1. Keith Hamilton OIE Headquarters, Paris
Early warning devices and tools to diagnose known and unknown emerging diseases
OIE perspective
Keith Hamilton
OIE Headquarters, Paris

2. WORLD ORGANISATION FOR ANIMAL HEALTH OIE
An intergovernmental organisation
172 Members
Founded in 1924
Headquarters in Paris
9 Regional offices and
sub offices
Mandate : “to improve Animal Health
worldwide”
OIE office internationale des epizooties
Intergovernmental org
1924 predates UN 20+ members. The OIE was set up following an outbreak of Rinderpest in Belgium caused by some Zebu cattle in transit from India to Brazil.
Now - there are 172 member countries + territories of the OIE. Make up IC meet each year at OIE General Assembly
Regional offices and sub offices Mali, Botswana, Lebanon, Bulgaria, Brussels, Panama, Argentina, Japan, Thailand. Some of these we have a RAHC = fao and oie share a building – brings them closer – gabarone, mali, lebanon
Broad mandate – can be summarised in the objectives

3. OIE OBJECTIVES Transparency of global disease situation
Provide expertise, encourage international solidarity
Collect, analyse, disseminate scientific info.
Standards for safe global trade in animals and animal products (WTO SPS agreement)
Promotion of Veterinary Services
Food safety (farm level) and animal welfare
The lists A+B COMBINED to 1 LIST 100+ diseases affecting mammals, fish, molluscs, bees.
Listed diseases – a serious threat to animal health or production or human health.
Members report occurrences of these diseases to the OIE, once reported the info is then disseminated to Members. Allows countries to take preventative action reduce the likelihood of further spread.
Thru network of ref labs, collaborating centres and codes/guidelines, OIE provides expertise to help countries control disease. Important for developing countries. OIE is looking to extend this capacity and expertise to areas where it is needed through twinning.
Constantly review scientific info about disease control – made available to help members to imp. Control. Info disseminated in science and tech reviews
Int. standards and guidelines for the control of major animal diseases are developed and set by the OIE on the basis of scientific principles. Supports the requirement of the Sanitary and Phytosanitary Agreement of the WTO that ‘sanitary measures should be scientifically justifiable’. OIE standards are recognised as the reference. measures that countries can use to protect themselves against import of disease through trade.
The ability to control disease depends on the strength of national veterinary services. This is a global concern and we want to eliminate disease at source. OIE is assisting countries in improving their veterinary services. One initiative the Performance Vision strategy programme aims to identify gaps – this is the first step.
Imp. Synergy with codex alimentarius. OIE deals with risk at farm level BEFORE it is a product e.e salmonella- poultry. Codex Al deals with it once a product

4. OIE STANDARDS (avaılable on oıe websıte)
Terrestrial Animal Health
Code
Manual of Diagnostic Tests and Vaccines for Terrestrial Animals
Aquatic Animal Health Code
Manual of Diagnostic Tests for Aquatic Animals
safeguard world trade without unjustified barriers i.e. based on scientific principles
WTO recognises OIE standards, guidelines and recommendations as the international standards for animal health and zoonoses.
Sanitary and Phytosanitary Agreement of the WTO that ‘sanitary measures should be scientifically justifiable’.
CODE
Lays down standards, guidelines and recommendations that should be followed to ensure safe international trade in animals and animal products
One for terrestrial animals and one for aquatic animals
MANUAL
The OIE standards for laboratory testing and vaccination are laid out in the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Again, one for terrestrial animals and one for aquatic animals.
Code and Standards adopted each year at gen. session by consensus of IC. Any proposed changes are debated before adoption

