Preventive Veterinary Medicine 117 (2014) 295–300

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Short communication

Effectiveness of the BSE interventions in Japan Katsuaki Sugiura a,∗ , A. Benedictus b , H. Hogeveen b a Department of Global Agricultural Sciences, Graduate school of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan b Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, The Netherlands

a r t i c l e

i n f o

Article history: Received 28 February 2014 Received in revised form 17 June 2014 Accepted 23 June 2014 Keywords: BSE Effectiveness Food safety Stochastic model Japan

a b s t r a c t Using a stochastic simulation model, we estimated the effectiveness of the three BSE interventions (SRM removal, post-mortem testing and cohort culling) in Japan, in terms of the amount of bovine ID50 that would be prevented from entering the human food supply and the number of life years that would be saved from resulting vCJD cases. The average reduction of the BSE load on the human food supply under SRM removal was 97% over the period from 2002 to 2009. The average reduction of the BSE load under most-mortem testing was 83% over the period from 2002 to 2007. The risk reducing effect of the three interventions combined was 99%. The maximum number of life years saved by the three interventions combined was 40.84 in 2006. © 2014 Elsevier B.V. All rights reserved.

1. Introduction BSE is a progressive and fatal nervous disease in adult cattle, which was first confirmed in the United Kingdom (UK) in November 1986. Epidemiological studies conclusively demonstrated that the cause of BSE was oral exposure to the BSE agent (Wilesmith et al., 1988). The vehicle of transmission is meat-and-bone meal (MBM), which is derived from unwanted animal slaughter products and fallen stock. Research established that the highest concentration of agent at the clinical stage of disease is in the central nervous system (CNS) with lesser amounts in some lymphoreticular tissues like, spleen, tonsil and Peyer’s patches in the distal ileum or any tissues contaminated by them. The latter tissues may be infected at an earlier stage of disease than the CNS and before clinical signs are evident. BSE attracted worldwide public concern in March 1996 when the UK Secretary of State for Health announced the

∗ Corresponding author. Tel.: +81 358415383; fax: +81 358415191. E-mail address: [email protected] (K. Sugiura). http://dx.doi.org/10.1016/j.prevetmed.2014.06.019 0167-5877/© 2014 Elsevier B.V. All rights reserved.

occurrence of the first 10 human cases, mostly in young people of a new form of CJD and a presumptive link to BSE. The most plausible exposure pathway is thought to be through consumption of meat products (e.g., mechanically recovered meat derived from the vertebral column) contaminated with BSE-infected tissue and in particular, CNS. The first case of BSE in Japan was confirmed in September 2001. The Japanese government’s position had been that the risk from BSE occurring in Japan was remote. When the first BSE case occurred, the BSE-crisis set in, with consumers having no confidence in the government’s plans to arrest the progress of the disease or to protect consumers from exposure. To restore public confidence, the Japanese government, with the view that the cost of any intervention could not be the major issue in any decisions, adopted a BSE control strategy composed of three elements. The first element of BSE control is the reduction of the incidence of new BSE infections by instituting a feed ban for animal protein supplements. From 18 September 2001, a ban on the domestic use of ruminant protein in ruminant feed was introduced (MAFF, 2001a). From 4 October

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2001, a ban on the importation and domestic use of all processed animal proteins (PAP) for the production of feed for ruminants, pigs and chickens and fertilizer was introduced (MAFF, 2001b). These interventions were not evaluated in this paper because they were taken to protect primarily animal health and would have only an indirect and delayed effect on public health. The second element is the monitoring of BSE prevalence. From 18 October 2001, all slaughter cattle of all ages are screened for BSE by a rapid test to detect prion protein PrPSc in the brain (MAFF, 2001c). Testing of all fallen-stock animals was introduced in April 2004. The screening of slaughter cattle and fallen-stock is done by prefectural laboratories and non-negative samples are sent to national reference laboratories for confirmatory diagnosis. Slaughter animals are not allowed to leave the slaughterhouses until the test is completed. The third element if BSE control is the prevention of BSE infectivity entering the human food supply. Any BSE case that is detected as a result of testing at slaughter houses is disposed of and incinerated. The age and feed cohorts of any positive animal (animals that were born in the same year or were fed protein supplements from the same source) are identified, culled, tested for BSE and incinerated. In addition, specified risk materials (SRMs) from all cattle slaughtered for human consumption are removed and incinerated from 27 September 2001 (MHLW, 2001). SRMs are those tissues that are considered to contain the BSE agent in a BSE infected animal, and includes the brain, the spinal cord, eyes and the distal ileum and expanded later to include the vertebral column. With the declining BSE incidence in Japan, the question is raised whether these stringent measures are still justified. The purpose of this study was to evaluate the cost-effectiveness, defined as the costs per human life year saved, of BSE interventions in Japan. We used a stochastic simulation model developed by Benedictus et al. (2009). We adjusted and reparameterized their model according to the Japanese situation. 2. Materials and methods

