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![Figure 1: Upper panel – May 2015 OIE global FMD
status showing outbreaks in FMD-free
countries/zones that occurred between Jan 2005
and Jan 2016 - map adapted from OIE members
FMD status map extracted 4th April 2016 from
http://www.oie.int/en/animal-health-in-the-
world/official-disease-status/fmd/en-fmd-carte/.
Middle panel - global burden of FMD in cattle in
2008 (burden in sheep and goats has a similar
distribution). Prevalence index based on
estimates of incidence, population distribution
and other risk factors, adapted from (Sumption
et al., 2008). Note progress in South America
since 2008 [compare with upper panel].
Lower panel - density of poor livestock keepers,
updated 2012 (Thornton et al., 2002). Central
America, zones in Kazakhstan and Southern
Africa, parts of both South East Asia and South
America are among the few places where FMD is
not present in poor livestock keeper populations.](https://image.slidesharecdn.com/fmdcontrolvaccination-160609130521/75/Foot-and-mouth-disease-Control-and-vaccination-6-2048.jpg)
![Current evaluation methods
• Vaccine protection:
– Challenge studies – PD50, PPG
• Small numbers
• Unnatural challenge
– In vitro serological vaccine matching studies
• r-values, Expected percentage protection
• Do not actually assess if animals are protected
– Sero-surveys
• To assess post-vaccinal antibody response
• Population immunity (Structural Protein [SP] titre)
– With antibody titre as a correlate of protection
– Cannot tell if sero-positive from natural infection or vaccination
» High sero-prevalence =good or bad vaccination programme
13](https://image.slidesharecdn.com/fmdcontrolvaccination-160609130521/75/Foot-and-mouth-disease-Control-and-vaccination-13-2048.jpg)
![22
FMD vaccine protection:
- Requires several doses (≥3PD50)
- Declines with time since vaccination
Mass vaccination
Mass vaccination
Population immunity ≈ Population vaccination history
[No. of doses, time since last dose]
Population vaccine history ≈ Population age structure](https://image.slidesharecdn.com/fmdcontrolvaccination-160609130521/75/Foot-and-mouth-disease-Control-and-vaccination-22-2048.jpg)
![36
• Using regression models fitted to data from
extensive post-vaccination sero-monitoring study
[n=647]
• Predict immunity for simulated population
LPBE SP titre = Time since vaccination + No. of times vaccinated
From coverage to immunity](https://image.slidesharecdn.com/fmdcontrolvaccination-160609130521/75/Foot-and-mouth-disease-Control-and-vaccination-36-2048.jpg)
![37
Population immunity predictions
Primary courseAutumn mass
vaccination
Two-dose primary course:
Increases proportion of
6-12 month cattle above
threshold by 25-40%
Log10 (SP titre) ≥2: 32% [25%-40%]
Log10 (SP titre) ≥ 2: 27% [20%-35%]
Log10 (SP titre) ≥ 2: 30% [24%-38%]
Log10(SP titre)
Threshold titre is useful but
Titre ≈ Protection
Antigenic similarity of:
1) Vaccine – 2) Test – 3) Field virus](https://image.slidesharecdn.com/fmdcontrolvaccination-160609130521/75/Foot-and-mouth-disease-Control-and-vaccination-37-2048.jpg)
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Foot-and-mouth disease: Control and vaccination
The lecture by Dr. Theo Knight-Jones at the University of Zambia discusses foot-and-mouth disease (FMD) control strategies, focusing on vaccination methods, their advantages, and challenges. Key points include the viral nature of FMD affecting cloven-hoofed animals, the urgent need for effective vaccines considering the disease's rapid transmission and economic impact on livestock productivity and trade. The document also evaluates current FMD vaccines, their effectiveness, and potential failures in vaccination programs, advocating for improved strategies and novel vaccine developments.
