Particularities of Field Paratuberculosis Vaccination Evaluation

Paratuberculosis is an infection that has been unchecked for at least a century throughout most of the world and therefore is widespread nowadays. Since it is also chronic and sub- clinical in the majority of cases, defining pro­tection criteria for vaccine evaluation is not an easy task.

Table 22.3. Average protection conferred by paratuberculosis vaccines (Bastida and Juste, 2011).

evaluate productive losses, specific and overall mortality, clinical incidence or pathological le­sions.

22.5.1 Microbiological variables

Excretion of MAP in faeces is an objective pa­rameter of vaccine effect. In this sense there are two related goals: (i) reduction of the number of shedding individual animals, and (ii) reduction of the amount of bacteria that accumulates in their tissues and can be spread in the environment. To detect MAP, isolation in pure culture has been the gold standard, although it is being increasingly replaced by the faster, cheaper and even more sen­sitive specific DNA amplification by polymerase chain reaction. It has been seen that, although a reduction in the number of shedders does not im­mediately occur, a decrease in the amount of bac­teria in faeces is quickly and consistently observed (Argente, 1992; Reddacliff etal., 2006; Juste etal., 2009; Sweeney et al., 2009; Bannantine et al., 2014; Hines et al., 2014; Dhand et al., 2016). This bacterial load can also be determined in post­mortem studies through the processing of tissue samples using microbiological techniques. This load is closely related to the type of lesion observed (Alonso-Hearnetal., 2012; Hines etal., 2014).

22.5.2 Pathological variables

Paratuberculosis vaccine effect is containment of the evolution of the lesion at resistance fo­cal forms with low bacterial load. Therefore the analysis of the lesion type of the vaccinated ani­mals in comparison with the others is another way to evaluate its effect (Juste et al., 1994; Juste and Perez, 2011).

22.5.3 Clinical and productive indices

Reduction of clinical cases and of negative effects on milk or meat production are the target vari­ables for industrial use of a paratuberculosis vac­cine. However, for the reasons above mentioned, this might be difficult to determine and therefore several indicators have been used.

22.5.4 Vaccination versus testing and culling

Although vaccine protection is not 100%, a rea­sonable estimate based on the literature reviewed

above can provide an estimated protective effi­cacy of 89%. Using a simulation model (Juste and Casal, 1993) on a herd of 1000 individuals with a 10% infection and 25% replacement rate, this protection will drive infection to disappearance in 7 years. The simulation allows us to estimate that protection rate is not so critical above 60% and that infection will not disappear faster with a 100% protection rate, nor much slower with any protection above 60%. This must be contrasted with the alternative strategy of testing and culling that, with the highest sensitivity of any diagnostic test being about 50%, can only eliminate infec­tion in 19 years. Only with a sensitivity of 100% is it possible to reduce this time to eradication to a period shorter than with vaccination. The differ­ence is that at a cost of ˆ10 per test per animal per year and ˆ15 per vaccination per animal once in its lifetime, the accumulated cost-benefit ratio at 20 years is 2.72 and 9.3, respectively (Fig. 22.1). Vaccination thus appears to be a sustainable ap­proach to paratuberculosis control that can be much easier to accept both by farmers (Doyle, 1964) and the general population since it pre­serves life instead of destroying it through culling.

Fig. 22.1. Comparison of number of infected animals evolution according to test and vaccine performance (Juste and Casal, 1993). Notice that changes in sensitivity strongly affect time to eradication, while changes in protection have small effect.

22.5.3 Interference with bovine tuberculosis diagnosis

One of the reasons why vaccination against paratuberculosis in cattle has been strongly lim­ited is the interference with the immune tech­niques used in bovine tuberculosis eradication programmes, which have the highest priority because of the zoonotic nature of tuberculosis. However the problem can be easily fixed using either better interpretation algorithms or more specific antigens (Stabel et al., 2011; Perez de Val et al., 2012; Garrido et al., 2013; Hines et al., 2014; Roy et al., 2017; Serrano et al., 2017).

22.5.4 Non-specific effects (NSE)

There is controversy regarding the NSE of vac­cines, and in particular of BCG in humans (Wenner Moye, 2019). There are observations on field results that indicate that early adminis­tration of vaccines reduces overall child mortal­ity (Timmermann et al., 2015; Aaby et al., 2017; Jenum et al., 2018; Welaga et al., 2018; Wenner Moye, 2019). This effect appears to be related to the so-called trained innate immunity (Kleinnijenhuis et al., 2015; Gyssens and Netea, 2019), which could respond to primitive mechanisms such as an increase in macrophage lytic capacity (Juste et al., 2016b; Pooley et al., 2018). That seems to be confirmed in field conditions as there is about 36% of overall mortality reduction in vaccinated herds vs testing and culling that corresponds to animals younger than 2 years (Juste et al., 2016a); that is, before the accepted paratuberculosis clinical onset age.

22.6