Overcoming Diagnostic Challenges in Cryptococcal Meningitis: : Highlighting the Prozone Phenomenon

Diego Caceres; Carlos Espinoza Vásquez

doi:10.17533/udea.hm.v16n1a04

Authors

Diego Caceres IMMY https://orcid.org/0000-0001-8749-9809
Carlos Espinoza Vásquez Hospital Clínico San Borja Arriarán

DOI:

https://doi.org/10.17533/udea.hm.v16n1a04

Keywords:

Cryptococcus, meningitis, HIV, AIDS, Antigen, prozone effect, false-negative results

Abstract

Cryptococcosis is a severe fungal disease associated with high mortality, especially in people with Advanced HIV Disease (AHD). Early diagnosis is critical for improving patient outcomes, and the use of rapid point-of-care test for Cryptococcus spp. antigen (CrAg) detection is crucial. However, diagnostic challenges remain, particularly the prozone effect, which can lead to false-negative results. We describe a case of prozone phenomenon in a patient with AHD diagnosed with cryptococcal meningitis. Initial CrAg testing in serum, as part of the clinical investigation process, yielded a negative result. However, after following a protocol for semi-quantification of CrAg, a positive result was observed at higher dilutions, confirming that the prozone effect was the cause of the false-negative result. Here we highlighted the importance of recognizing the prozone phenomenon in patients with high fungal burden and underscores the need for appropriate laboratory protocols to address this diagnostic limitation.

|Abstract

= 77 veces | PDF

= 55 veces|

Downloads

Download data is not yet available.

References

[1]. Rajasingham R, Wake RM, Beyene T, Katende A, Letang E, Boulware DR. Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing. J Clin Microbiol. 2019; 57(1):e01238-18. https://doi.org/10.1128/jcm.01238-18.

[2]. Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, et al. The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis. 2022;22(12):1748-1755. https://doi.org/10.1016/s1473-3099(22)00499-6.

[3]. World Health Organization. WHO fungal priority pathogens list to guide research, development and public health action [Internet]. 2022. Available from: https://www.who.int/publications/i/item/9789240060241.

[4]. Wake RM, Molloy SF, Jarvis JN, Harrison TS, Govender NP. Cryptococcal Antigenemia in Advanced Human Immunodeficiency Virus Disease: Pathophysiology, Epidemiology, and Clinical Implications. Clin Infect Dis. 2023;76(4):764-770. https://doi.org/10.1093/cid/ciac675.

[5]. World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV [Internet]. 2022 June. Available from: https://www.who.int/publications/i/item/9789240052178.

[6]. Lourens A, Jarvis JN, Meintjes G, Samuel CM. Rapid diagnosis of cryptococcal meningitis by use of lateral flow assay on cerebrospinal fluid samples: influence of the high-dose "hook" effect. J Clin Microbiol. 2014;52(12):4172-5. https://doi.org/10.1128/jcm.01683-14.

[7]. Lee GH, Arthur I, Leung M. False-Negative Serum Cryptococcal Lateral Flow Assay Result Due to the Prozone Phenomenon. J Clin Microbiol. 2018;56(4):e01878-17. https://doi.org/10.1128/JCM.01878-17.

[8]. Tadeo KK, Nimwesiga A, Kwizera R, Apeduno L, Martyn E, Okirwoth M, et al. Evaluation of the Diagnostic Performance of a Semiquantitative Cryptococcal Antigen Point-of-Care Assay among HIV-Infected Persons with Cryptococcal Meningitis. J Clin Microbiol. 2021;59(8):e0086021. https://doi.org/10.1128/jcm.00860-21.

[9]. Jarvis JN, Tenforde MW, Lechiile K, Milton T, Boose A, Leeme TB, et al. Evaluation of a Novel Semiquantitative Cryptococcal Antigen Lateral Flow Assay in Patients with Advanced HIV Disease. J Clin Microbiol. 2020;58(9):e00441-20. https://doi.org/10.1128/jcm.00441-20.

[10]. Skipper C, Tadeo K, Martyn E, Nalintya E, Rajasingham R, Meya DB, et al. Evaluation of Serum Cryptococcal Antigen Testing Using Two Novel Semiquantitative Lateral Flow Assays in Persons with Cryptococcal Antigenemia. J Clin Microbiol. 2020;58(4):e02046-19. https://doi.org/10.1128/jcm.02046-19.