Multicentre field evaluation of Xpert MTB/XDR in sub-Saharan Africa.
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Massou Faridath, Diarra Bassirou, Ba Diallo Awa, Bah Kindy Sadio, Vuchas Comfort, Neh Angela, Sander Melissa, Adebiyi Emmanuel O, Aderemi Bolaji Olufemi, Agbla Schadrac C, Floyd Sian, Kaswa Michel K, Aloni Muriel, Sissy Musala, Ushizimpumu Bertin, Niyigena Esdras Belamo, Ngabonziza J C S, Abebe Gemeda, Tadesse Mulualem, Bah Boubacar, Camara Lansana, Gaye Diallo Aissatou, Camara Makhtar, Diallo Fatimata, Togo Antièmé Combo Georges, Ferré Alice, Badalato Nelly, Penn-Nicholson Adam, Schumacher Samuel G, Odjougbele Sourou Toussaint, Houeto Sabine, Mulders Wim, Frissette Krista, Kebede Wakjira, El Tayeb Osman, Merle Corinne S, de Jong Bouke Catherine, Supply Philip, Affolabi Dissou, Rigouts Leen
Аннотация
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.