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

Abstract

Background: Mortality 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.

Methods: 351 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.

Results: The 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).

Conclusions: In 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.

Figure 1. Study participant flow chart.

Figure 2. Venn diagram showing the proportions of patients confirmed dead at 2 months (n = 75) who had positive sputum and/or blood cultures (“confirmed TB”), Xpert MTB/RIF positive, and Determine TB LAM LFA positive.

Mutually exclusive proportions of patients are shown in each compartment. 17% of the patients who died were LAM positive, but were neither Xpert nor culture confirmed. 24% of the patients who died were positive by all assays.

Figure 3. Kaplan-Meier survival curves of LAM negative patients (solid line), and LAM positive patients (dashed line).

Participants who could not be traced at 2 months were considered lost to follow-up on the day after enrollment.