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Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study.

Longley, N; Jarvis, JN; Meintjes, G; Boulle, A; Cross, A; Kelly, N; Govender, NP; Bekker, LG; Wood, R; Harrison, TS (2015) Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study. Clinical Infectious Diseases, 62 (5). pp. 581-587. ISSN 1537-6591
SGUL Authors: Harrison, Thomas Stephen

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BACKGROUND: Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with late-stage human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) may reduce cryptococcal disease and deaths. Prospective data are limited. METHODS: CrAg was measured using lateral flow assays (LFA) and latex agglutination (LA) tests in 645 HIV-positive, ART-naive patients with CD4 counts ≤100 cells/µL in Cape Town, South Africa. CrAg-positive patients were offered lumbar puncture (LP) and treated with antifungals. Patients were started on ART between 2 and 4 weeks and followed up for 1 year. RESULTS: A total of 4.3% (28/645) of patients were CrAg positive in serum and plasma with LFA. These included 16 also positive by urine LFA (2.5% of total screened) and 7 by serum LA (1.1% of total). In 4 of 10 LFA-positive cases agreeing to LP, the cerebrospinal fluid (CSF) CrAg LFA was positive. A positive CSF CrAg was associated with higher screening plasma/serum LFA titers.Among the 28 CrAg-positive patients, mortality was 14.3% at 10 weeks and 25% at 12 months. Only 1 CrAg-positive patient, who defaulted from care, died from cryptococcal meningitis (CM). Mortality in CrAg-negative patients was 11.5% at 1 year. Only 2 possible CM cases were identified in CrAg-negative patients. CONCLUSIONS: CrAg screening of individuals initiating ART and preemptive fluconazole treatment of CrAg-positive patients resulted in markedly fewer cases of CM compared with historic unscreened cohorts. Studies are needed to refine management of CrAg-positive patients who have high mortality that does not appear to be wholly attributable to cryptococcal disease.

Item Type: Article
Additional Information: © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: HIV, antiretroviral therapy, cryptococcal antigen, cryptococcal meningitis, screening, Microbiology, 06 Biological Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Clinical Infectious Diseases
ISSN: 1537-6591
Language: eng
12 November 2015Published
Publisher License: Creative Commons: Attribution 4.0
Project IDFunderFunder ID
096190/Z/11/ZWellcome Trust
098316Wellcome Trust
P30 AI 045008National Institutes of Health
PubMed ID: 26565007
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