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Appendix 77
MINIMUM STANDARDS FOR LABORATORIES WORKING WITH
FOOT-AND-MOUTH DISEASE VIRUS
in vitro
AND
New Roles for “Auxiliary Labs” in the Diagnosis of FMD?
Bernd Haas, FLI Riems, Germany
in vivo
Conclusions:
Several member states maintain national laboratories able to
diagnose FMD in case of an outbreak which are important for the
whole European Community.
However, they lack the funding for a facility fully complying with the
„Minimum Standards“.
Technically, modern diagnostic methods (PCR, ELISA) allow to test samples
from suspect cases in „Auxiliary Labs“ in a safe, fast and efficient way.
However, current regulations do not fully reflect this situation.
MINIMUM STANDARDS FOR LABORATORIES WORKING WITH
FOOT-AND-MOUTH DISEASE VIRUS
in vitro
AND
in vivo
History
Loeffler‘s animal facility:
‚High containment‘ anno 1900
Recommendations:
Update “Minimum Standards“ and Council Directive 2003/85/EC
in respect to auxiliary labs
Allocate sufficient funding for diagnostic and research laboratries
‚...Germany could be considered free of FMD if there weren‘t
Prof. Loeffler‘s experiments...‘
History
Loeffler, 1906:
History
FLI 1990
... that the situation of a future institute should really
be such that it of itself could completely exclude any
spread of the infective matter. Undoubtedly, an island
would be best suited for this purpose.
Loeffler,
1910
1950th - present:
„High Security buildings“
• Constant negative pressure
• Double HEPA filters
(exhaust)
• Automatic flaps
(inlet and exhaust)
• Thermal decontamination
of waste water (within
containment)
• Chemical decontamination
of equipment
• Compulsory Shower-Out
FMD-Islands
Riems, Plum Island, Lindholm
• Animal Carcass Rendering
• Emergency Power Supply
Open Session of the EuFMD: 2012, Jerez de la Frontera, Spain
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Appendix 77
History
Diagnostic Tests
Containment Standards
high
2001 epidemic, UK:
UK, Dk, Ge, Nl, It, CH…
risk
MINIMUM
STANDARDS
1985/93
Large animal
inoculation
MINIMUM
STANDARDS
2009
Five auxiliary laboratories set up
For serological testing by solid-phase-competition ELISA (SPCE)
Guinea pigs
3 million samples tested
200 000 samples a week
Cell culture
Required sample througput by far exceeded maximum performance
of FMD lab (despite IAH/WRL worked in 3 shifts !)
ELISA
low
First EuFMD draft of „Minimum Standards for auxiliary labs“
PCR
2001
1910
timeline
Reagent bank
2010
Minimum Standards - Hazard identification
What is a suspect case of FMD?
Threshold for sending samples to lab for FMD testing
The main sources of FMDV are:
high
high
infected pigs, cattle, sheep, goats and other susceptible large animals
text-book clinical signs of FMD in several animals
laboratory based physical and chemical processing of large quantities of virus
oral/foot lesions (vesicles!) in single animal
infected laboratory animals, e.g. baby mice and guinea pigs
oral/foot lesions (vesicles) in several animals
infected tissue cultures
oral/foot lesions (vesicles) in single animal
unspecific clinical signs several animals
diagnostic specimens (if FMD)
low
unspecific clinical signs in single animal
low
diagnostic specimens inactivated in microbiological safety cabinet
diagnostic specimens inactivated on the premise
What is a suspect case of FMD?
Threshold for sending samples to lab for FMD testing
high
send samples to foreign lab
(foreign language, legal aspects, special courier, costs…)
send samples to national lab (trouble, costs, standstill..)
send samples to regional lab
screening/routine program in labs, including FMD as a DD
Sending samples to a foreign lab
Language
Legal aspects
Special courier needed
Time
Restricted numbers of samples (in a crisis foreign lab
may not be available due to other/national outbreaks)
Data handling
Costs
low
…
Open Session of the EuFMD: 2012, Jerez de la Frontera, Spain
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Appendix 77
Minimum Standards - Authorization of Labs
1. infection of experimental and/or large animals with FMDV;
Legal Aspects
„Real FMDV lab“
2. activities which produce high amounts of infectious FMDV,e.g. large scale
virus production at a capacity that involves more than 10 litres of cell culture
3. activities involving the handling, and in particular, the propagation of
infectious FMDV, but are limited to 10 litres of cell culture, and during
which the FMDV is enclosed in containers which can be effectively
autoclaved or disinfected;
4. test diagnostic samples for antibody to FMDV,
„Auxiliary FMD lab“
by methods that do not involve live FMDV manipulation;
Lower standards for
5. test diagnostic samples for FMDV genome by methods Secondary Containment
MINIMUM CONTAINMENT STANDARDS FOR FMD LABORATORIES:
in application of Article 65(d) and Annex XII of Council Directive 2003/85/EC
MINIMUM STANDARDS OF BIORISK MANAGEMENT FOR
LABORATORIES UNDERTAKING DIAGNOSTIC INVESTIGATIONS OF
LOW-RISK SAMPLES DURING AN OUTBREAK OF FMD:
in application of point 13 of Annex XV to Council Directive 2003/85/EC on
laboratories for serology and for testing inactivated samples employed in
case of a FMD outbreak
that do not involve live FMDV manipulation (e.g. RT-PCR);
usually: „normal lab“
6. apply on the genome of FMDV methods of
molecular biology that do not involve live FMDV manipulation
Legal Aspects
Legal Aspects
point 13 of Annex XV to Council Directive 2003/85/EC:
Article 65 of Council Directive 2003/85/EC requires the Member States
(MS) to ensure that:
National Laboratories shall cooperate with other laboratories designated by the
competent authorities for performing tests, for example serological tests, that do not
involve handling of live foot-and-mouth disease virus. These laboratories shall not carry
out virus detection in samples taken from suspect cases of vesicular diseases. Such
laboratories need not comply with the bio-security standards referred to in Annex XII,
point 1, but must have established procedures which ensure that the possible spread of
foot- and-mouth disease virus is effectively prevented. Samples giving inconclusive
results in tests must be transmitted to the National Reference Laboratory for carrying out
confirmatory tests.
(a) laboratories and establishments, in which live foot-and-mouth disease
virus, its genome, antigens or vaccines produced from such antigens are
handled for research, diagnosis or manufacture, are strictly controlled by
the competent authorities;
(b) the handling of live foot-and-mouth disease virus for research and
diagnosis is carried out only in approved laboratories listed in Part A of
Annex XI;
….
(d) the laboratories and establishments referred to in points (b) and (c)
are operated at least according to the biosecurity standards set out in
Annex XII.
Suggested improvements
EuFMD / DG SANCO
Modify “Minimum Standards” according to risk:
“Real” FMD labs doing research and diagnostic work on
foreign samples which contain or may contain
live FMDV “in peace times”
vs
“Auxiliary” labs investigating only suspect samples
from own country (PCR, ELISA in MSC) without using
live FMDV as a reagent
Thank you for your attention!
Open Session of the EuFMD: 2012, Jerez de la Frontera, Spain
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Appendix 77
Open Session of the EuFMD: 2012, Jerez de la Frontera, Spain
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