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

M Zignol, AM Cabibbe, AS Dean, P Glaziou, N Alikhanova, C Ama, S Andres, A Barbova, A Borbe-Reyes, DP Chin, DM Cirillo, C Colvin, A Dadu, A Dreyer, M Driesen, C Gilpin, R Hasan, Z Hasan, S Hoffner, A HussainN Ismail, SMM Kamal, FM Khanzada, M Kimerling, TA Kohl, M Mansjö, P Miotto, YD Mukadi, L Mvusi, S Niemann, SV Omar, L Rigouts, M Schito, I Sela, M Seyfaddinova, G Skenders, A Skrahina, S Tahseen, WA Wells, A Zhurilo, K Weyer, K Floyd, MC Raviglione

Research output: Contribution to journalArticle

Abstract

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, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (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. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development. © 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
Pages (from-to)675-683
Number of pages9
JournalThe Lancet Infectious Diseases
Volume18
Issue number6
DOIs
Publication statusPublished - 2018

Fingerprint

Population Surveillance
Drug Resistance
Tuberculosis
Pyrazinamide
Ofloxacin
Pharmaceutical Preparations
Isoniazid
Rifampin
Capreomycin
United States Agency for International Development
Azerbaijan
Republic of Belarus
Ukraine
Kanamycin
Philippines
Bangladesh
Amikacin
Pakistan
Licensure
South Africa

Cite this

Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study. / Zignol, M; Cabibbe, AM; Dean, AS; Glaziou, P; Alikhanova, N; Ama, C; Andres, S; Barbova, A; Borbe-Reyes, A; Chin, DP; Cirillo, DM; Colvin, C; Dadu, A; Dreyer, A; Driesen, M; Gilpin, C; Hasan, R; Hasan, Z; Hoffner, S; Hussain, A; Ismail, N; Kamal, SMM; Khanzada, FM; Kimerling, M; Kohl, TA; Mansjö, M; Miotto, P; Mukadi, YD; Mvusi, L; Niemann, S; Omar, SV; Rigouts, L; Schito, M; Sela, I; Seyfaddinova, M; Skenders, G; Skrahina, A; Tahseen, S; Wells, WA; Zhurilo, A; Weyer, K; Floyd, K; Raviglione, MC.

In: The Lancet Infectious Diseases, Vol. 18, No. 6, 2018, p. 675-683.

Research output: Contribution to journalArticle

Zignol, M, Cabibbe, AM, Dean, AS, Glaziou, P, Alikhanova, N, Ama, C, Andres, S, Barbova, A, Borbe-Reyes, A, Chin, DP, Cirillo, DM, Colvin, C, Dadu, A, Dreyer, A, Driesen, M, Gilpin, C, Hasan, R, Hasan, Z, Hoffner, S, Hussain, A, Ismail, N, Kamal, SMM, Khanzada, FM, Kimerling, M, Kohl, TA, Mansjö, M, Miotto, P, Mukadi, YD, Mvusi, L, Niemann, S, Omar, SV, Rigouts, L, Schito, M, Sela, I, Seyfaddinova, M, Skenders, G, Skrahina, A, Tahseen, S, Wells, WA, Zhurilo, A, Weyer, K, Floyd, K & Raviglione, MC 2018, 'Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study', The Lancet Infectious Diseases, vol. 18, no. 6, pp. 675-683. https://doi.org/10.1016/S1473-3099(18)30073-2
Zignol, M ; Cabibbe, AM ; Dean, AS ; Glaziou, P ; Alikhanova, N ; Ama, C ; Andres, S ; Barbova, A ; Borbe-Reyes, A ; Chin, DP ; Cirillo, DM ; Colvin, C ; Dadu, A ; Dreyer, A ; Driesen, M ; Gilpin, C ; Hasan, R ; Hasan, Z ; Hoffner, S ; Hussain, A ; Ismail, N ; Kamal, SMM ; Khanzada, FM ; Kimerling, M ; Kohl, TA ; Mansjö, M ; Miotto, P ; Mukadi, YD ; Mvusi, L ; Niemann, S ; Omar, SV ; Rigouts, L ; Schito, M ; Sela, I ; Seyfaddinova, M ; Skenders, G ; Skrahina, A ; Tahseen, S ; Wells, WA ; Zhurilo, A ; Weyer, K ; Floyd, K ; Raviglione, MC. / Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study. In: The Lancet Infectious Diseases. 2018 ; Vol. 18, No. 6. pp. 675-683.
@article{200fad9ad0a74538ad390315e1ef5ae2,
title = "Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study",
abstract = "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, and fabG promoter combined (isoniazid resistance), 54{\%} (39-68) for pncA (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. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development. {\circledC} 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.",
author = "M Zignol and AM Cabibbe and AS Dean and P Glaziou and N Alikhanova and C Ama and S Andres and A Barbova and A Borbe-Reyes and DP Chin and DM Cirillo and C Colvin and A Dadu and A Dreyer and M Driesen and C Gilpin and R Hasan and Z Hasan and S Hoffner and A Hussain and N Ismail and SMM Kamal and FM Khanzada and M Kimerling and TA Kohl and M Mansj{\"o} and P Miotto and YD Mukadi and L Mvusi and S Niemann and SV Omar and L Rigouts and M Schito and I Sela and M Seyfaddinova and G Skenders and A Skrahina and S Tahseen and WA Wells and A Zhurilo and K Weyer and K Floyd and MC Raviglione",
year = "2018",
doi = "10.1016/S1473-3099(18)30073-2",
language = "English",
volume = "18",
pages = "675--683",
journal = "The Lancet Infectious Diseases",
issn = "1473-3099",
publisher = "Lancet Publishing Group",
number = "6",

}

TY - JOUR

T1 - Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study

AU - Zignol, M

AU - Cabibbe, AM

AU - Dean, AS

AU - Glaziou, P

AU - Alikhanova, N

AU - Ama, C

AU - Andres, S

AU - Barbova, A

AU - Borbe-Reyes, A

AU - Chin, DP

AU - Cirillo, DM

AU - Colvin, C

AU - Dadu, A

AU - Dreyer, A

AU - Driesen, M

AU - Gilpin, C

AU - Hasan, R

AU - Hasan, Z

AU - Hoffner, S

AU - Hussain, A

AU - Ismail, N

AU - Kamal, SMM

AU - Khanzada, FM

AU - Kimerling, M

AU - Kohl, TA

AU - Mansjö, M

AU - Miotto, P

AU - Mukadi, YD

AU - Mvusi, L

AU - Niemann, S

AU - Omar, SV

AU - Rigouts, L

AU - Schito, M

AU - Sela, I

AU - Seyfaddinova, M

AU - Skenders, G

AU - Skrahina, A

AU - Tahseen, S

AU - Wells, WA

AU - Zhurilo, A

AU - Weyer, K

AU - Floyd, K

AU - Raviglione, MC

PY - 2018

Y1 - 2018

N2 - 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, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (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. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development. © 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.

AB - 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, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (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. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development. © 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.

U2 - 10.1016/S1473-3099(18)30073-2

DO - 10.1016/S1473-3099(18)30073-2

M3 - Article

VL - 18

SP - 675

EP - 683

JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

SN - 1473-3099

IS - 6

ER -