gulf of California.
Year(s) Of Engagement Activity 2017
 
Description Workshop on the use of new sequencing technologies for environmental samples in the University de la Frontera, Chile 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact In collaboration with the former postdoc working on the project (Michel Abanto), now working as academic in the University de la Frontera (Chile), we have organised a workshop in the University de la Frontera on the analysis of genomic data in epidemiology and ecology to provide basic skills on bioinformatic analyses to the postgraduate students in this university. This activity also contributed to establish new link with academics in this university and explore future collaborations on the field of ecology genomics.
Year(s) Of Engagement Activity 2017