Small Ruminant Research Why Is It Important?

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1 Small Ruminant Research Why Is It Important? Julie Fitzpatrick Director of the Moredun Research Institute, Chair in Food Security, University of Glasgow Sheep Health and Welfare Group Annual Conference, Worcester, 21 st November 2012

2 Food Security Food security is the sustainable production of sufficient amounts of high quality, safe food required to underpin health and wellbeing of human populations world-wide

3 Food, Energy, Water and Climate Change: The Perfect Storm 7 Billion People by 2030; 9 Billion People by 2050 Professor Sir John Beddington, Chief Scientist

4 Global Temperature Changes IPCC (2007)

5 Climate Change Intergovernmental Panel on Climate Change ( 20% greenhouse effect due to agriculture - 50% CH 4, 70% N 2 0, 5% CO 2 Mitigation - 21% reduction in CH 4 attributable to improved management of ruminants feed, genetics, reproduction - Reducing impact of endemic (production) diseases

6 Climate Change Adaptation - Emerging and re-emerging pathogens - especially viruses - Zoonoses increase - Cross-species transmission - Changed disease patterns - Reducing the impact of emerging and exotic disease Image courtesy, Sandra Scholes, AHVLA

7 Bill and Melinda Gates Foundation and DFID GALVmed Disease Cattle Small Ruminants Poultry Endoparasites X X X Peste des Petits Ruminants (PPR) Contagious Bovine Pleuropneumonia (CBPP) X Ectoparasites X X X Trypanosomes X X Contagious Caprine Pleuropneumonia (CCPP) Cattle (especially dairy), Small Ruminants, Chickens Livestock Health, Livestock Genetics and Reproduction, Postharvest and Markets X X Newcastle Disease Goat Pox and Sheep Pox X X Rift Valley Fever (RVF) X X East Coast Fever X

8 Sustainable Intensification More food, fewer inputs, less waste Optimal use of natural resources, especially land lowland, upland, hill competition with other use Exploitation of technologies (old and new) Biological Efficiency is the answer

9 The Moredun Foundation Global Issues Food Security Climate Change Animal Health and Welfare Local Issues Policies and Policymakers Communities Environment

10 Large animal accommodation BBSRC valuation (2009) - 100m Moredun Scientific High security unit, including small animal containment Moredun Research Institute

11 Moredun Research Institute Mission: To lead in livestock health solutions for global food security

12 Biologically Efficient Farm Animals Vaccines Diagnostic Tests Disease Control Programmes Endemic (Production) Diseases

13 Vaccines Prevention is Better than Cure Barber s Pole (Haemonchus contortus) Brown stomach worm (Teladorsagia circumcincta) Caseous Lymphadenitis

14 Vaccine Against Haemonchus contortus Globally, the most important nematode parasite of sheep and goats Blood sucker Prefers warm climates Resistance to drugs a serious problem No vaccine for this or any other species of gut worm of any host

15 Life Cycle of Haemonchus

16 Vaccine to kill adult worms and stop egg laying?

17 Haemonchus Vaccine Gut ( hidden ) Antigen Approach Because Haemonchus feeds on blood, molecules on the surface of the worm s gut are appropriate vaccine targets

18 When surface proteins from the worm gut are injected into a sheep.. The sheep responds and makes antibodies (IgG) which circulate in the blood. If a vaccinated sheep gets infected, the parasites ingest blood so that antibodies bind to the worms intestines. The worms starve to death leading to greatly reduced egg output and worm numbers.

19 Low Dose Native Vaccine Mean cumulative faecal egg count (±se) Dose of native antigen / shot (ug) A dry grain of rice weighs about 22,000 ug!!

20 Machine for rapid recovery of adult Haemonchus from infected abomasa Nematode Extraction System - NemESys Harvest 1Kg of worms from 200 infected lambs in<2hrs 0.4 million doses of vaccine in ~2 weeks by one person 2 mins`

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22 Haemonchus contortus Australian Sheep Trials Dr W. David Smith

23 How Close to Market? Long research phase > 5 million Fit with aims/objectives of commercial companies Not a recombinant vaccine Competition with existing products Not a main issue for EU Co-funding for commercialisation Registration costs

24 More trials with grazing calves, goats and ewes underway Nelore cattle In Brazil Boer Goats in South Africa Bergamasco ewes in Brazil Vaccine Developed in Scotland!

