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Cryptococcal Antigen Screening in Asymptomatic HIV-Infected Antiretroviral Naïve Patients in Cameroon and Evaluation of the New Semi-Quantitative Biosynex CryptoPS Test.

Temfack, E; Kouanfack, C; Mossiang, L; Loyse, A; Fonkoua, MC; Molloy, SF; Koulla-Shiro, S; Delaporte, E; Dromer, F; Harrison, T; et al. Temfack, E; Kouanfack, C; Mossiang, L; Loyse, A; Fonkoua, MC; Molloy, SF; Koulla-Shiro, S; Delaporte, E; Dromer, F; Harrison, T; Lortholary, O (2018) Cryptococcal Antigen Screening in Asymptomatic HIV-Infected Antiretroviral Naïve Patients in Cameroon and Evaluation of the New Semi-Quantitative Biosynex CryptoPS Test. Front Microbiol, 9. p. 409. ISSN 1664-302X https://doi.org/10.3389/fmicb.2018.00409
SGUL Authors: Harrison, Thomas Stephen Molloy, Sile

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Abstract

Background: Cryptococcal meningitis (CM) is a major cause of AIDS-related mortality in Africa. Detection of serum cryptococcal antigen (CrAg) predicts development of CM in antiretroviral (ART) naïve HIV-infected patients with severe immune depression. Systematic pre-ART CrAg screening and pre-emptive oral fluconazole is thus recommended. We postulated that a semi-quantitative CrAg screening approach could offer clinically relevant advantages.Methods:ART-naïve asymptomatic adult outpatients with <100 CD4cells/mm3presenting to the Yaoundé Central Hospital, Cameroon were screened for CrAg using the IMMY lateral flow assay (LFA). CrAg positive patients were consented for lumbar puncture and those with proven CM were treated with combination antifungal therapy and those with no CM were offered long-term oral fluconazole. Simultaneous on-site evaluation of CrAg detection using the new LFA Biosynex®CryptoPS test was performed and both tests were subsequently compared to a reference commercialized CrAg enzyme immunoassay (EIA).Results:Prevalence of serum CrAg in 186 screened adults was 7.5% (95%CI: 4.5-12.4). In CrAg positive patients, CM prevalence was 45.5% (95%CI: 18.3-75.7). IMMY and Biosynex CryptoPS strongly agreed in serum, plasma, and cerebrospinal fluid (Kappa: 98.4, 99.5, 100%, respectively, p < 0.001), and disagreed in urine (29 isolated positive CrAg in urine with IMMY, none with Biosynex and none of whom had proven CM). Compared to EIA, serum specificities were 96.6 and 98.3%, respectively. With Biosynex CryptoPS, all CM patients were serum T2-band positive compared to nonewithout CM. Median EIA reciprocal titre was 160 (IQR: 13.5-718.8) and titres >160 strongly correlated with proven CM and Biosynex CryptoPS T2-band positivity. During the 1-year follow up period, there was no incident case of CM among screened patients and overall incidence of all-cause mortality was 31.5 per 100 person-years-at-risk (95%CI: 23.0-43.1).Conclusion:HIV-associated asymptomatic cryptococcosis is common in Cameroon, warranting integrated systematic screening and treatment. Biosynex CryptoPS holds promise, at point of care, for rapidly stratifying CrAg positive patients for optimal management including lumbar puncture and combination antifungal therapy when needed.Summary findings:Prevalence of CrAg and meningitis (CM) is high in Cameroon. Biosynex CryptoPS is comparable to IMMY LFA in CrAg screening. Its T2-band correlates with high antigen titres and CM, thus promising for identifying patients requiring effective induction therapy.Note:This study was presented in part at the 10th International Conference on Cryptococcus and Cryptococcosis (ICCC) in Iguazu in Brazil from 26 to 30thMarch 2017 and won a prize oral presentation.

Item Type: Article
Additional Information: Copyright © 2018 Temfack, Kouanfack, Mossiang, Loyse, Fonkoua, Molloy, Koulla-Shiro, Delaporte, Dromer, Harrison and Lortholary. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: cryptococcal antigen, cryptococcosis, lateral flow assay, point of care, screening
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Front Microbiol
ISSN: 1664-302X
Language: eng
Dates:
DateEvent
13 March 2018Published
21 February 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
33/CCS6/AO 2013-1French National Agency for Research on AIDS and Viral HepatitisUNSPECIFIED
PubMed ID: 29593675
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109719
Publisher's version: https://doi.org/10.3389/fmicb.2018.00409

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