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![Upper panel – August 2014, OIE global FMD
status, with recent outbreaks in free zones
identified.
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,
Rweyemamu et al. 2008). Note progress in South
America since 2008 [compare with upper panel].
Lower panel - density of poor rural livestock
keepers from (Thornton, Kruska et al. 2002).
Central America, parts of South East Asia and
some areas in South America are the few
exceptions where FMD was not present in poor
livestock keeper populations.](https://image.slidesharecdn.com/fmdcontrolandvaccination-150224012954-conversion-gate01/75/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/fmdcontrolandvaccination-150224012954-conversion-gate01/75/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/fmdcontrolandvaccination-150224012954-conversion-gate01/75/Foot-and-mouth-disease-Control-and-vaccination-22-2048.jpg)
![37
• 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/fmdcontrolandvaccination-150224012954-conversion-gate01/75/Foot-and-mouth-disease-Control-and-vaccination-37-2048.jpg)
![38
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/fmdcontrolandvaccination-150224012954-conversion-gate01/75/Foot-and-mouth-disease-Control-and-vaccination-38-2048.jpg)
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Foot-and-mouth disease: Control and vaccination
The document discusses foot-and-mouth disease (FMD), focusing on control strategies and vaccination methods, along with their advantages and disadvantages. Key points include the disease's high infectious nature, the necessity of vaccination in endemic areas, and challenges in achieving adequate vaccination coverage due to varying herd immunity and logistics. It also highlights the importance of evaluating vaccine effectiveness and the need for improved biosecurity measures to aid in FMD control.
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Foot-and-mouth disease: Control and vaccination
- 1. Foot-and-mouth disease: Control andvaccination Theo Knight-Jones Lecture to 5th year veterinary medicine students University of Zambia 16 February 2015
- 2. Overview 1. Control strategiesof FMD 2. Vaccination as a control strategy. Why use this method (Advantages and disadvantages)? 3. Vaccination strategies 4. Available FMD vaccines 5. Vaccine selection for a particular region? How to determine a vaccine to use 6. Period of vaccination in a herd (how long is the protection) 7. Revaccination 8. Possible failures in FMD vaccination
- 3. FMD – Essentialinfo • Viral disease of “Cloven hoofed animals” • Picornavirus - 7 serotypes • High morbidity - low mortality
- 4. FMD direct impact •Highly infectious – Ro 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. Upper panel –August 2014, OIE global FMD status, with recent outbreaks in free zones identified. 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, Rweyemamu et al. 2008). Note progress in South America since 2008 [compare with upper panel]. Lower panel - density of poor rural livestock keepers from (Thornton, Kruska et al. 2002). Central America, parts of South East Asia and some areas in South America are the few exceptions where FMD was 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 (1991-92) 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 doses7-8 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 If 3 dosesneeded for “adequate” protection If multiple doses needed, variation in immunity resulting from variation in coverage becomes exaggerated District with 100% coverage: After 3 rounds: 100% of cattle vaccinated 3 times District with 50% coverage: After 3 rounds: 50% x 50% x 50% = 12.5% vaccinated 3 times
- 29. 29 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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- 34. 34 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
- 35. 35 Vaccinated ≥3 times= Adult cattle Percentage vaccinated ≥3 times in lifetime – if eligible cattle always vaccinated
- 36. 36 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
- 37. 37 • 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
- 38. 38 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
- 39. 39 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
- 40. 40 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
- 41. 41 • 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
- 42. 42 What are they? Possiblereasons for failures in FMD vaccination programme?
- 43. Vaccine programme evaluation Potent vaccine Potent vaccine Vaccine coverage Field Protection Pre-field application In the field
- 44. 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