Tracking Cryptococcal Meningitis to Monitor Human Immunodeficiency Virus Program Success During the Treat All Era: An Analysis of National Data in Botswana

Abstract

Abstract Background Cryptococcal meningitis (CM) causes substantial mortality in African countries with a high prevalence of human immunodeficiency virus (HIV), despite advances in disease management and increasing antiretroviral therapy (ART) coverage. Reliable diagnosis of CM is cheap and more accessible than other indicators of advanced HIV disease burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring CM incidence has the potential to serve as a valuable metric of HIV programmatic success. Methods Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analyzed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. CM case frequency was enumerated using a case definition and incidence calculated using national census data. Results A total of 1744 episodes of CM were identified; incidence declined from 15.0 (95% confidence interval [CI], 13.4–16.7) cases/100 000 person-years in 2015 to 7.4 (95% CI, 6.4–8.6) cases/100 000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40–44 years. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. Conclusions CM incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test, highlighting the potential of using CM as key metric of program success in the Treat All era.