www.nr.no Space-time modeling of the spread of a disease between marine fish farms Magne Aldrin, Norwegian Computing Center and the University of Oslo Ragnar Bang Huseby, Norwegian Computing Center in collaboration with the National Veterinary Institute and with A. Frigessi and others at the University of Oslo INFER March 2011 Similar ideas used in work on • Foot-and-mouth disease • Swine fever virus • Hospital infections 1 The aquaculture industry • In Norway: Export value of farmed fish > export value of wild fish! • 1200 fish farms in Norway, spread along the coast, mostly producing salmon 2 Industry threatened by infectious diseases • Infectious Salmon Anaemia (ISA) epidemics: ? Scotland 1999: cost 100 million £ ? Shetland 2009: cost 40 million £ ? Chile 2008: 7000 jobs lost 3 Norway: 70 ISA outbreaks 2003-2009 0°0' 10°0'E 20°0'E 30°0'E a Probability of infection from neighbourhood versus other sources 70°0'N Neighbour Other 65°0'N ± 60°0'N 100 Kilometers 10°0'E 20°0'E 4 ISA outbreaks in Troms 2007-2009 17°0'E Most likely infection pathway a Probability 0 - 0,25 0,25 - 0,5 0,5 - 0,75 69°10'N 0,75 - 1 69°0'N 68°50'N 68°40'N ± 5 Kilometers 17°0'E 5 Data • Monthly data 2003-2009 • Information on all farms active in this period ? Biomass of fish, tells when a farm is active ? Sea distances between all farms ? Local contact networks between all farms (same ownership, may share staff and equipment) 6 Three diseases Marine Environment and Health Series No. 22, 2005 _______________________________________________________________________________________________ 2 PANCREAS DISEASE IN IRELAND: EPIDEMIOLOGICAL SURVEY RESULTS FOR 2003 AND 2004 Hamish Rodger & Susie Mitchell • Information on outbreaks of three diseases ? When and where ? 500 HSMI ? 300 PD ? 70 ISA • No information on infection time, except infection time < outbreak time Vet-Aqua International, Oranmore Business Park, Oranmore, Co. Galway 2.1.Introduction Pancreas disease aetiology & clinical disease Pancreas disease (PD) is an infectious viral disease of marine stage farmed Atlantic salmon (Salmo salar) that was first described by Munro et al. (1984) in Scotland. The disease has been reported in Ireland (1984), Norway (1985), France (1986), USA (1987) and Spain (1989) (Kent & Elston, 1987, Raynard et al., 1992) with the most serious impacts from the disease reported in Ireland, Norway and Scotland. The causal agent of the disease is an atypical alphavirus, the salmon pancreas disease virus (SPDV), of which there appear to be at least two subtypes (Hodneland et al., 2005, Weston et al., 2005); one subtype is associated with PD in Scotland and Ireland and another is associated with PD in Norway. A third salmonid alphavirus, very closely related to SPDV, and known as the sleeping disease (SD) virus, causes a similar condition in rainbow trout (Oncorhynchus mykiss) in freshwater and is reported in France, Italy, Germany and the UK (Castric et al., 1997, Bergmann et al., 2005). The name salmonid alphavirus (SAV) has been proposed for these closely related viral isolates (Weston et al., 2002). Infection with these viruses can lead to clinical disease due to acinar pancreatic necrosis and fibrosis as well as a range of myopathies (cardiac, skeletal, oesophageal) (Ferguson et al., 1986, Rodger et al., 1994, McLoughlin et al., 2002). Clinically affected fish present with lethargy, anorexia and increased mortality. Mortalities can reach over 40% in affected pens and failure to thrive is a further consequence of the disease resulting in poor condition, thin fish that are susceptible to parasitism and secondary bacterial disease (Figure 1). Figure 1: Three salmon from a pen affected by pancreas disease (PD) in Ireland with the top two fish exhibiting low condition factor, typical of those affected by chronic PD. In a farm affected by PD, the majority of fish will exhibit pancreatic regeneration and recovery and appetite then returns. However, in fish affected by the later developing and longer lasting myopathies, further mortalities can then ensue when the fish exhibit a strong feeding response (Rodger et al., 1991), probably due to either cardiac muscle exhaustion, further exertional 7 Basic data unit in our modeling • Fish cohort: A group of fish at a fish farm • Stocked at some time and slaugthered/removed 2-3 years later • Only one cohort at a fish farm at a time • During some years a farm have several subsequent cohorts • Note: we do not consider individual fish 8 Susceptible and infectious cohorts susceptible a) stocked removed susceptible time infectious b) stocked infected susceptible visible outbreak removed time infectious c) stocked infected removed time 9 Two sub-models • Infection process - but infection time unobserved ? Infection rate λ • Outbreak process - outbreak time observed ? Outbreak rate γ 10 Model overwiev Fixed and known time Susceptible λ Infected and infectious Fixed and known time Removed γ Visible outbreak of disease Fixed and known time 11 Infection model Additive-multiplicative model for the total infection rate (intensity) for fish cohort i at time t λi(t) = Si(t) · κsi(t) · [λdi(t) + λci(t) + λpi(t) + λoi(t)] 12 Multiplicative