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One Health approach to integrate Guadeloupe research on vector-borne and emerging diseases in the ERA: from characterization of emergence mechanisms to innovative approaches for prediction and control

Final Report Summary - EPIGENESIS (One Health approach to integrate Guadeloupe research on vector-borne and emerging diseases in the ERA: from characterization of emergence mechanisms to innovative approaches for prediction and control)

Executive Summary:
Emerging infectious diseases, particularly those involving arthropod vectors and wildlife, threaten human health, stockbreeding and food security worldwide. They are responding fast and deeply to global changes , particularly in the Caribbean, which is at the crossroads between North America, South America and Europe.
The objective of the EPIGENESIS project was to expand Guadeloupe research potential on emerging and vector-borne diseases (VBD) involving the necessary sectors and disciplines along with the ‘One-Health’ concept to strengthen cross-sectorial collaborations with key stakeholders and enhance pluridisciplinary research to end up with good, operational tools and recommendations for end-users and decision-makers.
The development of the research capacities was successful and included several components: acquisition of cutting edge equipment; recruitment of experienced scientists (post-doc) on new scientific disciplines (molecular microbiology, proteomics, bioinformatics, medical entomology, spatial epidemiology, animal health economics); development of strategic partnerships with European research entities allowing exchange of scientists, two-way secondments and organization of series of trainings; organization or participation in key regional and international conferences; enhanced communication programme to priority targets (decision-makers, end-users and general public, student community) in Guadeloupe and the Caribbean; and development of socio-economic studies to improve awareness and adoption of the high level research outputs, in close link with priority needs of our societies.
Important scientific results and tools have been generated during the project in all disciplines: improved understanding of the E. ruminantium genetic diversity and pathogenesis, improved knowledge of heartwater epidemiology in Guadeloupe; improved knowledge of West Nile epidemiology in Guadeloupe and development of dichotomic and molecular tools for the identification of mosquito species; platform of GIS tools for national veterinary services in the Caribbean to ease data collection, analysis, surveillance and risk mapping and other epidemiological tools for risk assessment and evaluation of cost of massive vaccination campaigns... Socio-economic studies were conducted also to assess and enhance the economic benefit of supranational health networks like CaribVET (economic evaluation of CaribVET, evaluation of GIS tools adoption and use, guidelines for improved economic evaluation of capacity building programmes).
EPIGENESIS project with all these activities has allowed the creation of a Center for Research and surveillance on Vector-borne diseases in the Caribbean (CRVC-CIRAD). Ongoing developments of the CRVC in link with CaribVET following the Epigenesis outcomes, with the recruitment of permanent researchers and establishment of long-terms collaborations with several European partners will sustain the high scientific level of the work conducted. The sustained efforts to follow-up on transfer activities, economic analyses and communication to priority targets (decision and policy makers in particular) will be organized to ensure long lasting effects of the project and contribute to the significant change of scale obtained as a result of the EPIGENESIS project. Moreover, the settlement of the CaribVET headquarters in the CRVC represents great opportunities for the Guadeloupe Region to attract national and foreign researchers and contribute to the economic development of the territory.

Project Context and Objectives:
Emerging infectious diseases, particularly those involving arthropod vectors and wildlife, threaten human health, stockbreeding and food security worldwide. They are also responding fast and deeply to global changes (increased travels and trade, natural hazards, societal and climate change...) particularly in the Caribbean, which is at the crossroads between North America, South America and Europe. Anticipation of health crises through relevant research programmes and innovative disease-control strategies is increasingly necessary to preserve animal health, food security and human health in interconnected Caribbean territories and Europe. Recent outbreaks of Chikungunya and Zika highlight the importance of reinforcement of research on vector-borne diseases (VBD) in the Caribbean.
The objective of the EPIGENESIS project was to expand Guadeloupe research potential on emerging and vector-borne diseases (VBD) involving the necessary sectors and disciplines along with the ‘One-Health’ concept. Considering the complexity and the interconnected nature of new challenges faced by the society it is indeed necessary to strengthen i) cross-sectorial collaborations with key stakeholders and ii) enhance pluridisciplinary research to end up with good, operational tools and recommendations for end-users and decision-makers. Moreover, enhanced communication to priority targets (decision-makers, end-users and general public, student community) in Guadeloupe and the Caribbean, as well as development of socio-economic studies are important to improve awareness and adoption of the high level research outputs, in close link with priority needs of our societies.
The 3 years project started in September 2013 relied on integrated and pluridisciplinary approaches, from genomics to spatial risk-mapping, surveillance and prevention strategies against diseases. Its final objective was the adoption of new knowledge produced along the project by all stakeholders and transfer of research products to end-users. Specific objectives were to: (i) reinforce Guadeloupe Scientific &Technological potential on emerging and VBD through the acquisition of cutting edge equipment and recruitment of experienced scientists; (ii) develop strategic partnerships with outstanding European research entities (exchange of scientists, two-way secondments, trainings); (iii) disseminate scientific information and knowledge to the scientific community, decision-makers and the general public (by publications, organization and participation to meetings, workshops and conferences, media and communication); (iv) increase Guadeloupe innovation potential (diagnostic, vaccines, data collection and surveillance tools, early warning system).
Sustainability of the project will be ensured by the following developments:
- The creation of a Center for Research and surveillance on Vector-borne diseases in the Caribbean (CRVC-CIRAD) and the CaribVET Secretariat in Guadeloupe
- Recruitment of researchers and development of new competences especially in bioinformatics, economics, medical entomology, sociology and spatial epidemiology
- Follow-up on transfer activities, organize continuous communication on main project outcomes and finalize economic evaluation with data collected during the project to improve communication with decision-makers in particular.
The EPIGENESIS project was highly structuring and the upgraded research and improved technological development capacities is expected to contribute significantly to 1/ improve the integration of the Guadeloupe Research in the European Research Area, and 2/ give more visibility to the regional and international research community as well as attract local, national and foreign researchers. With support of the regional authorities and EU structural funds, it will contribute to regional development through better preparedness against disease outbreaks and risk management, paving the way for “smart specialization”. The project included a strategy for the involvement of stakeholders in all research stages, from the research question to the discussion of the results and recommendations, which will enhance dissemination and communication to specific targets (decision makers, end-users, ground stakeholders, student community, general public...). The final aim is to improve use and adoption of knowledge and new tools, recommendations and research products, hence contributing to sustainability of the project.

