by Paul Govern
Cryptococcal meningitis, or CM, is a potentially fatal fungal infection of the brain and spinal fluid. It can develop after breathing in the spores of Cryptococcus fungi, which are found around the world. The infection is seen most often in people who are immunocompromised.
CM is characterized by the U.S. Centers for Disease Control and Prevention (CDC) as a major cause of illness among people living with the human immunodeficiency virus, or HIV, the virus that causes AIDS.
The CDC, in publishing this appraisal, refers to an August 2022 report in The Lancet that used a predictive model to estimate CM incidence and mortality worldwide among people with HIV. Globally, it’s estimated that some 38.4 million people are living with HIV. The predictive model estimated that 152,000 cases of CM occur worldwide each year among people with HIV, resulting in an estimated 112,000 CM-related deaths.
A retrospective cohort study reported Feb. 23 in Clinical Infectious Diseases explores this question in epidemiological detail, drawing on patient data gathered between 1996 and 2017 at clinical sites in 33 countries. Led by researchers at Vanderbilt University Medical Center, the study uses data from the International Epidemiology Database to Evaluate AIDS, or IeDEA, a global research consortium established in 2006 by the U.S. National Institutes of Health.
In all, the study involves 518,852 patients with HIV followed for a median of 3.4 years, of whom 3,857, or 0.7%, were diagnosed with CM.
“We found some reasons for optimism in the IeDEA data, with the incidence of cryptococcal meningitis among people with HIV decreasing slightly over time,” said a leader of the study, infectious diseases specialist Anna Person, MD, associate professor of Medicine. “However, in low- and middle-income countries, we also found that many of our sites across the world did not have access to recommended first-line therapies for the treatment of cryptococcal meningitis, and we hope this study will highlight an urgent need for health equity in access to resources for those living with HIV.
“The global fight against HIV/AIDS, and by extension the fight against CM, is unfortunately still a story of the haves and the have nots. There is still much work to be done to improve prevention and care for HIV across the world. Global studies like this one bring into focus disease and outcomes prevalence differences in resourced and less well-resourced countries among people living with HIV.”
Key findings of the study include:
- Among people in the cohort with CM, the all-cause mortality rate was estimated at 32%.
- Older age, lower CD4 count (a type of white blood cell), and earlier calendar year of CM diagnosis were associated with higher risk of all-cause mortality.
- Among those diagnosed with CM, 64% were diagnosed after the start of antiretroviral therapy (ART) for HIV, with a median of 253 days from ART start to CM diagnosis.
- In a 2017 survey of the 89 participating study sites, access to recommended first-line drugs for CM was wanting, with only 34% of sites reporting access to amphotericin B and only 12% reporting access to 5-flucytosine.
Catherine McGowan, MD
VUMC serves as the coordinating center for the Caribbean, Central, and South America Network for HIV Epidemiology, or CCASAnet, which constitutes one of IeDEA’s seven regional HIV cohorts. The new report’s senior author, infectious diseases specialist Catherine McGowan, MD, associate professor of Medicine, is one of three principal investigators for CCASAnet.
In leading the new study, Person and McGowan collaborated with investigators representing five IeDEA regional cohorts. Also among the study leaders was Brenda Crabtree Ramirez, MD, of the National Institute of Medical and Nutritional Sciences in Mexico City.
Others from VUMC on the study include Ahra Kim, MPH, Fernanda Maruri, MPH, and Bryan Shepherd, PhD. The study was supported by the National Institutes of Health (AI069923).