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Review
. 2023 Feb 18;76(4):764-770.
doi: 10.1093/cid/ciac675.

Cryptococcal Antigenemia in Advanced Human Immunodeficiency Virus Disease: Pathophysiology, Epidemiology, and Clinical Implications

Rachel M Wake  1   2 , Síle F Molloy  1   3 , Joseph N Jarvis  4   5 , Thomas S Harrison  1   2   6 , Nelesh P Govender  1   3   6   7   8
Affiliations
Review

Cryptococcal Antigenemia in Advanced Human Immunodeficiency Virus Disease: Pathophysiology, Epidemiology, and Clinical Implications

Rachel M Wake et al. Clin Infect Dis. .

Abstract

Cryptococcal antigen (CrAg) is detectable in blood prior to the onset of symptomatic cryptococcal meningitis (CM), a leading cause of death among people with advanced human immunodeficiency virus (HIV) disease globally. Highly sensitive assays can detect CrAg in blood, and screening people with HIV with low CD4 counts, followed by preemptive antifungal treatment, is recommended and widely implemented as part of a global strategy to prevent CM and end cryptococcal-related deaths. Cryptococcal antigenemia encompasses a spectrum of conditions from preclinical asymptomatic infection (cerebrospinal fluid [CSF] CrAg-negative) through subclinical (CSF CrAg-positive without overt meningism) to clinical symptomatic cryptococcal disease, usually manifesting as CM. In this review, we summarize current understanding of the pathophysiology, risk factors for, and clinical implications of cryptococcal antigenemia within this spectrum. We also provide an update on global prevalence, recommended screening and treatment strategies, and future considerations for improving outcomes among patients with cryptococcal antigenemia.

Keywords: HIV; acquired immunodeficiency syndrome; cryptococcal meningitis; cryptococcosis; diagnostic screening programs.

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Conflict of interest statement

Potential conflicts of interest. J. J. reports grants or contracts from European and Developing Countries Clinical Trials (EDCTP) and Center for Disease Control (CDC) (paid to institution) and speaker fees from Gilead Sciences, Inc, and reports serving as chair of a data and safety monitoring board (DSMB) for the ARTIST trial, Harvest trial, and CASTLE trial. T. H. reports speaker fees from Gilead Sciences, Inc and Pfizer and reports grants or contracts from Medical Research Council (MRC), Wellcome Trust (WT), Department for International Development (DFID) Global Health Trials, and EFFECT Trial (paid to institution). N. G. reports grants from National Institute for Health and Care Research (NIHR), CDC, National Institutes of Health (NIH), Gates Foundation, and National Health Laboratory Service (NHLS) Research Trust (paid to institution) and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from SA HIV Clinicians Society (paid to author); reports servings as a DSMB member for the ACACIA trial, an advisory board member for 5FC-Crypto, and an advisory board chair for DREAMM; is the president and council member for Federation of Infectious Diseases Societies of Southern Africa (FIDSSA), a member of the CryptoMAG, Ambassador for GAFFI, a board member for the Medical Mycology Society Nigeria, and a member for LIGHT Africa; and includes receipt of equipment, materials, drugs, medical writing, gifts, or other services from Immy CrAg tests and OIDx Histoplasma antigen tests (paid to institution). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Cryptococcal antigen screening and treatment algorithm from the Southern African HIV Clinicians Society 2019 guideline for the prevention, diagnosis, and management of cryptococcal disease among HIV-infected persons [29]. Abbreviations: ART, antiretroviral therapy; CM, cryptococcal meningitis; CrAg+, cryptococcal antigen-positive in blood; CSF, cerebrospinal fluid; LP, lumbar puncture; pOI, opportunistic infection; pTB, tuberculosis; 5-FC, flucytosine.
Figure 2.
Figure 2.
Cryptococcal antigen titers, risk of subsequent CM and mortality among people living with advanced HIV disease without cryptococcal antigenemia, and with cryptococcal antigenemia at different stages of the clinical spectrum: asymptomatic, subclinical CM and overt/clinical CM. Abbreviations: AMB; amphotericin B deoxycholate, ART; antiretroviral therapy, CD4; CD4 T-lymphocyte cell count, CM; cryptococcal meningitis, CrAg; cryptococcal antigen, HIV; human immunodeficiency virus, IQR; interquartile range, LP; lumbar puncture, L-AmB; liposomal amphotericin B, N/A; not applicable.
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References

    1. Rajasingham R, Smith RM, Park BJ, et al. . Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 2017; 17:873–81. - PMC - PubMed
    1. Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, Harrison TS. Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa. Clin Infect Dis 2009; 48:856–62. - PMC - PubMed
    1. World Health Organization . Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach [Internet]. Geneva, Switzerland: World Health Organization; 2021. Available at: https://apps.who.int/iris/handle/10665/342899. Accessed 19 May 2022. - PubMed
    1. World Health Organization . Rapid Advice. Diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children. Geneva, Switzerland: WHO; 2011. - PubMed
    1. Mfinanga S, Chanda D, Kivuyo SL, et al. . Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial. Lancet 2015; 385:2173–82. - PubMed

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