Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries; a multi-country population-based surveillance study

Matteo Zignol, Andrea Maurizio Cabibbe, Anna S. Dean, Philippe Glaziou, Natavan Alikhanova, Cecilia Ama, Sonke Andres, Anna Barbova, Angeli Borbe-Reyes, Daniel P. Chin, Daniela Maria Cirillo, Charlotte Colvin, Andrei Dadu, Andries Dreyer, Michele Driesen, Christopher Gilpin, Rumina Hasan, Zahra Hasan, Sven Hoffner, Alamdar HussainNazir Ismail, S. M. Mostofa Kamal, Faisal Masood Khanzada, Michael Kimerling, Thomas Andreas Kohl, Mikael Mansjo, Paolo Miotto, Ya Diul Mukadi, Lindiwe Mvusi, Stefan Niemann, Shaheed V. Omar, Leen Rigouts, Marco Schito, Ivita Sela, Mehriban Seyfaddinova, Girts Skenders, Alena Skrahina, Sabira Tahseen, William A. Wells, Alexander Zhurilo, Karin Weyer, Katherine Floyd, Mario C. Raviglione

Research output: Contribution to journalA1: Web of Science-articlepeer-review


Background In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis.

Methods Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing.

Findings Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA, andfabG promoter combined (isoniazid resistance), 54% (39-68) for pucA (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing.

Interpretation Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation. Copyright (C) 2018 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

Original languageEnglish
JournalLancet Infectious Diseases
Issue number6
Pages (from-to)675-683
Number of pages9
Publication statusPublished - 2018




Dive into the research topics of 'Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries; a multi-country population-based surveillance study'. Together they form a unique fingerprint.

Cite this