From Rev. sci. tech. Off. int. Epiz., 2006, 25 (1), 271-292
Technology, public policy and control of transboundary livestock diseases in our lifetimesR.G. Breeze
Centaur Science Group, 1513 28th St NW, Washington, DC 20007 United States of America
EIDSS: Electronic Infectious Disease Surveillance SystemThe EIDSS provides the means to report suspicious disease outbreaks in real time and to track the progress of case investigations, epidemiological investigations in the area and the results of sample testing. The EIDSS contains a GIS and will locate disease outbreaks by use of a geographical positioning device. This is vital when street addresses, premise identifiers, and unique animal and personal identifiers are not available. Historical records of disease distribution will also be incorporated. The system has the ability to track multiple samples from the same patient taken at different times and places. There are built-in links between human and veterinary health for cases of zoonotic disease.
Although initially confined to the EDP list of diseases, the EIDSS is intended to encompass all public and animal disease surveillance information in the future.
The EIDSS data is entered in the language of the country but can be searched in many languages. Combined with the rapid results obtained from real-time PCR detection, the EIDSS can report positive laboratory detections in close to real time, at most in a few hours depending on distance.
The Rapid Response teams will be able to detect and report from the site of the outbreak should that be needed.
International standards, quality control, training programmes and regulatory changesThe TADR system uses the same equipment, test protocols and test reagents in all countries and the results are intended to be fully compatible with standards of international organisations like the World Health Organization (WHO) and of the US Centers for Disease Control and Prevention.
There is a quality control and quality assurance programme and the laboratories will meet international performance standards.
There is an extensive training programme in every aspect of this very new system: operation and maintenance of laboratory infrastructure; operation and maintenance of laboratory biological safety and analytical equipment; epidemiology and disease surveillance techniques; laboratory assays and their quality assurance.
Extensive regulatory changes have to be made to existing country laws and regulations to accommodate unfamiliar concepts, equipment and procedures. This is an enormous task that could never be completed without earnest support from the countries themselves. Critical to success in matters that fall under many departments of government is an agreement at the Presidential or Cabinet level that the National Security Council and the Ministries of Health, Defence, Agriculture, Justice, Finance, Foreign Affairs and Customs and Excise will work together to identify and overcome barriers.
Technology is outpacing regulatory capabilityThe TADR system provides the architectural backbone for a more extensive nationwide detection and reporting system that will cover common diseases as well as EDPs and is a model that can be extended to other countries by other funding sources.
With the TADR architecture in mind, the impacts of future technology can be anticipated.
The TADR system is using real-time PCR tests that identify pathogens one by one in a highly sensitive and specific manner.
These tests are the state of the art for answering the question: is this a case of FMD or not?
It would require three separate real-time PCR test procedures, which could proceed simultaneously in the same machine, to answer the question: are FMD virus, CSF virus and African swine fever virus present in this sample? Many tests would be required to determine the cause of a fever of unknown origin, although specific causes could be ruled out one by one by single tests. The reason for this is that there are inherent limitations on the number of fluorescent dyes that can be used and discriminated in a PCR test procedure when testing for multiple pathogens at the same time (a multiplex test).
The next generation is one of multiplex tests that can detect all transboundary pathogens in a single procedure.
PCR technology using various combinations of 64 distinct molecular mass tags instead of dyes can identify many pathogens simultaneously.
With this approach, 22 different viral, bacterial and Mycoplasma respiratory pathogens (2) and ten different causes of viral haemorrhagic fever (10) can be simultaneously and rapidly discriminated in human clinical samples.
Mass tag PCR costs about the same as real-time PCR except for the onetime cost of the mass spectrometer, but it is a logical next step up diagnostically from single PCR tests: the technology also builds on experience with PCR and quality assured laboratory practices.
The latest generation of microarray tests incorporates 30,000 viral, bacterial and parasite genetic sequences representing all vertebrate infectious agents on a single chip (W.I. Lipkin, personal communication and unpublished data, 2006).
The technology for microarray chips that can detect all livestock (not just transboundary pathogens) infectious agents simultaneously is already upon us though their current production cost makes them too expensive for veterinary use at the moment.
The trend in technology is crystal clear. Technology has already allowed tests that could once only be conducted in sophisticated national reference laboratories to be conducted in less elaborate regional laboratories at lower levels of biological containment or on the farm. It has also allowed tests that even national reference laboratories could not do to become commonplace at the regional level. With time and money, and a firm basis of experience with current technologies, the TADR model will become increasingly sophisticated at the regional and lower levels, as well as centrally. This has significant implications for how transboundary disease diagnosis is regulated and approved at the national and OIE levels and for the future roles of the World Reference Laboratories, which are more likely to be handling viral and host genomic information transmitted electronically from the countries themselves rather than actual samples of virus from which information has historically gone in the opposite direction.
The research that defined real-time PCR tests for FMD, CSF and other transboundary diseases, was disclosed and demonstrated to veterinary regulatory agencies in the USA and Great Britain and to members of the US Animal HealthAssociation in 2001; the scientific paper was published in 2002 (3). In 2006, a joint effort by British and US FMD diagnostic scientists essentially confirmed what was known in 2001 (7). But the test has still not been recognised by the OIE for international use for the diagnosis of FMD, even though the 2006 study (7) rediscovered that it would detect the presence of dead virus that could not be grown in cell culture and was, therefore, the new state of the art, as it had been since 2001. 'Validation' studies on the other tests are still in progress. In the meantime, there have been three highly significant technology advances: mass tag, FilmArray and the multi-pathogen chip. Our regulatory approval processes are completely broken when they cannot even keep up with generations of technology, far less specific applications. Transboundary disease diagnosis will never go back to being the province of a small club in select laboratories. We need to get these new generations of tests validated and out where they can be used within one year or less from discovery. The matter of pathogen detection has been trivial for some time and the tough question has become how to best use the new tests and the information they generate." (Read paper in full pdf)