Sotiria-Eleni Antoniou, Ioannis Malemis

CVMP and IWP Focus Group on Lumpy Skin Disease Vaccines European Medicine Agency, 31 January 2017, LONDON, UK

HELLENIC REPUBLIC

MINISTRY OF RURAL DEVELOPMENT AND FOOD DIRECTORATE GENERAL OF SUSTAINABLE ANIMAL

PRODUCTION & VETERINARY MEDICINE

ANIMAL HEALTH DIRECTORATE DEPARTMENT OF INFECTIOUS AND PARASITIC DISEASES

Lumpy Skin Disease Experience in Greece

HELLENIC REPUBLIC MINISTRY OF HEALTH

NATIONAL ORGANIZATION FOR MEDICINES

First LSD Outbreak in Greece

18 August 2015 Suspicion 2 Beef Holdings: 72 & 75 animals free grazing within the Evros Delta River National Park within 15 km from the closest confirmed LSD outbreak in Turkey (ADNS)

Clinical examination: nodules in the neck and elsewhere in the body (without ulcerations), nasal and eye discharge

20 August 2015 laboratory confirmation of LSD

24 & 25 August 2015 Depopulation

Evros River Yellow line borders

with Turkey

Turkey

Greece

Delta of Evros River

Turkey Greece

Borders

Overview of Measures

Legal Framework: describes measures and actions European Law: Directive 92/119 National Law : Presidential Decree: 138/1995 (harmonize Dir 92/119) National Contingency Plan : Ministerial Decision, 258933/18-8-2008

Control Measures Overview Measures in Case of Suspicion and Confirmation Measures are applied through Regional Decisions Official Information of the owners (tasks, obligations) Involvement in the control of the implementation of measures (Police,

Coastguard, Municipality, Army) Movements prohibition or restriction Zoning (protective and surveillance zone) Total Stamping out Cleaning and Disinfection Vector Controls Emergency Vaccination

1st wave of LSD (20 Aug - 15 Dec 2015)

14/10/2015 RU Chalkidiki ≈ 1,5 month post 1st Outbreak ≈ 210 km distance

1/10/2015 RU Kavala ≈ 42 days post 1st outbreak ≈ 120 km distance

20/8/2015 RU Evros For 27 days post 1st outbreak ≈ 25 km max distance

16/9/2015 RU Evros 27 days post 1st outbreak ≈ 40 km distance

7/10/2015 Limnos Island ≈ 49 days post 1st outbreak ≈ 120 km distance

100%

100% 100%

100%

100%

100%

100%

85 %

82 %

Re–emergence of LSD on 6 April 2016

6 April 2016 Serres RU

~ 40%

• An interval of more than 3 months since the last LSD outbreaks in 2015

• Regional Unit of Serres where vaccination coverage was 60%

• 2 Herds: 1 beef free grazing and unvaccinated

• !! 1 dairy herd vaccinated on 26th November 2015 !!

2nd wave of LSD (6 Apr – 25 Nov 2016)

15/07/2016 RU Achaia ≈ 300 km distance

6 /04 RU Serres Re-emergence

13/06/2016 Limnos

26/08 RU Larissa & Kozani

23/05 RU Pella 16/6 RU Imathia 30/6 RU Florina

19/10/2016 Evros

25/11/2016 Preveza

LSD Distribution Scenario 2016 6 /04 LSDV Entered in RU Serres 40 % vac. coverage

Moved to EAST 100 % vac. coverage

Moved to WEST 100 % vac. coverage

Crossed the Vaccination Aea Entered Areas (unvaccinated, low cover.)