(TD) and non-detectable BSE cases (TND). TC animals were not included in the calculation of the load on the human food supply, because they would not have entered the human food supply anyway. Apart from those described below we used the same assumptions and parameter values as in the model by Benedictus et al. (2009). 2.1.1. Load on the food supply caused by detectable BSE-infected animals at slaughter houses The load on the human food supply, formed by a testdetectable animal j (LFS TDj ), was estimated by:

5 i=1

LFS TDj =

Organ Weighti × Organ Titeri × Ri 2SC /2

where Organ1 –Organ5 are brain, spinal cord, trigeminal nerve ganglia (TRG), dorsal root ganglia (DRG) and distal ileum respectively. Ri is a reduction parameter, representing the weight-proportion of a particular organ entering the food supply. SC represents the time (in months) preceding clinical onset. The titer doubling time in clinical BSE animals was assumed to be two months (EFSA, 2005). The assumed values of the weight and titer of organs are shown in Table 1. 2.1.2. Load on the food supply posed by non-detectable BSE-infected animals The load of the food supply posed by a non-detectable BSE-infected animal j, LFS TNDj was estimated by:

5 LFS TNDj =

i=1

Organ Weighti × Organ Titeri × Ri 2SSD /2

where SSD represents the time (in months) preceding clinical onset, and the value for each animal was randomly selected from a uniform distribution between the values of 3 and 39 months inclusive. The non-detectable cases related to a test-detectable case j were assumed to be in an incubation stage 3–39 months before clinical onset. The titer doubling time for non-detectable BSE animals was assumed to be two months in the same way as for clinical BSE animals (EFSA, 2005).

2.1. Model description We assumed there are three types of BSE-infected animals: test-detectable BSE infected cattle at rendering plants (TC), test-detectable BSE cattle at slaughterhouses

2.1.3. Total load on the food supply posed by detectable and non-detectable BSE-infected animals The total amount of ID50s entering the food supply in a non-intervention scenario in a given year can thus be

Table 1 Total mass weight, tissue infectivity in clinical BSE cases and infectivity reduction parameters before and after SRM removal. Tissue

Brain Spinal cord Trigeminal nerve ganglia Dorsal root ganglia Distal ileum a b c

Total massa (g)

500 200 20 30 800

Tissue infectivity in clinical BSE case (CoID50/g)

50 50 50 50 5

Proportion of organ entering food safety Pre-interventionb (R)

Under SRM removalc (R SRM)

0.164 0.086 0.172 0.086 0.914

0.0002 0.004 0.0 0.000 0.05

Total mass weight and infectivity of tissues are based on LFRA and MLC (1997) and EFSA (2011) reports. Reduction factors before SRM removal were estimated based on the result of interviews and questionnaires to meat distributors. Reduction factors under SRM removal were based on Comer (1997).

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Table 2 Input parameters and values and probability distributions used in the model. Parameters

Abbreviations

Values and distributions

Sources

Total number of BSE cases detected

N

MHLW (2012a)

Number of BSE cases detected at slaughter

N SL

Number of cohort animals culled

C

Incubation stage of detected cases (months preceding clinical onset) Incubation stage of detected cases (months preceding clinical onset) Total number of bovine ID50s that entered British food supply in 1980–2003 Total expected number of vCJD cases in the UK

SC

2, 4, 5, 7, 10, 3, 1, 1 from 2002 to 2009 respectively 2, 4, 3, 4, 4, 2, 0, 0 from 2002 to 2009 respectively 89, 300, 91, 83, 177, 38, 5, 6 from 2002 to 2009 respectively Uniform[0,3]

SCS

Uniform[3,39]

F boID50

54,000,000

Ncases

Pert[163,500,1000]

LYL

Normal [56.6, 12.1]

Ratio MM

Beta(165, 16)/Beta(40, 68)

Number of life years lost due to occurrence of vCJD Genetic ratio of likelihood of Japanese people over British people contracting vCJD

expressed as the sum of detectable and non-detectable infectivity: LFS =

N SL  j=1

LFS TDj +

3×N 

LFS TNDj

MAFF (2008)

