Foot and mouth disease virus (FMDV): the disease and diagnosis
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1 Foot and mouth disease virus (FMDV): the disease and diagnosis Peter Nettleton
2 Important characteristics of FMDV Unbelievably tiny- Within one millimetre there are one million nanometres (nm) FMDV is 25 nm in diameter. Simple structure An outer protective protein coat inside which is the genetic code. Can only multiply (replicate) within living cells.
3 FMDV Icosahedral structure Four structural proteins VP 1, 2, 3,
4 FMDV ss +ve sense linear RNA Non-structural proteins (nsp) Fixed trigger points for vaccination are difficult to define, due to the many variables involved in different outbreaks Scudamore & Harris, 2002
5 Virus Attachment and Entry Nucleus Plasma Membrane Virus Replication SPs and NSPs produced Virus Assembly only SPs Release When cell dies all contents are released
6 FMD virus growth FMDV vaccine production
7 Virus Attachment and Entry Nucleus Virus Replication SPs and NSPs produced Natural Infection Antibody to SP and NSP produced Virus Assembly only SPs Plasma Membrane Purified Vaccine Antibody to SP produced
8 FMDV characteristics FMDV is tiny and tough It consists of 4 capsid proteins surrounding the viral nucleic acid carrying its genetic code. Most important capsid protein is VP1 Antibody against VP1 neutralises that virus There are many different FMDVs:- 7 types, A,O,C, Asia1, SAT 1, 2 and 3 and many subtypes or strains because of continuous mutation of the viral RNA.
9 FMDV Typing of a new isolate Comparison with other FMD viruses at WRLFMD, Pirbright Genetic relatedness to previously characterised viruses What type is it? Which other FMD virus(es) is it most like? Is there a vaccine virus to protect against it? Will antibody produced by the vaccine neutralise the new virus and protect vaccinated animals?
10 FMDV- Sequencing of the nucleotides coding for the VP 1 gene and comparison with other isolates in a phylogenetic tree Thomson & Bastos (2004) In Infectious Diseases of Livestock Ed by Coetzer & Tustin. Publ by Oxford, Southern Africa
11 FMDV Selection of the best vaccine The vaccine must produce high levels of neutralising antibody against the virus in the vaccine and against the new virus Sera from vaccinated animals are diluted and each dilution is tested against the vaccine virus and the new virus The antibody titre is the highest dilution of serum that will neutralise each virus. Eg 1/320 against the new virus and 1/1280 against the vaccine virus Ratio r = titre of antiserum against new virus = 320 = 0.25 titre of antiserum against vaccine virus 1280 Ideally r >0.3
12 Foot and Mouth Disease - Clinical signs Foot Lameness, lesions between clits and on coronary bands Mouth Salivation, lesions in and around mouth General Dull, inappetance, fevered, lesions elsewhere, death of young stock
13 Cloven-footed domestic livestock hosts of FMDV Pigs produce the most virus Cattle produce less Sheep produce least
14 FMDV What about virus carriers? FMDV can be detected in the throat of ruminants more than 28 days after infection In Africa, there is good evidence that carrier buffalo can transmit SAT viruses to cattle In other countries, whether or not transmission of FMDV from carrier cattle, sheep or goats to other susceptible stock is still unresolved
15 UK wildlife as sources of FMDV - All species of deer susceptible - No confirmed cases in UK - Low risk as a source of FMDV - Farmed and free-living wild boar - Must be denied access to food waste - Low but growing risk as source of FMD
16 FMDV outbreaks in
17 FMDV from a wild boar in Bulgaria Valdazo-Gonzalez et al (2011) Vet Rec 168, 247
18 Foot-and-Mouth Disease - Diagnosis Rapid detection and reporting of sick animals Rapid inspection and clinical diagnosis Rapid collection and submission of correct clinical specimens
19 FMDV-Rapid virus detection tests Penside lateral flow device Detects virus protein (antigen) Positive confirms presence of FMDV Virus (antigen) detection ELISA Yellow colour confirms presence of FMDV Can also type the virus
20 FMDV-Rapid PCR test to detect viral RNA - Very sensitive, can detect virus before clinical signs - Semi-quantitative - Allows genetic fingerprinting of virus
21 FMDV Antibody detection tests Solid and liquid phase blocking ELISAs Can screen large numbers of sera from any species Will detect antibody from 3 weeks to years after infection NSP antibody tests (e.g. 3ABC) Can screen large numbers of sera Will detect antibody only against NSPs and are used to screen vaccinated animals to detect any that may have been infected with FMDV
22 FMDV serosurveillance after disease
23 FMDV - Summary FMDV is a formidable foe due to its toughness, infectivity and variability We know a lot about the viruses and how they spread and cause disease We have excellent diagnostic tools A new virus can be characterised in hours Very good vaccines are readily available
24 FMDV - Acknowledgements The organisers IAH Pirbright DEFRA OIE, EU, FAO, IAEA Many vets and farmers for valuable discussions All of you for coming today
25
REFERENCE LABORATORY TESTING
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