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

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

Jayne Ellis  1   2 , Ananta S Bangdiwala  3 , Fiona V Cresswell  1   4 , Joshua Rhein  1   3 , Edwin Nuwagira  5 , Kenneth Ssebambulidde  1 , Lillian Tugume  1 , Radha Rajasingham  3 , Sarah C Bridge  3   5 , Conrad Muzoora  5 , David B Meya  1   3 , David R Boulware  3
Affiliations

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

Jayne Ellis et al. Open Forum Infect Dis. .

Erratum in

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.

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Figures

Figure 1.
Figure 1.
Stepwise diagnostic algorithm used in investigation of suspected HIV-associated meningitis. Figure 1 demonstrates the diagnostic workup for adults with HIV, presenting with meningitis symptoms. This is a stepwise diagnostic algorithm, such that diagnostic tests are sequentially run until a positive diagnosis is made (as indicated in the gray boxes), and then no further investigations are employed. Participants with a positive finger-stick CrAg but negative CSF CrAg had additional “other meningitis” workup performed. Abbreviations: CSF, cerebrospinal fluid; LFA, lateral flow assay; LP, lumbar puncture; PCR, polymerase chain reaction; WBC, white blood cell count.
Figure 2.
Figure 2.
Etiology of HIV-associated meningitis in Ugandan adults, 2015–2017. Figure 2 demonstrates the proportional frequencies (%) of fungal, mycobacterial, bacterial, and fungal meningitis in 842 Ugandan adults with HIV presenting with suspected meningitis. Abbreviations: ICP, Intra cranial pressure; IRIS, immune reconstitution inflammatory syndrome; TBM, tuberculous meningitis.
See this image and copyright information in PMC

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