Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications

Bertin C. Bisimwa; Jean B. Nachega; Robin M. Warren; Grant Theron; John Z. Metcalfe; Maunank Shah; Andreas H. Diacon; Nadia A. Sam-Agudu; Marcel Yotebieng; André N.H. Bulabula; Patrick D.M.C. Katoto; Jean Paul Chirambiza; Rosette Nyota; Freddy M. Birembano; Eric M. Musafiri; Sifa Byadunia; Esto Bahizire; Michel K. Kaswa; Steven Callens; Zacharie M. Kashongwe

doi:10.1093/cid/ciaa873

Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications

Bertin C. Bisimwa, Jean B. Nachega, Robin M. Warren, Grant Theron, John Z. Metcalfe, Maunank Shah, Andreas H. Diacon, Nadia A. Sam-Agudu, Marcel Yotebieng, André N.H. Bulabula, Patrick D.M.C. Katoto, Jean Paul Chirambiza, Rosette Nyota, Freddy M. Birembano, Eric M. Musafiri, Sifa Byadunia, Esto Bahizire, Michel K. Kaswa, Steven Callens, Zacharie M. Kashongwe

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Background: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). Methods: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. Results: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. Conclusions: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Original language	English (US)
Pages (from-to)	E362-E370
Journal	Clinical Infectious Diseases
Volume	73
Issue number	2
DOIs	https://doi.org/10.1093/cid/ciaa873
State	Published - Jul 15 2021
Externally published	Yes

Bibliographical note

Funding Information:
J. B. N. is supported by the US National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), the Clinical Trial Unit (CTU) of the AIDS Clinical Trial Group (ACTG) at Stellenbosch University (grant number 2UM1AI069521-08); the University of Pittsburgh HIV-comorbidities Research Training Program in South Africa (NIH/Fogarty International Center [FIC]; grant number 1D43TW010937-01A1); and the African Association for Health Professions Education and Research (NIH/FIC; grant number 1R25TW011217-01). J. Z. M. is supported by the NIH/ NIAID R01AI131939 and NIH/FIC D43TW009539. G. T. acknowledges support from the EDCTP 2 program supported by the European Union (grant number SF1401, Optimal Diagnosis). Also, G. T. and R. M. W. are partially funded by the South African government through the South African Medical Research Council. A. H. D. is supported by the National Research Foundation of South Africa. N. A. S.-A. is supported by the NIH/National Institute of Child Health and Human Development (NICHD) (grant number R01HD089866) and by an NIH/FIC award under the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA), for the Central and West Africa Implementation Science Alliance (CAWISA; grant number 65662). M. Y. is partially supported by the NIH/NIAID through the Central Africa-International epidemiology Databases to Evaluate AIDS (CA-IeDEA) award number U01 AI096299. Z. M. K. and B. C. B. were supported by Universitaire Ontwikkelingssamenwerking (VLIR-UOS) (grant number PRDC 2012MP80). All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The other authors report no potential conflicts.

Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Keywords

DRC
GenoType MTBDRplus assay
drug resistance
inhA mutations
rpoB mutations

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Bisimwa, B. C., Nachega, J. B., Warren, R. M., Theron, G., Metcalfe, J. Z., Shah, M., Diacon, A. H., Sam-Agudu, N. A., Yotebieng, M., Bulabula, A. N. H., Katoto, P. D. M. C., Chirambiza, J. P., Nyota, R., Birembano, F. M., Musafiri, E. M., Byadunia, S., Bahizire, E., Kaswa, M. K., Callens, S., & Kashongwe, Z. M. (2021). Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications. Clinical Infectious Diseases, 73(2), E362-E370. https://doi.org/10.1093/cid/ciaa873

Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications. / Bisimwa, Bertin C.; Nachega, Jean B.; Warren, Robin M. et al.
In: Clinical Infectious Diseases, Vol. 73, No. 2, 15.07.2021, p. E362-E370.

Research output: Contribution to journal › Article › peer-review

Bisimwa, BC, Nachega, JB, Warren, RM, Theron, G, Metcalfe, JZ, Shah, M, Diacon, AH, Sam-Agudu, NA, Yotebieng, M, Bulabula, ANH, Katoto, PDMC, Chirambiza, JP, Nyota, R, Birembano, FM, Musafiri, EM, Byadunia, S, Bahizire, E, Kaswa, MK, Callens, S & Kashongwe, ZM 2021, 'Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications', Clinical Infectious Diseases, vol. 73, no. 2, pp. E362-E370. https://doi.org/10.1093/cid/ciaa873

Bisimwa BC, Nachega JB, Warren RM, Theron G, Metcalfe JZ, Shah M et al. Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications. Clinical Infectious Diseases. 2021 Jul 15;73(2):E362-E370. doi: 10.1093/cid/ciaa873

