BACKGROUND: Cryptococcal meningitis is a leading cause of death in patients with acquired immunodeficiency syndrome and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. Screening for cryptococcal antigen in patients who enroll in ART programs may identify those at risk of cryptococcal meningitis and permit targeted use of preemptive therapy. METHODS: In this retrospective study, cryptococcal antigen was measured in stored plasma samples obtained from patients when they enrolled in a well-characterized ART cohort in South Africa. The predictive value of screening for cryptococcal antigen before initiation of ART for development of microbiologically confirmed cryptococcal meningitis or death during the first year of follow-up was determined. RESULTS: Of 707 participants with a baseline median CD4 cell count of 97 cells/microL (interquartile range, 46-157 cells/microL), 46 (7%) were positive for cryptococcal antigen. Antigenemia was 100% sensitive for predicting development of cryptococcal meningitis during the first year of ART, and in multivariate analysis, it was an independent predictor of mortality (adjusted hazard ratio, 3.2; 95% confidence interval, 1.5-6.6). Most cases (92%) of cryptococcal meningitis developed in patients with a CD4 cell count <or= 100 cells/microL. In this subset of patients, a cryptococcal antigen titer >or 1:8 was 100% sensitive and 96% specific for predicting incident cryptococcal meningitis during the first year of ART in those with no history of the disease. CONCLUSIONS: Cryptococcal antigen screening before initiation of ART in patients with a CD4 cell count <or=100 cells/microL is highly effective for identifying those at risk of cryptococcal meningitis and death and might permit implementation of a targeted preemptive treatment strategy.
BACKGROUND:Cryptococcal meningitis is a leading cause of death in patients with acquired immunodeficiency syndrome and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. Screening for cryptococcal antigen in patients who enroll in ART programs may identify those at risk of cryptococcal meningitis and permit targeted use of preemptive therapy. METHODS: In this retrospective study, cryptococcal antigen was measured in stored plasma samples obtained from patients when they enrolled in a well-characterized ART cohort in South Africa. The predictive value of screening for cryptococcal antigen before initiation of ART for development of microbiologically confirmed cryptococcal meningitis or death during the first year of follow-up was determined. RESULTS: Of 707 participants with a baseline median CD4 cell count of 97 cells/microL (interquartile range, 46-157 cells/microL), 46 (7%) were positive for cryptococcal antigen. Antigenemia was 100% sensitive for predicting development of cryptococcal meningitis during the first year of ART, and in multivariate analysis, it was an independent predictor of mortality (adjusted hazard ratio, 3.2; 95% confidence interval, 1.5-6.6). Most cases (92%) of cryptococcal meningitis developed in patients with a CD4 cell count <or= 100 cells/microL. In this subset of patients, a cryptococcal antigen titer >or 1:8 was 100% sensitive and 96% specific for predicting incident cryptococcal meningitis during the first year of ART in those with no history of the disease. CONCLUSIONS: Cryptococcal antigen screening before initiation of ART in patients with a CD4 cell count <or=100 cells/microL is highly effective for identifying those at risk of cryptococcal meningitis and death and might permit implementation of a targeted preemptive treatment strategy.
Authors: Sara A Mirza; Maureen Phelan; David Rimland; Edward Graviss; Richard Hamill; Mary E Brandt; Tracie Gardner; Matthew Sattah; Gabriel Ponce de Leon; Wendy Baughman; Rana A Hajjeh Journal: Clin Infect Dis Date: 2003-02-27 Impact factor: 9.079
Authors: J G Hakim; I T Gangaidzo; R S Heyderman; J Mielke; E Mushangi; A Taziwa; V J Robertson; P Musvaire; P R Mason Journal: AIDS Date: 2000-07-07 Impact factor: 4.177
Authors: Neil French; Katherine Gray; Christine Watera; Jessica Nakiyingi; Eric Lugada; Michael Moore; David Lalloo; James A G Whitworth; Charles F Gilks Journal: AIDS Date: 2002-05-03 Impact factor: 4.177
Authors: Elizabeth L Corbett; Gavin J Churchyard; Salome Charalambos; Badara Samb; Vicky Moloi; Tim C Clayton; Alison D Grant; Jill Murray; Richard J Hayes; Kevin M De Cock Journal: Clin Infect Dis Date: 2002-04-05 Impact factor: 9.079
Authors: Cristina Mussini; Patrizio Pezzotti; José M Miró; Esteban Martinez; Juan Carlos Lopez Bernaldo de Quiros; Paola Cinque; Vanni Borghi; Andrea Bedini; Pere Domingo; Pedro Cahn; Philippe Bossi; Andrea de Luca; Antonella d'Arminio Monforte; Mark Nelson; Nneka Nwokolo; Silvia Helou; Ricardo Negroni; Gaia Jacchetti; Spinello Antinori; Adriano Lazzarin; Andrea Cossarizza; Roberto Esposito; Andrea Antinori; Judith A Aberg Journal: Clin Infect Dis Date: 2004-01-29 Impact factor: 9.079
Authors: Nelesh P Govender; Jaymati Patel; Marelize van Wyk; Tom M Chiller; Shawn R Lockhart Journal: Antimicrob Agents Chemother Date: 2011-03-28 Impact factor: 5.191
Authors: Lincoln Pac; Mara Murray Horwitz; Anne Marion Namutebi; Brandon J Auerbach; Aggrey Semeere; Teddy Namulema; Miriam Schwarz; Robert Bbosa; Allan Muruta; David B Meya; Yukari C Manabe Journal: J Acquir Immune Defic Syndr Date: 2015-04-15 Impact factor: 3.731
Authors: Beatriz Grinsztejn; Valdilea G Veloso; Ruth K Friedman; Ronaldo I Moreira; Paula M Luz; Dayse P Campos; José H Pilotto; Sandra W Cardoso; Jeanne C Keruly; Richard D Moore Journal: AIDS Date: 2009-10-23 Impact factor: 4.177