Drug-resistant tuberculosis: how to interpret rapid molecular test results

This training toolkit by the European Laboratory Initiative for TB, HIV and Viral Hepatitis provides a unique combination of practical guidance and expert advice on the interpretation of selected WHO-endorsed tests for drug-resistant tuberculosis (DR-TB). More specifically, it covers the latest guidance for the interpretation of rapid molecular assays for DR-TB by Cepheid (GeneXpert MTB/RIF and GeneXpert MTB/RIF Ultra) and Hain Lifescience (GenoTypeMTBDRplus VER 2.0 and GenoTypeMTBDRsl VER 2.0). Participants can exchange experiences through a course forum. Laboratory experts are available to address key questions via the forum and a dedicated pilot email service. The course is particularly relevant for laboratory experts who perform drug-susceptibility testing (DST) for TB and clinicians who use DST results in their routine clinical practice. We hope this training will help refine your practice, thereby strengthening the global capacity to diagnose DR-TB.

Language: English
Advanced (Avancé)

Course information

This course is also available in the following language: Русский.

Overview: Addressing drug-resistant tuberculosis (DR-TB) is a global priority to accelerate progress towards the elimination of TB. In many countries, patients with DR-TB are either not diagnosed at all or receive a delayed diagnosis, leading to further spread and increased severity of the disease. WHO-endorsed rapid molecular tests have dramatically improved the speed and quality of diagnosis of DR-TB and should be adopted more widely, complemented with phenotypic alternatives where necessary. This course provides updated guidance for the interpretation of selected genotypic drug-susceptibility testing (gDST) assays, based on a review by the European Laboratory Initiative on TB, HIV and Viral Hepatitis (ELI). Specifically, the training covers the Hain Lifescience GenoTypeMTBDRplus VER 2.0 and GenoTypeMTBDRsl VER 2.0 line probe assays for first- and second-line anti-TB drugs (FL-LPA and SL-LPA) and the Cepheid GeneXpert MTB/RIF (Xpert) and GeneXpert MTB/RIF Ultra (Ultra). The course includes a dedicated interpretation guide and template, developed by ELI, to enable users to implement the substantial changes to the interpretation of both LPAs in their routine diagnostic service. You will first learn about the principles of gDST and the changes to the interpretation of the above-mentioned assays (Modules A and B). We will then focus on how to resolve problems with the LPAs and on how to minimize contamination (Modules C and D).

To complement the practical guidance, each training module has a forum where participants can exchange their experiences. Laboratory experts are available to address key questions through both the forum and a dedicated pilot email service. The most relevant points will be compiled within a dedicated course section on “important updates and frequently asked questions”. This way, the course will be continuously refined based on the feedback from participants and the wider scientific community.

An additional module to explain the reasons for discordances between genotypic and phenotypic DST results and how to resolve them is planned.

Learning objectives: By the end of this course, participants should be able to implement the latest WHO guidelines for the interpretation of Xpert, Ultra, FL-LPA and SL-LPA for gDST.

Course duration: Approximately 5 hours (2 for the online modules and 3 for the practical examples).

Certificates: A Record of Achievement is offered at the end of the course upon passing 80% of test questions.

Disclaimer: All reasonable precautions have been taken by the authors to verify the information contained in this course. However, the published material is being distributed without warranty of any kind, either expressed or implied. Responsibility for the interpretation and use of the material lies with the reader. In no event shall the authors be liable for damages arising from its use.

Course contents

  • Introduction:

    Welcome message by Dr Masoud Dara, Coordinator, Communicable Diseases, WHO Regional Office for Europe.
  • Module A. Principles of genotypic drug-susceptibility testing:

    By the end of this module, participants should understand how mutations cause drug-resistance, the strength and limitations of gDST testing, and the reasons for the changes to the interpretation of WHO-endorsed gDST assays.
  • Module B. Changes to the interpretation of genotypic drug-susceptibility testing assays:

    By the end of this module, participants should understand the minor changes to the interpretation of Xpert and Ultra and how to use the ELI interpretation guide and ELI interpretation templates to implement the major changes to the interpretation of the FL-LPA and SL-LPA.
  • Module C. Hain line-probe assays: ramp rate and troubleshooting:

    By the end of this module, participants should understand the importance of using the correct ramp rate for the LPAs and how to resolve other problems with these assays.
  • Module D. How to minimize contamination:

    By the end of this module, participants should understand the different approaches to minimize contamination in laboratories.
  • Important updates and frequently asked questions:

    Notable findings from the scientific literature and frequent questions from participants will be shared in this section.
  • Course credits:

    This course is a collaborative product by ELI core group members: Dr Claudio Köser (University of Cambridge, Cambridge, United Kingdom) and Dr Natalia Shubladze (National Centre of Tuberculosis and Lung Diseases and the National Reference Mycobacteriology Laboratory, Tbilisi, Georgia). The development of the modules and supporting technical materials was guided by Dr Masoud Dara (WHO Regional Office for Europe) and led by Dr Soudeh Ehsani (WHO Regional Office for Europe). Critical review was provided by the ELI core group members Dr Daniela Cirillo (San Raffaele Scientific Institute, Milan), Professor Francis Drobniewski (Imperial College London, London, United Kingdom) and Dr Gulmira Kalmambetova (National Reference Laboratory, Bishkek, Kyrgyzstan), as well as Global Laboratory Initiative (GLI) core group member Dr Elisa Tagliani (San Raffaele Scientific Institute, Milan, Italy). Special thanks for further review and contributions are given to Dr Doris Hillemann (Research Centre Borstel, Borstel, Germany), Dr Altyn Iskakova (National Reference Laboratory, Bishkek, Kyrgyzstan), Dr Andrea Kühn (Hain Lifescience, Nehren, Germany), Mr Alexey Ostrovsky (Independent information technology advisor, Tbilisi, Georgia) and Dr Gabriela Torrea (Institute of Tropical Medicine, Antwerp, Belgium). Ms Léa Clapier (Consultant to the WHO Regional Office for Europe) supported the publication of the course. Financial support for development and publication was provided by the United States Agency for International Development and the Federal Government of Germany.

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Certificate Requirements

  • Gain a Record of Achievement by earning at least 80% of the maximum number of points from all graded assignments.