@article{9cc97103e38c4eb69a77b4bac1c56d6f,

title = "Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications",

abstract = "Background: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). Methods: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. Results: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. Conclusions: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.",

keywords = "DRC, GenoType MTBDRplus assay, drug resistance, inhA mutations, rpoB mutations",

author = "Bisimwa, {Bertin C.} and Nachega, {Jean B.} and Warren, {Robin M.} and Grant Theron and Metcalfe, {John Z.} and Maunank Shah and Diacon, {Andreas H.} and Sam-Agudu, {Nadia A.} and Marcel Yotebieng and Bulabula, {Andr{\'e} N.H.} and Katoto, {Patrick D.M.C.} and Chirambiza, {Jean Paul} and Rosette Nyota and Birembano, {Freddy M.} and Musafiri, {Eric M.} and Sifa Byadunia and Esto Bahizire and Kaswa, {Michel K.} and Steven Callens and Kashongwe, {Zacharie M.}",

note = "Funding Information: J. B. N. is supported by the US National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), the Clinical Trial Unit (CTU) of the AIDS Clinical Trial Group (ACTG) at Stellenbosch University (grant number 2UM1AI069521-08); the University of Pittsburgh HIV-comorbidities Research Training Program in South Africa (NIH/Fogarty International Center [FIC]; grant number 1D43TW010937-01A1); and the African Association for Health Professions Education and Research (NIH/FIC; grant number 1R25TW011217-01). J. Z. M. is supported by the NIH/ NIAID R01AI131939 and NIH/FIC D43TW009539. G. T. acknowledges support from the EDCTP 2 program supported by the European Union (grant number SF1401, Optimal Diagnosis). Also, G. T. and R. M. W. are partially funded by the South African government through the South African Medical Research Council. A. H. D. is supported by the National Research Foundation of South Africa. N. A. S.-A. is supported by the NIH/National Institute of Child Health and Human Development (NICHD) (grant number R01HD089866) and by an NIH/FIC award under the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA), for the Central and West Africa Implementation Science Alliance (CAWISA; grant number 65662). M. Y. is partially supported by the NIH/NIAID through the Central Africa-International epidemiology Databases to Evaluate AIDS (CA-IeDEA) award number U01 AI096299. Z. M. K. and B. C. B. were supported by Universitaire Ontwikkelingssamenwerking (VLIR-UOS) (grant number PRDC 2012MP80). All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The other authors report no potential conflicts. Publisher Copyright: {\textcopyright} 2020 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.",

year = "2021",

month = jul,

day = "15",

doi = "10.1093/cid/ciaa873",

language = "English (US)",

volume = "73",

pages = "E362--E370",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo

T2 - Diagnostic and Clinical Implications

AU - Bisimwa, Bertin C.

AU - Nachega, Jean B.

AU - Warren, Robin M.

AU - Theron, Grant

AU - Metcalfe, John Z.

AU - Shah, Maunank

AU - Diacon, Andreas H.

AU - Sam-Agudu, Nadia A.

AU - Yotebieng, Marcel

AU - Bulabula, André N.H.

AU - Katoto, Patrick D.M.C.

AU - Chirambiza, Jean Paul

AU - Nyota, Rosette

AU - Birembano, Freddy M.

AU - Musafiri, Eric M.

AU - Byadunia, Sifa

AU - Bahizire, Esto

AU - Kaswa, Michel K.

AU - Callens, Steven

AU - Kashongwe, Zacharie M.

N1 - Funding Information: J. B. N. is supported by the US National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), the Clinical Trial Unit (CTU) of the AIDS Clinical Trial Group (ACTG) at Stellenbosch University (grant number 2UM1AI069521-08); the University of Pittsburgh HIV-comorbidities Research Training Program in South Africa (NIH/Fogarty International Center [FIC]; grant number 1D43TW010937-01A1); and the African Association for Health Professions Education and Research (NIH/FIC; grant number 1R25TW011217-01). J. Z. M. is supported by the NIH/ NIAID R01AI131939 and NIH/FIC D43TW009539. G. T. acknowledges support from the EDCTP 2 program supported by the European Union (grant number SF1401, Optimal Diagnosis). Also, G. T. and R. M. W. are partially funded by the South African government through the South African Medical Research Council. A. H. D. is supported by the National Research Foundation of South Africa. N. A. S.-A. is supported by the NIH/National Institute of Child Health and Human Development (NICHD) (grant number R01HD089866) and by an NIH/FIC award under the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA), for the Central and West Africa Implementation Science Alliance (CAWISA; grant number 65662). M. Y. is partially supported by the NIH/NIAID through the Central Africa-International epidemiology Databases to Evaluate AIDS (CA-IeDEA) award number U01 AI096299. Z. M. K. and B. C. B. were supported by Universitaire Ontwikkelingssamenwerking (VLIR-UOS) (grant number PRDC 2012MP80). All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The other authors report no potential conflicts. Publisher Copyright: © 2020 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

PY - 2021/7/15

Y1 - 2021/7/15

N2 - Background: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). Methods: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. Results: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. Conclusions: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

AB - Background: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). Methods: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. Results: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. Conclusions: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

KW - DRC

KW - GenoType MTBDRplus assay

KW - drug resistance

KW - inhA mutations

KW - rpoB mutations

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U2 - 10.1093/cid/ciaa873

DO - 10.1093/cid/ciaa873

M3 - Article

C2 - 32590841

AN - SCOPUS:85091844937

SN - 1058-4838

VL - 73

SP - E362-E370

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 2

ER -

Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications

Abstract

Bibliographical note

Keywords

UN SDGs

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