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Similar to Foot-and-mouth disease: Control and vaccination
Foot-and-mouth disease: Control and vaccination
- 1. Foot-and-mouth disease: control andvaccination Dr Theo Knight-Jones [email protected] Lecture to 5th year veterinary students at the University of Zambia Lusaka, Zambia 1 June 2016
- 2. Overview 1. Control strategiesfor FMD 2. Vaccination as a control strategy. Why use this method (Advantages and disadvantages)? 3. Vaccination strategies 4. Current FMD vaccines 5. Vaccine selection and evaluation 6. Vaccine field evaluation studies 7. Possible failures in FMD vaccination 8. Novel FMD vaccines
- 3. FMD – Essentialinfo • Viral disease of “Cloven hoofed animals” • Picornavirus - 7 serotypes • High morbidity - low mortality
- 4. FMD direct impact •Highly infectious – R0 2 - 70 (depending on the setting) – High attack rate in outbreaks (>70%) – Repeated outbreaks affecting many animals – Rapid spread – 3-5 day incubation & pre-infectious period – UK 2001 - >56 farms infected before disease detected • Reduced productivity – Especially commercial dairy – Prevents use of high productivity breeds – Reduced traction (beasts of burden)
- 5. FMD indirect impact •Trade restrictions – FMD free countries block imports from FMD affected countries/zones • Disastrous for exporting countries – Cost of control • Movement/trade restrictions – May discourage reporting • Vaccination (only measure in most endemic countries) • Culling & compensation » Impact on other industries (tourism)
- 6. Figure 1: Upperpanel – May 2015 OIE global FMD status showing outbreaks in FMD-free countries/zones that occurred between Jan 2005 and Jan 2016 - map adapted from OIE members FMD status map extracted 4th April 2016 from http://www.oie.int/en/animal-health-in-the- world/official-disease-status/fmd/en-fmd-carte/. Middle panel - global burden of FMD in cattle in 2008 (burden in sheep and goats has a similar distribution). Prevalence index based on estimates of incidence, population distribution and other risk factors, adapted from (Sumption et al., 2008). Note progress in South America since 2008 [compare with upper panel]. Lower panel - density of poor livestock keepers, updated 2012 (Thornton et al., 2002). Central America, zones in Kazakhstan and Southern Africa, parts of both South East Asia and South America are among the few places where FMD is not present in poor livestock keeper populations.
- 7. FMD conjectured statusand serotypes Paton et al. 2009
- 8. Control measures a) Movementrestrictions a) Close markets b) Between farms, zones, … c) Wildlife b) Other biosecurity a) Fomite control b) Vector control (people, insects, objects,….) c) Cleaning and disinfection of affected premises d) Culling (affected, dangerous contacts,…) e) Vaccination a) Mass vaccination b) Targeted vaccination a) Ring/reactive vaccination b) Zonal (Cordon Sanitaire) c) Specific risk group c) Private verses public funded vaccination • Use of control zones – see Botswana, South Africa • Which measures reduce exposure and which reduce susceptibility? Lancisi 1711 http://post.queensu.ca/~forsdyke/rindpst0.htm
- 9. FMD vaccines • Inactivated •Serotype specific protection – Variation in protection between strains within serotype – Multivalent vaccines used • Short duration (<6 months?) – from serology & challenge studies • Repeated vaccination throughout life • Two dose 30 days apart primary course – Important but often not given • Poor stability (3-8ºC) • Sometimes can distinguish infected from vaccinated+uninfected – NSP purified vaccines • Non-Structural Protein (NSP) serology
- 10. Approximate global FMDvaccination Used to eradicate FMD from Europe (1991-2) Region Million doses/Year Comments China 1.6 billion doses 5 government producers South America 500 Brazil: 350 million doses Asia (excluding China) 200 India: 150 million doses Middle East 20 European region 20 Mainly Turkey Africa 15 Hamond, 2010
- 11. What are theadvantages and disadvantages of using vaccination to control FMD?
- 12. Vaccination • Vaccination basedcontrol: – Advantages • May not need to cull • Protection even if cannot apply other control measures to reduce virus exposure • Sounds simple! – Disadvantages • Short duration of immunity • Limited spectrum of protection • Population turnover – young are highly susceptible • Cost – who pays? • Ongoing protection needed • False sense of security-affects risk behaviour • Vaccine quality/vaccine match • Coverage – herd immunity needed • Probably need biosecurity as well • Incentives for continued vaccination when not working • Needs thorough evaluation • Logistics of vaccinating million of livestock • Strain on veterinary services • Top down approach – inconsiderate of field situation needs of farmers • Mask infection/transmission – carriers • Affects ability to prove disease freedom • Affects trading restrictions if free but vaccinate
- 13. Current evaluation methods •Vaccine protection: – Challenge studies – PD50, PPG • Small numbers • Unnatural challenge – In vitro serological vaccine matching studies • r-values, Expected percentage protection • Do not actually assess if animals are protected – Sero-surveys • To assess post-vaccinal antibody response • Population immunity (Structural Protein [SP] titre) – With antibody titre as a correlate of protection – Cannot tell if sero-positive from natural infection or vaccination » High sero-prevalence =good or bad vaccination programme 13
- 14.