25 Teladorsagia circumcincta Vaccine Dr Alastair Nisbet, Professor Jacqui Matthews Cocktail of recombinant proteins from L4 larvae

26 Trial 1: 2010 Trickle infection, 2000 L3, 3 times per week Immunisation Post mortem Week Faecal egg counts

27 Trial 1. Faecal worm egg counts 200 Faecal egg count (eggs per gramme) Trickle infection start, day Day of experiment relative to first immunisation Cumulative Faecal Worm Egg Count Group 1 Trial 1 Sheep Group Group 2

28 CLA Vaccine Mean total score Mutated gene in bacterium increases iron regulated proteins Greatly reduced lesion burden in vaccinated animals G1 G2 G3 G4 G5 Treatment group DIVA gene deletion allows marker

29 How Close to Market? Teladorsagia A multi-valent recombinant nematode vaccine is a global holy grail Cost of combined research/commercial trials Return on investment for big pharma CLA Why no EU registration for existing product? Platform technology Use in other species e.g. pigs and Streptococcus suis Limitations of value of commercial sheep internationally

30 Diagnostic Tests Find it fast and deal with disease Sheep Scab

31 Diagnostic Test for Sheep Scab Psoroptes ovis Dr. Alistair Nisbet, Dr John Huntley, Dr Stew Burgess Clinical Disease Subclinical Disease?

32 Antigen identification by cdna library immunoscreening Trial serum Pick immunoreactive colonies Sequence Immunopositives Express recombinant protein Pso o 2 = Candidate Antigen

33 Experimental Infection Serological Results 1.0 IgG against mite antigen over time in experimental sheep 0.8 OD450nm T = weeks post infection mean of controls

34 Experimental Infection Serological Results P = OD 450nm pre-bleeds 6 wk exp

35 Outbreak Sample Analysis Clinical signs of sheep scab observed in 15 of 160 animals (ranging from mild to moderate) - majority of animals (145) showed no physical or behavioural signs of sheep scab infestation blood obtained ELISA results then used to determine the disease status of all animals throughout the outbreak All 15 showing clinical signs, were positive by ELISA Of the 145 animals which showed no clinical signs, 106 were positive by test! Post-treatment antibodies declined two months later, with some positive for longer Requirement to know if animals have been treated recently prior to testing

36 Sheep Scab Diagnostic Test Recombinant protein assay High sensitivity Pre-clinical, latent infestations High specificity Low +ves with chewing lice, ticks and gastrointestinal worms Sheep scab notifiable in Scotland Use in eradication or disease control programmes? Psoroptic mange in imported cattle recently ELISA developed; lateral flow under development

37 Vaccine Candidates Test antigens in vivo Cocktail of recombinants then individually Reduction in mite numbers Reduction in lesion size

38 How Close to Market? Is there a market for sheep scab diagnostic? Is there a market for sheep scab vaccine? Control or eradication? Treat or prevent? Cost of use Cost of development Head in the sand versus rapid diagnostics by farmers, vets and advisors

39 Disease Control Programmes Manage livestock for efficiency and sustainability Molecular Epidemiology

40 1617_HaeIII+1617_MboII+1617_AluI+1617_RsaI Enzootic Abortion - Genome Sequencing Project Dr. David Longbottom, Dr. Nick Wheelhouse European-wide survey on genomic diversity and molecular evolution of Chlamydia abortus in collaboration with The Wellcome Trust Sanger Institute Genomic sequencing and typing of >100 strains Lead to development of new typing tools (SNP based molecular phylogenomic analysis) Aid in the development of next generation vaccines and new diagnostic tools Greater understanding of molecular pathogenesis of EAE Strains of different geographical origin and host species 1617_all 1617_HaeIII 1617_AluI 1617_RsaI 1617_MboII LV350 T20 Zar-2B S124/3A 03DC36 C7/98 S82/3 DC4 C1/98 DC7 C17/98 C20/98 C9/98 C94/2 C10/98 03DC34 83/12 86/30 A22 AB7 C95/23 C95/27 H574 S26/3/#3 S3/3 S404/5 S507 S95/3 T17 C21/98 Krauss 15 Krauss 532 AO-4 T19 AO-7 S26/3/#2 Syva-1 T28 AO-2 Z339 C94/1 Krauss 53 S26/3 S26/3/#4 FAG S152/3 Krauss 8385 LLG POS DC1

41 Enzootic Abortion - Molecular Epidemiology Summary C. abortus was detected in 14 OEA cases from vaccinated flocks (Spring 2008) Wild-type C. abortus was identified in 9 of these cases The 1B vaccine strain was identified in placental samples from 5 OEA cases (2008) The vaccine genotype was only identified in samples from vaccinated animals In addition the 1B strain was identified in 3 samples submitted in 1994 (Enzovax trial) Identical mutations were present both in 2008 and 1994 which suggests the vaccine has not changed Use of modern technologies to solve problems

42 UK Small Ruminants and Global Food Security UK small country; big impact Sir John Beddington and Sir Robert Watson, May 2012 What is needed for global food security is Technology and Rural Development.

43 Moredun Staff Acknowledgements Scientific and Farming Collaborators national and international Scottish Government QMS Eblex Defra BBSRC Commercial companies