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High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients

Wake, RM; Britz, E; Sriruttan, C; Rukasha, I; Omar, T; Spencer, DC; Nel, JS; Mashamaite, S; Adelekan, A; Chiller, TM; et al. Wake, RM; Britz, E; Sriruttan, C; Rukasha, I; Omar, T; Spencer, DC; Nel, JS; Mashamaite, S; Adelekan, A; Chiller, TM; Jarvis, JN; Harrison, TS; Govender, NP (2018) High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients. Clin Infect Dis, 66 (5). pp. 686-692. ISSN 1537-6591 https://doi.org/10.1093/cid/cix872
SGUL Authors: Harrison, Thomas Stephen

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Abstract

Background High mortality rates among asymptomatic cryptococcal antigen (CrAg)–positive patients identified through CrAg screening, despite preemptive fluconazole treatment, may be due to undiagnosed cryptococcal meningitis. Methods Symptoms were reviewed in CrAg-positive patients identified by screening 19233 individuals with human immunodeficiency virus infection and CD4 cell counts <100/µL at 17 clinics and 3 hospitals in Johannesburg from September 2012 until September 2015, and at 2 hospitals until June 2016. Cerebrospinal fluid samples from 90 of 254 asymptomatic patients (35%) and 78 of 173 (45%) with headache only were analyzed for cryptococcal meningitis, considered present if Cryptococcus was identified by means of India ink microscopy, culture, or CrAg test. CrAg titers were determined with stored blood samples from 62 of these patients. The associations between blood CrAg titer, concurrent cryptococcal meningitis, and mortality rate were assessed. Results Cryptococcal meningitis was confirmed in 34% (95% confidence interval, 25%–43%; 31 of 90) of asymptomatic CrAg-positive patients and 90% (81%–96%; 70 of 78) with headache only. Blood CrAg titer was significantly associated with concurrent cryptococcal meningitis in asymptomatic patients (P < .001) and patients with headache only (P = .003). The optimal titer for predicting cryptococcal meningitis was >160 (sensitivity, 88.2%; specificity, 82.1%); the odds ratio for concurrent cryptococcal meningitis was 34.5 (95% confidence interval, 8.3–143.1; P < .001). Conclusions About a third of asymptomatic CrAg-positive patients have concurrent cryptococcal meningitis. More effective clinical assessment strategies and antifungal regimens are required for CrAg-positive patients, including investigation for cryptococcal meningitis irrespective of symptoms. Where it is not possible to perform lumbar punctures in all CrAg-positive patients, blood CrAg titers should be used to target those most at risk of cryptococcal meningitis.

Item Type: Article
Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in Clinical Infectious Diseases following peer review. The version of record Rachel M Wake, Erika Britz, Charlotte Sriruttan, Ivy Rukasha, Tanvier Omar, David C Spencer, Jeremy S Nel, Sello Mashamaite, Adeboye Adelekan, Tom M Chiller, Joseph N Jarvis, Thomas S Harrison, Nelesh P Govender; High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients, Clinical Infectious Diseases, Volume 66, Issue 5, 10 February 2018, Pages 686–692 is available online at: https://doi.org/10.1093/cid/cix872
Keywords: Cryptococcal, Cryptococcosis, Diagnosis, Mass screening, Meningitis, Mortality, 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: Clin Infect Dis
ISSN: 1537-6591
Language: eng
Dates:
DateEvent
10 February 2018Published
5 October 2017Published Online
3 October 2017Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
UNSPECIFIEDSouth African Medical Research Councilhttp://dx.doi.org/10.13039/501100001322
1604.0Meningitis Research Foundationhttp://dx.doi.org/10.13039/501100000403
CDC-RFA-GH15-1575U.S. Centers for Disease Control and PreventionUNSPECIFIED
PubMed ID: 29028998
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109338
Publisher's version: https://doi.org/10.1093/cid/cix872

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