Cryptococcal Meningitis

In sub-Saharan Africa, due to the prevalence of adults living with HIV, Cryptococcus (a fungus found in soil) is the most common cause of meningitis. The global burden of HIV-associated cryptococcal meningitis is an important aspect of strategies aimed at prevention and determining treatment needs of those at risk of or infected with this an opportunistic infection.


Cryptococcus can enter the body by inhalation of dust or dried bird droppings and leads to cryptococcal meningitis, a potentially fatal fungal infection of the lining of the brain and spinal cord. The risk of being infected by cryptococcus is significantly increased when an individual has a compromised immune system, such as those who are HIV-positive. The risk is even greater with a CD4 cell count lower than 100 per µL. Low CD4 cell counts indicate a compromised immune system, as they are targeted by the HIV virus.

Rajasingham and colleagues recently published a report in The Lancet Infectious Diseasesto provide an updated estimate on the global burden of HIV-associated cryptococcal meningitis. Previously, the only study to report a global estimate was published 2008 and reported the global incidence of cryptococcosis as 957 900 cases per year. One of the main limitations of this previous study was that it primarily reported on cohorts prior to the initiation of pre-antiretroviral therapy (ART). Since 2008, there has been a significant increase in the distribution of ART leading to a reduction in AIDS-related deaths by 45%.

The 2014 Joint UN Programme on HIV and AIDS estimates were used to assess the risk of cryptococcal infection and death in low-income and middle-income countries in the developing world. The report assessed adults (aged 15 and older) with HIV who are currently receiving ART.

With 31.8 million adults (reported in December, 2013) globally living with HIV, 21.7 million of these adults are located in sub-Saharan Africa. Of these 31.8 million individuals, 19.5 million are eligible for ART (according to the WHO 2010 guidelines), but only 11.3 million are actually receiving ART. It was estimated that globally 4.3 million adults have a CD4 cell count less than 100 cells per µL, and 1.8 million (42%) of these people not on ART which puts them at particularly high risk for opportunistic infections such as cryptococcosis.

The study estimates the average global incidence of cryptococcal infection in 2014 to be 6% among HIV-positive people (corresponding to 278 000 people globally) whose CD4 cell count was less than 100 cells per µL. The number of cases of cryptococcal meningitis globally was estimated to be 223 100, with 73% of these cases occurring in sub-Saharan Africa and second highest incidence was reported in Asia and the Pacific (19%).

Annual fatalities due to cryptococcal meningitis were estimated to be 181 100 deaths globally, with 75% of these deaths occurring in sub-Saharan Africa. The study also estimated that globally, 15% of AIDS-related deaths are caused by cryptococcal meningitis, making it the second most common cause of AIDS-related mortality, close behind tuberculosis. Whilst the absolute number of deaths due to cryptococcal meningitis has decreased since the previous estimate in 2008, the proportion of AIDS-related deaths is similar.

As the prevention of cryptococcus infection would have a significant impact on costs to health-care systems by reducing costs on antifungals, diagnostics and medical supplies, the importance of ART adherence becomes even more evident from these estimates. This study highlights the ongoing and substantial global burden of HIV-associated cryptococcal meningitis, particularly in the developing world.

Written By: Lacey Hizartzidis, PhD