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International network for capacity building for the control of emerging viral vector borne zoonotic diseases

Final Report Summary - ARBO-ZOONET (International network for capacity building for the control of emerging viral vector borne zoonotic diseases)

Executive summary:

ARBO-ZOONET is an international network for capacity building for the control of the emerging viral vector borne zoonotic diseases, in particular: West Nile fever (WNF), Rift Valley fever (RVF) and Crimean-Congo haemorrhagic fever (CCHF).

Through a large network of 25 beneficiaries including key laboratories in Europe and neighbouring countries, the purpose of this project was to work out integrated control measures in case of outbreaks of these diseases. The different aspects of the issues addressed include vector control, vaccination programmes, improved therapy strategies, diagnostic tools and surveillance, public awareness, capacity building and improvement of infrastructure in endemic regions.

Amongst various actions, the ARBO-ZOONET project has generated information in different areas:

1) it created common knowledge on the diseases, shared and exchanged data, expertise, experiences and scientific information through general and specific meetings;
2) it established surveillance systems monitoring disease occurrence and assessed new vaccines;
3) it developed, distributed and harmonised tools for disease detection and control tools;
4) it disseminated knowledge through specific technical workshops and trained staff of relevant third countries;
5) it interlinked different scientific disciplines and established exchanges with other networks.

The consortium was gathered for coordination action. It has addressed these scientific questions which are of joint interest for other European Union (EU) networks with which we established close links. The information generated by ARBO-ZOONET should enable the development of effective control measures, which could be a great help for the EU as well as for national health authorities to respond with efficacy to outbreaks of diseases.

Project context and objectives:

ARBO-ZOONET is an international network for capacity building for the control of the emerging viral vector borne zoonotic diseases, in particular: WNF, RVF and CCHF.

WNF, RVF and CCHF are arthropod-borne diseases of different domestic and wild animals and can also affect humans, posing a great threat to public health because of their epidemic and zoonotic potential. Their geographical distribution has expanded in recent decades. WNF outbreaks have already occurred in Europe, CCHF is endemic in many countries including Europe. Last year, the presence of the CCHFV genome was detected in ticks captured in Spain, a country where the disease has never been reported. In 2000, RVF was reported for the first time outside of the African continent; cases being confirmed in Saudi Arabia and Yemen, Madagascar and Comoros. This virgin-soil epidemic raises the threat of expansion into other parts of Asia and Europe. There is a general public concern regarding emerging zoonotic diseases which has gained new relevance in the light of global warming. This is especially true regarding the spread of vector-borne diseases such as CCHF, RVF and WNF.

The purpose of this project, through a large network, was to work out integrated control measures which include vector control, vaccination programmes, improved therapy strategies, diagnostic tools and surveillance, public awareness, capacity building and improvement of infrastructure in endemic regions.

The project will address these areas specifically aiming to:

1. create common knowledge on the diseases, share and exchange data, expertise, experiences and scientific information;
2. maintain and expand surveillance systems, monitor disease occurrence, and vaccine use;
3. introduce, distribute and harmonise disease detection and control tools;
4. disseminate knowledge and train staff of relevant third countries;
5. interlink different scientific disciplines which look at the problem from different angles.

A coordinated research programme including key laboratories in Europe and neighbouring countries can address scientific questions of joint interest enabling the development of effective control measures, which could be a great help for the EU's response to outbreaks of diseases.

The consortium gathered for coordination action is composed of 25 partners from Europe, Asia and Africa. The project also tried to create links with other consortia working on related projects such as EPIZONE, ICTTD-3, ASEM-DIALOG, CONFLUTECH, EPISOUTH, EDEN and EDENEXT and CCHFEVER, a consortium which emerged mainly from ARBO-ZOONET. In addition, we kept in mind to prepare young scientists for the future and gave them significant responsibilities in this consortium.

Project results:

In addition to work package (WP) 1 which deals with 'Coordination, management, review and assessment', the project was composed of six WPs dealing respectively with 'Geographical and temporal risk assessment' (WP2), 'Capacities and proficiency in diagnostics and detection' (WP3), 'Surveillance' (WP4), 'Establishment of virulence standards' (WP5), 'Intervention strategies' (WP6) and 'Knowledge dissemination and technology transfer' (WP7).

Below are the results / foregrounds achieved in the respective WPs.