- 15. Current evaluation methods •Sero-prevalence surveys as indicator of burden • Vaccine protection: – Serological correlate of protection • Limited protection against different serotypes/strains • New strains appear frequently • Vaccine coverage: – Distributed method • Number of doses distributed/Estimated population size • Vaccination programme impact – ? 15
- 16. Protection in thefield may vary Cold chain Shelf life Batch variability Variable animal response Field protection: protection that counts Match with field virus Time since last vaccinated Number of doses in lifetime Level/duration of virus exposure
- 17. FMD vaccine evaluation Challenge studies invitro matching assays Post- vaccination serology Vaccine effectiveness Other…
- 18. 1. Are vaccinatedanimals protected? 2. Are the animals being vaccinated (adequately)? Key questions for a vaccination programme: Vaccine effectiveness Vaccine coverage
- 19. Vaccine coverage… questions •What levels of coverage are achieved? – Are there important groups of under-vaccinated stock? • How does coverage vary over the annual production cycle? – Considering population turnover – How does this relate to key epidemiological events? • Spring turn out to grazing • Times of mass trading & livestock movements
- 20. Reduction in riskin similarly exposed vaccinated compared to unvaccinated animals in the field Vaccine effectiveness
- 21. FMD vaccine studiesin Turkish cattle
- 22. 22 FMD vaccine protection: -Requires several doses (≥3PD50) - Declines with time since vaccination Mass vaccination Mass vaccination Population immunity ≈ Population vaccination history [No. of doses, time since last dose] Population vaccine history ≈ Population age structure
- 23. 23 Mass vaccination twicea year: Population age-sex-vaccination distribution Beef suckler cattle: Percentage of population
- 24. 24 Mass vaccination twicea year: Population age-sex-vaccination distribution Beef fattener cattle: 9-10 doses 7-8 doses 5-6 doses AgeFemales 4-5 years 3-4 years 2-3 years 1-2 years 0-1 years Males Percentage of population Females Different production system = different age structure = different population immunity
- 25. 25 Population vaccine history& immunity varies by region
- 26. 26 Structure changes withbirths & deaths over the annual production cycle New births = New unvaccinated animals Population immunity is constantly changing with population turnover & declining antibodies
- 27. 27 Post-vaccination immunity alsodeclines with time Vaccinated Spring+Autumn 2012 Vaccinated Autumn 2011+ Spring+Autumn 2012 Protection threshold once twice 3 times 2.3 2.4 2 0 Log10 (SP titre) Autumn mass vaccination Vaccinated Autumn 2012 depending vaccine history
- 28. 28 Population coverage model •Describe population immunity over the production cycle with 2012 Turkish mass vaccination policy • Simulated the Turkish cattle population for each province • Age-structure by day and month of birth • Using data from national random surveys for each province and census data • Dynamic population model representing the changing age structure for each province over the annual production cycle
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- 33. 33 Percentage never vaccinated6 months after mass vaccination – if eligible cattle always vaccinated Unvaccinated = Cattle too young at prior vaccination + New births since prior vaccination median values reported
- 34. 34 Vaccinated ≥3 times= Adult cattle Percentage vaccinated ≥3 times in lifetime – if eligible cattle always vaccinated
- 35. 35 Field studies androutine data found 40–99.9% vaccinated But not all eligible cattle will be vaccinated Results: • Six months after the last round of vaccination almost half of the cattle aged ≤24 months remain unvaccinated Betapert distribution (minimum=40%, maximum=100%, most likely=80%) • Only 50% of all cattle would have been vaccinated more than once with the last dose received ≤6 months ago
- 36. 36 • Using regressionmodels fitted to data from extensive post-vaccination sero-monitoring study [n=647] • Predict immunity for simulated population LPBE SP titre = Time since vaccination + No. of times vaccinated From coverage to immunity
