title: Utility of urine and serum lateral flow assays to determine the prevalence and predictors of cryptococcal antigenemia in HIV-positive outpatients beginning antiretroviral therapy in Mwanza, Tanzania.
abstract: BACKGROUND
  Detection of subclinical cryptococcal disease using cryptococcal antigen screening among HIV-positive individuals presents a potential opportunity for prevention of both clinical disease and death if patients with detectable cryptococcal antigen are identified and treated pre-emptively. Recently developed point-of-care cryptococcal antigen tests may be useful for screening, particularly in resource-limiting settings, but few studies have assessed their utility.
  
  
  METHODS
  The objectives of this study were to determine the prevalence and factors associated with cryptococcal antigenemia in HIV-positive patients with CD4(+) T-cell counts ≤200 cells/µL who were initiating ART, and also to evaluate the utility of the point-of-care urine lateral flow assay (LFA) cryptococcal antigen test using two different diluents, compared to gold standard serum antigen testing, as a screening tool. Urine and serum of outpatients initiating antiretroviral therapy at two hospitals in Mwanza were tested for cryptococcal antigen, and demographic and clinical characteristics were obtained using structured questionnaires and patients' files. Patients with asymptomatic cryptococcal antigenemia received oral fluconazole in accordance with World Health Organization recommendations.
  
  
  RESULTS
  Among 140 patients screened, 10 (7.1%) had asymptomatic cryptococcal antigenemia with a positive serum cryptococcal antigen. Four of these ten patients had CD4 counts between 100 and 200 cells/µL. The prevalence of cryptococcal antigen detected in urine using a standard (older) and a test (newer) diluent were 44 (31.4%) and 19 (13.6%), with Kappa coefficients compared to serum of 0.28 and 0.51 (p<0.001 for both). Compared to the new LFA diluent for urine cryptococcal antigen, the standard diluent had higher sensitivity (100% versus 80%) but lower specificity (74% versus 92%) using serum cryptococcal antigen as a gold standard.
  
  
  CONCLUSIONS
  Our findings suggest that HIV-positive outpatients with CD4 counts <200 cells/µL, rather than 100, should be screened for asymptomatic cryptococcal antigenemia given its association with mortality if untreated. Agreement of the urine LFA with the serum LFA was not sufficient to recommend routine screening with urine LFA.
authors.affiliation: Department of Internal Medicine, Catholic University of Health and Allied Sciences Bugando, Mwanza, Tanzania; kinangam@yahoo.co.uk.
authors.forename: Kinanga A
authors.initials: KA
authors.lastname: Magambo
authors.affiliation: Department of Internal Medicine, Catholic University of Health and Allied Sciences Bugando, Mwanza, Tanzania.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Kalluvya
authors.affiliation: Department of Internal Medicine, Catholic University of Health and Allied Sciences Bugando, Mwanza, Tanzania.
authors.forename: Shikha W
authors.initials: SW
authors.lastname: Kapoor
authors.affiliation: Department of Microbiology and Immunology, Catholic University of Health and Allied Sciences Bugando, Mwanza, Tanzania.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Seni
authors.affiliation: Department of Internal Medicine, Muhimbili National Hospital, Dar-es-Salaam, Tanzania.
authors.forename: Awilly A
authors.initials: AA
authors.lastname: Chofle
authors.affiliation: Center for Global Health, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Fitzgerald
authors.affiliation: Department of Internal Medicine, Catholic University of Health and Allied Sciences Bugando, Mwanza, Tanzania; Center for Global Health, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Downs
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000097:blood* / Q000652:urine*; D058345:Asymptomatic Infections / Q000453:epidemiology; D002846:Chromatography, Affinity / Q000379:methods*; D003430:Cross-Sectional Studies; D003453:Cryptococcosis / Q000175:diagnosis* / Q000453:epidemiology; D003454:Cryptococcus / Q000276:immunology* / Q000302:isolation & purification; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D010045:Outpatients; D019095:Point-of-Care Systems; D015995:Prevalence; D012307:Risk Factors; D044967:Serum / Q000382:microbiology; D013636:Tanzania / Q000453:epidemiology; D014556:Urine / Q000382:microbiology
chemical_list: D000956:Antigens, Viral
keywords: Cryptococcus; HIV; Mwanza; cryptococcal antigenemia; lateral flow assay; outpatient
references.citation: N Engl J Med. 1997 Jul 3;337(1):15-21
references.pmid: 9203426
references.citation: Clin Infect Dis. 2009 Apr 1;48(7):856-62
references.pmid: 19222372
references.citation: J Int AIDS Soc. 2014 Jan 28;17:18821
references.pmid: 24476751
references.citation: Clin Infect Dis. 2010 Aug 15;51(4):448-55
references.pmid: 20597693
references.citation: Br Med Bull. 2005 Apr 18;72:99-118
references.pmid: 15838017
references.citation: AIDS. 2009 Jun 1;23(9):1182-3
references.pmid: 19451796
references.citation: J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):e31-6
references.pmid: 24675586
references.citation: AIDS. 2007 Oct 18;21(16):2119-29
references.pmid: 18090038
references.citation: Clin Vaccine Immunol. 2013 Jan;20(1):52-5
references.pmid: 23114703
references.citation: J Int AIDS Soc. 2011 Oct 11;14:48
references.pmid: 21988905
references.citation: PLoS One. 2012;7(11):e49541
references.pmid: 23166705
references.citation: Clin Infect Dis. 2011 Nov;53(10):1019-23
references.pmid: 21940419
references.citation: J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):e85-91
references.pmid: 22410867
references.citation: AIDS. 2008 Oct 1;22(15):1897-908
references.pmid: 18784453
references.citation: AIDS. 2009 Feb 20;23(4):525-30
references.pmid: 19182676
references.citation: N Engl J Med. 2013 Apr 4;368(14):1291-1302
references.pmid: 23550668
references.citation: Trop Med Int Health. 2013 Sep;18(9):1075-1079
references.pmid: 23937699
references.citation: J Infect. 1999 Jul;39(1):32-7
references.pmid: 10468126
references.citation: AIDS. 2002 May 3;16(7):1031-8
references.pmid: 11953469
references.citation: Clin Infect Dis. 2011 Aug;53(4):321-5
references.pmid: 21810743
references.citation: Yeast. 2004 Jul 30;21(10):809-12
references.pmid: 15300677
references.citation: Trop Med Int Health. 2007 Aug;12(8):929-35
references.pmid: 17697087