title: 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.
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Bareng A S
authors.initials: BA
authors.lastname: Nonyane
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakiyingi
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: Olive
authors.initials: O
authors.lastname: Mbabazi
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: Gloria
authors.initials: G
authors.lastname: Lubega
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Maunank
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Moulton
authors.affiliation: Department of Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Jerrold
authors.initials: J
authors.lastname: Ellner
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Dorman
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000652:urine; D000328:Adult; D000946:Antigens, Fungal / Q000652:urine; D002846:Chromatography, Affinity; D003453:Cryptococcosis / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000652:urine; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015233:Models, Statistical; D019095:Point-of-Care Systems; D012307:Risk Factors; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D014454:Uganda / Q000453:epidemiology
chemical_list: D000946:Antigens, Fungal