Disseminated tuberculosis among hospitalised HIV patients in South Africa: a common condition that can be rapidly diagnosed using urine-based assays

Andrew D Kerkhoff,Rosie Burton,David A Barr,Graeme Meintjes,Stephen D Lawn,Charlotte Schutz,Mark P Nicol

doi:10.1038/s41598-017-09895-7

Abstract

HIV-associated disseminated TB (tuberculosis) has been under-recognised and poorly characterised. Blood culture is the gold-standard diagnostic test, but is expensive, slow, and may under-diagnose TB dissemination. In a cohort of hospitalised HIV patients, we aimed to report the prevalence of TB-blood-culture positivity, performance of rapid diagnostics as diagnostic surrogates, and better characterise the clinical phenotype of disseminated TB. HIV-inpatients were systematically investigated using sputum, urine and blood testing. Overall, 132/410 (32.2%) patients had confirmed TB; 41/132 (31.1%) had a positive TB blood culture, of these 9/41 (22.0%) died within 90-days. In contrast to sputum diagnostics, urine Xpert and urine-lipoarabinomannan (LAM) combined identified 88% of TB blood-culture-positive patients, including 9/9 who died within 90-days. For confirmed-TB patients, half the variation in major clinical variables was captured on two principle components (PCs). Urine Xpert, urine LAM and TB-blood-culture positive patients clustered similarly on these axes, distinctly from patients with localised disease. Total number of positive tests from urine Xpert, urine LAM and MTB-blood-culture correlated with PCs (p < 0.001 for both). PC1&PC2 independently predicted 90-day mortality (ORs 2.6, 95%CI = 1.3–6.4; and 2.4, 95%CI = 1.3–4.5, respectively). Rather than being a non-specific diagnosis, disseminated TB is a distinct, life-threatening condition, which can be diagnosed using rapid urine-based tests, and warrants specific interventional trials.

Highlights

Tuberculosis (TB) is a leading infectious cause of death worldwide, with an estimated 1.8 million deaths in 20151; it remains the leading cause of death in people living with HIV, contributing to 1 in 3 HIV-related deaths[2, 3]
41 patients had a positive Mycobacterium tuberculosis (MTB) blood culture, which accounted for 10.0% (95%CI, 7.3–13.3) of all HIV-infected inpatients and nearly one-third (n = 41/132; 31.1%) of all HIV-infected inpatients with newly diagnosed TB (‘TB positive | blood culture positive’)
MTB blood cultures were positive in 10% of unselected HIV-infected South African adults requiring acute medical admission, and nearly one-third of those with newly diagnosed active TB disease

Summary

Introduction

Tuberculosis (TB) is a leading infectious cause of death worldwide, with an estimated 1.8 million deaths in 20151; it remains the leading cause of death in people living with HIV, contributing to 1 in 3 HIV-related deaths[2, 3]. We suggest that a clear distinction should be made between this (anatomically limited) extra-pulmonary TB disease and the disseminated disease seen in association with advanced HIV infection. This HIV-associated disseminated TB disease phenotype implies ongoing blood stream distribution, which is supported by some clinical studies showing a high prevalence of Mycobacterium tuberculosis (MTB) blood culture positivity in HIV-associated TB9, 10. MTB positive blood cultures are rarely seen in immune-competent patients, including those with extra-pulmonary disease (miliary TB accounts for

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