Project Results:
1. Gain of knowledge on the diversity and the pathogenesis of a bacterium, Ehrlichia ruminantium, causing a tropical fatal disease transmitted by ticks

The EPIGENESIS project was focused on vector borne diseases and their prevention and control. One objective of the project was to improve our knowledge on E. ruminantium, a tick-transmitted bacterium responsible of a fatal tropical ruminant disease, heartwater. This disease has an important economic impact for regions where it is present: Caribbean, Indian Ocean islands and Southern Africa. It induces an important loss of productivity with loss of ruminant especially sensitive exotic breeds and a financial cost for farmers by the use of antibiotics or acaricides. The final objective of the project was to propose innovative means of control of the disease by development of vaccines or other therapeutic approaches.
By an extensive genetic analysis of 194 E. ruminantium isolates from different areas worldwide, we highlighted the history of introduction of E. ruminantium due to cattle movement from West Africa to Caribbean and from Southern Africa to the Indian Ocean islands. Moreover, the results stressed that the high recombination events between strains has likely played an important role in the maintenance of the genetic diversity of E. ruminantium and its evolution (Cangi et al, 2016). By its inherent intra cellular characteristics the bacterium finds a way to adapt by exchange of genetic materials within host and vectors. The presence of high numbers of E. ruminantium strains in a small region and its ability to generate diversity by recombination limits the feasibility to protect animals using a vaccine targeting one strain, independently on the type of vaccine used. Several experimental vaccines have been developed in our Unit research or in other research institutes. Attenuated vaccines have been produced previously from 3 different strains by several passages in cell culture: Gardel strain from Guadeloupe, Senegal strain and Welgevonden strain from South Africa.
In order to identify the mechanisms of attenuation of E. ruminantium strains, comparison between virulent and attenuated strains were performed along the project both using analysis of two sequenced genomes and protein profiling expression in bovine host cells. Genomic analysis allowed identifying a mutation in one gene that can be responsible for attenuation. Further experiments will be performed to confirm this hypothesis. Development of new attenuated vaccines based on targeted mutation on isolated strains is under investigations.
On the other hand, protein gene expression of virulent and attenuated Gardel strains was analyzed after cultivation in bovine endothelial cells (Marcelino et al, 2015). Despite their different behavior in vivo and in vitro, these strains share 80% of their proteins. This core proteome included chaperones, proteins involved in the metabolism, protein DNA RNA biosynthesis and processing and bacterial effectors. For both virulent and attenuated strains, 85% of the identified proteins were isoforms, suggesting the importance of post translational modifications in E. ruminantium biology. There was also identification of strain-specific proteins with an increased number of proteins involved in cell division, metabolism, transport and protein processing for attenuated strain and overexpression of other proteins and isoforms involved in pathogenesis for virulent strain. These results are in accordance with the respective phenotypes of attenuated and virulent strains.
There was also a need to improve the molecular diagnostic to detect pathogens in ticks and more particularly, E. ruminantium to perform epidemiological molecular studies. Thus, we developed a new high throughput method including automatic extraction of nucleic acids from ticks and qPCR targeting a specific gene of E. ruminantium. This new method is highly sensitive, specific and reproducible with the advantage to reduce considerably the risk of contamination between samples and the time to complete the analysis. The first part of the method consisting in nucleic extraction from ticks can be used widely in any tick species to screen bacteria and both DNA and RNA viruses as it extracts both RNA and DNA. Considering the second part of the method targeting E. ruminantium it can be used to detect the pathogen in blood from sick animals with heartwater suspicions.
The main potential of EPIGENESIS project was its interdisciplinarity. One example reflecting this approach, is a scientific work performed during the project, and applying a theoretical economic model, the “Game theory” model, to conceptualize the pathogen/host interactions in different scenarios like for instance attenuation versus virulence (Tago et al, 2016).