WP1: Coordination, management, review and assessment

A project website was created and maintained throughout the entire project. It provides:

- general information about the project;
- links to the partner institutions;
- WP descriptions;
- reviews of activities;
- announcements of new activities;
- downloads of the ARBO-ZOONET newsletter, publications, presentations and other material;
- a special geographical information system (GIS)-forum, later established also offered possibilities to discuss online;
- a leaflet about the project was produced, including general information about the project, the partners and the project objectives.

The project regularly produced newsletters, which were disseminated to the partners and associates as well as to other interested persons as hard copies. Besides, all newsletters were made available as an electronic document to be downloaded from the arbo-zoo.net website.

The newsletters included reports on meetings, technical workshops and other project activities as well as articles and short communications dealing with findings and planned activities relevant to the project, e.g. reports on arboviral outbreaks, analysis of existing surveillance systems etc.

All partners were asked and did participate in the creation of the newsletter.

A number of publications listed at the end of this report resulted from the work carried out during the 54 months of the project.

WP2: Geographical and temporal risk assessment

For the 3 diseases, a map of the distribution including human or animal outbreaks or serological evidence was drawn, reviews of the literature associated with relevant bibliographic references have been performed and the main conclusions were summarised:

CCHF: The methodology and the main results of an analysis of the climatic factors involved in CCHF outbreaks and spread are provided.

RVF: A literature review of the main ecosystems that experienced RVF outbreaks. For each ecosystem type, climate and landscape characteristics are listed as well as the main potential vectors and the mechanisms suspected to have triggered the outbreaks.

WN: A review of the main environmental and climatic factors involved in WN outbreaks, either in Europe or in United States of America (USA). Results are often contradictory. Following the 2010 European outbreak (Greece, Romania, Italy, Spain), recent human and horses case data are analysed in regards with temperature data in the frame of two ECDC projects:

With regard to WNF and RVF, a literature review was performed to identify the main known, or suspected vectors as well as, for RVF, their presence in European countries. For West Nile the putative presence of the main vector, Cx pipiens was mapped associating its presence / absence with each of the 44 landscape types of the Corin Land Cover database (this association was performed by two expert entomologists from CIRAD). For RVF, the same work was performed for the 5 main potential vectors of the disease existing in Europe.

With regard to CCHF, the methodology used is detailed in:

- Agustin Estrada-Pena, Lisa Jameson, Jolyon Medlock, Zati Vatansever, and Farida Tishkova. Unraveling the Ecological Complexities of Tick-Associated Crimean-Congo Hemorrhagic Fever Virus Transmission: A Gap Analysis for the Western Palearctic. Vector Borne Zoonotic Dis 2012. In press.

Agustin Estrada-Pena, Nely Sanchez, and Adrian E. 'An Assessment of the Distribution and Spread of the Tick Hyalomma marginatum in the Western Palearctic Under Different Climate Scenarios'. Vector Borne Zoonotic Dis 2012. In press

RVF: the map of the density of the 3 main reservoirs of the disease, cattle, sheep and goats, was built from the Statistic Division of Food and Agriculture Organisation (FAOSTAT) database for the 27 countries of Europe

WN: Firstly a significant association was demonstrated between the prevalence rate and some ecological features. This preliminary work need to be validated using datasets compiled from literature review (in progress). Secondly, 407 bird species were described according to their ecological characteristics. Thirdly, each landscape type of the Corin Land cover is being associated with proeminent bird species (in progress). Next step will be to calculate a geographical risk index and map it.

A map of the main wetlands was built using the 'water' layers of Corin Land cover database.

RVF: A literature review was published to highlight the main likely routes and transportation ways of introduction by Chevalier, V., Pépin, M., Plée, L. & Lancelot, R., 2010. Rift Valley fever - A threat for Europe? Eurosurveillance; Special Issue. 15 (10) 11 March 2010. Available from http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19506

Then, a quantitative model has been developed, but needed country data to be implemented and to provide a quantitative result. Due to this constraint, a map of the risk of transmission of the virus should be introduced by using GIS multi-criterion decision analysis. The result is a map of risky areas that need to be validated with mosquito trapping data, and that should be taken with caution given the lack of knowledge on European vector competency in particular.

WNF: A metapopulation model was built; it showed that the epidemiological patterns observed in Europe may be explained by the regular introduction of the virus by migrating birds from West Africa. This model was then used to compute and compare different surveillance systems in different epidemiological contexts characterised by an annual incidence rate in horses (V. Chevalier, S. Lecollinet, B. Durand, 2011. West Nile virus (WNV) in Europe: a comparison of surveillance system designs in a changing epidemiological context. 'Vector Borne Zoonotic Diseases'. 11(8):1085-91).

