Comparison of Xpert MTB/RIF with other nucleic acid technologies for diagnosing pulmonary tuberculosis in a high HIV prevalence setting: A prospective study

Background: the xpert mtb/rif (cepheid) non-laboratory-based molecular assay has potential to improve the diagnosis of tuberculosis (tb),especially in hiv-infected populations,through increased sensitivity,reduced turnaround time (2 h),and immediate identification of rifampicin (rif) resistance. in a prospective clinical validation study we compared the performance of xpert mtb/rif,mtbdrplus (hain lifescience),lightcycler mycobacterium detection (lctb) (roche),with acid fast bacilli (afb) smear microscopy and liquid culture on a single sputum specimen. methods and findings: consecutive adults with suspected tb attending a primary health care clinic in johannesburg,south africa,were prospectively enrolled and evaluated for tb according to the guidelines of the national tb control programme,including assessment for smear-negative tb by chest x-ray,clinical evaluation,and hiv testing. a single sputum sample underwent routine decontamination,afb smear microscopy,liquid culture,and phenotypic drug susceptibility testing. residual sample was batched for molecular testing. for the 311 participants,the hiv prevalence was 70% (n = 215),with 120 (38.5%) culture-positive tb cases. compared to liquid culture,the sensitivities of all the test methodologies,determined with a limited and potentially underpowered sample size (n = 177),were 59% (47%-71%) for smear microscopy,76% (64%-85%) for mtbdrplus,76% (64%-85%) for lctb,and 86% (76%-93%) for xpert mtb/rif,with specificities all >97%. among hiv+ individuals,the sensitivity of the xpert mtb/rif test was 84% (69%-93%),while the other molecular tests had sensitivities reduced by 6%. tb detection among smear-negative,culture-positive samples was 28% (5/18) for mtbdrplus,22% (4/18) for lctb,and 61% (11/18) for xpert mtb/rif. a few (n = 5) rif-resistant cases were detected using the phenotypic drug susceptibility testing methodology. xpert mtb/rif detected four of these five cases (fifth case not tested) and two additional phenotypically sensitive cases. conclusions: the xpert mtb/rif test has superior performance for rapid diagnosis of mycobacterium tuberculosis over existing afb smear microscopy and other molecular methodologies in an hiv- and tb-endemic region. its place in the clinical diagnostic algorithm in national health programs needs exploration. © 2011 scott et al.