Cuella-Martin Isabel, Hakizayezu Francois, Ahmed Aymen, Runyambo Docteur, Niyompano Hosee, Keysers Jelle, De Rijk Willem Bram, Mulders Wim, Mitchell Ellen M H, Decroo Tom, Habimana Yves Mucyo, Migambi Patrick, Muvunyi Claude Mambo, de Jong Bouke C, Rigouts Leen, Ngabonziza Jean Claude Semuto
Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium.
Clin Infect Dis. 2025 Mar 22. doi: 10.1093/cid/ciaf132.
Xpert MTB/RIF Ultra (Ultra) aimed to improve the specificity in identifying rifampicin-resistant tuberculosis (RR-TB), compared to Xpert MTB/RIF.
In a nationwide study in Rwanda, patients diagnosed with RR-TB by Ultra between December 2021 and January 2024 underwent repeat Ultra testing, complemented by rpoB gene sequencing and phenotypic drug-susceptibility testing (pDST), serving as reference tests.
Of 129 patients initially diagnosed with RR-TB by Ultra, only 41 (32%) had concordant rifampicin results upon repeat Ultra testing. The remaining 88 patients (68%) had unconfirmed resistance on repeat Ultra. Reference testing was available for 40 (98%) of 41 confirmed cases, all verified as true RR-TB. Among 88 unconfirmed cases, reference testing was available for 61 (69%), with seven (11%) confirmed as true RR-TB, while 54 (89%) were found to have rifampicin-susceptible TB. Notably, 89% of 55 patients with very low bacillary loads on their initial Ultra had false RR-TB results, a significantly higher risk of false resistance compared to other bacillary load categories combined (risk ratio: 8.20; 95% CI: 3.56-18.85; p<0.001). Consequently, 53% (54/101) of initial RR patients with available reference testing received unnecessary RR-TB treatment.
Ultra represents a valuable tool for rapid RR-TB detection, however, in low prevalence settings its low positive predictive value for RR detection is largely driven by samples with very low bacillary loads. As programs expand active case-finding and early detection of asymptomatic disease, the proportion of TB detected with very low bacillary load will increase. Diagnostic algorithms require adjustments to prevent unnecessary RR-TB treatment.
与Xpert MTB/RIF相比，Xpert MTB/RIF Ultra（Ultra）旨在提高利福平耐药结核病（RR-TB）的识别特异性。
在卢旺达的一项全国性研究中，2021年12月至2024年1月期间被Ultra诊断为RR-TB的患者接受了重复Ultra检测，并辅以rpoB基因测序和表型药敏试验（pDST）作为参考检测。
在最初被Ultra诊断为RR-TB的129例患者中，重复Ultra检测时只有41例（32%）利福平检测结果一致。其余88例患者（68%）重复Ultra检测时耐药未得到确认。41例确诊病例中有40例（98%）可进行参考检测，均被证实为真正的RR-TB。在88例未确诊病例中，61例（69%）可进行参考检测，其中7例（11%）被证实为真正的RR-TB，而54例（89%）被发现为利福平敏感结核病。值得注意的是，最初Ultra检测时细菌载量极低的55例患者中，89%出现了RR-TB假阳性结果，与其他细菌载量类别相比，假耐药风险显著更高（风险比：8.20；95%置信区间：3.56-18.85；p<0.001）。因此，在可进行参考检测的初始RR患者中，53%（54/101）接受了不必要的RR-TB治疗。
Ultra是快速检测RR-TB的重要工具，然而，在低流行环境中，其对RR检测的低阳性预测值很大程度上是由细菌载量极低的样本导致的。随着项目扩大主动病例发现和无症状疾病的早期检测，细菌载量极低的结核病检测比例将会增加。诊断算法需要调整，以防止不必要的RR-TB治疗。