- 37. 37 Population immunity predictions PrimarycourseAutumn mass vaccination Two-dose primary course: Increases proportion of 6-12 month cattle above threshold by 25-40% Log10 (SP titre) ≥2: 32% [25%-40%] Log10 (SP titre) ≥ 2: 27% [20%-35%] Log10 (SP titre) ≥ 2: 30% [24%-38%] Log10(SP titre) Threshold titre is useful but Titre ≈ Protection Antigenic similarity of: 1) Vaccine – 2) Test – 3) Field virus
- 38. 38 District coverage andpopulation immunity Modelled proportion vaccinated in a district at autumn vaccination against the percentage of cattle with a serotype O SP titre ≥1:102 in mid February
- 39. 39 Sustained antibodies aftersingle dose From: Selman P, Chénard G, Dekker A (2006) Cedivac-FMD; Duration of Immunity in cattle, sheep and pigs. Open session of the EuFMD, Paphos, Cyprus, 17-19 October 2006 Immunity reflects coverage Fewer problems
- 40. 40 • Major immunitygaps despite biannual mass vaccination • Improved vaccine required • ≥6PD50 vaccine now routine in Turkey • Two-dose primary course used in certain areas • Immunity gaps will still exist • Each round of vaccination may exclude a quarter of all cattle • Often unavoidable • Improved biosecurity measures required • Avoid over reliance on vaccine protection Conclusions: Mass vaccination in Turkey 2012
- 41. 41 What are they? Possiblereasons for failures in FMD vaccination programme?
- 42. Vaccine programme evaluation Potent vaccine Potent vaccine Vaccine coverage Field Protection Pre-field application In the field
- 43. Why is FMDcontrol so challenging? • Highly infectious with rapid transmission • Multispecies including wildlife • Multiple serotypes with variation within serotypes • Some farmers/regions lack motivation to control FMD • Vaccines: – Short lived protection against limited range of strains – Expensive & unstable (cold-chain required) • Subclinical infections • Livestock population turnover & movements • Cost/impact of control measures
- 44. Conventional inactivated FMDvaccines • Adaptation of wild type virus to cell culture • Virulent virus grown on BHK cells • Inactivated (BEI) • Non-structural proteins removed • Adjuvanted with alum or oil emulsion • Stored frozen for stockpiling and formulated later
- 45. Virus structure Genome Capsid - Intactviral capsids key for immune response - Inactivated FMD vaccine is made from whole virus particles and contains viral capsids but capsids degrade with time and the vaccine becomes less effective
- 46. Novel FMD vaccines -Recombinant Adenovirus vectored capsids - Baculovirus produced stabilised capsids - Chimeric vaccine virus with improved culture adaptation and changeable cassette for antigenicity & DIVA - Synthetic peptides (vaccine containing one or more chemically produced antigenic proteins)
- 47. Adeno virus vectorvaccine - Recombinant human adenovirus contains genetic code for FMDV capsids. - Adenovirus cannot replicate but infected cells will produce FMDV capsids leading to FMD immunity - No need to handle live FMD virus in production
- 48. Baculovirus - Recombinant baculovirus(insect virus) - Contains FMDV capsid code in genome - Insect cell culture infected with virus produced empty viral capsids - Mutation introduced to increase capsid stability - These are formulated as a vaccine
- 49. Chimeric vaccine virus -Mutant virus made by joining sections of genomes from different viruses - Use virus with good vaccine production properties - Replace structural protein antigen section with code from virus that you wish to protect against - Delete code coding for protein not needed in vaccine to differentiate vaccinated and infected animals - Produce mutant virus in cell culture - Use to produce inactivated vaccine in normal way
- 50. Questions 1. Control strategiesfor FMD 2. Vaccination as a control strategy. Why use this method (Advantages and disadvantages)? 3. Vaccination strategies 4. Current FMD vaccines 5. Vaccine selection and evaluation 6. Vaccine field evaluation studies 7. Possible failures in FMD vaccination 8. Novel FMD vaccines
- 51. This presentation islicensed for use under the Creative Commons Attribution 4.0 International Licence. better lives through livestock ilri.org