Towards operational use of BCG vaccine in possums and cattle in New Zealand Graham Nugent 1, Jackie Whitford 1, Ivor Yockney 1, Frank Aldwell 2, Bryce Buddle 3 1.Landcare Research, Lincoln 2.Centre for Innovation, Otago University, Dunedin 3.AgResearch, Hopkirk Research Institute, Palmerston North Research contracted by Animal Health Board and the Foundation for Research, Science and Technology

Outline NZ bovine tuberculosis (TB) control context –Declining TB in livestock –Test-and-cull of livestock + Intensive lethal control of possums = TB control norm –Future: Containment vs eradication Background research –Vaccine Efficacy in possums –Modelling predictions Current/proposed large-scale operational tests of the efficacy of BCG vaccine in protecting cattle and possums from Tb.

Strategic context - potential for vaccination Test-and-cull plus lethal possum control have reduced livestock TB by 92% since 1994 Not sufficient funding to attempt to simultaneously eradicate TB from all affected areas → Eradication in some areas but containment in others

What is containment? Strategy for where the number of livestock at risk is low but large TB+ve possum popn nearby makes the cost per cow protected very high. One management option: Conduct some possum control on and near farm, but accept that some TB possums will still disperse from deep forest onto farmland →Creates inevitable risk of ongoing infection in cattle Alternative management option =>Vaccinate cattle and/or vaccinate possums near farmland

Cattle lipid-BCG trial AIM: To determine whether oral lipid BCG reduces the incidence of TB in cattle sympatric with infected possums? 4yr trial from Feb 2009

Cattle vaccination trial: Study site Remote part of the N South Is –one of the last large farmed Tb areas with an uncontrolled possum population

Livestock TB levels c.10% of livestock have TB when slaughtered at 2.5yrs of age

Wildlife TB Levels All 4 major wildlife hosts unmanaged, fully sympatric with cattle and long infected with TB Indicates high natural force of infection at our study site.

Cattle trial design and schedule Cohort and vaccination date TreatmentsSlaughter 2.5 yr cattle (n = 90) Feb 2009 Subcut 10^6 vs oral 10^8 vs control yr cattle (n = 170) April 2009 Oral 10^8 vs control yr calves (n = ) Sep 2009 Oral 10^8 vs control yr calves (n = ) May 2010 ? vs control 2012

Vaccination and skin test reactivity N skin tested after 8 weeks % Skin test positive % Skin test +ves blood +ve* No BCG929%37% (3/8) BCG 10 8 cfu (oral)2245%0% (0/10) BCG 10 6 cfu (subcut)1968%0% (0/13) * Blood tested with BCG-specific antigens Some TB in no-BCG cattle not detected by first skin test + some false positives? Marked increase in reactivity with vaccination – more with subcutaneous than oral despite the higher dose Is there an oral dose that produces very little reactivity but still protects against TB?

Preliminary results 1- (April 1.5yr old cohort) In April 2009, 281 animals subsumed into trial cfu lipid BCG non-vaccinated controls In Feb 2010, 139 of these cattle both skin tested and blood tested 20% (18/86) vaccinates skin-test positive, - all reactions minor (range 1-4mm) and - None blood test positive 9.4% (5/53) of the non-vaccinates skin test positive, - all reactions >2mm (range 2-8mm). five non-vaccinates blood test positive (4 ST +ves, 1 ST –ve).

Preliminary results 2 Difference in BT+ves significant (Fisher’s Exact Test, p = 0.007). –vaccinates (0%) and non-vaccinates (9.4%) => V preliminary indication oral vaccine has very high efficacy in ~ 2y cattle? Level of false skin test positivity lower after 10 months All five blood-test positive animals were male. => Are ~2yr males more prone to TB than females?

Parallel possum trial planned –same site –projected start in 2011 Aim: To compare the effect on TB levels in possums (and in wildlife generally) of; – lethal control alone, –oral (lipid BCG) vaccination alone, –lethal control + vaccination combined, –Doing nothing ( = control) All actual treatments applied at same cost Possum trial

Background (1) Orongorongo trial (Tompkins et al 2009). –protection (95% efficacy) of wild possums from natural TB for 1 y. – with lipid BCG orally administered at fixed dose to already captured possums –Effective but impractical solution for operational use  Need to test efficacy against wild possums with free choice baiting (ideally aerially delivered)

Background (2) Lethal control by aerial poisoning is highly effective →$20-30/ha to deliver >200 lethal doses and >95% kills →Instant reduction in possum TB →cf no immediate change with vaccination →Not greatly constrained in NZ (yet) Vaccination only worthwhile if lethal control banned? OR possibly if it can be combined with lethal control => USED modeling to determine viability of combined use

Strategies for possum TB control Predictions of a spatial model vaccination alone much slower and expensive cull alone fastest,cheapest, but cull+BCG close; – esp if cull survivors can be vaccinated at same time at no extra cost Ramsey D, Efford M [sub] The cost-effectiveness of vaccination strategies for the control of bovine tuberculosis in brushtail possums in New Zealand: predictions from a spatially-explicit, individual-based model. J Appl. Ecol

A B A D C C B D Design schematic 4 Treatments x 2 A = no control B = BCG only C = BCG + light cull D = Intensive cull only 3 km 1000 ha per block

Monitoring outcomes TB in possums is rare (1-2% prevalence) →Will be difficult to show between-treatment differences statistically Three complementary approaches → Use of released pigs as GPS-collared sentinels to compare trends over three years → Use of released GPS-collared TB+ possums and focal kill outs of all residents within contact → Entire-area complete trap out and necropsy

Some preparatory steps 1 Delivery of lipid bait in sachets – Muzzle acceptance trial  Wholly eaten at six sites occasions → but total only 9 baits eaten  Some possums only eating part of bait  8 adult possums trapped → all RB marked (but two backriders not marked)

Some preparatory steps 2 Development of much more realistic challenge model Experimentally infected Naturally infected Injection of paws

Summary Not enough $$$ for simultaneous eradication of possum TB everywhere – esp. since cheapest tool (aerial 1080) is under threat NZ developing BCG vaccination as a complementary option, esp. for TB containment scenarios –Moving to be ready to operationalise the technique to reduce TB- possum flow through containment buffers, and to reduce outbreaks in cattle caused by immigrant TB possums

Special thanks… Colin and Tina Nimmo, Muzzle Stn Paul Livingstone, Kevin Crews, Scott Loeffler, AHB Duncan Beattie, Assure NZ Geoff de Lisle, Gary Yates, AgResearch