Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing

Abstract

Over the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evolved from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent development and distribution of a point-of-care lateral flow assay. This assay is highly sensitive and specific in cerebrospinal fluid (CSF), but is also sensitive in the blood to detect CrAg prior to meningitis symptoms. CrAg screening of HIV-infected persons in the blood prior to development of fulminant meningitis and preemptive treatment for CrAg-positive persons are recommended by the World Health Organization and many national HIV guidelines. Thus, CrAg testing is occurring more widely, especially in resource-limited laboratory settings. CrAg titer predicts meningitis and death and could be used in the future to customize therapy according to burden of infection.

Keywords: Cryptococcus; diagnostics; point-of-care; prevention.

FIG 1

Venn diagram of distribution of CSF diagnostic testing in Uganda and South Africa during 2006 to 2012 (n = 832) (8).

FIG 2

Venn diagram of the distribution of positivity by blood CrAg, CSF CrAg, and CSF culture (16).

FIG 3

Survival by CrAg titer in 287 asymptomatic HIV-infected persons with cryptococcal antigenemia in four cohorts in Ethiopia, South Africa, Tanzania, and Uganda (26, 27, 29, 32).