The Changing Epidemiology of HIV-Associated Adult Meningitis, Uganda 2015-2017

Jayne Ellis, Ananta S. Bangdiwala, Fiona V. Cresswell, Joshua Rhein, Edwin Nuwagira, Kenneth Ssebambulidde, Lillian Tugume, Radha Rajasingham, Sarah C. Bridge, Conrad Muzoora, David B. Meya, David R. Boulware

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations


Background: Central nervous system (CNS) infections remain a major public health problem in Sub-Saharan Africa, causing 15%-25% of AIDS-related deaths. With widespread availability of antiretroviral therapy (ART) and the introduction of improved diagnostics, the epidemiology of infectious meningitis is evolving. Methods: We prospectively enrolled adults presenting with HIV-associated meningitis in Kampala and Mbarara, Uganda, from March 2015 to September 2017. Participants had a structured, stepwise diagnostic algorithm performed of blood cryptococcal antigen (CrAg), CSF CrAg, Xpert MTB/RIF for tuberculous (TB) meningitis (TBM), Biofire multiplex polymerase chain reaction, and traditional microscopy and cultures. Results: We screened 842 consecutive adults with HIV presenting with suspected meningitis: 57% men, median age 35 years, median CD4 26 cells/mcL, and 55% presented on ART. Overall, 60.5% (509/842) were diagnosed with first-episode cryptococcal meningitis and 7.4% (62/842) with second episode. Definite/probable TB meningitis was the primary diagnosis in 6.9% (58/842); 5.3% (n = 45) had microbiologically confirmed (definite) TB meningitis. An additional 7.8% (66/842) did not meet the diagnostic threshold for definite/probable TBM but received empiric TBM therapy. Bacterial and viral meningitis were diagnosed in 1.3% (11/842) and 0.7% (6/842), respectively. The adoption of a cost-effective stepwise diagnostic algorithm allowed 79% (661/842) to have a confirmed microbiological diagnosis at an average cost of $44 per person. Conclusions: Despite widespread ART availability, Cryptococcus remains the leading cause of HIV-associated meningitis. The second most common etiology was TB meningitis, treated in 14.7% overall. The increased proportion of microbiologically confirmed TBM cases reflects the impact of new improved molecular diagnostics.

Original languageEnglish (US)
Article numberofz419
JournalOpen Forum Infectious Diseases
Issue number10
StatePublished - Oct 1 2019

Bibliographical note

Funding Information:
This work was supported by the National Institute of Neurologic Diseases and Stroke (R01NS086312), the Fogarty International Center (K01TW010268, R25TW009345), the National Institute of Allergy and Infectious Diseases (T32AI055433), United Kingdom Medical Research Council/DfID/Wellcome Trust Global Clinical Trials (M007413/1), and the Wellcome Trust (210772/Z/18/Z). We thank the University of Minnesota Foundation for provision of the Bactec MGIT culture system for the MSF Epicentre Laboratory in Mbarara, Uganda.

Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.


  • bacterial meningitis
  • cryptococcal meningitis
  • tuberculous meningitis
  • viral meningitis


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