Point of care urine tests predict mortality among hospitalised HIV-positive adults

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

Manabe YC, Nonyane BA, Nakiyingi L, Mbabazi O, Lubega G, Shah M, Moulton LH, Joloba M, Ellner J, Dorman SE. PLoS One. 2014 Jul 7;9(7):e101459. doi: 10.1371/journal.pone.0101459. eCollection 2014.

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/microl 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.

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Editor’s notes: Despite increasing coverage of antiretroviral therapy, HIV-positive people continue to experience high mortality, particularly those sick enough to require hospital admission. Tuberculosis (TB) is well-known to be one of the most important causes of death among HIV-positive people in sub-Saharan Africa. Diagnosis of TB remains difficult, particularly in the sickest people who may have low concentrations of acid-fast bacilli in sputum, or may not be able to produce sputum at all. However, most people can give a sample of urine, and point of care tests using urine specimens have great potential to accelerate diagnosis of TB, and also cryptococcal disease.

In this study of hospitalised HIV-positive adults in Uganda, mortality was extremely high; 21% had died by two months and 32% by six months, even though some 38% of people were on antiretroviral therapy at enrollment. Urine was tested using point of care assays for LAM (a component of the mycobacterial cell wall) and cryptococcal antigen. People whose urine tested positive on either test were twice as likely to have died by two months. Further studies are needed to determine to what extent clinical outcomes can be improved by early testing using these assays, followed by treatment for TB or cryptococcal disease (or both).

Avoid TB deaths
Comorbidity
Africa
Uganda
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