2. Improved knowledge of Heartwater epidemiology in Guadeloupe

Heartwater is transmitted by Amblyomma variegatum, also known as Tropical Bont Tick (TBT). In the Caribbean, TBT is found in several islands of the Lesser Antilles. In the Caribbean, heartwater is only present in Guadeloupe, Marie-Galante and Antigua. Epidemiology of heartwater in the Caribbean is not well known. An in-depth study organized in 1989 described the epidemiological situation of Heartwater as hypo-endemic, where isolated cases appear regularly, anytime in the year and regularly, and almost every month. Mainly small ruminants and young cross-bred or pure European cattle are affected by Heartwater, while creole cattle were almost completely resistant. Only a few cases of clinical Heartwater were observed in cattle older than two and a half years of age, and the results suggested that immunity in cattle lasts for at least two years, when maintained by reinfections.
During the EPIGENESIS project, we used the data of the five years and a half (2010-2015) passive surveillance targeting the neurological symptoms of ruminants including heartwater in Guadeloupe. The epidemiological data of 735 samples collected in Grande Terre, Basse Terre and Marie-Galante were analyzed and times series analysis conducted to improve knowledge of the distribution of Heartwater in the bovine population of Guadeloupe, and whether spatial and/or temporal patterns could be detected. Co-occurrence with other tick-borne diseases (anaplasmosis, babesiosis) was also looked at. Different factors were considered, such as age, race, acaricides use and spatio-temporal distribution.
A scientific publication is in preparation. Preliminary results show low mean annual incidence and a proportion of Heartwater clinical cases higher in young animals, suggesting that animals have acquired immunity over time. In contrast to the situation in Africa where most cases occur at the beginning of the rainy season, there is no significant seasonal nor spatial pattern of heartwater in Guadeloupe. This suggests that the disease is very difficult to predict, and can be found anytime during the year and anywhere in Guadeloupe. An analysis of the co-occurrences found in about 50 cases between the infection with Heartwater, B. bovis and B. bigemina was conducted, in order to see if they occur independently or are mutually exclusive. The final results of the analysis will be discussed with the Veterinary Services in Guadeloupe and recommendations in terms of research, surveillance and control developed.

3. Knowledge on mosquito diversity and the species distribution in Guadeloupe

The Caribbean region is an endemic area for several mosquito borne diseases. The knowledge on mosquito diversity and bioecology in the Caribbean is ancient and incomplete over large areas. Nowadays, the emergence of new (and recrudescence of endemic) mosquito borne diseases highlights the importance of updating knowledge and capacity building on entomology across the Caribbean.
One of such mosquito borne emerging diseases in the Caribbean region is West Nile (WN) fever, a zoonotic disease. Since its discovery in Uganda (1937), WN fever historically remained confined in Africa. However, in the last decades, it has been one of the arboviruses being most spread globally. West Nile Virus (WNV) was introduced in the American continent for the first time in 1999, in the USA. Shortly after, the disease spread southwards into the Caribbean, Central and South America. In the Caribbean region, disparate information on mosquitoes and hosts is available, and viral isolations have been much more difficult than expected. Therefore the dynamics of WNV in the Caribbean still remains puzzling.

a. Understanding the mosquito role in the circulation of West Nile Virus in Guadeloupe

WNV has ecologically complex transmission cycles that can involve rural, urban and enzootic cycles. To date, in Guadeloupe, seroconversions were detected exclusively in poultry and equines at rural landscapes. The longitudinal study targeted the identification of potential WNV vectors in Guadeloupe. The aim of the study was focused on the surveillance of mosquito populations through periodic samplings using standard CDC traps at sentinel farms and surrounding landscapes. A spatio-temporal study of mosquito populations was performed at two poultry sentinel farms and surrounding landscapes. During the first year, 45,615 mosquitoes were collected and identified throughout 26 sampling periods. The diversity of mosquitoes reported was important, with mosquitoes of 10 genera collected: Culex, Deinocerites, Ochlerotatus, Aedes, Anopheles, Wyeomyia, Mansonia, Limatus, Uranotaenia and Psorophora. The three genera with most abundant collections were Culex, Ochlerotatus and Deinocerites respectively. Culex mosquitoes were more abundant at the mangrove and swamp forest than in farm environments.
Overall, the longitudinal study has been useful to point the mosquito species with a potential involvement with WNV transmission: Cx. nigripalpus, Och. taeniorhyncus and De. magnus out of the 37 species present in Guadeloupe.
The analysis of samples for mosquito species identification for the second year is under process.

b. Inventory of the mosquito species in Guadeloupe and development of key identification tools for tropical mosquitoes

A representative sampling of different Guadeloupe ecosystems was performed. Landscapes were categorized into four categories: i) urban habitats, ii) rural habitats, iii) natural habitats, and iv) humid habitats including either swamp forest or mangroves. A random allocation of 30 sampling sites was performed and automatically attributed to landscape categories. Active and passive collection methods of mosquito were used at each sampling site, including trap models CDC 1012, CDC gravid and BG Sentinel. Mosquitoes species collected were from 10 genera: Culex, Deinocerites, Ochlerotatus, Aedes, Anopheles, Wyeomyia, Mansonia, Limatus, Isostomyia and Psorophora. Two of the species detected, at least, have never been reported before in Guadeloupe. The genetic analyses of species diversity by molecular tools is currently done to support morphological analysis.
During the project, there was an improvement of mosquito identification tools in Guadeloupe. Results obtained from mosquito diversity study and morphological analyses allowed to improve raw material available and improve a dicothomic key for the mosquito diversity present in Guadeloupe. The key has been updated with the support of Avia-GIS expert including the new species detected in Guadeloupe and is ready for an inter-laboratory evaluation including Institut Pasteur Guadeloupe and Agence Regional de Santé (ARS).

