Performance of the Abbott RealTi m e MTB and MTB RIF/INH Assays in a Setting of High Tuberculosis and HIV Coinfection in South Africa

Abstract

South Africa is a country with a high incidence of tuberculosis (TB), complicated by coinfection with human immunodeficiency virus (HIV). The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is used in South Africa as the test for the initial diagnosis of TB, and other molecular platforms such as the m2000 (Abbott Molecular, Des Plaines, IL, USA) are widely used for molecular monitoring of HIV load. The latter platform is now also equipped with the RealTime (RT) MTB and RealTime MTB RIF/INH assays for TB and first-line drug resistance screening but has not been evaluated in settings of HIV and TB coinfection. A prospective clinical validation study was conducted at a community health center in Johannesburg, South Africa, and consenting individuals with presumptive pulmonary TB were enrolled. The performance of the Abbott assays was compared with those of the Xpert MTB/RIF, liquid culture, drug susceptibility testing, and clinical case definitions. A statistical analysis was performed on 206 individuals (73% were HIV positive). The sensitivity and specificity of the RT MTB were 82.5% (confidence interval [CI], 67.2 to 92.7) and 93.1% (CI, 86.2 to 97.2) on raw sputum and 77.5% (CI, 61.5 to 89.2) and 95.1% (CI, 88.9 to 98.4) on concentrated sputum, respectively, compared with those from liquid culture. The RT MTB correctly identified 17/35 more smear-negative culture-positive specimens than the Xpert MTB/RIF. Both the RT MTB and the Xpert MTB/RIF displayed sensitivities Ͼ70% and specificities Ͼ90% in HIV-positive individuals. The available drug resistance results concurred with MTBDRplus and drug susceptibility profiles. The RT MTB assay has similar diagnostic performance to the Xpert MTB/RIF and is suited to testing presumptive TB patients coinfected with HIV. The existing laboratory information system connectivity, training, and technical support make this a viable polyvalent option to scale up TB alongside HIV laboratory testing services in South Africa.

Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults

“…Eleven studies (4196 participants) reported a higher percentage (> 25%) of participants with a history of tuberculosis ( Adelman 2015 ; Al‐Darraji 2013 ; Boehme 2010 ; Kawkitinarong 2017 ; Ko 2016 ; Lawn 2011 ; Mutingwende 2015 ; O'Donnell 2015 ; Reddy 2017 ; Reechaipichitkul 2017 ; Theron 2011 ) and 16 studies (8205 participants) reported a lower percentage (≤ 25%) of participants with a history of tuberculosis ( Balcha 2014 ; Barmankulova 2015 ; Bates 2013a ; Bjerrum 2016 ; Boehme 2010 ; Boum 2016 ; Carriquiry 2012 ; Dorman 2018 ; Hanrahan 2013 ; Helb 2010 ; LaCourse 2016 ; Luetkemeyer 2016 ; Mbelele 2017 ; Scott 2017 ; Sohn 2014 ; Yoon 2017 ). In studies with a higher percentage of participants with previous tuberculosis, Xpert MTB/RIF pooled sensitivity (95% CrI) was 86% (82% to 89%), similar to the pooled sensitivity of 85% (81% to 89%) in studies with a lower percentage of participants with previous tuberculosis.…”

Evaluation of a new automated Abbott RealTime MTB RIF/INH assay for qualitative detection of rifampicin/isoniazid resistance in pulmonary and extra-pulmonary clinical samples of <em>Mycobacterium tuberculosis</em>

“…The most important disadvantage in the study was the high percentage (33%) of samples with a low LOD. 13 …”

Performance of Xpert MTB/RIF, Xpert Ultra, and Abbott RealTi m e MTB for Diagnosis of Pulmonary Tuberculosis in a High-HIV-Burden Setting

“…ability in test performance in smear-negative disease, with sensitivity ranging between 26% and 67% (1)(2)(3)(4)(5)(6). This is particularly problematic in children and people living with HIV (particularly advanced HIV disease) who are more likely to have smear-negative disease and also experience high TB-associated mortality (7), highlighting the need for new tests with improved sensitivity for the detection of paucibacillary disease.…”

“…The RT-MTB assay identifies both rifampin (RIF) and isoniazid (INH) resistance via the RealTime MTB RIF/INH reflex test (RT-MTB RIF/INH), which targets the rifampin resistance-determining region (RRDR) of rpoB, as well as the katG and upper inhA gene promoter regions. In analytical studies, RT-MTB has a LoD of 32 CFU/ml (13), and in clinical studies, the test sensitivity ranged from 74% in smearnegative specimens (6) to 100% in smear-positive pulmonary specimens (14)(15)(16)(17)(18). However, most of the studies of RT-MTB to date, aside from those by Scott and colleagues (6), did not include specimens from people living with HIV, which may impact the results.…”