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

doi:10.1093/ofid/ofz419

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

Open Forum Infect Dis. 2019 Sep 29;6(10):ofz419. doi: 10.1093/ofid/ofz419. eCollection 2019 Oct.

Authors

Jayne Ellis^{1

2}, Ananta S Bangdiwala³, Fiona V Cresswell^{1

4}, Joshua Rhein^{1

3}, Edwin Nuwagira⁵, Kenneth Ssebambulidde¹, Lillian Tugume¹, Radha Rajasingham³, Sarah C Bridge^{3

5}, Conrad Muzoora⁵, David B Meya^{1

3}, David R Boulware³

Affiliations

¹ Infectious Diseases Institute, Makerere University, Kampala, Uganda.
² Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK.
³ University of Minnesota, Minneapolis, Minnesota, USA.
⁴ Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
⁵ Mbarara University of Science and Technology, Mbarara, Uganda.

Abstract

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.

Keywords: HIV/AIDS; bacterial meningitis; cryptococcal meningitis; tuberculous meningitis; viral meningitis.

Abstract

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