4. Economic study of the benefit of a regional animal health network, CaribVET for surveillance and prevention of animal and zoonotic diseases

a. Economic evaluation of CaribVET – a model of supranational animal health network

CaribVET is coordinated by CIRAD and is a unique institutional network (veterinary services from 33 Caribbean countries and territories, 6 regional or international organizations) highly connected to science and research (4 organizations, universities and research institutes including CIRAD highly involved). launched with voluntary contributions based on expertise available, trust and cooperation spirit, CaribVET is now considered as a model of supranational animal health network worldwide by the World Animal Health organization (OIE) and the scientific community: it is also the largest network in terms of number of partners (43). The Network is meant to be sustainable and to garner the efforts of research institutes, VS of all member states, and international and regional organizations for co-planning and optimize the effectiveness of coordinated actions.
In addition to outstanding contributions in time and expertise from its members, the network is exclusively funded by projects. CaribVET is therefore highly dependent on international sources of funding and therefore, sustainability remains a concern. Despite its bottom-up development and institutional and regional political endorsement (Caricom Secretariat, chief veterinary officers), ministries of agriculture often question the real benefit brought to their country. The OIE is interested in the economic evaluation of CaribVET with the aim to develop a standard for the evaluation of other supranational animal health networks. For all these reasons, an economic study on the benefits provided by CaribVET was carried out within EPIGENESIS. The outcomes of this evaluation will meet the expectations of the network members and users, and the OIE. In addition, it will be important in the future to improve management and funding strategy of the network.
The main economic concepts associated with supranational animal health networks were generated during the project. A conceptual model of the organizational structure of CaribVET was also built. An economic model enabled to show i) how the adoption of a supranational approach by the Veterinary services changes ministry of Agriculture’s resource allocation problem, and ii) how these networks can contribute solving the externality problem. Two contrasted situations were analyzed and compared: veterinary services of several Member countries/territories, in collaboration with other organizations (facilitators) coordinate and collaborate with each other; and market solution, i.e. without collaboration between Member countries/territories and organizations. The sources of benefits of such networks and the biggest challenges associated with their development have been identified.
The provision of animal health services in a territory/country generates positive externalities to neighboring territories/countries. A regional animal health network such as CaribVET allows information flows and cooperation among stakeholders in order to maximize the utility of the entire region, taking into account the status, resources, and priorities of each territory. Within the framework of supranational animal health network these externalities should be taken into account when choosing the amount of resources allocated to research, surveillance, and control activities in order to reach the socially optimal provision of animal health services (the allocation that maximizes the welfare of the entire region).
Language and sometimes political barriers, free-riding, and the low institutionalization of VS are some of the challenges to the success of a regional approach. These challenges are derived from the heterogeneity of territories and the public good nature of animal health. Mechanisms to avoid the free-riding problem are hard to propose in an international framework, in which sanctions are not feasible. The efforts to construct regional animal health networks should continue despite the difficulties. The capacities in surveillance and diagnostic built from these efforts can be useful for other interests such as the provision of human or plant health (One Health approach). The need for integrated approaches and solutions at the regional level arises. Since single countries/territories cannot efficiently manage animal health in isolation, the interconnection of neighboring and farther countries sharing similar constraints and in link with different regions in the world makes animal health a global issue where regional networks can become adapted structures to build a functional world-wide platform of animal health.
Several key activities of CaribVET were selected for an economic evaluation (disease prioritization tool, surveillance network assessments, IATA certification and sample shipment simulation exercises, and the ILCT testings’). Although quantitative evaluation could not be organized due to lack of data, they clearly showed the benefits especially for the countries which implemented the activities (use of disease prioritization tool impacted budget / activities in 83% of the respondent users, implementation of SNAT recommendations) are beneficial to the VS, improving laboratory capacities, leading to improved animal health.
Several key recommendations were made in order to improve the cost/benefits of the activities, several of which have been implemented or will soon be: follow-up teams to assist with the implementation of recommendations, conduct bi-annual evaluation of non-monetary costs, develop ex ante studies to enable quantitative economic evaluations and associated guideline for easier data collection, improve compliance of members with sharing of data and information, etc...

b. Development of VacciCost Tool – A tool to evaluate resources required for massive vaccination campaigns

Vaccination is one of the main tools currently available to control animal diseases. VacciCost is a tool designed to help decision-makers in the estimation of the resources required to implement mass livestock vaccination campaigns. The tool focuses on the operational costs of the campaign. The resource requirements are classified in eight categories: vaccines, injection supplies, personnel, transport, maintenance and overhead, training, social mobilization, and surveillance and monitoring. This categorization allows identifying the most expensive components of a vaccination campaign, which is crucial to design cost-reduction strategies. The tool was probed in Senegal for evaluation of the cost of vaccination against peste des petits ruminants (PPR), which has been chosen by the international organizations as the next disease to be eradicated globally, after successful eradication of rinderpest in 2011. VacciCost is useful to prepare national budget allocations and complementary fundings from international bodies in order to achieve eradication.
CaribVET SC recommended its members to use the tool, especially countries affected by Classical Swine Fever (CSF) in the Caribbean. Cuba is already being using the tool, and other Caribbean countries showed strong interest (Dominican Republic, Haiti). Other countries which are not affected by CSF are much interested in using it for vaccination against Newcastle Disease, Rabies (in livestock)...
After publication of the work, VacciCost has been added to the Catalogue of CaribVET products that provide fact sheet for each tool along with access to the guidelines etc. for easier use and implementation of the materials.

c. Guideline for the economic evaluation of capacity building programme

No quantitative economic evaluation could be undertaken during the project to assess the economic benefits of CaribVET, mainly due to lack of data. Following the recommendations of the 11th CaribVET’s Steering Committee meeting, a guideline was prepared in order to detail the type of information/data that is required to perform economic evaluations of different activities with a focus on capacity development (trainings).
Systematic evaluation increases accountability and allocates a value to the capacity building activities. Moreover, it facilitates the comparison of different activities in order to choose the most effective ones, and provides arguments to funders for maintaining or modifying their capacity building strategy. The evaluation process consists of several stages, from planning to implementation and finishing with communication. To properly evaluate the impact of an activity, collecting data before and after the capacity-development activity is implemented. Conducting this type of evaluation requires substantial data not only regarding the groups/populations/agents.
The guideline is very well structured and is being used to evaluate the cost and benefits of the Avian Influenza (AI) Risk Mapping capacity building Pilot project by early 2017.