WP3: Capacities and proficiency in diagnostics and detection

Electronic lists of the types of assays in consortium labs, together with standard operation practice (SOP) documentation were produced. They include information on the testing capacities (throughput, types of samples, sources of samples), as well as partners' functions in their country's public health / veterinary / food safety infrastructure. An electronic list of reference material that can be shared with others for diagnostic controls was produced samples of CCHFV and RVFV (different strains, different genome concentrations) were prepared to be send to several laboratories for diagnostic testing. Evaluation and summary of obtained data sets from the laboratories. The results of the external quality assurance (EQA) study on molecular detection of CCHFV and RVFV is being published.

Samples of WNV (different strains, different genome copies) were sent to several laboratories for diagnostic testing. Data sets obtained by the laboratories were analysed and summarised. The results of the EQA study on molecular detection of WNV have been published.

Serum panels of CCHFV and RVFV serum were sent to several laboratories for diagnostic testing. Evaluation and summary of obtained data sets from the laboratories. Publication of results of the EQA study on antibody detection for CCHFV and RVFV.

Similarly, samples of WNV serum panel were sent to several laboratories for diagnostic testing. Evaluation and summary of obtained data sets from the laboratories. Publication of results of the EQA study on antibody detection for WNV.

Centrally-ordered oligonucleotides for CCHFV, RVFV, WNV detection pre-tested and assembled together with controls and SOP documents, were distributed through the consortium.

Slides for immunofluorescent assay or pre-coated EIA plates, together with controls and SOP documentation, were distributed through the consortium (for CCHFV, RVFV, WNV).

WP4: Surveillance

Review of diagnostic performances of diagnostic methods for WNV, CCHF virus and RVF. The main objective of this document is to show the latest available knowledge about the sensitivity and specificity of diagnostic test for CCHF, WND and RVF.

Three disease-specific questionnaires (CCHF, RVF, WNV) have been prepared to collect precise information on the surveillance activities in place in the different countries. All questionnaires are built to collect information on humans and animals' surveillance and diagnosis as well as on vectors' surveillance and virus detection.

The evaluation of the answers to the questionnaires has been included in a specific document ('WP4: Surveillance. Analysis of surveillance systems in place for WNV, CCHF virus and RVF') has been published also in the ARBO-ZOONET newsletter no.7.

During the project a web-based GIS collecting relevant information on notification of cases and diseases occurrence.

The web-based GIS includes also all relevant published and publicly available data on pathogen distributions and filed surveillance results. Assessment of impact of diseases introduction / spread and preventive / control interventions.

The main objective of this document is to analyse the impact of CCHF, West Nile disease (WND) and RVF spread in Europe both from the public and veterinary health perspectives. The analysis is completed by an economic assessment of the diagnostic procedures possibly in place for the surveillance of these diseases. Final recommendations are given for each disease for the implementation of cost-effective surveillance and preventive actions.

'Assessment of impact of diseases introduction / spread and preventive / control interventions'. The main objective of this document is to analyse the impact of CCHF, WND and RVF spread in Europe both from the public and veterinary health perspectives. The analysis is completed by an economic assessment of the diagnostic procedures possibly in place for the surveillance of these diseases. Final recommendations are given for each disease for the implementation of cost-effective surveillance and preventive actions.

WP5: Establishment of virulence standards

A list of available virus strain for CCHF, RVF and WNF viruses was established by the partners of the WP5.

Due to difficulties encountered for sending around selected strains (RVFV and CCCHFV are select agents) to the partners (see previous report), we could not compare the methods at different laboratories.

- the results of comparison of different assays have been published: Virol J. 2011 Feb 24;8:81.Weidmann M, et.al;
- a course with focus on the diagnostic for CCHFV organised- this has been a joint action between ARBO-ZOONET (WP5 and WP) and the CCH Fever programme;
- a technical w-shop for CCHFV have been organised. This has been a joint action between ARBO-ZOONET (WP5 and WP) and the CCH fever programme.

The activities have been summarised in the table prepared for Delivery 5.1 - the table included available strains and facilities available within the partners and recently the methods for virus isolation and studying the virulence factors are available.

WP6: Intervention strategies

The objectives of WP6, which is a coordination action aimed at intervention strategies for WNV, RVFV and CCHFV, can be summarised as follows:

- assessment of vaccine development and use;
- assessment of antiviral therapies;
- identification of research gaps.

