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A combined measure of tuberculous lesions for assessing the efficacy of vaccination against tuberculosis (Mycobacterium bovis) in European badgers (Meles meles) supports the 3Rs principle of reduction

Birch, Colin P.D., Chambers, Mark A. and Lesellier, Sandrine (2019) A combined measure of tuberculous lesions for assessing the efficacy of vaccination against tuberculosis (Mycobacterium bovis) in European badgers (Meles meles) supports the 3Rs principle of reduction VACCINE.

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Abstract


Background

An oral vaccine is a potential tool to tackle the reservoir of Mycobacterium bovis in European badgers (Meles meles), which contributes to tuberculosis of cattle in the British Isles. Inferences about vaccine protection against experimental challenge with M. bovis depend on the measurement of tuberculosis. Assessment of tuberculosis in larger species, such as badgers, is typically based on the tuberculous lesions visible at post-mortem examination and histopathology. We have developed a robust scoring system for tuberculous lesions by combining several parallel measures, which we call the “disease burden score” (DBS).


Methods

Alternative scoring systems were compared within a regression analysis applied to observations from a total of 168 badgers from eight studies, including 107 badgers subjected to vaccination treatment and 61 non-vaccinated controls. The analysis included incidental observations that were recorded from each badger as potential covariate factors explaining some of the variation among animals sourced from the wild.


Results

DBS was found to be the most accurate and reliable of the scoring systems compared. By taking account of significant covariates affecting disease, application of the DBS reduced residual variance by 22.9%. A previously used measure, based on assessment of visible lesions, was suboptimal due to non-uniform variance that increased with expected value, although square root transformation addressed this issue. The covariate model fitted to DBS included sex (males had higher DBS), weight (negatively associated with DBS) and immunological evidence of prior exposure to Mycobacterium avium (positively associated with DBS).


Conclusions

We identified improved measures of tuberculous disease derived from data already collected. We also demonstrated that the proper scaling of measurements of disease in such models is necessary and can be determined empirically. The covariates which were most strongly associated with the severity of disease are important in experimental studies involving outbred animals with variable background.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
NameEmailORCID
Birch, Colin P.D.
Chambers, Mark A.m.chambers@surrey.ac.uk
Lesellier, Sandrine
Date : 14 November 2019
Funders : Department for Environment, Food and Rural Affairs (DEFRA)
DOI : 10.1016/j.vaccine.2019.10.079
Copyright Disclaimer : Crown Copyright © 2019 Published by Elsevier Ltd.
Uncontrolled Keywords : Regression; Statistical standardization; Covariates; Tuberculosis; Outbred; Experimental design
Depositing User : Diane Maxfield
Date Deposited : 06 Oct 2020 13:21
Last Modified : 06 Oct 2020 13:21
URI: http://epubs.surrey.ac.uk/id/eprint/858673

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