title: Comparison of Xpert MTB/RIF with other nucleic acid technologies for diagnosing pulmonary tuberculosis in a high HIV prevalence setting: a prospective study.
abstract: 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.
  
  
  RESULTS
  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. Please see later in the article for the Editors' Summary.
authors.affiliation: Department of Molecular Medicine and Hematology, University of the Witwatersrand, Johannesburg, South Africa. lesley.scott@nhls.ac.za
authors.forename: Lesley E
authors.initials: LE
authors.lastname: Scott
authors.forename: Kerrigan
authors.initials: K
authors.lastname: McCarthy
authors.forename: Natasha
authors.initials: N
authors.lastname: Gous
authors.forename: Matilda
authors.initials: M
authors.lastname: Nduna
authors.forename: Annelies
authors.initials: A
authors.lastname: Van Rie
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.forename: Willem F
authors.initials: WF
authors.lastname: Venter
authors.forename: Adrian
authors.initials: A
authors.lastname: Duse
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
mesh_terms: D000328:Adult; D000368:Aged; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005260:Female; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000904:Antibiotics, Antitubercular; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C505805:rpoB protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin