Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

Radha Rajasingham, Rachel M Smith, Benjamin J Park, Joseph N Jarvis, Nelesh P Govender, Tom M Chiller, David W Denning, Angela Loyse, David R Boulware, Radha Rajasingham, Rachel M Smith, Benjamin J Park, Joseph N Jarvis, Nelesh P Govender, Tom M Chiller, David W Denning, Angela Loyse, David R Boulware

Abstract

Background: Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease.

Methods: We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis.

Findings: We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8-6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500-340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600-282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600-193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400-234 300), with 135 900 (75%; [95% CI 93 900-163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10-19).

Interpretation: Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority.

Funding: None.

Conflict of interest statement

Declaration of interests

DWD and family hold founder shares in F2G Ltd, in Novocyt. DWD acts or has recently acted as a consultant to Astellas, Sigma Tau, Basilea, Scynexis, Cidara, Biosergen, Quintilles, Pulmatrix, and Pulmocide. DWD has been paid for talks on behalf of Astellas, Dynamiker, Gilead, Merck, and Pfizer. DWD is a long-standing member of the Infectious Disease Society of America Aspergillosis Guidelines group, the European Society for Clinical Microbiology and Infectious Diseases Aspergillosis Guidelines group, and the British Society for Medical Mycology Standards of Care committee. DWD has a patent in assays for fungal infection licensed. NPG received grants from National Institutes of Health (NIH), another from MSD, personal fees from Fujifilm Pharma and Astellas, grants from Centers for Disease Control and the National Health Laboratory Service Research Trust, outside of this Article. DRB received grants from NIH and UK Medial Research Council, during the conduct of the study. JNJ received grants from Gilead Sciences Europe, outside of the Article. All other authors declare no competing interests.

Copyright © 2017 Elsevier Ltd. All rights reserved.

Figures

Figure 1. Cryptococcal antigenaemia prevalence studies of…
Figure 1. Cryptococcal antigenaemia prevalence studies of HIV-infected outpatient populations from 1989 to 2016
Error bars are 95% CI, the vertical dotted line represents the mean cryptococcal antigenaemia prevalence for all studies combined. Estimates of USA and UK were not included in final summary estimate of low-income and middle-income countries. Studies of populations in hospital were not included (appendix p 11). All references for the studies in this figure are in the appendix. MSF=Médecins Sans Frontieres. N=north. SE=southeast. SW=southwest.
Figure 2. Annual incidence of cryptococcal infection…
Figure 2. Annual incidence of cryptococcal infection by country
The annual number of people positive with cryptococcal antigenaemia estimated at 278 000 (95% CI 195 500–340 600) globally in 2014. We estimated 223 100 annual incident cases of cryptococcal meningitis in 2014..

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