Point-of-care lateral flow assays for tuberculosis and cryptococcal antigenuria predict death in HIV infected adults in Uganda.

Bareng A. S. Nonyane,Moses Joloba,Jerrold Ellner,Susan E. Dorman,Lawrence H. Moulton,Maunank Shah,Olive Mbabazi,Gloria Lubega,Paul Sandstrom,Yukari C. Manabe,Lydia Nakiyingi

doi:10.1371/journal.pone.0101459

Abstract

BackgroundMortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB) and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA) result for urine lipoarabinomannan (LAM) and cryptococcal antigenuria was associated with mortality.Methods351 hospitalized, HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospectively enrolled at Mulago National Referral Hospital in Uganda as part of a prospective accuracy evaluation of the lateral flow Determine TB LAM test. Stored frozen urine was retrospectively tested for cryptococcal antigen (CRAG) using the LFA. We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation.ResultsThe median CD4 of the participants was 57 (IQR: 14–179) cells/µl and 41% (145) were microbiologically confirmed TB cases. LAM LFA was positive in 38% (134), 7% (25) were CRAG positive, and 43% (151) were positive for either test in urine. Overall, 21% (75) died within the first 2 months, and a total of 32% (114) were confirmed dead by 6 months. At 2 months, 30% of LAM or CRAG positive patients were confirmed dead compared to 15.0% of those who were negative. In an adjusted model, LAM or CRAG positive results were associated with an increased risk of death (RRR 2.29, 95% CI: 1.29, 4.05; P = 0.005).ConclusionsIn hospitalized HIV-infected patients, LAM or CRAG LFA positivity was associated with subsequent death within 2 months. Further studies are warranted to examine the impact of POC diagnostic ‘test and treat’ approach on patient-centered outcomes.

Highlights

Mortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, disseminated tuberculosis (TB) and cryptococcal disease
Mycobacteremia doubled the risk of in-hospital death from 22% to 44% (OR1.97, 95% confidence intervals (CI) = 1.19, 3.27, P = 0.026) in a study of patients who fulfilled systemic inflammatory response syndrome (SIRS)
The median CD4 was 57 (IQR: 14–179) cells/ml; 47.6% (167) of participants had a CD4,50 cells/ml and 37.6% (132) of participants were on antiretroviral therapy at enrollment

Summary

Introduction

Febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, disseminated tuberculosis (TB) and cryptococcal disease. Hospitalized patients in SSA continue to suffer high mortality (range 30–45%); the majority of these patients are HIV-infected and die from undiagnosed and untreated opportunistic infections [2,3,4,5,6]. Several studies have examined predictors of mortality in hospitalized HIV patients or among TB suspects and have found a significant proportion of patients have disseminated tuberculosis with mycobacteremia (range 13–42%) which may present with only fever progressing to septic shock [3,9,11,12,13,14].

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