Moved to South 50- 100 % vac. coverage 95-100% coverage

50-70% coverage

0

5

10

15

20

25

34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96

Num

ber

of o

utbr

eaks

Week

Number of outbreaks (August 2015 - November 2016)

2015 117 outbreaks 7 Regional Units 20 Aug - 15 Dec (4 months) 24 out of 117 outbreaks: vaccinated

herds suspicion was notified less than 28 days post vaccination

6080 animals culled

2016 104 outbreaks 15 Regional Units (11 new) 6 Apr - 25 Nov (7 months) Unvaccinated animals or Vaccinated but

not immunized at the time of infection (except 1 herd)

~ 6000 animals culled

Overview of the Epizootic

Decision on Emergency Vaccination Since the beginning of the epizootic, emergency vaccination was

decided and European Commission was informed Evros Area historically suffers from animal diseases crises (e.g. Sheep Pox in 2013-2014, BT 2014 e.t.c) Devastating effects for the local farming industry with negative impact to

local Society and Economy

High costs for the State : Cost of control measures Stamping out, Vaccination, Compensation Cost for Veterinary Services The involvement of vectors on the transmission of the disease complicates

the control: environmental conditions (wetlands), type of production (free grazing beef cattle)

Unclear if the stamping out policy alone was sufficient to stop the disease spread

“Each rule has its exception” 2 rules with 2 exceptions

Legislative limits on Vaccination

Dir. 92/119 artc.19: Preventive Vaccination in EU is not allowed

Dir. 92/119 artc.19: Emergency Vaccination may implemented as a supplementary control measure taken when the disease broke out

No marketing authorization of LSD vaccines in Greece or in EU

Dir. 2001/82 artc. 5: Veterinary medicinal products are not allowed to be placed on the market of a MS, unless a marketing authorization has been granted by the CA of that MS.

Dir. 2001/82 artc. 8: In the event of serious epizootic diseases, Member States may provisionally allow the use of immunological veterinary medicinal products without a marketing authorization, in the absence of a suitable medicinal product and after informing the Commission of the detailed conditions of use.

Homologous live attenuated virus vaccines: “Lumpy Skin Disease Vaccine for Cattle”, Onderstepoort Biological Products,

OBP, South Africa (Neethling type) 2 ml/per dose, subcutaneous “Lumpyvax” by MSD Animal Health-Intervet, South Africa (SIS type) 1 ml/per dose, subcutaneous Compulsory vaccination of all susceptible species (cattle, buffaloes)

Vaccination from age 0 according to the instructions (animals from unvaccinated cattle)

28 days standstill of vaccinated animals (3 weeks to full disease protection +1

week to cover the maximum disease incubation period)

Annual booster vaccination An electronic application (online database) has been developed for

registration of vaccinated animals and farms (connected with the central data base of Reg. 1760/2000)

Vaccines

Vaccination Plan Vaccination Started: on 5/09/2015 RU Evros after the first confirmation of LSD: 20/08/2015 RU Evros At the beginning around the outbreaks in affected Regional Units Xanthi, Rodopi, Kavala, Chalkidiki, In October 2015 creation of buffer zone in free areas and progressive

extension according to the availability of the vaccines 1st Priority: Thessaloniki, Drama, Serres, Kilkis, 2nd Priority: Imatia, Pella, Pieria

In May 2016 when the disease crossed the buffer zone: The Vaccination of total mainland firstly and the islands later decided Vaccination Campaign is under the official control of the Veterinary

Authorities

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

5,000

5,500

6,000

6,500

7,000

7,500 5

/9/2

015

14/

9/20

15 2

7/9/

2015

6/1

0/20

15 1

6/10

/201

5 2

6/10

/201

5 4

/11/

2015

13/

11/2

015

22/

11/2

015

1/1

2/20

15 1

0/12

/201

5 1

9/12

/201

5 3

0/12

/201

5 1

2/1/

2016

22/

1/20

16 2

/2/2

016

12/

2/20

16 2

1/2/

2016

1/3

/201

6 1

1/3/

2016

21/

3/20

16 1

/4/2

016

11/

4/20

16 2

0/4/

2016

29/

4/20

16 1

1/5/

2016

20/

5/20

16 3

0/5/

2016

8/6

/201

6 1

7/6/

2016

26/

6/20

16 5

/7/2

016

14/

7/20

16 2

4/7/

2016

2/8

/201

6 1

1/8/

2016

20/

8/20

16 2

9/8/

2016

7/9

/201

6 1

6/9/

2016

25/

9/20

16 4

/10/

2016

13/

10/2

016

22/

10/2

016

31/

10/2

016

9/1

1/20

16 1

8/11

/201

6 2

7/11

/201

6 6

/12/

2016

15/

12/2

016

24/

12/2

016

Num

ber

of

Vacc

inat

ions

Dates

Vaccination Campaign (August 2015- Dec 2016) Number of Vaccinations per Day in Greece