EFSA (2005), Ferguson and Donnelly (2003) EFSA (2005) Ferguson and Donnelly (2003) Sneath (2004), Cooper and Bird (2003) Andrews (2012), MHLW (2012b) Collinge and Palmer (1991), Doh-ura et al. (1991)

of the British people (Beta(40, 68)) having gene encoding prion protein with codon 129 methionine homozygotes (Doh-ura et al., 1991; Collinge and Palmer, 1991), assuming that people with this genotype present more susceptibility to or shorter incubation period of vCJD.

j=1

where N SL is the number of BSE positive animals detected by post-mortem testing at the slaughterhouses in a given year. N is the total number of BSE cases reported in that year. We assumed that for every test-positive BSE case, there were three non-detectable BSE animals slaughtered for human consumption (EFSA, 2005). 2.1.4. Link between vCJD and BSE infectivity entering the food supply The transmission risk, expressed as the number of life years lost (LYL) per bovine ID50, posed to humans from the consumption of BSE contaminated products, was calculated by: RISK =

MHLW (2012a)

Ncases × LYL × Ratio MM F boID50

where Ncases is the total predicted number of vCJD cases in the UK, LYL is the amount of life year lost per vCJD case, F boID50 is the amount of infectivity that enter the food supply in the UK, and Ratio MM is a genetic likelihood ratio of Japanese people contracting vDJD over British people. The distributions used for Ncases , LYL and F boID50 are shown in Table 2. The average age of death in a vCJD case is 28 years (Andrews, 2012). The average life expectancy of a 28 year old in Japan is 56.6 years (MHLW, 2012b). The number of life years saved as the result of the prevention of one vCJD case was assumed to take a Normal distribution with 56.6 years as the mean and a standard deviation of 12.1 years, based on the Life Table for 2011 of the Japanese people (MHLW, 2012b). We calculated Ratio MM as the ratio of proportion of the Japanese people (Beta(165, 16)) to that

2.2. Effect of BSE interventions BSE interventions aim to reduce the amount of BSE infectivity that would enter the food supply as a result of slaughtered BSE-infected animals. For every intervention, the effect was calculated in terms of the amount of bovine ID50 prevented from entering the food supply. This amount was then converted into the number of life years saved by using the transmission risk of BSE described in Section 2.1.4. 2.2.1. SRM removal Removal and disposal of SRM in all cattle slaughtered for human consumption will result in a decrease of carcass infectivity entering the human food supply. In the model, this reduction was accommodated by adjusting the organspecific reduction parameter Ri . The values for reduction parameter Ri used in the baseline model, represents the proportion of a given organ that would enter the food supply in a pre-BSE situation, and were estimated based on the result of interviews and questionnaires to meat distributors conducted by the authors in January 2013. In Japan, 34% of bovine carcass and organs are distributed through wholesale markets and the rest through local meat centers (MAFF, 2012). As a result of interviews and questionnaire survey, it was found that 6.7–10.0% of brains, and 50% of spinal cord, dorsal root ganglia and distal ileum were transacted for human consumption in the Tokyo Wholesale Meat Market before SRM removal was introduced in 2001. Likewise, 85–90% of brains, and 100% of spinal cord, dorsal root ganglia and distal ileum were transacted for human

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Table 3 BSE load of the human food supply in different scenarios for the year 2002–2009 in terms of the amount of bovine ID50. Scenarios

2002 Mean

5th–95th pct.

Mean

5th–95th pct.

Mean

5th–95th pct.

Mean

5th–95th pct.

Baseline scenario SRM removal Post-mortem testing (PMT) PMT and cohort culling SRM removal and PMT SRM removal, PMT and cohort culling

12,614 346 1517

8367–17354 230–476 36–4263

25,228 693 3034

19121–31859 525–875 382–6776

20,438 561 3793

14738–26698 405–733 692–7950

27,504 755 5310

20796–34749 571–954 1469–10136

691–7946

5307

1466–10130

1517

2003

36–4262

2004

3028

379–6767

2005

3791

42

1–117

83

10–186

104

19–218

146

40–278

42

1–117

83

10–186

104

19–218

146

40–278

Scenarios

2006 Mean

5th–95th pct.

Baseline scenario SRM removal Post-mortem testing (PMT) PMT and cohort culling SRM removal and PMT SRM removal, PMT and cohort culling

29,780 818 7586 7577 208 208

22560–37606 619–1032 2920–13228 2909–13219 80–363 80–363

2007 Mean 13,373 367 2276 2275 62 62

consumption in the Osaka Wholesale Meat Market before SRM removal was introduced. No SRM were transacted for human consumption at local meat centers. We assumed that the Tokyo and Osaka markets represent the wholesale market distribution in Japan and estimated the values for the reduction parameters as the weighted average of these proportions. The adjusted value R SRMi represents the proportion of an organ that would enter the food supply under SRM removal practices. As there is no data available about of the effectiveness of SRM removal, we used values estimated by Comer (1997), which is very close to zero for any organ containing BSE infectivity.

