Viral, Bacterial, Metabolic, and Autoimmune Causes of Severe Acute Encephalopathy in Sub-Saharan Africa: A Multicenter Cohort Study

Arthur Edridge*, Ruth Namazzi, Andrew Tebulo, Anan Mfizi, Martin Deijs, Sylvie Koekkoek, Bob de Wever, Arie van der Ende, Jeanine Umiwana, Menno D. de Jong, Judith Jans, Nanda Verhoeven-Duif, Maarten Titulaer, Clara van Karnebeek, Karl Seydel, Terrie Taylor, Brenda Asiimwe-Kateera, Lia van der Hoek, Jean Claude Kabayiza, Macpherson MallewaRichard Idro, Michael Boele van Hensbroek, Job B.M. van Woensel

*Corresponding author for this work

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Objectives: To assess whether viral, bacterial, metabolic, and autoimmune diseases are missed by conventional diagnostics among children with severe acute encephalopathy in sub-Saharan Africa. Study design: One hundred thirty-four children (6 months to 18 years) presenting with nontraumatic coma or convulsive status epilepticus to 1 of 4 medical referral centers in Uganda, Malawi, and Rwanda were enrolled between 2015 and 2016. Locally available diagnostic tests could be supplemented in 117 patients by viral, bacterial, and 16s quantitative polymerase chain reaction testing, metagenomics, untargeted metabolomics, and autoimmune immunohistochemistry screening. Results: Fourteen (12%) cases of viral encephalopathies, 8 (7%) cases of bacterial central nervous system (CNS) infections, and 4 (4%) cases of inherited metabolic disorders (IMDs) were newly identified by additional diagnostic testing as the most likely cause of encephalopathy. No confirmed cases of autoimmune encephalitis were found. Patients for whom additional diagnostic testing aided causal evaluation (aOR 3.59, 90% CI 1.57-8.36), patients with a viral CNS infection (aOR 7.91, 90% CI 2.49-30.07), and patients with an IMD (aOR 9.10, 90% CI 1.37-110.45) were at increased risk for poor outcome of disease. Conclusions: Viral and bacterial CNS infections and IMDs are prevalent causes of severe acute encephalopathy in children in Uganda, Malawi, and Rwanda that are missed by conventional diagnostics and are associated with poor outcome of disease. Improved diagnostic capacity may increase diagnostic yield and might improve outcome of disease.

Original languageEnglish
Article number113360
JournalJournal of Pediatrics
Early online date22 Feb 2023
Publication statusPublished - Jul 2023

Bibliographical note

Funding Information:
Funded by the Dutch Research Council (NWO). The funder/sponsor did not participate in the work. The authors report no conflict of interest.

Publisher Copyright:
© 2023 The Authors


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