5. Development of epidemiological tools to improve the prevention, surveillance in the Caribbean

a. Caribbean Veterinary Information System (C-VIS), platform of GIS tools for Caribbean veterinary services

The objective of the spatial epidemiology project within EPIGENESIS was to identify and gather within a platform most appropriate tools adapted to the Caribbean context and to develop capacity of various partners involved in the CaribVET network in GIS. This is intended to help collecting, cleaning and analyzing spatial epidemiological databases and use them for risk mapping and explore the potential of existing databases for spatial epidemiological analysis
The Caribbean Veterinary Information System platform (C-VIS) is a collection of tools linked together to assist national veterinary services in disease surveillance. It consists of 4 main components: data collection tool (KoboToolbox® open access), Geographical Information System (QGIS® open access), a secure spatial data catalog (GeoNetwork, on AviaGIS server) and an online mapping tool, LIZMAP (on the CIRAD servers). The use of C-VIS in the region has been discussed with the Chief Veterinary Officers in the region, members of the CaribVET Steering Committee, and further developed with members of technical working groups of CaribVET during the regional Workshop on AI preparedness plan held in Barbados (July 2015).
Along with the GIS tools, training materials were developed to impart knowledge with other members of CaribVET, the GIS bulletins. In all, 9 GIS Bulletins on animal health surveillance in the Caribbean region were developed in English and translated in Spanish. They were posted on the EPIGENESIS website and disseminated to all the members of CaribVET and anyone interested in GIS, in order to help anyone with self-learning.
Other training materials were developed to go further on risk mapping principles. Regular communication and coordination with other partners on the EPIGENESIS activities and its role in the HPAI surveillance and preparedness allowed the synergistic organization of a series of two regional training workshops that were supported by IICA and USDA.

b. Implementation of the C-VIS tools in the Caribbean: Avian Influenza Risk Mapping Pilot project, integrated in the HPAI regional preparedness plan

The implementation of the C-VIS tools in the Caribbean was done within the frame of a pilot project on AI Risk Mapping and surveillance, running from Nov. 2015 to July 2016 in the 12 countries with highest poultry production. Highly Pathogenic Avian Influenza (HPAI) was indeed chosen as a disease model as it emerged in North America since early 2015 and was likely to be introduced by migratory birds during the migratory seasons. The risk mapping project was one of the 5 key components of a preparedness plan.
The utilization and adoption of the CVIS platform by the Veterinary Services of the countries and territories of the Caribbean was further studied during this pilot project thanks to the funding support of CaribVET partners. The project has been organized in 5 main steps:
1- A train-the-trainer workshop was organized in Belize (Nov 2015) for 15 veterinary officials from 13 Caribbean countries. The primary focus of the training was to develop the GIS capacities and improve the skills of the participants on the use of new technologies such as mobile devices, KoboToolbox® for data collection and QGIS® for data management and analysis. They also learned how to develop risk maps based on disease risk factors, especially for AI. An evaluation of the impact of the training and monitoring/follow-up of the trained officials was organized after the workshop in order to provide maximum support to the national veterinary services and ensure optimal adoption of the tools in the region. The training was organized with support from the IICA and Caricom Secretariat.
2- From November 2015, regular evaluations and follow-up of the participant activities were organized with an online forum to strengthen the community of participants and provide an online platform for continuous E-learning. The forum was administered and moderated by 2 epidemiologists at CIRAD. Exercises and training materials summarizing and developing step by step the knowledge acquired during the workshop delivered in Belize earlier were posted regularly: power points, factsheets, video tutorials, guidance/instructions, link to GIS bulletins.
3- A sociological component has been implemented at the mid-term of the project to identify the factors influencing the use of the C-VIS tools and recommendations for maximizing the diffusion of the tool in the region (see Section 4).
4- Enhanced preparation and selection to enable trainees to attend the advanced workshop on GIS and risk mapping of HPAI.
5- Organization of an advanced level training workshop in the Dominican Republic (Sept 2016) on GIS, Qualitative Risk Mapping of AI and introduction to optimization of monitoring systems. The participants were trained by experts from Cirad FVI (Cécile Squarzoni Diaw), Cirad Cmaee (Caroline Coste) and one expert from USDA CEAH (Andrew Fox), as part of a workshop organized by the Caribbean Animal Health Network (CaribVET) from 19 to 23 September. The training was organized with support from the USDA and CARICOM.
Main results of the AI Risk mapping project in the Caribbean.
- The Veterinary Services in the Caribbean now have 8 additional experts (Barbados, Belize, Guyana, Jamaica, Dominican Republic, St. Lucia, St. Vincent and the Grenadines, Suriname) in the mapping and risk analysis of the introduction and spread of diseases. Their expertise will be used to enhance monitoring of Avian Influenza in the region, but can also be adapted to other diseases.
- Harmonizing surveillance in the region: the course took place in three phases: initial training (Belize, November 2015), online training (January-August 2016) and advanced training (Dominican Republic, September 2016). It enabled the participants to i) list the risk factors in their country and map the population at risk; ii) identify potential entry points, iii) assess risks and iv) learn about risk-based monitoring methods. The training course allowed the participants to create risk maps using GIS and qualitative analytical methods, thus increasing the cost / benefit ratio of monitoring systems.
- Testing risk maps and new teaching methods: the workshop produced important results. Each country developed three risk maps: a map of introduction routes, a disease spread probability map and a map showing a summary of risks. A first draft of a regional risk map was produced using national results. Through research in socio-economics and engineering and thanks to regional health networks, new teaching methods were tested during this pilot program with the objective of increasing the performance and impact of regional training. A new training cycle will enable countries to strengthen their surveillance protocols based on the AI risk. The scientific results achieved will be presented at the GeoVET international conference which takes place between 7 and 11 November 2016 in Chile.

