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Massive Diagnostic Yield of HIV-Associated Tuberculosis Using Rapid Urine Assays in South Africa
Stephen D. Lawn, Andrew Kerkhoff, Rosie Burton, Charlotte Schutz, Gavin van Wyk, Monica Vogt, Pearl Pahlana, Mark Nicol, Graeme Meintjes *Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom, University of Cape Town, Cape Town, South Africa, Department of Medicine, University of Cape Town, Cape Town, South Africa, Department of Clinical Research, University of Cape Town, Cape Town, South Africa, Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa, Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa
Background: Autopsy studies of HIV/AIDS deaths in medical in-patients in sub-Saharan Africa have all reported a high frequency of disseminated tuberculosis (TB), indicating frequent failure of diagnosis. This observational study aimed to identify improved means of rapid TB diagnosis.
Methodology: Unselected HIV-infected medical admissions to a South African district hospital were intensively investigated. Sputum, urine and blood specimens were systematically obtained within the first 24 hours. Multiple additional respiratory and non-respiratory samples were obtained throughout admission as clinically indicated. Sputum samples were tested using fluorescence microscopy, liquid culture and Xpert MTB/RIF (Xpert). Urine samples were tested using Xpert (urine-Xpert of both unconcentrated and concentrated samples) and Determine TB-LAM (urine-LAM). Other non-respiratory samples were cultured. TB diagnoses were defined by detection of Mycobacterium tuberculosis in any sample using culture or Xpert.
Results: HIV-status was ascertained in 1,013 of 1,018 (99.5%) admissions and 585 of 609 (96.1%) HIV-infected patients were enrolled. All those without an existing TB diagnosis (n=427) were included in this analysis. 3,471 TB investigations were done on 1,745 samples from a median of 3 anatomic sites per patient. TB was diagnosed in 139 patients (median CD4 count, 80 cells/μL) and symptoms were very poorly predictive. TB prevalence was 32.6% (95%CI, 28.1-37.2). Disease was extrapulmonary in 83% of cases and pulmonary in just 54% (P<0.001). Using samples obtained in the first 24-hours, the proportions of final diagnoses made by sputum microscopy, sputum-Xpert, urine-LAM and urine-Xpert (30-40 ml concentrated urine) were 19.4%, 26.6%, 38.1% and 59.0%, respectively. Rapid urine tests used together diagnosed 69.1% (96 of 139) of cases. This further increased to 80.6% (112 of 139) of cases when combined with sputum Xpert testing. However, of those with CD4 counts <100 cells/μL, 85.1% (63 of 74) could be diagnosed with urine rapid tests alone.
Conclusions: The prevalence of TB was so high and the presentation so non-specific that routine microbiological investigation for TB should be done in all HIV-infected medical in-patients in high-burden settings. Compared to Xpert testing of one sputum sample alone, the addition of urine-based testing increased the diagnostic yield of the initial TB screen 3.0-fold from 26.6% to 80.6% (P<0.001). Urine-based rapid diagnostics should be considered for routine use in this patient population.