5. Some purposes of diagnostic tests
Demonstrate ‘apparent freedom’ from infection in defined populations
(including countries, zones, compartments or individual herds)
a) historical freedom
b) free with vaccination
c) re-establishment of freedom post-outbreaks
Certify freedom from infection or agent in individual animals or products for trade/movement purposes
Eradication of infection from defined populations
Confirmatory diagnosis of clinical cases
Estimate prevalence of infection to facilitate risk analysis (surveys, herd health schemes, disease control programmes)
Determine immune status in individual animals or populations (post-vaccination)
Molecular epidemiology
Characterise disease agents – pathogenicity, susceptibility to drugs etc
Disease surveillance, control and safe trade are supported by reliable, accurate and validated diagnostic laboratory tests.
Freedom from country or zone or compartment.
Zoning/compartmentalisation – establish a subpopulation with different health status within national borders; Zone – sep by natural or artificial geographical barriers/ Compartment – sep by biosec management system
OIE recognises official freedom for 4 diseases fmd, cbpp, bse and rinderpest. For other diseases – self declared disease freedom.
Disease freedom based on EVIDENCE from surveillance – UNDERPINNED by quality Sx, DX tests and
lab QMS
Free with vaccination – post Vx surveillance imp to demonstrate infection is not circulation in vaccinated animals
Need a test to detect infection in vaccinated animals – a DIVA test.
Example AI – Vx with killed Vx – birds can still become infected but not show signs – clinical sx less sensitive
Post Vx Sx is important – use heterologous vx with different NA to circ filed virus and serological test to detect specific NA. Other options with recombinant Vx but as yet not very effective.
2. Preimport or export test must be reliable and sensitive. A positive can be tested by a more specific test to confirm. OIE code specifies PRESCRIBED tests for trade purposes. Alternative tests can be used if bilateral agreement.
3. Eradication – if successful 2nd disease ever to have been eradicated. Last phase - to demonstrate freedom from Somali ecosystem
4. Many diseases clinical signs are not definitive. Need lab confirmation especially if other diseases – that cause similar signs - are circulating. Many areas affected by AI, ND also circulating therefore mass mortality could be either of due to another non infectious cause. Also CSF and PMWS, PRRS etc
Post vaccination Sx check coverage, delivery and immunogenicity of Vx. Serology not enough to demonstrate adequate protection. Would need challenge studies.
7. Molecular epidemiology – with sequencing, especially whole genome sequencing, readily available can do phylogenetic studies to see how closely related different strains are to each other.
8. Sequencing – can also allow characterisation of disease agents eg the OIE code defines LPAI and HPAI – one criteria for defining HPAI is a multiple basic AA sequence at HA cleavage site.

6. Standards for diagnostic laboratories
Specialist commissions
Biological Standards (mammals, birds, bees)
Aquatic Animal Health Standards (fish and aquatic invertebrates)
Designation of Reference Laboratories
capacity building through twinning projects
Publication of laboratory manuals
Ad hoc groups related to new technologies
Biotechnology (disbanded)
horizon-scanning role
position papers on emerging technologies
advice to OIE, including the specialist commissions
Ad hoc group on Molecular Diagnostics
Ad hoc group on Vaccinology
4 specialist OIE Commissions. Elected every 3 years by the IC. 2 of them relate to Dx lab standards
Biological Standards commission – founded 1949, current chair steve edwards
BSC responsible for:
Establishing and approving diagnostic methods
Recommending most effective biological products, such as vaccines
Review and approve applications for OIE Ref Lab status (twinning aims to improve distribution)
Oversee production of OIE Manual of diagnostic tests and vaccines
OIE Manual – Standards for dx tests and vaccine production – recognised by WTO as the international standards… Contribute to INTERNATIONAL HARMONISATION of surveillance and diagnostic methods
AD HOC groups – EXAMINE specific scientific and technical issues that guide to specialist commissions. Therefore report to IC and Commissions
Ad hoc group on biotech provide recs on new technology. Will be replaced by 2 more specialist groups.

7. Principle mandate of OIE Reference Laboratories
to function as a centre of expertise and standardisation for a designated disease(s) or topics;
to store and distribute to national laboratories biological reference products and any other reagents used in the diagnosis and control of the designated disease(s) or topics;
to develop new procedures for diagnosis and control of the designated disease(s) or topics;
to gather, process, analyse and disseminate epizootiological data relevant to their speciality;
to place expert consultants at the disposal of the Office International des Epizooties.
OIE Ref Labs specialise in a specific disease and have a designated expert.
Applications through submission of a dossier to OIE BSC
Twinning – current bias to N Hemisphere and developing countries – look to provide a better geographical distribution through twinning.
Mandate includes but is not just about upholding standards

