=Paper= {{Paper |id=Vol-1498/HAICTA_2015_paper11 |storemode=property |title=A Stochastic Simulation Model for the Efficacy of Vaccination Against Mycobacterium avium subsp. paratuberculosis in Dairy Sheep and Goats |pdfUrl=https://ceur-ws.org/Vol-1498/HAICTA_2015_paper11.pdf |volume=Vol-1498 |dblpUrl=https://dblp.org/rec/conf/haicta/KostoulasAL15 }} ==A Stochastic Simulation Model for the Efficacy of Vaccination Against Mycobacterium avium subsp. paratuberculosis in Dairy Sheep and Goats== https://ceur-ws.org/Vol-1498/HAICTA_2015_paper11.pdf
        A Stochastic Simulation Model for the Efficacy of
        Vaccination Against Mycobacterium avium subsp.
           paratuberculosis in Dairy Sheep and Goats

          Polychronis Kostoulas1, Elissavet Angelidou2, Leonidas Leontides3
    1
      Laboratory of Epidemiology, Biostatistics and Animal Health Economics, Faculty of
        Veterinary Medicine, University of Thessaly, Greece, e-mail: pkost@vet.uth.gr
    2
      Laboratory of Epidemiology, Biostatistics and Animal Health Economics, Faculty of
       Veterinary Medicine, University of Thessaly, Greece, e-mail: eaggel@vet.uth.gr
    3
      Laboratory of Epidemiology, Biostatistics and Animal Health Economics, Faculty of
       Veterinary Medicine, University of Thessaly, Greece, e-mail: leoloent@vet.uth.gr



        Abstract. We assessed the benefits of vaccination against Mycobacterium
        avium subsp. paratuberculosis (MAP) on the average daily milk yield (DMY)
        of sheep and goat flocks. A stochastic simulation model was used to estimate
        the DMY pre and post vaccination of the flock replacements. The average
        DMY increased steadily for the first ten years post vaccination and then
        reached a plateau. Medians for the DMY were significantly higher post
        vaccination. The expected difference between the prevalence of MAP infection
        between and after the initiation of the vaccination program was the most
        influential factor for the DMY benefits. Vaccination of replacements in a MAP
        infected flock is expected to improve the overall milk productivity in the long
        term.

        Keywords: Paratuberculosis, milk, vaccination, stochastic simulation.



1 Introduction

Paratuberculosis is a chronic intestinal infection of domestic and wild ruminants,
which is caused by Mycobacterium avium subsp. paratuberculosis (MAP). As a
result of the progressing MAP infection, infected animals develop reduced
productivity, body weight, fertility and, ultimately, die or are prematurely culled.
One of the main approaches to reduce the impact of paratuberculosis in sheep and
goat flocks is through vaccination of the replacement stock in order to increase their
resistance to infection. Vaccination of all sheep in an affected flock has been shown
to provide effective disease control in Australia (Windsor, 2006) and underpins the
national control program along with a risk-based trading system. Yet, the expected
benefits of vaccination in dairy sheep and goats have not yet been quantified. Only
scarce and conflicting reports about the direct benefit of vaccination on milk
production exist in dairy cows (Juste et al., 2009). Hence, the objective of this study
was to assess the expected benefits of vaccination on the milk productivity of dairy
sheep and goats.




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2 Materials and Methods

   A stochastic simulation model was used to assess the expected benefits on the
average daily milk yield (DMY) from a vaccination of replacements program. The
infection and milk production status of the 200 sheep and goat flock is simulated for
30 years. For the first ten years, the model assumes that vaccination does not take
place, while vaccination of the flock replacements starts at the eleventh year and is
simulated until the thirtieth year. The yearly assumed replacement rate, the infection
rate and the expected average DMY for vaccinated and unvaccinated animals was
derived from relevant published literature (Kostoulas et al., 2006; Liapi et al., 2012;
Angelidou et al., 2014) and the expert opinion of two authors (EA and LL).
Summary of the derived estimates and their corresponding distributions are in Table
1. The model assumes that animals who get infected remain infected for their
productive life or until replaced.
   Following the primary analysis, sensitivity analysis was performed to assess the
impact of different infection rates and DMYs on the expected benefits of vaccination.
   The DMY estimates were based on 200 simulations. The model was developed
and ran in R. Codes are freely available from the first author upon request.

Table 1. Input parameters for the replacement rate (RR), infection rate (IR) and the average
daily milk yield (DMY) for vaccinated and unvaccinated against Mycobacterium avium subsp.
paratuberculsosis sheep and goats.

