The diagnostic accuracy of urine-based Xpert MTB/RIF in HIV-infected hospitalized patients who are smear-negative or sputum scarce

• Published in: PloS one Vol. 7; no. 7; p. e39966
• Main Authors: Peter, Jonathan G, Theron, Grant, Muchinga, Tapuwa E, Govender, Ureshnie, Dheda, Keertan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.07.2012; Public Library of Science (PLoS)
• Subjects: Accuracy; Adult; AIDS-Related Opportunistic Infections - complications; AIDS-Related Opportunistic Infections - diagnosis; AIDS-Related Opportunistic Infections - urine; Antigens; Antigens, Bacterial - analysis; Antigens, Bacterial - immunology; Automation; CD4 antigen; Cell culture; Centrifugation; Creatinine; Critical care; Diagnosis; Diagnostic systems; Drug Resistance, Bacterial; Drug therapy; Enzyme-Linked Immunosorbent Assay; Feasibility Studies; Health aspects; HIV; HIV infections; HIV Infections - complications; HIV patients; Hospital patients; Hospitalization - statistics & numerical data; Hospitals; Human immunodeficiency virus; Humans; Immunosuppression; Immunotherapy; Infection; Infections; Infectious diseases; Male; Medical diagnosis; Medicine; Meningitis; Microscopy; Mortality; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - isolation & purification; Mycobacterium tuberculosis - physiology; Opportunist infection; Patients; Pelleting; Physiology; Polymerase chain reaction; Reagent Strips - metabolism; Rifampin - pharmacology; Sensitivity; Sensitivity and Specificity; Smear; Sputum; Sputum - microbiology; Tuberculosis; Tuberculosis - complications; Tuberculosis - diagnosis; Tuberculosis - urine; Urinalysis - instrumentation; Urinalysis - methods; Urine; United States > US; South Africa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0039966

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. 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). 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.