Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance

a prospective multicentre diagnostic accuracy study

study team

Research output: Contribution to journalArticle

Abstract

Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (−2·7%, −3·9 to −1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.

Original languageEnglish (US)
Pages (from-to)76-84
Number of pages9
JournalThe Lancet Infectious Diseases
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2018

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Rifampin
Mycobacterium tuberculosis
Sputum
Tuberculosis
Multiple Drug Resistance
HIV
National Institute of Allergy and Infectious Diseases (U.S.)
Republic of Belarus
Pharmaceutical Preparations
Uganda
Kenya
South Africa
Pulmonary Tuberculosis
Drug Resistance
Netherlands
Brazil
India
China
Primary Health Care
Thorax

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

@article{08fa66d529a349a58e6c6f00602a3314,
title = "Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study",
abstract = "Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63{\%} and 46{\%}, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17{\%}, 95{\%} CI 10 to 24); 90{\%} and 77{\%}, respectively, for the 115 HIV-positive participants with culture-positive sputum (13{\%}, 6·4 to 21); and 88{\%} and 83{\%}, respectively, across all 462 participants with culture-positive sputum (5·4{\%}, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96{\%} and 98{\%} (−2·7{\%}, −3·9 to −1·7) overall, and 93{\%} and 98{\%} for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.",
author = "{study team} and Dorman, {Susan E.} and Schumacher, {Samuel G.} and David Alland and Pamela Nabeta and Armstrong, {Derek T.} and Bonnie King and Hall, {Sandra L.} and Soumitesh Chakravorty and Cirillo, {Daniela M.} and Nestani Tukvadze and Nino Bablishvili and Wendy Stevens and Lesley Scott and Camilla Rodrigues and Kazi, {Mubin I.} and Moses Joloba and Lydia Nakiyingi and Nicol, {Mark P.} and Yonas Ghebrekristos and Irene Anyango and Wilfred Murithi and Reynaldo Dietze and {Lyrio Peres}, Renata and Alena Skrahina and Vera Auchynka and Chopra, {Kamal Kishore} and Mahmud Hanif and Xin Liu and Xing Yuan and Boehme, {Catharina C.} and Ellner, {Jerrold J.} and Denkinger, {Claudia M.} and Dorman, {Susan E.} and Schumacher, {Samuel G.} and David Alland and Pamela Nabeta and Armstrong, {Derek T.} and Bonnie King and Hall, {Sandra L.} and Soumitesh Chakravorty and Cirillo, {Daniela M.} and Nestani Tukvadze and Nino Bablishvili and Wendy Stevens and Lesley Scott and Camilla Rodrigues and Kazi, {Mubin I.} and Moses Joloba and Lydia Nakiyingi and Manabe, {Yukari C}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/S1473-3099(17)30691-6",
language = "English (US)",
volume = "18",
pages = "76--84",
journal = "The Lancet Infectious Diseases",
issn = "1473-3099",
publisher = "Lancet Publishing Group",
number = "1",

}

TY - JOUR

T1 - Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance

T2 - a prospective multicentre diagnostic accuracy study

AU - study team

AU - Dorman, Susan E.

AU - Schumacher, Samuel G.

AU - Alland, David

AU - Nabeta, Pamela

AU - Armstrong, Derek T.

AU - King, Bonnie

AU - Hall, Sandra L.

AU - Chakravorty, Soumitesh

AU - Cirillo, Daniela M.

AU - Tukvadze, Nestani

AU - Bablishvili, Nino

AU - Stevens, Wendy

AU - Scott, Lesley

AU - Rodrigues, Camilla

AU - Kazi, Mubin I.

AU - Joloba, Moses

AU - Nakiyingi, Lydia

AU - Nicol, Mark P.

AU - Ghebrekristos, Yonas

AU - Anyango, Irene

AU - Murithi, Wilfred

AU - Dietze, Reynaldo

AU - Lyrio Peres, Renata

AU - Skrahina, Alena

AU - Auchynka, Vera

AU - Chopra, Kamal Kishore

AU - Hanif, Mahmud

AU - Liu, Xin

AU - Yuan, Xing

AU - Boehme, Catharina C.

AU - Ellner, Jerrold J.

AU - Denkinger, Claudia M.

AU - Dorman, Susan E.

AU - Schumacher, Samuel G.

AU - Alland, David

AU - Nabeta, Pamela

AU - Armstrong, Derek T.

AU - King, Bonnie

AU - Hall, Sandra L.

AU - Chakravorty, Soumitesh

AU - Cirillo, Daniela M.

AU - Tukvadze, Nestani

AU - Bablishvili, Nino

AU - Stevens, Wendy

AU - Scott, Lesley

AU - Rodrigues, Camilla

AU - Kazi, Mubin I.

AU - Joloba, Moses

AU - Nakiyingi, Lydia

AU - Manabe, Yukari C

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (−2·7%, −3·9 to −1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.

AB - Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (−2·7%, −3·9 to −1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.

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U2 - 10.1016/S1473-3099(17)30691-6

DO - 10.1016/S1473-3099(17)30691-6

M3 - Article

VL - 18

SP - 76

EP - 84

JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

SN - 1473-3099

IS - 1

ER -