Article Category:
Research Article

Etiology and Outcomes of Meningitis among Adults in Three Ugandan Referral Hospitals, 2018–2023: A Prospective Cohort Study in a High-HIV Endemic Setting

Timothy Mugabi Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Suzan Namombwe Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Biyue Dai Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota;

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Elizabeth Nalintya Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Laura J. Nsangi Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Mable Kabahubya Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Sarah M. Najjuka Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Samuel Okurut Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Olivie C. Namuju Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Enos Kigozi Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda;

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Kisakye D. Kabbale Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Bakka Wilber Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Samuel Jjunju Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda;

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Conrad Muzoora Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda;

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Lillian Tugume Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;

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Martineau Louine Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California;

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Michael R. Wilson Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California;

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Nathan C. Bahr Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota;

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Fiona V. Cresswell Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;
MRC/UVRI-LSHTM Uganda Research Unit, Entebbe, Uganda;
Center for Global Health and Infection, Brighton and Sussex Medical School, Brighton, United Kingdom;

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David B. Meya Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;
Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota;

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Jayne Ellis Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda;
Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom

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David R. Boulware Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota;

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Radha Rajasingham Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota;

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DOI:
https://doi.org/10.4269/ajtmh.24-0373
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Ahead of Print
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Studies describing the global burden of meningitis often exclude HIV- or tuberculosis (TB)-related etiologies, thereby presenting a limited view of meningitis etiology in low- and middle-income countries. This study provides an updated evaluation of the etiology of meningitis and treatment outcomes in Uganda given advancements in molecular and TB diagnostics. We conducted a prospective observational cohort study from December 2018 to October 2023, for which adults with suspected meningitis were recruited from three referral hospitals in Uganda. We used a comprehensive diagnostic algorithm to determine microbiological etiologies of cases. Participants were followed through hospital discharge, and mortality was summarized by meningitis etiology. We enrolled 1,577 participants with suspected meningitis, of whom 96% (n = 1,511/1,577) had HIV infection and 51% (n = 772/1,577) were antiretroviral therapy naive. The median CD4 cell count was 39 cells/µL (interquartile range: 14–97 cells/µL). Cryptococcal meningitis was the most frequently diagnosed etiology of meningitis (62%) followed by TB meningitis (21%). Inpatient mortality was highest among participants diagnosed with possible TB meningitis (32%) followed by probable TB meningitis (29%) and bacterial meningitis (24%). Among the 4% (n = 66/1,577) of HIV-seronegative participants, TB meningitis was the most frequently (38%) diagnosed cause of meningitis. Despite improvements in access to HIV therapy, cryptococcal meningitis and tuberculous meningitis persist as the most common etiologies of meningitis in Uganda. Improved access to meningitis diagnostics and treatments is critically needed to mitigate the morbidity and mortality, particularly in the resource-limited settings of HIV and TB endemic regions.

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Author Notes

Financial support: This research was supported by the National Institute of Neurological Disorders and Stroke (NINDS; Grant nos. R01 NS086312 and K23 NS110470), the Fogarty International Center, and the National Institute of Allergy and Infectious Diseases (Grant nos. R01 AI170158, K23 AI138851, and R01 AI145437) of NIH. A Wellcome Trust Clinical PhD Fellowship (Grant no. 203905/Z/16/Z awarded to J. Ellis) and Wellcome Trust Fellowships (Grant nos. 210772A/Z/18/Z and 300088/Z/24/Z awarded to F. V. Cresswell) also supported this work. L. Tugume was supported by the Fogarty International Center of NIH (Grant no. D43TW009345 awarded to the Northern Pacific Global Health Fellows Program).

Disclosures: The study conformed to U.S. and international standards of Good Clinical Practice, the Declaration of Helsinki, and international ethical guidelines for biomedical research involving human subjects. The parent study protocols were approved by the Human Subjects Protection Board at the Mulago Research and Ethics Committee, the Uganda National Council for Science and Technology, and the University of Minnesota Institutional Review Board. All participants or surrogates (in cases of incapacity) provided written informed consent before enrollment. The funder had no role in study conduct or data analysis. Data were accessible to all of the authors.

Current contact information: Timothy Mugabi, Suzan Namombwe, Elizabeth Nalintya, Laura J. Nsangi, Mable Kabahubya, Sarah M. Najjuka, Samuel Okurut, Olivie C. Namuju, Kisakye D. Kabbale, Bakka Wilber, Lillian Tugume, David B. Meya, and Jayne Ellis, Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda, E-mails: tmugabi@idi.co.ug, snamombwe@idi.co.ug, enalintya@idi.co.ug, lnsangi@idi.co.ug, mkabahubya@idi.co.ug, najjukasarah@gmail.com, okuruts@gmail.com, cnamuju@idi.co.ug, dikisakye@gmail.com, bakkawilber@gmail.com, lilliqntugume18@gmail.com, david.meya@gmail.com, and jayne.ellis1@lshtm.ac.uk. Biyue Dai, Nathan C. Bahr, David R. Boulware, and Radha Rajasingham, Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, E-mails: biydai@umn.edu, bahrx026@umn.edu, boulw001@umn.edu, and radha@umn.edu. Enos Kigozi, Samuel Jjunju, and Conrad Muzoora, Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda, E-mails: kigozi.enos@gmail.com, junjusamuel93@gmail.com, and conradmuzoora@yahoo.com. Martineau Louine and Michael R. Wilson, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, E-mails: martineau.louine@ucsf.edu and michael.wilson@ucsf.edu. Fiona V. Cresswell, MRC/UVRI-LSHTM Uganda Research Unit, Entebbe, Uganda, and Center for Global Health and Infection, Brighton and Sussex Medical School, Brighton, United Kingdom, E-mail: fiona.cresswell@lshtm.ac.uk.

Address correspondence to Radha Rajasingham, University of Minnesota, 689 23rd Ave. SE, Minneapolis, MN 55455. E-mail: radha@umn.edu
Copyright:
© American Society of Tropical Medicine and Hygiene 2025
Received:
05 Jun 2024
|
Accepted:
11 Jan 2025
|
Published Online:
15 Apr 2025
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
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