Review of performance and test accuracy of diagnostic tests used during the bovine tuberculosis

101 Pages·2017·4.04 MB·English

Review of performance and test accuracy of diagnostic tests used
during the bovine tuberculosis control program implemented in
Germany in 2012
von Valerie-Beau Patricia Pucken
Inaugural-Dissertation zur Erlangung der Doktorwürde der
Tierärztlichen Fakultät der Ludwig-Maximilians-Universität München
Review of performance and test accuracy of diagnostic tests used
during the bovine tuberculosis control program implemented in
Germany in 2012
von Valerie-Beau Patricia Pucken
aus Bad Godesberg jetzt Bonn
München 2018
Aus dem Zentrum für Klinische Tiermedizin der Tierärztlichen Fakultät der
Ludwig-Maximilians-Universität München
Lehrstuhl für Innere Medizin und Chirurgie der Wiederkäuer

Arbeit angefertigt unter der Leitung von:

Univ.-Prof. Dr. Gabriela Knubben-Schweizer
Gedruckt mit Genehmigung der Tierärztlichen Fakultät der
Ludwig-Maximilians-Universität München
Dekan: Univ.-Prof. Dr. Reinhard K. Straubinger, Ph.D
Univ.-Prof. Dr. Gabriela Knubben-Schweizer
Berichterstatter:
Korreferenten: Univ.-Prof. Dr. Rolf Mansfed
Univ.-Prof. Dr. Kaspar Matiasek
Priv.-Doz. Dr. Sven Reese
Univ.-Prof. Dr. Mathias Ritzmann
Tag der Promotion: 10.02.2018
Für dich

"Heute nun
Schreibe ich Dir."
(Hanns-Josef Ortheil)
Table of Contents VI
TABLE OF CONTENTS
I. INTRODUCTION ...................................................................................... 1
II. LITERATURE OVERVIEW .................................................................... 3
1. Tuberculosis ................................................................................................3
1.1. The pathogen ................................................................................................3
1.2. Bovine tuberculosis ......................................................................................4
1.2.1. Eradication of bovine TB in Germany .........................................................5
2. Diagnosis of bovine tuberculosis ...............................................................6
2.1. Ante-mortem tests ........................................................................................7
2.1.1. Intradermal tuberculin test ...........................................................................7
2.1.1.1. Single intradermal tuberculin test ................................................................7
2.1.1.2. Comparative cervical tuberculin test ............................................................8
2.1.2. Bovigam® assay ..........................................................................................8
2.2. Post-mortem tests .........................................................................................9
2.2.1. Necropsy.......................................................................................................9
2.2.2. Polymerase chain reaction ............................................................................9
2.2.3. Culture ........................................................................................................10
3. Estimating test accuracy ..........................................................................10
3.1. Sensitivity and specificity ..........................................................................11
3.2. The latent class analysis theorem ...............................................................13
3.2.1. Bayesian approach......................................................................................13
3.3. Cohen's Kappa ............................................................................................14
III. PUBLICATIONS ..................................................................................... 15
1. Publication 1 .............................................................................................15
2. Publication 2 .............................................................................................30
IV. DISCUSSION ........................................................................................... 65
1. Publication 1 .............................................................................................65
2. Publication 2 .............................................................................................67
3. Conclusion .................................................................................................70
V. SUMMARY............................................................................................... 73
Table of Contents VII
VI. ZUSAMMENFASSUNG ......................................................................... 75
VII. REFERENCES ........................................................................................ 77
VIII. ACKNOWLEDGEMENTS .................................................................... 91
Abbreviations VIII
ABBREVIATIONS
DNA Deoxyribonucleic acid
EIA Sandwich enzyme immunoassay
EU European Union
FLI Friedrich-Loeffler-Institute
HSe Herd level sensitivity
IFN-gamma Interferon-gamma
NVL Non-visible lesions
OTF Officially Bovine Tuberculosis-Free
PCR Polymerase chain reaction
PPD Purified protein derivate
SICT test Single intra-dermal cervical tuberculin test
SICCT test Single intra-dermal comparative cervical tuberculin test
TB Tuberculosis

I.Introduction 1
I. INTRODUCTION
Bovine tuberculosis (bovine TB) is a chronic disease which can affect almost all
mammals, whereby the infection of cattle, wild animals and humans is of greatest
importance. As a compulsorily notifiable disease it is listed in the World
Organisation for Animal Health (OIE) Terrestrial Health Code (Anonymous,
2017b). Due to negative consequences on trade of animals, animal products and its
zoonotic character it concerns public health, international trade and is a significant
economic burden (Cousins, D. V., 2001; Thoen, C. O. et al., 2006). As a result the
control of bovine TB with stringent test and slaughter regimes is an ambition all
over the world. In Europe the success with such control programs is achieved by
reaching the "Officially Bovine Tuberculosis-Free (OTF) Status". This status is
defined in the European Union (EU) law and is reached if not more than 0.01% of
cattle farms have been diagnosed bovine TB positive during the last six years and
99.9% of cattle farms were officially bovine TB free during the last 10 years1.
Within test and slaughter regimes herds or animals at risk are tested with ante
mortem tests like the intradermal tuberculin test or the Bovigam® assay. Animals
being tested positive are culled and confirmation of disease is done post mortem
with pathological examinations, polymerase chain reaction and bacteriological
examination. The proper execution of the diagnostic tests and high test accuracies
are essential for the success of such control programs (Humblet, M.-F. et al., 2011;
Schiller, I. et al., 2010a).
Since Germany received the status OTF in 1996 the further perpetuation of this
status is important for international trade and public health. Bovine TB cases that
were found during routine abattoir inspection lead to the implementation of a one-
time bovine TB control program in Germany in 2012. During this control program
discrepancies in the right execution of the intradermal tuberculin tests led to
discussions between stakeholders (Anonymous, 2013; 2014; 2015) and a legal
dispute1. The objective of the first study was therefore to review farm-animal
practitioners' current knowledge on execution of the intradermal tuberculin tests in
comparison to current and former legislation and literature. Furthermore, persons
involved in the bovine TB control program noticed discrepancies between the
1 97/76/EC: Commission Decision of 17 December 1996 laying down the methods of control for
maintaining the officially tuberculosis free status of bovine herds in certain Member States and
regions of Member States