Cryptococcal meningitis causes 15% of AIDS–related deaths globally

Cryptococcal meningitis caused an estimated 15% of AIDS–related deaths globally in 2014 but remains a neglected factor in the response to the HIV/AIDS epidemic, researchers said.

Radha Rajasingham, MD, assistant professor of medicine in the division of infectious diseases and international medicine at the University of Minnesota, and colleagues estimated that there are more than 180,000 global deaths annually from cryptococcal meningitis, mostly in sub-Saharan Africa.

Rajasingham and colleagues said their estimates, which were based on an analysis of UNAIDS data, showed that the prevalence of cryptococcal infection was largely unchanged in low- and middle-income countries since the last global burden of cryptococcal meningitis was published in 2008, despite the expansion of ART, which has led to a significant worldwide reduction in AIDS–related deaths. They said the estimates can help guide national prevention strategies for cryptococcal meningitis.

“These updated accurate disease estimates enable appropriate ordering of essential antifungals, diagnostics, and medical supplies,” Rajasingham and colleagues wrote in The Lancet Infectious Diseases.

A ‘metric of ... failure’

Rajasingham and colleagues noted that the Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. According to the CDC, the fungus causes cryptococcal meningitis after spreading from the lungs to the brain, a condition largely affecting patients with HIV/AIDS.

The researchers estimated that there are around 223,000 new cases of cryptococcal meningitis each year, resulting in 181,100 related deaths in 2014, including 135,900 in sub-Saharan Africa.

The estimates are lower than in 2008, largely because of rapid ART expansion, a 45% decrease in AIDS–related mortality from 2005 to 2013 in sub-Saharan Africa, and a difference in how they estimated the prevalence of cryptococcal antigenemia, Rajasingham and colleagues said.

However, they said cryptococcosis remains the second most common cause of AIDS–related mortality, only narrowly trailing tuberculosis.

“Although the absolute number of cryptococcal deaths has decreased since the previous 2008 estimate, the proportion of AIDS–related mortality remains similar,” they wrote.

In an effort to address the threat of cryptococcal meningitis, Rajasingham and colleagues said health agencies like WHO, the U.S. President’s Emergency Plan for AIDS relief and HHS have advocated screening for cryptococcal antigenemia among patients with CD4-positive T-cell counts of less than 100 cells/µL who are not receiving effective ART.

“The importance of asymptomatic cryptococcal antigenemia as a precursor to symptomatic meningitis and death has been further defined [since 2008] and more cryptococcal antigenemia prevalence data have been published,” they wrote in their study.

This screening coupled with pre-emptive antifungal therapy has been part of national guidelines in the U.S. and several countries in Africa and is under consideration elsewhere, according to Rajasingham and colleagues. They said estimating the global burden of cryptococcal meningitis helps stakeholders compare the cost of treatment vs. prevention, with prevention methods showing both survival and cost-saving benefits.

For example, in Uganda, which has an annual estimated incidence of 12,200 cases of cryptococcal meningitis, the researchers estimated that screening and pre-emptively treating patients would cost only 15% as much as the $5 million to $6 million it would take to diagnose and treat patients with the disease.

“Our analysis highlights the substantial ongoing burden of HIV–associated cryptococcal disease, primarily in sub-Saharan Africa,” Rajasingham and colleagues wrote. “Cryptococcal meningitis is a metric of HIV treatment program failure; timely HIV testing and rapid linkage to care remain an urgent priority.”

Study ‘a seminal contribution’

According to Peter R. Williamson, MD, PhD, chief of the translational mycology unit in the Laboratory of Clinical Infectious Diseases at the National Institute of Allergy and Infectious Diseases, the study by Rajasingham and colleagues is “a seminal contribution to the quantification of the global burden of cryptococcal disease in patients infected with HIV.”

Williamson wrote in a related editorial also published in The Lancet Infectious Diseases that the global burden of cryptococcal meningitis is “severely hampering control of the HIV pandemic.”

“These sobering data for the stubbornness of cryptococcal meningitis have been confirmed in a study in Botswana where, despite nearly achieving the lofty ‘90-90-90’ goal of 90% HIV detection, 90% enrollment in therapy, and 90% achievement of undetectable viral loads, cryptococcal meningitis rates have shown no reductions over the most recent 2010–14 time interval,” Williamson wrote. – by Gerard Gallagher

References:

Rajasingham R, et al. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30243-8.

Williamson PR. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30245-1.

Disclosures: Please see the full study for a list of all authors’ relevant financial disclosures. Williamson reports no relevant financial disclosures.