TECHNICAL REPORT Mastering the basics of TB control Development of a handbook on TB diagnostic methods www.ecdc.europa.eu ECDC TECHNICAL REPORT Mastering the basics of TB control Development of a handbook on TB diagnostic methods Suggested citation: European Centre for Disease Prevention and Control. Mastering the basics of TB control: Development of a handbook on TB diagnostic methods. Stockholm: ECDC; 2011. Stockholm, May 2011 ISBN 978-92-9193-242-9 doi 10.2900/39099 © European Centre for Disease Prevention and Control, 2011 Reproduction is authorised, provided the source is acknowledged. TECHNICAL REPORT Mastering the basics of TB control Contents Executive summary ................................................................................................................................... 2 Introduction ............................................................................................................................................. 3 How this report relates to other available work in this field ........................................................................... 3 What this document is/is not...................................................................................................................... 3 Intended use and users ............................................................................................................................. 3 Material and methods ................................................................................................................................ 3 Results ..................................................................................................................................................... 4 Discussion and conclusions ........................................................................................................................ 5 References ............................................................................................................................................... 5 Annex 1. Handbook of TB diagnostic methods ............................................................................................. 6 Annex 2. Partners ..................................................................................................................................100 iii Mastering the basics of TB control TECHNICAL REPORT Abbreviations EPTB Extrapulmonary tuberculosis ERLN-TB European Reference Laboratory Network for Tuberculosis EU/EEA European Union/European Economic Area IGRA Interferon-γ release assays LTBI Latent TB infections NRL National reference laboratory TB Tuberculosis TST Tuberculin skin test Executive summary Tuberculosis (TB) remains to be a major cause of morbidity and mortality in Europe. To improve both the prognosis of TB patients and TB disease surveillance, care of patients with TB should always start with a quality- assured laboratory diagnosis. In 2007, a survey (2) on current mycobacterial laboratory services indicated that a European laboratory network on TB would add value for Europe. As a result of this survey, the European Reference Laboratory Network for Tuberculosis (ERLN-TB) was launched in January 2010. One of the main goals of this network is to support the harmonisation of methods in the EU/EEA. A key deliverable of 2010 was the ‘Handbook of TB diagnostic methods’, which is presented here. The handbook consists of nine chapters describing the most relevant and reliable laboratory diagnostic methods. It covers biosafety, quality assurance, latent TB infection, smear microscopy, identification of M. tuberculosis and drug resistance, culture, drug susceptibility testing, molecular methods, and information related to the diagnosis of TB for physicians. This first edition is intended to contribute to the harmonisation of methods for TB diagnosis and therefore also covers issues of comparability of TB diagnosis within the EU/EEA. ECDC will continue to work with the ERLN-TB to evaluate the impact of this collaborative technical report and make further provisions for the development of the document. The experience gained from writing this technical report on diagnostic methods could be applied to other European reference laboratory networks, which would certainly benefit from the developed body of knowledge. There are also several tools available that would support interaction and collaboration between reference laboratories and laboratory experts, particularly in respect to improving the implementation of diagnostic techniques and further training/capacity building. This is exactly where ECDC’s added value lies, as outlined in the ECDC founding regulation (1): to prevent and control communicable diseases in Europe by, among other measures, fostering the collaboration between experts and reference laboratories. 2 TECHNICAL REPORT Mastering the basics of TB control Introduction Tuberculosis (TB) is a major cause of morbidity and mortality in Europe. High-quality laboratory diagnosis of TB is the basis for both individual patient treatment and surveillance. In 2007, Drobniewski et al. (2) assessed existing mycobacterial laboratory services and quality control practices throughout the EU and confirmed the key role of national reference laboratories (NRL) for TB and their services. The main conclusion of the survey (2) was that a network of reference laboratories for tuberculosis could contribute to improve the performance of mycobacterial laboratories in Europe. Based on these results, the European Reference Laboratory Network for Tuberculosis (ERLN-TB) was launched in January 2010, with the aim of strengthening TB diagnostics in the European Union. ERLN-TB is funded and coordinated by ECDC. One or two officially nominated reference laboratories from each Member State represent the Network, including EEA countries and candidate countries. The three main goals of the network are: to support the harmonisation of methods within the EU/EEA; develop External Quality Assurance (EQA) schemes; and provide training activities within the Network to ensure EU-wide capacity-building for TB diagnostics. One of the main activities conducted during the Network’s first year was the development of a handbook of key diagnostic methods for tuberculosis (Annex 1), the results of which you are reviewing now. The aim of this handbook is to provide Network members, as well as other laboratories involved in the diagnosis of tuberculosis, with an agreed list of key diagnostic methods and their protocols in various areas of TB diagnosis, ranging from microbiological diagnosis of active TB to the diagnosis of LTBI. This handbook aims to provide a single source of reference by compiling all methods, with a strong focus on standard (reference) and evidence- based methods. This handbook also wants to contribute to the improvement of disease surveillance data for Europe: data sent to ECDC’s TESSy (The European Surveillance System) or other surveillance systems should be robust and backed by quality laboratory diagnostics. How this report relates to other available work in this field This technical report presents a compilation of methods currently applied in Europe. It describes common work carried out and endorsed by European laboratory experts. It also features methods and procedures developed or refined by ERLN-TB network partners. What this document is/is not This document is a technical report about developing a handbook of agreed methods in the field of TB diagnostics for laboratories serving reference functions in Europe. In Annex 1 it provides a comprehensive compilation of key methods for the diagnosis of TB. Relevant stakeholders should use this compilation as a basis for the validation, development, updating, and dissemination of information. The current document is not an official handbook of methods. Intended use and users The report will be of interest to public health professionals and policy makers in the field of global TB control, particularly those involved in European initiatives which foster the progress towards elimination of TB. For laboratory experts, this document provides the basis for developing a future handbook of basic- and reference- level methods (to be agreed and validated) for the diagnosis of TB. Material and methods The first annual meeting of the ERLN-TB was held in 2010 in Stockholm. During this meeting, the Network partners came to a consensus agreement about the relevant topics to be included in a handbook on (reference) laboratory methods for the diagnosis of TB. The approach was to include several standardised and reliable methods, rather than to focus on one single method. A dedicated writing committee was formed to compile the first draft of these methods, using a handbook format. Each chapter includes descriptions of standardised diagnostic methods and highlights key considerations regarding biosafety and quality assurance. A draft of the handbook was sent out to all ERLN-TB network partners for review and endorsement. An approved version was submitted to ECDC in September 2010. The current version of the handbook underwent final 3 Mastering the basics of TB control TECHNICAL REPORT consultation and received endorsement for publication by the ERLN-TB during its second annual meeting in January 2011. Results The first edition of the ERLN-TB handbook (Annex 1) consists of nine chapters, each with a list of relevant references. Below is a summary of each chapter. 1 Biosafety in clinical laboratory diagnosis of tuberculosis M. tuberculosis can cause laboratory-acquired infections