Tuberculin PPD Potency Assays in Naturally Infected Tuberculous Cattle as a Quality Control Measure in the Irish Bovine Tuberculosis Eradication Programme.

Anthony Duignan,Douwe Bakker,Margaret Good,Kevin Kenny

doi:10.3389/fvets.2019.00328

Abstract

The Irish Bovine Tuberculosis (bTB) eradication programme operates under national legislation and fulfills OIE and EU trade requirements. Tuberculin purified protein derivative (PPD), a preparation obtained from the heat-treated products of growth and lysis of Mycobacterium bovis or Mycobacterium avium (as appropriate), is critical to the diagnosis of tuberculosis (TB). Standardization of Tuberculin PPD potency, the relative activity in sensitized animals compared to a reference standard, is essential to underpin the reliability of certification for international trade and to ensure that disease eradication programmes are effective and efficient. A Bovine International Standard Tuberculin PPD (BIS) was established by the WHO in 1986 and is used to determine comparative potencies of Tuberculin PPDs. Ideally, Tuberculin PPD potency should be evaluated in the species in which the tuberculin will be used but due to practical difficulties in performing potency assays in cattle, for routine PPD production, they are usually assayed in guinea pigs. Low potency tuberculin PPD is less efficient and thus inferior for bTB diagnosis. Difficulties experienced in the Irish bTB eradication programme have included the supply of sub-standard potency, and thus inferior, bovine (M. bovis) Tuberculin PPD in the late 1970s. The purpose of this paper is to outline the critical role of Tuberculin PPD assays carried out on naturally infected tuberculous cattle, as required by the OIE and under EU legislation in the quality control for the Irish Bovine Eradication Programme. Such assays ensure that the Tuberculin PPD used meets the diagnostic sensitivity and specificity requirements to underpin a successful national eradication programme.

Highlights

Bovine tuberculosis is an important infectious disease of cattle that constitutes a “One Health” concern as a public health risk due to its zoonotic potential (WHO) [1], and has significant economic and trade implications for the European Union (EU) and the World Organization for Animal Health [Office International des Epizooties (OIE)] [2, 3]
Annex B of the EU trade Directive [2] defines Tuberculin as “Tuberculin purified protein derivative (Tuberculin PPD, bovine or avian) is a preparation obtained from the heat-treated products of growth and lysis of Mycobacterium bovis or Mycobacterium avium capable of revealing a delayed hypersensitivity in an animal sensitized to microorganisms of the same species.”
The potency of Bovine Tuberculin PPD 3000 supplied for use in Ireland is estimated in Lelystad in guinea pigs sensitized with living M. bovis relative to the Bovine International Standard Tuberculin PPD (BIS) PPD on behalf of the manufacturer

Summary

INTRODUCTION

Bovine tuberculosis (bTB) is an important infectious disease of cattle that constitutes a “One Health” concern as a public health risk due to its zoonotic potential (WHO) [1], and has significant economic and trade implications for the European Union (EU) and the World Organization for Animal Health [Office International des Epizooties (OIE)] [2, 3]. The means of sensitization of guinea pigs and the number of guinea pigs used for assay by the manufacturer will affect the accuracy of the potency estimate and further result in inter-laboratory differences in potency estimates These differences result in a wide variance both in protein content and antigenic profile and differences in potency and specificity between various Tuberculin PPD products are to be expected and these, plus the relative potency of the avian and bovine Tuberculin PPDs used for SICTT and the Interferon-γ (IFN-γ) assay, will have an impact on test efficacy, Se, Sp, and Predictive Value [44, 48,49,50,51,52]. The potency of Bovine Tuberculin PPD 3000 supplied for use in Ireland is estimated in Lelystad in guinea pigs sensitized with living M. bovis relative to the BIS PPD on behalf of the manufacturer.

DISCUSSION

Findings

ETHICS STATEMENT