Comparison of the effectiveness of Neethling LSD and 10xRM65 sheeppox attenuated vaccines - The results of a randomized controlled field study Koret School of Veterinary Medicine Israel Veterinary services Kimron Veterinary Institute Hachaklait

1 Presented by Prof. Eyal Klement - Koret School of Veterinary Medicine …Before we start…

• RM65 vaccine – an attenuated sheep-pox vaccine manufactured by ABIC® and JOVAC® • Each dose contains a minimum of 102.5 TCID50 of freeze dried live attenuated sheep-pox vaccine • 1 ml administered S.C.

2 …Before we start…

• Neethling vaccine – an attenuated lumpy skin disease vaccine manufactured by OBP • Virus titer dose - 103.5 TCID50* • 2 ml administered S.C.

*According to registration file

3 Background

• A large LSD outbreak spreading mostly in the north of Israel from July 2012. • Initially, only beef herds were affected. • On October, first cases began to appear among intensive zero- grazing high producing Holstein dairy cattle herds. • Vaccination with attenuated RM65 sheep-pox vaccine did not seem to affect outbreak progression.

4 Previous Israeli experience with RM65 vaccine • Large outbreaks in RM-65 vaccinated herds in Israel:

5 Data regarding Neethling and 10XRM65 vaccines • No controlled clinical trial evaluating the effectiveness of these vaccines • Anecdotal data pointing of possible effectiveness of the Neethling disease for controlling LSD in South Africa • Anecdotal data stating the RM65 vaccine in a x10 dose is more effective than the regular dose

6 Study aim

• To compare the field effectiveness of 10XRM65 and Neethling attenuated vaccines for prevention of LSD

7 Vaccine preparation

• Neethling – According to manufacturer instructions. 2 ml injected S.C. • 10xRM65 – Use 1/5 of the diluent recommended by the manufacturer and inject 2 ml S.C.

8 Study population

• 15 dairy cattle herds located in the north of Israel • 4694 cows and 3756 calves and heifers • All herds vaccinated 3- 5 months previously with an RM65 attenuated vaccine

9 Study design

• Cows randomized according to skin number: – Even – Neethling – Odd – 10xRM65 • In 7 farms all calves were vaccinated with the Neethling vaccine • In 8 farms all calves were vaccinated with 10XRM65 vaccine

10 Surveillance

• All cattle in the herds were monitored daily by the herdsmen for any sign of LSD or other illness • Suspected illness was examined by the herd veterinarian twice weekly and informed immediately to the study veterinarian • When possible, the study veterinarian collected blood and skin specimen biopsies from affected animals

11 Case definitions

• LSD case – a cow/calve with at least one typical LSD nodule • Severe case - typical skin nodules accompanied by fever (>39.5 oC) or by a decrease in milk yield of over 20% • Laboratory confirmed case – identification of wild strain by PCR from either skin biopsy or blood (Menasherow S et al. J Virol Methods, 2014)

12 Results

• 82 cases occurred in 8 herds which included 5546 vaccinated cows and calves (incidence = 1.5%) • Among cows only the incidence was 76/3077 (2.5%)

13 Crude effectiveness (cows only)

• In 5 herds – higher morbidity in 10xRM65 vaccinees. • In 2 herds – Higher morbidity in Neethling vaccinees • In 1 herd – Equal morbidity • RRMH = 1.49 (0.92-2.41) • P-value for heterogeneity = 0.122

14 Crude effectiveness – severe cases

• Only cows - RRMH = 3.65 (1.59-8.35) • No significant heterogeneity

15 Accumulation of cases in time

16 Accumulation of severe cases in time

17 Effectiveness (cows)- >14 days post vaccination • 42 cases among 10xRM65 vaccinated cows (incidence=2.7%) vs. 13 cases among Neethling vaccinated cows (0.84%): RRMH=2.64 (1.44-4.82) • 20 cases among 10xRM65 vaccinated cows (incidence=1.3%) vs. 1 case among Neethling vaccinated cows (0.06%): RRMH=11.2 (2.3-54.7)

18 Effectiveness (cows)- Isolation of wild strain • 22 cases among 10xRM65 vaccinated cows (incidence=1.4%) vs. 6 cases among Neethling vaccinated cows (0.84%): RRMH=4.28 (1.59-11.53)

19 Neethling’s disease

• 9 confirmed cases out of 2356 vaccinated cows (incidence= 0.4%). Of these 1 severe case • All occurring within 14 days from vaccination • No Isolation of Neethling strain from a non- Neethling vaccinated cow

20 Final conclusions

• Relative effectiveness – Neethling vaccine is significantly more effective in preventing LSD. – Relative effectiveness for preventing LSD in cows when full immunity is anticipated (i.e. >14 p.v.) = 62% – Relative effectiveness for preventing severe LSD = 91% – Relative effectiveness for preventing confirmed LSD = 77%

21 …However…

• Neethling’s disease: – 0.4% incidence of Neethling’s disease durig the 14 days post vaccination. – Mostly non-severe disease – … though no evidence of transmission of the Neethling strain to non-Neethling vaccinated cows • Outbreak control – Outbreak was fully controlled with extensive use of both vaccines. – Therefore it is conceivable that 10xRM65 is also effective in preventing LSD

22 So...

• Which vaccine is better?

• It depends on… – Risk assessment – Epidemiological condition

23 Thanks

• Prof. Nahum Shpigel – Study initiation, design and conduction • Dr. Nadav Galon and veterinary services – study support, and vaccination performance • Dr. Yonatan Ben-Gera – Study conduction and data coordination • Dr. Yevegeny Chinitz and Dr. Yehuda Stram – virus isolation and identification • Dr. Benny Sharir, Hachaklait veterinarians – vaccination and clinical surveillance • Herdsmen

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