New Approaches to the Diagnosis and Treatment of Cryptococcal Meningitis

Azure T. Makadzange, MD, DPhil; Grace McHugh, MBBS


Semin Neurol. 2014;34(1):47-60. 

In This Article

Abstract and Introduction


Cryptococcal meningitis remains one of the leading causes of morbidity and mortality among immunosuppressed individuals, particularly those with advanced acquired immunodeficiency syndrome. The greatest burden of disease is in sub-Saharan Africa and Asia where there is limited access to diagnostics and treatment for the disease. The authors review the available tools for diagnosing cryptococcal meningitis and review treatment for cryptococcal meningitis, highlighting the evidence behind current treatment guidelines.


The global burden of cryptococcal disease is high with 1 million new infections each year.[1] The greatest burden is in sub-Saharan Africa where cryptococcal meningitis is the fourth leading cause of mortality, accounting for over 600,000 deaths annually.[1] Disseminated cryptococcosis is the leading cause of meningitis in Zimbabwe,[2] and accounts for 40% of all cases of meningitis in Malawi.[3] Cryptococcal meningitis is also associated with very high mortality rates, particularly in resource limited settings.[4,5] Cryptococcosis is caused by an encapsulated yeast that belongs to the genus Cryptococcus. Cryptococcus neoformans and Cryptococcus gattii are responsible for the majority of cases of human cryptococcosis. Cryptococcus neoformans was originally classified into five groups (A–D and A/D) based on serology. Serologic typing classified C. gattii as C. neoformans serotype B and C, whereas serotypes A and D were C. neoformans var. grubii and C. neoformans var. neoformans, respectively. Molecular typing has enabled us to distinguish C. neoformans and C gattii as two distinct species. Each species has been further divided into four major molecular subtypes, often with distinct ecological niches (Table 1). Cryptococcus neoformans has a global distribution and has been found in association with pigeon droppings, soil, and decaying vegetation.[6–8]Cryptococcus gattii has primarily been isolated in tropical and subtropical climates and is found in association with eucalyptus trees.[9–12] Other Cryptococcus species that rarely cause human disease include C. albudius,[13,14]C. laurentii,[15,16] and C. luteolus.[17]