8. OIE Quality Standard
To ENSURE CONFIDENCE in test results – test must be validated w. respect to INTENDED APPLICATION eg MUST BE FIT FOR PURPOSE
i.e. to confirm clinical disease, to demonstrate freedom from infection follwoing vaccination, etc etc
Ensure confidence labs must have a recognised standard of QUALITY
Booklet brings OIE QS in line with ISO Labs co,mplying with OIE QS are complying with ISO 17025
Guidance on lab QMS
Test methods and procedures must be appropriate for specific diagnostic applications in order for the test results to be of any relevance i.e. assay must be ‘fit for purpose’

9. Prescribed and Alternative Tests
Established principle in OIE of “Prescribed Tests” for international trade
Prescribed tests – required by OIE code for international movement of animals and animal products
Historically assumed a level of validation sufficient to certify animals/products as low risk for trade
No formal framework for assessment of the validation data – decisions based on expert advice
Many traditional tests lack formal validation data
In future new proposals for “Prescribed Test” status will need to fulfil the requirements of the OIE Validation Template
Second category of “Alternative Tests”
Validation less complete
May have an application for trade in certain circumstances (on bilateral agreement)
Prescribed and alternative tests are listed for each disease at the beginning of the OIE manual of diagnostic tests and vaccines for terrestrial animals
Prescribed tests are required by the OIE terrestrial animal health code for the international movement of animals and animal products. To demonstrate freedom from disease prior to import or export. Not possible to have a prescribed test for every listed disease
Alternative tests – suitable for diagnosis of disease within local setting. Might be use for import/export after a bilateral agreement
There are also ‘other tests’ described in the manual

10. The OIE Validation System
Template available on the OIE website
Provides a framework
May need to be adapted for individual applications
Administered by a secretariat at the OIE
Scientific oversight by the OIE Biological Standards Commission
Appointment of expert panels for individual dossiers
Covered by confidentiality agreements
OIE provides a framework for validation of diagnostic tests – available on the website
Framework can apply for validation of prescribed tests or for commercial kits
Oversight by BSC

11. The OIE Procedure for validation and certification of diagnostic assays – aim and scope
Developed to meet the needs of Member Countries, the aim of this procedure is :
1. to certify commercial diagnostic kits as validated fit for some specific purpose(s)
2. to produce an OIE register of recognised diagnostic kits (available on the OIE web site at:
All diagnostic tests for diseases, including zoonosis, caused by pathogens present in animals can be certified by this procedure.
Procedure for diagnostic kits

12. The OIE Procedure for validation and certification of diagnostic assays - briefly
Launched in May 2005, it is a dossier based procedure (Independent and internationally recognised experts nominated to evaluate the dossiers submitted)
The procedure takes 135 days (the clock is stopped when clarification or additional data are requested by the panel of experts).
OIE Register currently comprises 4 diagnostic kits certified (kit for Rabies, BSE, White Spot Disease, AI) - several dossiers are currently in the pipeline
For further information on the procedure the contact person is Dr François Diaz,

13. OIE and new technologies
Establish a balance between novel concepts and tried and tested methods
OIE Manual chapter 1.1.7
OIE standards must be applicable globally
Technology applied to diagnostics must be validated and of practical value
much more than just a feasibility study
funding issues
need for specialist equipment?
training issues
There is a chapter in the OIE manual dedicated to biotechnology – it is a general overview for non specialists.
Applicable globally, therefore technology must be adaptable, not prohibitively expensive, test samples easily transportable, reagents readily available, equipment maintainable etc
When determining whether a new technology is ready and in need of an OIE guideline – does that technology have a specific application and has it been validated to at least the bench level

14. Summary
Diagnostic tests wide range of applications, applied globally, need to be fit for purpose
OIE standards recognised by WTO SPS agreement – facilitate safe trade, harmonised procedures
Need confidence in laboratory test results – especially for presecribed tests, validation, quality standards including quality management systems
OIE procedure for validation of tests

15. 12 rue de Prony, 75017 Paris, France - www.oie.int – oie@oie.int
Organisation Mondiale de la Santé Animale
World Organisation for Animal Health
Organización Mundial de Sanidad Animal
12 rue de Prony, Paris, France - –