  Input parameter Parity         Estimate                       Distribution
                                 Min      mode       Max
  RR              All            -        0.17       0.25       beta(17.4, 78.2)
  IR unvaccinated All            0.10     0.15       -          beta(14.5, 77.7)
  IR vaccinated   All            -        0.002      0.01       beta(1, 458)
  DMY healthy     1              0.7      1          1.2        triangular(0.7, 1, 1.2)
  animals         2              0.8      1.3        1.5        triangular(0.8, 1.3, 1.5)
                  3              0.8      1.35       1.65       triangular(0.8, 1.35, 1.65)
                  >4             0.8      1.25       1.5        triangular(0.8, 1.25, 1.5)
  Decrease (%) in 1              -        5          10         beta(6, 99)
  DMY infected 2                 -        10         15         beta(15, 130)
  animals         3              -        15         20         beta(28, 153)
                  >4             10       15         -          beta(14, 77)




3 Results

   Estimates for the average DMY for a period of 30 years are in Figure 1. For the
first ten years the flock did not follow a vaccination program and under endemic
disease status the DMY remains fairly similar. Since the initialization of a
vaccination of replacements program – year eleven and on – DMY steadily increases.
Estimates of the median DMY ten years pre vaccination, the first ten years post




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vaccination and the last ten years of the vaccination program reveal a significant
increase (Figure 2).
   Sensitivity analysis revealed that the most influential parameter on the benefits of
vaccination was the assumed infection rate in the cohort of vaccinated animals with
decreased rates leading to higher and earlier DMY benefits.
         1.10 1.12 1.14 1.16 1.18
DMY




                                    1   4   7 10   14    18   22    26      30

                                                   Years


Fig. 1. Predicted average daily milk yield (DMY) in kg before and after commencement of the
vaccination of replacements against Mycobacterium avium subsp. paratuberculosis (MAP) in a
200 sheep and goat flock. The vertical line at year 10 marks the initiation of vaccination.
Boxes represent inter-quartile ranges and the solid black line at the approximate center of each
box is the median; the arms of each box extend to cover the central 95% of the DMY
distribution with their ends corresponding to 2.5th and 97.5th percentile.




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          1.140
   DMY

          1.130
          1.120




                           A                   B              C




Fig. 2. Predicted median of the DMY ten years pre vaccination against MAP (A), ten years
post vaccination (B) and ten to twenty years post vaccination (C).



4 Discussion

   In this study we explored the potential benefits of a vaccination of replacements
program on the average DMY of dairy sheep and goats. Despite the fact that an
overlap was observed between the yearly DMY estimates this was mostly due to the
full stochastic approach rather than the absence of actual benefits on the DMY of
vaccinated animals. The benefits of vaccination have been masked under the
calculation of the average DMY for the whole herd, rather than the calculation of
separate DMYs for the vaccinated and unvaccinated animals. Hence, in a flock with
15% true prevalence of MAP infection an average improvement of approximately
12% in the DMY for the vaccinated cohort corresponds to a much lower benefit for
the average DMY of the flock. Clearly, the overall DMY gains further decrease in
herds/flock with lower prevalence of MAP infection. The latter could also explain
the conflicting reports on the direct benefits of vaccination in the milk production of
dairy cows (Juste et al., 2009). Still, as indicated by the calculation of median DMYs




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pre and post vaccination, the long-term benefits from vaccinating the replacement
stock are unquestionable.
   MAP vaccination constitutes one of the main approaches to reduce the impact of
paratuberculosis in sheep and goat flocks. MAP vaccination though not directly
preventing from infection, it reduces the occurrence of clinical cases of MAP and
MAP excretion from infected animals, thus, cutting off routes to new infections and
minimizing MAP-associated direct and indirect production losses (Windsor, 2006).
Our model is a first attempt to quantify the positive effect of MAP vaccination on the
milk productivity of dairy sheep and goats. Currently ongoing studies that aim to
measure the actual benefit in the DMY for vaccinated animals will provide additional
real life data and refine our estimates on the improvement of the milk productivity of
dairy sheep and goats.




References

1.   Angelidou E., Kostoulas P., Leontides L., Flock-level factors associated with the
     risk of Mycobacteriumavium subsp. paratuberculosis (MAP) infection in Greek
     dairy goat flocks. Preventive Veterinary Medicine, 117: 233-241.
2.   Juste R.A., Alonso-Hearn M., Molina E., Geijo M., Vazquez P., Sevilla I.A.,
     Garrido J.M., 2009.        Significant reduction in bacterial shedding and
     improvement in milk production in dairy farms after the use of a new inactivated
     paratuberculosis vaccine in a field trial. Biomedical Central Research Notes, 22:
     233.
3.   Kostoulas P., Leontides L., Enøe C., Billinis C., Florou M., Sofia M., 2006a.
     Bayesian estimation of sensitivity and specificity of serum ELISA and faecal
     culture for diagnosis of paratuberculosis in greek dairy sheep and goats.
     Preventive Veterinary Medicine, 76: 56-73.
4.   Liapi, M., Leontides L., Kostoulas, P., Botsaris, G., Iacovou, Y., Rees, C.,
     Georgiou, K., Smith, G.C., Naseby, D.C., 2011. Bayesian estimation of the true
     prevalence of Mycobacterium avium subsp. paratuberculosis infection in Cypriot
     dairy sheep and goat flocks. Small Ruminant Res. 95, 174-178.
5.   Windsor, P., 2006. Research into vaccination against ovine Johne’s disease in
     Australia. Small Ruminant Research, 62: 139-142.




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