TY - JOUR
T1 - Viral, Bacterial, Metabolic, and Autoimmune Causes of Severe Acute Encephalopathy in Sub-Saharan Africa
T2 - A Multicenter Cohort Study
AU - Edridge, Arthur
AU - Namazzi, Ruth
AU - Tebulo, Andrew
AU - Mfizi, Anan
AU - Deijs, Martin
AU - Koekkoek, Sylvie
AU - de Wever, Bob
AU - van der Ende, Arie
AU - Umiwana, Jeanine
AU - de Jong, Menno D.
AU - Jans, Judith
AU - Verhoeven-Duif, Nanda
AU - Titulaer, Maarten
AU - van Karnebeek, Clara
AU - Seydel, Karl
AU - Taylor, Terrie
AU - Asiimwe-Kateera, Brenda
AU - van der Hoek, Lia
AU - Kabayiza, Jean-Claude
AU - Mallewa, Macpherson
AU - Idro, Richard
AU - Boele van Hensbroek, Michael
AU - van Woensel, Job B. M.
N1 - 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
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85157970537&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jpeds.2023.02.007
DO - https://doi.org/10.1016/j.jpeds.2023.02.007
M3 - Article
C2 - 36828342
SN - 0022-3476
VL - 258
JO - Journal of pediatrics
JF - Journal of pediatrics
M1 - 113360
ER -