c. Preliminary Risk Map of Avian Influenza Risk in the Caribbean

Since 2015, Caribbean countries have increased AI surveillance and updated their AI Preparedness Plans. In order to optimize resource allocation, risk maps for Avian Influenza are being developed. Since very little data is available on AI in this region, an expert consultation is being organized to collect the qualitative knowledge that exists on this global burden for animal health. And following the recommendation of the 11th CaribVET SC meeting, experts of CIRAD, Barbados, Cuba, Belize, USDA-CEAH started to work together on the development of a single methodology for the identification of AI risk factors in the Caribbean.
A literature review was performed to identify the main risk factors for HPAI. As the Caribbean region is unique in its high variability over small distances in the structure of the poultry sector, a questionnaire was drafted to collect expert opinion, which will be used to validate the risk factors identified during the literature review. Surveillance data from the last LPAI outbreak in Belize, was submitted to epidemiological analysis in order to look at the risk factors.
An expert panel was prepared with international experts on Avian Influenza on the one hand, and experts on the poultry sector in the respective countries of the Caribbean on the other hand. The group will also include ornithologists, virologists, epidemiologists and poultry experts. Each expert will be asked to answer only the questions within his/her field of expertise. The expert panel would be the starting point of a snowball sampling . They will be asked to provide information on the risk of introduction of HPAI in the domestic poultry population of a Caribbean country. The objective is to identify the factors increasing or decreasing the risk HPAI and determine their relative importance. This information will be used to construct HPAI risk maps for the Caribbean region. The risk maps will be used as a decision support tool for the national veterinary services in the Caribbean in the preparedness plan for Avian Influenza.
This work has been started with a small group of experts from the Caribbean, during the AI risk mapping training workshop in the DR and will be updated with a larger panel of experts. It will help CaribVET develop regional risk maps for AI introduction and will provide new insight on the regional mitigation of the risks and define new strategies for optimal cost-efficient actions in the region by targeting some countries in future programmes for biosecurity, simulation exercises or else.

d. Creation of an alert system for the Caribbean: C-Alert

Initially, the Alert system for the Caribbean was described as an informatics platform that would integrate the results of studies concerning genetic diversity and spatio-temporal evolution of pathogenic strains as well as information on migration of animal hosts or climate with a multidisciplinary approach.
The objective was later revised with the CaribVET Steering Committee meeting according to the most important immediate need of the network and was largely triggered by the emergence in 2014 and 2015 in the Americas of two major diseases threatening the poultry (Avian influenza) and the swine (Porcine Epidemic diarrhea) sector in the region. The new objective was to provide CaribVET and regional managers with a tool that would give real-time information on potential risks of introduction of diseases in the region, in order to ease decision at the national and at the regional level and guide regional intervention. It was organized in link with another research programme on epidemic intelligence conducted by colleagues from CIRAD in France. A first version of the Caribbean Early Alert System, C-Alert has been developed by Avia-GIS, based on the brand new “Plateforme pour la détection automatique de l’information sanitaire sur le web” (Padi-Web) developed by CIRAD within the frame of international health monitoring (VSI), for primary application to the French context. For it to be used in the Caribbean context, the development of an innovative such as the C-alert tool was key to provide real-time alerts in the Caribbean on the events declared via the PADI-web system worldwide. The alert system is available at the Caribbean level through CaribVET. However, internal validation and testing by end-users to improve the tool could not be undertaken within the project.

e. Risk assessment tool adapted for Porcine Epidemic Diarrhea, an emerging disease for the Caribbean

After the emergence of Porcine Epidemic Diarrhea (PED) in the USA in 2013 and its further dissemination to other countries in the Americas and the Dominican Republic, the Steering Committee of the Caribbean Animal Health Network (CaribVET) added PED as a new priority for the region. This work aimed to develop a tool for risk analysis (RA) of swine diseases introduction/dissemination at national levels and applicable to the Caribbean region.
This tool was initially developed for Classical Swine Fever (CSF) and Teschovirus Encephalomyelitis (TE), and revised and adapted in 2015 for PED with the help of our CreSa european partner. The trilingual tool is a user friendly Excel Spreadsheet including the guidelines and questions for the risk assessment. It is divided in three sections: 1) Release assessment of the pathogen from the affected country, 2) Exposure (dissemination) assessment of the susceptible pig population and 3) Consequence assessment of the pathogen introduction.
The CaribVET SC in 2016 urged members to use and apply the tool, especially to help the veterinary Services at risk of CSF, PED or Teschen to detect gaps in surveillance. Emphasize was made that the tool has not been designated to demonstrate disease freedom and that Risk Swine tool should be considered as a preliminary step as it does not cover the areas required by the OIE for official disease freedom. It is a self-evaluation of the risk of swine disease introduction and dissemination into a country/territory and contributes to reduce the risk if gaps/weaknesses identified thank to the tool are corrected.