2008

2009

5th-95th pct.

Mean

5th-95th pct.

Mean

5th-95th pct.

8856–18412 243–505 160–5572 160–5572 4–153 4–153

759 21 759 759 21 21

2–2901 0–80 2–2901 2–2901 0–80 0–80

759 21 759 759 21 21

2–2909 0–80 2–2909 2–2909 0–80 0–80

untouched. Full-scale testing for BSE was modeled by setting the value of N SL to zero, assuming that all clinical and test-detectable animals were detected. As a result, load on the food supply under post-mortem testing practices was determined by the number of non-detectable slaughter animals.

2.2.3. Cohort culling The number of non-detectable BSE cases, based on the prevalence of these cases in the cohorts, was modeled by Binomial (C,PC ), where C is the number of cohort animals culled in a given year, and PC is the prevalence of nondetectable cases in the cohort. PC was assumed to be ten times higher than the prevalence of detectable cases in the total population, which was calculated from the total

2.2.2. Post-mortem testing Post-mortem testing prevents detectable animals from entering into food chain, leaving undetectable animals

Table 4 BSE load of the human food supply in different scenarios for the year 2002–2009 in terms of number of life year lost. Scenarios

2002

2003

2004

2005

Mean

5th–95th pct.

Mean

5th-95th pct–

Mean

5th–95th pct.

Mean

Baseline scenario SRM removal Post-mortem testing (PMT) PMT and cohort culling SRM removal and PMT SRM removal, PMT and cohort culling

17.42 0.48 2.09 2.09 0.06 0.06

6.32–32.73 0.17–0.90 0.04–6.62 0.04–6.62 0.00–0.18 0.00–0.18

34.86 0.96 4.20 4.19 0.12 0.11

13.42–63.21 0.37–1.73 0.41–10.92 0.40–10.90 0.01–0.30 0.01–0.30

28.22 0.77 5.24 5.24 0.14 0.14

10.67–51.75 0.29–1.42 0.70–12.97 0.70–12.96 0.02–0.36 0.02–0.36

37.96 1.04 7.32 7.32 0.20 0.20

Scenarios

2006

Baseline scenario SRM removal Post-mortem testing (PMT) PMT and cohort culling SRM removal and PMT SRM removal, PMT and cohort culling

2007

2008

Mean

5th-95th pct.

Mean

5th-95th pct.

41.13 1.13 10.48 10.47 0.29 0.29

15.82–74.33 0.43–2.04 2.64–22.72 2.63–22.70 0.07–0.62 0.07–0.62

18.47 0.51 3.14 3.14 0.09 0.09

6.75–34.71 0.19–0.95 0.18–8.83 0.17–8.82 0.00–0.24 0.00–0.24

Mean 1.04 0.03 1.04 1.04 0.03 0.03

5t–95th pct. 14.62–68.70 0.40–1.88 1.43–16.96 1.43–16.96 0.04–0.47 0.04–0.47

2009 5th-95th pct. 0.00–4.31 0.00–0.12 0.00–4.31 0.00–4.31 0.00–0.12 0.00–0.12

Mean 1.05 0.03 1.05 1.05 0.03 0.03

5th-95th pct. 0.00–4.33 0.00–0.12 0.00–4.33 0.00–4.33 0.00–0.12 0.00–0.12

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reported number of BSE tests performed in the given year and the number of detected animals in that year. To accommodate the effect of cohort culling, the number of non-detectable BSE cases was subtracted from N in the baseline scenario. 2.3. Scenarios The baseline scenario was tested against the intervention scenario for eight consecutive years from 2002 to 2009. The variables differing over the years, are the total number of BSE cases detected and the number of BSE cases detected at slaughter houses (N and N SL). For example, in 2005, 7 cases were detected, of which 4 were slaughter animals. This was represented in the model by using 4 as the value for N SL and 7 as the value for N. The simulation was performed using software @Risk 6.0 (Palisade) added into the spreadsheet software Excel 14.0 (Microsoft Corporation). Simulation was continued until convergence occurred. Convergence was met if the changes in standard deviation was

Effectiveness of the BSE interventions in Japan.

Using a stochastic simulation model, we estimated the effectiveness of the three BSE interventions (SRM removal, post-mortem testing and cohort cullin...
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