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Journal Articles The Lancet global health Year : 2022

Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study

Heng Sothy
  • Function : Author
Ky Santy
  • Function : Author
Huong Thi Thu Tran
  • Function : Author
Lam Van Nguyen
  • Function : Author
Em Bunnakea
  • Function : Author
Chaw Su Hlaing
  • Function : Author
Aye Mya Min Aye
  • Function : Author
Patrice Piola
  • Function : Author
Bruno Rosset
  • Function : Author
Jerome Honnorat
Sayaphet Rattanavong
  • Function : Author
Manivanh Vongsouvath
  • Function : Author
Sommanikhone Phangmanixay
  • Function : Author
Khounthavy Phongsavath
  • Function : Author
Ommar Swe Tin
  • Function : Author
Latt Latt Kyaw
  • Function : Author
Htay Htay Tin
  • Function : Author
Kyaw Linn
  • Function : Author
Thi Mai Hung Tran
  • Function : Author
Nguyen Thi Thu Thuy
  • Function : Author
Nguyen Hien
  • Function : Author
Phuc Huu Phan
  • Function : Author
Denis Laurent
  • Function : Author
Paul Newton
  • Function : Author
Catherine Ferrant
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Didier Fontenille
  • Function : Author
Lukas Hafner
  • Function : Author
Le Thanh Hai
  • Function : Author
Do Thu Huong
  • Function : Author
Marc Jouan
  • Function : Author
May July
  • Function : Author
Magali Lago
  • Function : Author
Jean-Paul Moatti
  • Function : Author
Bernadette Murgue
  • Function : Author
Khin Yi Oo
  • Function : Author
Mengheng Oum
  • Function : Author
Khansoudaphone Phakhounthong
  • Function : Author
Anh Tuan Pham
  • Function : Author
Do Quyen
  • Function : Author
Malee Seephonelee
  • Function : Author
Maud Seguy
  • Function : Author
Bountoy Sibounheunang
  • Function : Author
Kanarith Sim
  • Function : Author
Luong Minh Tan
  • Function : Author
Cho Thair
  • Function : Author
Win Thein
  • Function : Author
Phung Bich Thuy
  • Function : Author
Hervé Tissot-Dupont
  • Function : Author
Malavanh Vongsouvath
  • Function : Author
SEAe Consortium
  • Function : Author

Abstract

Background Encephalitis is a worldwide public health issue, with a substantially high burden among children in southeast Asia. We aimed to determine the causes of encephalitis in children admitted to hospitals across the Greater Mekong region by implementing a comprehensive state-of-the-art diagnostic procedure harmonised across all centres, and identifying clinical characteristics related to patients’ conditions. Methods In this multicentre, observational, prospective study of childhood encephalitis, four referral hospitals in Cambodia, Vietnam, Laos, and Myanmar recruited children (aged 28 days to 16 years) who presented with altered mental status lasting more than 24 h and two of the following minor criteria: fever (within the 72 h before or after presentation), one or more generalised or partial seizures (excluding febrile seizures), a new-onset focal neurological deficit, cerebrospinal fluid (CSF) white blood cell count of 5 per mL or higher, or brain imaging (CT or MRI) suggestive of lesions of encephalitis. Comprehensive diagnostic procedures were harmonised across all centres, with first-line testing was done on samples taken at inclusion and results delivered within 24 h of inclusion for main treatable causes of disease and second-line testing was done thereafter for mostly non-treatable causes. An independent expert medical panel reviewed the charts and attribution of causes of all the included children. Using multivariate analyses, we assessed risk factors associated with unfavourable outcomes (ie, severe neurological sequelae and death) at discharge using data from baseline and day 2 after inclusion. This study is registered with ClinicalTrials.gov, NCT04089436, and is now complete. Findings Between July 28, 2014, and Dec 31, 2017, 664 children with encephalitis were enrolled. Median age was 4·3 years (1·8–8·8), 295 (44%) children were female, and 369 (56%) were male. A confirmed or probable cause of encephalitis was identified in 425 (64%) patients: 216 (33%) of 664 cases were due to Japanese encephalitis virus, 27 (4%) were due to dengue virus, 26 (4%) were due to influenza virus, 24 (4%) were due to herpes simplex virus 1, 18 (3%) were due to Mycobacterium tuberculosis, 17 (3%) were due to Streptococcus pneumoniae, 17 (3%) were due to enterovirus A71, 74 (9%) were due to other pathogens, and six (1%) were due to autoimmune encephalitis. Diagnosis was made within 24 h of admission to hospital for 83 (13%) of 664 children. 119 (18%) children had treatable conditions and 276 (42%) had conditions that could have been preventable by vaccination. At time of discharge, 153 (23%) of 664 children had severe neurological sequelae and 83 (13%) had died. In multivariate analyses, risk factors for unfavourable outcome were diagnosis of M tuberculosis infection upon admission (odds ratio 3·23 [95% CI 1·04–10·03]), coma on day 2 (2·90 [1·78–4·72]), supplementary oxygen requirement (1·89 [1·25–2·86]), and more than 1 week duration between symptom onset and admission to hospital (3·03 [1·68–5·48]). At 1 year after inclusion, of 432 children who were discharged alive from hospital with follow-up data, 24 (5%) had died, 129 (30%) had neurological sequelae, and 279 (65%) had completely recovered. Interpretation In southeast Asia, most causes of childhood encephalitis are either preventable or treatable, with Japanese encephalitis virus being the most common cause. We provide crucial information that could guide public health policy to improve diagnostic, vaccination, and early therapeutic guidelines on childhood encephalitis in the Greater Mekong region.
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hal-03823946 , version 1 (14-12-2022)

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Jean David Pommier, Chris Gorman, Yoann Crabol, Kevin Bleakley, Heng Sothy, et al.. Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study. The Lancet global health, 2022, 10 (7), pp.e989-e1002. ⟨10.1016/S2214-109X(22)00174-7⟩. ⟨hal-03823946⟩
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