467 days of Vaccination / ~ 690.000 vaccinations Vaccinations per day 1.462 mean (2min, 7.507 max)

Vaccination Coverage Dec 2016

50-69% coverage 70-94% coverage

95-100% coverage

50-69% coverage 70-94% coverage

95-100% coverage

Less than 50%

Adverse Effects and Reactions to the Vaccine

Common expected findings (Information provided by vets and farmers)

• Oedema and pain around the point of injection • Local reactions with nodules around the point of injection • Dairy Cattle seems to be more sensitive to develop local reactions • Drop of milk production • Abortions

Cases of generalized symptoms

During 2015- 2016 221 outbreaks have been confirmed 69 concerned vaccinated animals

62 outbreaks suspicion was notified less than 28 days post vacc.

4 outbreaks, the suspicion notified 30 to 52 post vacc. 1 outbreak 5 months post vacc (1 infected / 379 animals)

2 outbreaks concerned calves coming from vaccinated cattle

3 out of 69 outbreaks vaccine strain was indentified, all the others were field strains

Stamping out was implemented to all bovine animals in the herds (pick period of the epizootic, risk to wait 21 days the results of sequencing and phylogenetic analysis)

2 suspicions : the vaccine strain identified and the measures lifted

The analysis of data are still in progress

Practical Aspects-Difficulties-Limitations Official Control and Supervion by the Veterinary Authorities

The whole procedure of vaccination is under the control of the official veterinary authorities (delivery at the airport, storage, distribution, vaccination, destroy of residual quantities)

High costs for Veterinary Authorities Managerial difficulties, coordination, control Strict Measures for vaccinated animals : Restrictions of the movements: animals were not allowed to be dispatched

outside vaccination area 28 days post vaccination standstill Restriction to trade activities of live bovine animals, their products, animal by-

products Unwillingness of stakeholders to implement vaccination Uncertainties and lack of information complicated the decision making

Challenges for the future Effectiveness of Vaccination

Experience shows that vaccination is the only effective measure against the disease especially preventive vaccination But to what extend ? When ?? and for how long ? According to which criteria? Is the absence of the outbreaks a verification of the absence of the LSD? Subclinical Cases, Mild Clinical Signs, Animals not develop Immunity, Under notification Clinical examination is the only available tool to estimate in large scale the situation on the field Scientific Research

• effective and safe vaccines • vaccines support DIVA protocol • vaccine vs field strain:Greek NRL: DIVA Real Time PCR • presence and excretion of vaccine strain • immune response to vaccination • duration of immunity • immunity in calves • Viraemia in vaccinated animals

Acknowledgements Many thanks to all colleagues of Veterinary Authorities of

Orestias, Evros, Xanthi, Limnos, Rodopi, Kavala, Chalkidiki, Thessaloniki, Serres, Kilkis, Drama, Pella, Imathia, Pieria, Kozani

Special thanks to: Achilleas Sachpatzidis (Director, Directorate of Veterinary Medicine of the East

Macedonia and Thrace Region) Evaggelia Plevraki and Maria Topkaridou (Veterinary Service of S.Evros) Evaggelos Tsiamadis and Stefanos Moraitis (Veterinary Service of Thessaloniki) Konstantia Tasioudi, Eirini Agianniotaki, Peristera Iliadou (NRL) Thomas Alexandropoulos (Chief Veterinary Officer) Ioannis Malemis (National Organization for Medicines) Chryssoula Dile (Director of Animal Health Directorate) Last but not least: The colleagues at DG SANTE of European Commission for their support The colleagues of Community Veterinary Emergency Team for their presence on

the spot and contribution Kris De Clercq and Coda- Cerva Laboratory International Atomic Energy Agency (IAEA), for training laboratory staff and

providing reagents

Thank you for your attention

Contact Details Department of Infectious and Parasitic Diseases Animal Health Directorate Directorate General of Sustainable Animal Production & Veterinary Medicine Ministry of Rural Development and Food Address: Veranzerou 46 str, Athens, Greece Email: seantoniou@minagric.gr Website: www.minagric.gr