terms • Si(t) is an at-risk indicator, which is 1 when fish cohort i is susceptible and 0 otherwise • κsi(t) is a factor proportional to the susceptibility of fish cohort i, dependent on ? size of the fish cohort (number of fish) ? sea temperature ? season 13 Four transmission pathways • λdi(t) - Transmission from infected fish cohorts at neighbouring farms, dependent on seaway distance to infected fish cohorts • λci(t) - Transmission from infected fish cohorts at farms in the same local contact network (e.q. same workers) • p λi (t) - Transmission from previous infected fish cohorts at the same fish farm i (e.g. remaining disease agent) • λoi(t) - Transmission via other, non-specified, pathways 14 Neighbourhood transmission λdi(t) The sum over the individual contributions from all other fish cohorts X λdi(t) = λdij (t) j6=i 15 Contribution from fish cohort j λdij (t) = Ij (t) · exp(−φ · dij ) · κij (t) • Ij (t): an indicator variable that is 1 if salmon farm j is infectious at time t, and 0 otherwise • dij : the seaway distance between fish cohorts i and j, i.e. the distance between their farms • φ: parameter - the effect of the seaway distance • κij (t): a factor proportional to the infectiousness of fish cohort j, dependent on ? the size of fish cohort j ? the time since it was infected, based on a SIR model 16 Outbreak model The outbreak rate for fish cohort i at time t γi(t) = Ii(t) · γi∗(t) • Ii(t) is an at-risk indicator, which is 1 when fish farm i is infected and yet not slaugthered and 0 otherwise • γi∗(t) a smooth function of time since cohort i was infected, based on a SIR model 17 A Bayesian data augmentation approach • Outbreak times are observed data, Dobs • Infection times are missing data, Dmis • Parameters θ Posterior p(Dmis, θ|Dobs) ∝ p(Dobs, Dmis|θ) · π(θ) 18 Probability density p(Dobs, Dmis|θ) • Contributions from each infection process: Z t∗ λi(t∗) · exp(− λ(t) dt) if infection occurs at t = t∗ tstart Z tend exp(− λ(t) dt) if cohort i is never infected tstart • Similar contributions from the outbreak processes 19 Priors • Mostly vague priors for the parameters, but some restricted to be non-negative • For some parameters, the possibility of zero effect is of special interest ? E.g. prior for the distance parameter φ: ∗ P (φ = 0) = 0.5 - i.e. no effect of seaway distance between fish cohorts (farms) ∗ P (φ > 0) = 0.5 and then φ ∼ Uniform(0,large number) 20 Estimation • 15-30 parameters with priors • More than 3000 cohorts with unknown infection times • Markov Chain Monte Carlo techniques 21 Results - Posteriors for HSMI Posterior 95 % cred.int. mean low high Mean time from infection to outbreak 2.7 2.1 3.4 - given visible outbreak months % of cohorts infected 20 18 22 % of infected cohorts with outbreak 76 70 82 22 Effect of sea temperature and season 0 2 4 6 8 12 A farm in Southern Norway 2006 2 4 6 8 10 12 months in year 23 Effect of distance - φ 40 Phi Relative infection rate 0 0.00 10 0.04 20 30 0.08 Prior Posterior 0.00 0.02 0.04 0.06 0.08 0.10 0 20 40 60 80 100 seaway distance (km) to infectious farm 24 Effect of time since infection 0.0 0.4 0.8 on infectiousness in the infection process and on the outbreak rate 0 5 10 15 20 months since infection 25 Relative importance of transmission pathways Proportion of infections related to neighbourhood transmission: average the following expression over all infections p d d c λi (t)/(λi (t) + λi (t) + λi (t) + λoi(t)) Similar definitions for the other pathways Pathway Neigbourhood 54 Relative importance in % Contact network 18 Previous cohort 9 Other 19 26 Potential use of models for spread of diseases • Better understanding of infection processes • Tracing transmission routes • Estimating the protective effect of vaccination, given data on vaccination • Investigating the effects of potential interventions by scenario simulations - what-if ? the accumulated effects of vaccination on a network of fish farms for a specified effect of the vaccine ? the effect of re-locations of fish farms 27 References • Aldrin, Lyngstad, Kristoffersen, Storvik, Borgan, Jansen (2011). Modelling the spread of infectious salmon anaemia (ISA) among salmon farms based on seaway distances between farms and genetic relationships between ISA virus isolates. To appear in the Journal of the Royal Society Interface. • Aldrin, Storvik, Frigessi, Viljugrein, Jansen (2010). A stochastic model for the assessment of the transmission pathways of heart and skeleton muscle inflammation, pancreas disease and infectious salmon anaemia in marine fish farms in Norway. Preventive Veterinary Medicine, Vol. 93, p. 51-61. • Scheel, Aldrin, Frigessi, Jansen (2007). A stochastic model for infectious salmon anemia (ISA) in Atlantic salmon farming. Journal of the Royal Society Interface, Vol. 4, p. 699-706. 28 Salmon Farming Industry ThanksHandbook for your 2009 attention! The Marine Harvest Salmon Industry Handbook The purpose of this document is to give financial analysts and investors a better insight into the salmon farming industry and in Marine Harvest’s view the most important value drivers. Our intention is to update and publish this document annually. Enjoy your lunch today! 29