title: The diagnostic accuracy of urine-based Xpert MTB/RIF in HIV-infected hospitalized patients who are smear-negative or sputum scarce.
abstract: BACKGROUND
  Hospitals in sub-Saharan Africa are inundated with HIV-infected patients and tuberculosis (TB) is the commonest opportunistic infection in this sub-group. Up to one third of TB-HIV co-infected patients fail to produce a sputum sample (sputum scarce) and diagnosis is thus often delayed or missed. We investigated the sensitivity of urine-based methods (Xpert MTB/RIF, LAM strip test and LAM ELISA) in such patients.
  
  
  RESULTS
  281 HIV-infected hospitalised patients with clinically suspected TB provided a spot urine sample. The reference standard was culture positivity for Mycobacterium tuberculosis on ≥1 sputum or extra-pulmonary sample. MTB/RIF was performed using 1 ml of both unprocessed and, when possible, concentrated urine. Each unconcentrated urine sample was also tested using the Clearview LAM ELISA and Alere LAM strip test. 42% (116/242) of patients had culture-proven TB. 18% (20/54) were sputum scarce. In sputum-scarce patients, the sensitivity of urine MTB/RIF and LAM ELISA was 40% (95%CI: 22-61) and 60% (95%CI: 39-78), respectively. Urine MTB/RIF specificity was 98% (95%CI: 95-100). Combined sensitivity of urine LAM ELISA and MTB/RIF was better than MTB/RIF alone [MTB/RIF and LAM: 70% (95%CI: 48-85) vs. MTB/RIF: 40% (95%CI: 22-61), p = 0.03]. Significant predictors of urine MTB/RIF positivity were CD4<50 cells/ml (p = 0.001), elevated protein-to-creatinine ratio (p<0.001) and LAM ELISA positivity (p<0.001). Urine centrifugation and pelleting significantly increased the sensitivity of MTB/RIF over unprocessed urine in paired samples [42% (95%CI: 26-58) vs. 8% (95%CI: 0-16), p<0.001]. Urine MTB/RIF-generated C(T) values correlated poorly with markers of bacillary burden (smear grade and time-to-positivity).
  
  
  CONCLUSIONS
  This preliminary study indicates that urine-based MTB/RIF, alone or in combination with LAM antigen detection, may potentially aid the diagnosis of TB in HIV-infected patients with advanced immunosuppression when sputum-based diagnosis is not possible. Concentration of urine prior to MTB/RIF-testing significantly improves sensitivity.
authors: Lung Infection and Immunity Unit, Division of Pulmonology & UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors: Jonathan G
authors: JG
authors: Peter
authors: Grant
authors: G
authors: Theron
authors: Tapuwa E
authors: TE
authors: Muchinga
authors: Ureshnie
authors: U
authors: Govender
authors: Keertan
authors: K
authors: Dheda
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000175:diagnosis / Q000652:urine; D000328:Adult; D000942:Antigens, Bacterial / Q000032:analysis / Q000276:immunology; D002498:Centrifugation; D024881:Drug Resistance, Bacterial; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D015658:HIV Infections / Q000150:complications*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D011934:Reagent Strips / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology*; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000652:urine; D016482:Urinalysis / Q000295:instrumentation / Q000379:methods*
chemical_list: D000942:Antigens, Bacterial; D011934:Reagent Strips; D012293:Rifampin