6. Sociological study on the use and adoptions of epidemiological tools by end-users in order to improve the transfer of these tools (AI risk mapping project)

Background and rationale for the implementation of a sociological study: past capacity building programme and organization of training workshop in CaribVET. Between 2008 and 2012, a four year capacity building project funded by USDA on Epidemiology, GIS and surveillance was organized in the same countries involved in the AI risk mapping pilot project – the Veterinary Epidemiology and Para-epidemiologist project (VEP). 10 participants of 10 islands were trained with theory, practice, hands on, simulation exercises and follow-up and monitoring of national activities. This project was very positively evaluated by the CVOs of the islands who benefitted from the project.
Since early 2015, CaribVET tries to systematically organize evaluation of gain of knowledge during the workshop, which is the immediate measure of workshop benefit (short term). Final evaluation of the workshop is organized, however mostly due to lack of time no follow-up is organized. Long term evaluation of the workshop were always planned, however never organized, also due to lack of availability.
Objectives of the sociological study (lead by EHESP and CIRAD). As part of the AI risk mapping pilot project, the sociological component intended to identify the major constraints preventing from using and adopting the epidemiological Tools developed during EPIGENESIS. During the first GIS workshop, participants were taught how to use KoboTooBox® (for data collection) and QGIS (for data management and analysis). They were encouraged to perform different tasks before and after the workshop in order to maintain the level of learning and in pursuance of adapting the knowledge in their respective home countries. However, the majority of participants were not able to complete the expected activities.
Non-structured and semi-structured interviews were carried out for the sake of understanding what went wrong, why the follow up stopped and how we could improve for further workshops.
For the non-directed interview, it was decided to involve more actively two participants from the workshop so as to carry out these interviews. They interviewed 4 persons. The analysis of the non-structured interview enabled the creation of the interview guide that was used for the semi-structured interviews.
The sociologist further conducted semi-structured interviews. The objective was to ask feedback on the working experience, the experience of the workshop, and their feeling about it. The other 11 participants were being contacted at the same time by e-mail and telephone. During the contact, they were asked if they managed to train at least one more person – since it was part of one of the tasks commanded – so as to arrange an interview with them too. As a result, there were 19 interviewees in this second step. All of them were done through an online platform from June 7th to June 21st 2016.
Several aspects were looked at: background of participants, structure of workshops, feasibility of tools’ usage, organization of the workshop, commitment... Recommendations were formulated to improve overall organization of workshop, and improve use of knowledge and new tools. Those recommendations were discussed with a group of researchers in CIRAD – epidemiologists, economists, and revised to be proposed to the group of CaribVET partners (see below suggestion of improvements and changes). Some of them were readily implemented as early as possible to improve preparation of participants, follow-up, monitoring and selection of participants.
- Before workshop: involve a young person with IT skills if they are essential; involve actively CVO to put emphasis about the importance of choosing the right persons (checking that requirements are well understood); make sure the nominees have the necessary pre-requisite ...
- During Workshop, Organization of sessions for participants to talk about themselves and share their experiences/expectations; dedicate time for participant to think about “how they could use/apply the new techniques/skills in their country; Encourage open communication, and identify new tools to optimize feedback of problems, gaps and challenges that may represent a constraint to learning process;
- After workshop: engage prizes for those completing the tasks; for instance, think of CaribVET grants (participation in congress, involvement in preparation of a manuscript) or specific support;
Several marked changes were made in June-Sept 2016 in order to reach the best results: participants were selected after careful examination of the participants’ skills, a Road Map for participants was prepared with preparatory exercises and monitoring to help some catching up. During the workshop, nearly all recommendations were applied. We are now putting into place the last batch of recommendations. A final economic and result evaluation of the Pilot AI Risk mapping programme is ongoing. Cost evaluation of the programme will also be organized in order to best present the results of this programme.
A guideline for good practices in Capacity building programmes is in preparation following the highly successful implementation of the programme. Objective is to have this guideline prepared with several CaribVET partners to be endorsed by the CaribVET SC, and used for key skills that need to be built in the country and that will justify so much efforts to ensure long-lasting effect should be to reduce the number of regional training with improvement of the organization of training workshops.

7. Highlights of the successful integration of disciplines around the enhanced capacity building programme and risk mapping project in the Caribbean

The integration of several scientific domains were highly synergistic and crucial for the success of the Avian Influenza risk mapping. This programme resulted in training about 30 persons in basic GIS out of which 9 from 8 countries reached an Expert level. At the end of the EPIGENESIS project, the 8 countries had prepared very good risk maps, although not final nor complete as some data were needed to be collected, and CaribVET has a preliminary risk map, that will be presented at the GeoVET conference in Chile.
The EPIGENESIS project was essential for CaribVET to analyze the sociological components of the training programmes which were never undertaken before. Taking into consideration the level of satisfaction of the participation regularly is important to be able to take correction actions and influence the result of the workshop. New evaluation forms will be prepared following the recommendations evidenced.
As sociological studies cannot be organized each time, some good practices should be stated clearly and validated/accepted by the CaribVET partners in order to markedly improve its results, and visibility: from the ground stakeholders, as well as from the Ministries in the region.
The major changes that occurred in the organization of training programme dealt with selection process, enhanced preparation and feedback before the training, enhanced follow-up and monitoring after the training. A transparent dialogue was established with Caricom in order to discuss the political aspects that were important to take into consideration as well.
The results of the AI Risk mapping project will be taken as example as it enabled to reach outstanding results, never achieved in the past, with marked gains of expertise in 8 countries and in 10 months. The big challenges are for CaribVET to be able to repeat the monitoring and follow-up efforts until the countries finalize their risk map, until a regional map is obtained.

