title: Evaluation of Xpert MTB/RIF for detection of tuberculosis from blood samples of HIV-infected adults confirms Mycobacterium tuberculosis bacteremia as an indicator of poor prognosis.
abstract: Tuberculosis (TB) remains a leading cause of death among HIV-infected adults, in part because of delayed diagnosis and therefore delayed initiation of treatment. Recently, the Gene-Xpert platform, a rapid, PCR-based diagnostic platform, has been validated for the diagnosis of TB with sputum. We have evaluated the Xpert MTB/RIF assay for the diagnosis of Mycobacterium tuberculosis bacteremia and investigated its impact on clinical outcomes. Consecutive HIV-infected adults with fever and cough presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, were recruited and followed up for 2 months. At presentation, three sputum samples were examined by smear, culture, and Xpert MTB/RIF assay for the presence of M. tuberculosis and blood was drawn for PCR with Xpert, for mycobacterial culture (Myco/F Lytic), and for aerobic culture. One hundred four patients were recruited, and 44 (43%) were sputum culture positive for M. tuberculosis. Ten were Xpert blood positive, for a sensitivity of 21% and a specificity of 100%. The 2-week mortality rate was significantly higher among patients who were Xpert blood positive than among those who were negative (40% versus 3%; multivariate odds ratio [OR] for death if positive, 44; 95% confidence interval [CI], 3 to 662). This effect persisted on assessment of the mortality rate at 2 months (40% versus 11%; OR, 5.6; 95% CI, 1.3 to 24.6). When screening uncomplicated patients presenting with a productive cough for pulmonary TB, Xpert blood offers no diagnostic advantage over sputum testing. Despite this, Xpert blood positivity is highly predictive of early death and this test rapidly identifies a group of patients in urgent need of initiation of treatment.
authors.affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi. nfeasey@liverpool.ac.uk
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Feasey
authors.forename: Padmapriya P
authors.initials: PP
authors.lastname: Banada
authors.forename: William
authors.initials: W
authors.lastname: Howson
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Sloan
authors.forename: Aaron
authors.initials: A
authors.lastname: Mdolo
authors.forename: Catharina
authors.initials: C
authors.lastname: Boehme
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Chipungu
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Allain
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Corbett
authors.forename: David
authors.initials: D
authors.lastname: Alland
mesh_terms: D000328:Adult; D016470:Bacteremia / Q000175:diagnosis*; D001431:Bacteriological Techniques / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008295:Malawi; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014376:Tuberculosis / Q000175:diagnosis*