Deliverables

The deliverables of this WP are one or more report(s) or publication(s) describing the research status, and gaps in the fields of anti-tick vaccines, WNV, RVFV and CCHFV vaccination, new vaccine development, antiviral treatment and new drug development.

After symposia or meetings organised by ARBO-ZOONET, the main data and communications have been published:

- in ARBO-ZOONET newsletter: 'Interventions against WNV, RVFV, and CCHFV: Where are we'? communicated by Rob Moormann in ARBO-ZOONET Newsletter 2010. 4:16-27;
- in vector-borne and zoonotic diseases: 'Interventions against WNF virus, RVF virus, and Crimean-Congo Hemorrhagic fever virus: Where are we'? By Kortekaas, J., Ergonül O., and R.J.M. Moormann. Vector-Borne and Zoonotic Diseases. 2010. 10:709-718;
- ARBO-ZOONET symposium, 'Interventions against WNV, RVFV, and CCHFV: Where are we'?
- Food and Agriculture Organisation (FAO) meeting on RVFV vaccine development, progress and constraints;
- European Network for the Coordination of RVF Animal experimentation and Diagnostics (ENCRAD).

The section on antiviral therapy was partly covered under D6.1 and not followed-up further.

Capacity building
- 3 south-African scientists (2 Doctor of Philosophy (PhD) students and 1 Post-doc) were trained in RVFV reverse genetics at the facilities of partner 17 (WP leader), resulting in joint projects.

WP7: Knowledge dissemination and technology transfer

The following workshops were conducted:

- ARBO-ZOONET satellite meeting at the 10th biennial conference of the society for tropical veterinary medicine theme: 'One health, one medicine: building bridge to face the challenge of emerging and zoonotic diseases' Lübeck, Germany, 29 June - 3 July 2009

- ARBO-ZOONET symposium: 'Interventions against WNV, RVFV and CCHFV: Where are we'? Istanbul / Turkey 19-20 November 2009

- ARBO-ZOONET symposium: 'Dealing with WNV, RVFV and CCHFV risk in Europe: Where are we (going)'? Montpellier, France; 26-27 November 2009.

The proceedings of the ARBO-ZOONET workshops were published and disseminated via:

- scientific publications in journals (Special Issue Vector Borne Diseases);
- the ARBO-ZOONET newsletter;
- articles on the project website with the possibility to download presentations.

The project organised and conducted a number of courses and training for young scientists. These were in particular:

- ARBO-ZOONET RVF diagnostic workshop 2009;
- regional training workshop on high pathogenic avian influenza (HPAI) and RVF in the Maghreb;
- workshop on WNV diagnostic techniques;
- short-term visits / individual training of Karen Mansfield, Susanne Jäckel and Darem Tabbaa;
- young ARBO-ZOONET inaugural meeting.

A detailed description of the events is enclosed in the periodic reports of the project. Reports on the conducted courses and trainings were published on the project website, the ARBO-ZOONET newsletter and within the periodic reports of the project. Disease specific diagnostic tools were disseminated via technical workshops, courses and trainings. Tutorials and protocols on diagnostic methods were disseminated via print outs, CDs and downloads.

The project organised workshops on:

- RVF diagnostic techniques;
- WNV diagnostic techniques;
- CCHF diagnostic techniques.

A novel diagnostic tool (enzyme-linked immunosorbent assay (ELISA)) for RVF was developed and validated by Susanne Jäckel in Germany and South Africa.

Darem Tabbaa was introduced in the LAMP method during his exchange visit.

The project trained a number of participants in the conducted workshops and technical workshops in modern diagnostic tools as well as in surveillance and epidemiological tools. Furthermore training was also provided to young scientists in the respective partner laboratories and via exchange visits among partner laboratories.

Surveillance as well as tools for outbreak investigations were disseminated via technical workshops, courses and trainings.
Tutorials and protocols on the taught methods were disseminated via print outs, CDs and downloads.

The project organised workshops on:

- basic epidemiological tools;
- advances epidemiological tools;
- vector taxonomy and ecology;
- GIS.

Potential impact:

The strategy of the project has been to train the staff in using tools and technologies required for a specific and effective detection and differentiation of the pathogens causing the mentioned diseases, professional epidemiological studies, effective control strategies, and a better disease outbreak management. A significant number of publications intended to evaluate the risk of spread and /or introduction of these diseases should be of help for human and animal health authorities. They highlighted the importance of the disease control and surveillance for Europe.

List of websites: http://www.arbo-zoo.net/
publishable-summary-211757.pdf