1. Cangi N., Gordon J., Bournez L., Pinarello V., Aprelon R., Huber K., Lefrançois T., Neves L., Meyer D. and Vachiéry N. 2016. Recombination is a major driving force of genetic diversity in the Anaplamataceae Ehrlichia ruminantium. Frontiers in Cellular and Infection Microbiology. DOI: 10.3389/fcimb.2016.00111.
2. Tago D., Meyer D. Economic Game theory to model the attenuation of virulence of an obligate intracellular bacterium. Frontiers in Cellular and Infection Microbiology. DOI: 10.3389/fcimb.2016.00086.
3. Marcelino I., Ventosa M., Pires E., Müller M., Lisacek F., Lefrançois T., Vachiéry N., Coelho A. 2015. Comparative proteomic profiling of Ehrlichia ruminantium pathogenic strain and its high-passaged attenuated strain reveals virulence and attenuation-associated proteins. Plos One. DOI:10.1371/journal.pone.0145328.

Potential Impact:
There are basically two main expected impacts from EPIGENESIS, science and training/transfer to end-users.
The first outcome of the project is science. The recruitment and integration of 6 new scientists in a small team of 15 persons was already a big challenge. Another challenge was to provide them with conditions and environment allowing them to produce cutting-edge science within 2 years. This is what actually occurred. All of our six scientists were able to generate enough important results to expect 4-5 publications each in top review. In such a short period of time, not all foreseen papers have been published. Out of 20 articles, 6 are published or their publication is pending. The average impact factor of these 6 papers is higher than 5, which proves the quality of the research that was achieved during the project.
Moreover, on the basis of scientific results obtained on E. ruminantium pathogenesis, we will expect to develop new vaccines or alternative therapeutic approaches to control heartwater. In case of success, this will have an important socio-economic impact on agriculture and herds not only in Guadeloupe but widely in other tropical countries affected by the disease.

In addition, EPIGENESIS has allowed producing a series of innovative epidemiological and medical entomology tools that will be published soon but are already probed by end-users. Briefly, these tools are:
- Vaccicost: cost prediction for large-scale vaccination programmes
- C-VIS Caribbean Veterinary Information System: integrated tools for data collection, analyses, sharing and representation
- Disease Prioritization Tool: rank priority diseases for surveillance or control in limited resources or environment
- RiskSwine tool: risk assessment tool for swine disease introduction
- Dichotomic mosquito key identification: available for other institutes such as Agence Regional de Santé Guadeloupe (ARS)
- C-Alert: Caribbean early alert system tool, real-time information on potential risks of introduction of diseases in the region to be validated by end-users

Generally speaking, the scientific impact of EPIGENESIS for our research group will be huge since the visibility of our production and expertise will be acknowledged worldwide. Moreover with the organization of regional and international workshops and conferences in the Caribbean and in Europe, we highly increased the visibility of Guadeloupean and Caribbean research on vector borne and emerging diseases and its integration in European Research Area. This scientific notoriety will strengthen our capacity to build new collaborations with research institutions in the Caribbean and other distant regions and raise funds from competitive research calls.
Another positive impact of the project was the possibility to create a research centre specialized in the study of vector-borne diseases. The Centre for Research and surveillance of Vector-borne diseases in the Caribbean (CRVC) has been built on the existing CIRAD laboratory, based in Guadeloupe. It is the result of the integration of more focused researches on vector-borne diseases, new competences (permanent position for entomology and bioinformatics) and high technology equipment and facilities. CRVC-CIRAD will carry out researches in two main directions: studies on pathogen-vector and host interactions focusing on two models (Ehrlichia ruminantium / ticks and West-Nile / mosquitoes) and epidemiological characterization of these two models. These two fields of research are complementary and interact for the final objective of improving the control of the two diseases. For better efficacy, CRVC will be the CIRAD component of the animal health network CaribVET. Within CaribVET, CRVC intends to expand its research partnership to address the challenge of controlling vector-borne diseases.
The second principal outcome of EPIGENESIS is the successful connection between basic and finalized research. Basic research is essential to address the issue of vector-borne diseases but scientists should also consider the expectations of society. This has been particularly challenging in the Caribbean these last years since several mosquito-borne diseases have regularly emerged and seriously affected the populations. Considering the high expectations of the society, EPIGENESIS had to make strong efforts to transfer the technologies developed during the project and train end-users.
In this context, whenever possible, the research results were finalized by the development of products or tools to be transferred to end-users (animal health laboratories and decision-makers). In order to optimize and protect the possibility to exploit the research results for the benefit of end-users, scientists from CRVC were trained to manage intellectual property rights, covering the whole process from the identification of a research idea up to the final outputs of the research. Beyond the training, CRVC has developed its own procedure for IPR management including publications, patents and commercial exploitations. This IPR strategy has allowed to examine the possibility to patent a rational strategy for E. ruminantium attenuation, opening the possibility to generate new live vaccines.
Similarly, different software-based tools have been developed during the project (see above). These tools are now under test by different Caribbean partners. After final validation, these tools will be made available for CaribVET. Interestingly, the project also included research and transfer activities in the field of socio-economics. From the very beginning of the project we knew that strategies of surveillance or control could not be simply plated onto pre-existing procedures. Shift to other methods is also difficult for the beneficiaries. This is one of the reasons that drove us towards the inclusion of more research in socio-economics and human sciences.

List of Websites:
Contact détails:
CRVC, Center of research and surveillance on vector borne diseases in the Caribbean
Domaine de Duclos
97170 Petit Bourg
Phone: + 590 590 25 54 44