Evolution of Laboratory Diagnostics for Cryptococcosis and Missing Links to Optimize Diagnosis and Outcomes in Resource-Constrained Settings

Abstract

Cryptococcal meningitis is one of the leading causes of death in sub-Saharan Africa among patients with advanced HIV disease. Early diagnosis is crucial in improving treatment outcomes. Despite advances and the availability of modern and point-of-care diagnostics for cryptococcosis, gaps still exist in resource-constrained settings, leading to unfavorable treatment outcomes. Here, we review the current outstanding issues or missing links that need to be filled to optimize the diagnosis of cryptococcosis in resource-constrained settings to improve treatment outcomes. We highlight the evolution of cryptococcosis diagnostics; the roles of early fungicidal activity, cryptococcal antigen titers, antifungal susceptibility testing, and therapeutic drug monitoring; and the missing links to optimize diagnosis and outcomes, including practical recommendations.

Keywords: cryptococcal meningitis; cryptococcosis; fungal diagnostics; laboratory diagnostics; resource-constrained setting.

Figure 1.

Fungal culture. Cryptococcus neoformans isolates from cerebrospinal fluid on Sabouraud dextrose agar with chloramphenicol.

Figure 2.

India ink staining. The background is stained, but the cells and capsule do not take up the stain.

Figure 3.

Procedures for cryptococcal antigen lateral flow and semiquantitative assays. A, Lateral flow assay takes 5 steps, and results are obtained in 10 minutes. B, Semiquantitative assay procedure. Images obtained from kit inset.

Figure 4.

Histopathology sections. Section of the kidney showing Cryptococcus neoformans in the glomerulus: A, hematoxylin and eosin stain; B, Grocott methenamine silver stain. C and D, Section of the brain showing C neoformans in the meninges: hematoxylin and eosin stain. Black arrows indicate the location of the cryptococcal yeast cells in the tissue sections.