TY - JOUR
T1 - Multicentre field evaluation of Xpert MTB/XDR in sub-Saharan Africa
AU - Massou, Faridath
AU - Diarra, Bassirou
AU - Ba Diallo, Awa
AU - Bah, Kindy Sadio
AU - Vuchas, Comfort
AU - Neh, Angela
AU - Sander, Melissa
AU - Adebiyi, Emmanuel O
AU - Aderemi, Bolaji Olufemi
AU - Agbla, Schadrac C
AU - Floyd, Sian
AU - Kaswa, Michel K
AU - Aloni, Muriel
AU - Sissy, Musala
AU - Ushizimpumu, Bertin
AU - Niyigena, Esdras Belamo
AU - Ngabonziza, J C S
AU - Abebe, Gemeda
AU - Tadesse, Mulualem
AU - Bah, Boubacar
AU - Camara, Lansana
AU - Gaye Diallo, Aissatou
AU - Camara, Makhtar
AU - Diallo, Fatimata
AU - Togo, Antièmé Combo Georges
AU - Ferré, Alice
AU - Badalato, Nelly
AU - Penn-Nicholson, Adam
AU - Schumacher, Samuel G
AU - Odjougbele, Sourou Toussaint
AU - Houeto, Sabine
AU - Mulders, Wim
AU - Frissette, Krista
AU - Kebede, Wakjira
AU - El Tayeb, Osman
AU - Merle, Corinne S
AU - de Jong, Bouke Catherine
AU - Supply, Philip
AU - Affolabi, Dissou
AU - Rigouts, Leen
N1 - FTX: CC BY NC
Copyright ©The authors 2026.
PY - 2026/3
Y1 - 2026/3
N2 - BACKGROUND: The World Health Organization-endorsed Xpert MTB/XDR assay provides a rapid method to detect resistance to isoniazid, fluoroquinolones, injectables aminoglycosides and ethionamide, yet evaluation of its performance, particularly in endemic settings, remains limited.METHODS: We conducted a prospective multicentre study (June 2017 to March 2021) in nine sub-Saharan African countries, enrolling adults with pulmonary tuberculosis confirmed by Xpert MTB/RIF or Ultra. Xpert MTB/XDR results were compared to a World Health Organization-endorsed targeted next-generation sequencing reference used on the same sputum, with discordance resolved using whole genome sequencing and phenotypic drug-susceptibility testing when available. Diagnostic accuracy for each drug was calculated, also accounting for genotypic heteroresistance detection.RESULTS: Among 1238 included patients, Xpert MTB/XDR demonstrated high specificity (≥98%) across all drugs yet showed variable sensitivity, detecting 606 out of 637 isoniazid-resistant (95%, 95% CI 94-97%), 22 out of 33 fluoroquinolones-resistant (67%, 95% CI 48-81%) and 159 out of 279 ethionamide-resistant (57%, 95% CI 51-63%) samples. The assay reliably detected most common resistance-conferring mutations, such as katG_S315T, fabG1_C-15T, and gyrA_A90V and D94G, yet failed to detect low-frequency heteroresistance (≤10-35%) and off-target mutations, mostly for ethionamide. Amikacin resistance was rare (0.2%). Sensitivity for fluoroquinolones was higher (78%) among rifampicin-resistant samples, highlighting its utility as a reflex test in rifampicin-resistant patients.CONCLUSIONS: Xpert MTB/XDR offers rapid diagnosis of resistance with high specificity. While limitations in detecting low-frequency and off-target variants affect its sensitivity, most frequent, fixed in-target mutations are readily detected. Future studies should evaluate strategies to integrate Xpert MTB/XDR with other diagnostic approaches in national tuberculosis programmes.
AB - BACKGROUND: The World Health Organization-endorsed Xpert MTB/XDR assay provides a rapid method to detect resistance to isoniazid, fluoroquinolones, injectables aminoglycosides and ethionamide, yet evaluation of its performance, particularly in endemic settings, remains limited.METHODS: We conducted a prospective multicentre study (June 2017 to March 2021) in nine sub-Saharan African countries, enrolling adults with pulmonary tuberculosis confirmed by Xpert MTB/RIF or Ultra. Xpert MTB/XDR results were compared to a World Health Organization-endorsed targeted next-generation sequencing reference used on the same sputum, with discordance resolved using whole genome sequencing and phenotypic drug-susceptibility testing when available. Diagnostic accuracy for each drug was calculated, also accounting for genotypic heteroresistance detection.RESULTS: Among 1238 included patients, Xpert MTB/XDR demonstrated high specificity (≥98%) across all drugs yet showed variable sensitivity, detecting 606 out of 637 isoniazid-resistant (95%, 95% CI 94-97%), 22 out of 33 fluoroquinolones-resistant (67%, 95% CI 48-81%) and 159 out of 279 ethionamide-resistant (57%, 95% CI 51-63%) samples. The assay reliably detected most common resistance-conferring mutations, such as katG_S315T, fabG1_C-15T, and gyrA_A90V and D94G, yet failed to detect low-frequency heteroresistance (≤10-35%) and off-target mutations, mostly for ethionamide. Amikacin resistance was rare (0.2%). Sensitivity for fluoroquinolones was higher (78%) among rifampicin-resistant samples, highlighting its utility as a reflex test in rifampicin-resistant patients.CONCLUSIONS: Xpert MTB/XDR offers rapid diagnosis of resistance with high specificity. While limitations in detecting low-frequency and off-target variants affect its sensitivity, most frequent, fixed in-target mutations are readily detected. Future studies should evaluate strategies to integrate Xpert MTB/XDR with other diagnostic approaches in national tuberculosis programmes.
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001721029100004
U2 - 10.1183/23120541.00427-2025
DO - 10.1183/23120541.00427-2025
M3 - A1: Peer-reviewed journal articles
C2 - 41809859
SN - 2312-0541
VL - 12
JO - ERJ Open Research
JF - ERJ Open Research
IS - 2
ER -