Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study

doi:10.1186/s12879-017-2572-9

Multicenter Study

. 2017 Jul 14;17(1):494.

doi: 10.1186/s12879-017-2572-9.

Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study

Junhong Ai¹, Zhengde Xie², Gang Liu¹, Zongbo Chen³, Yong Yang⁴, Yuning Li⁵, Jing Chen⁶, Guo Zheng⁶, Kunling Shen⁷

Affiliations

¹ Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Virology Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
² Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Virology Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China. xiezhengde@bch.com.cn.
³ The Affiliated Hospital of Qingdao University, Shandong province, Qingdao, China.
⁴ The First Hospital of Yulin, Shanxi province, Yulin, China.
⁵ The First Hospital of Lanzhou University, Gansu province, Lanzhou, China.
⁶ Nanjing Children's Hospital, Jiangsu province, Nanjing, China.
⁷ National Clinical Research Center for Respiratory Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, Respiratory Department, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China. kunlingshen@hotmail.com.

PMID: 28705180
PMCID: PMC5513334
DOI: 10.1186/s12879-017-2572-9

Multicenter Study

Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study

Junhong Ai et al. BMC Infect Dis. 2017.

. 2017 Jul 14;17(1):494.

doi: 10.1186/s12879-017-2572-9.

Authors

Junhong Ai¹, Zhengde Xie², Gang Liu¹, Zongbo Chen³, Yong Yang⁴, Yuning Li⁵, Jing Chen⁶, Guo Zheng⁶, Kunling Shen⁷

Affiliations

¹ Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Virology Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
² Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Virology Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China. xiezhengde@bch.com.cn.
³ The Affiliated Hospital of Qingdao University, Shandong province, Qingdao, China.
⁴ The First Hospital of Yulin, Shanxi province, Yulin, China.
⁵ The First Hospital of Lanzhou University, Gansu province, Lanzhou, China.
⁶ Nanjing Children's Hospital, Jiangsu province, Nanjing, China.
⁷ National Clinical Research Center for Respiratory Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, Respiratory Department, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China. kunlingshen@hotmail.com.

PMID: 28705180
PMCID: PMC5513334
DOI: 10.1186/s12879-017-2572-9

Abstract

Background: In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children.

Methods: This was a multicentre prospective study. Two hundred and sixty one viral encephalitis patients and 285 viral meningitis patients were enrolled. The mean age of viral encephalitis and meningitis were 5.88 ± 3.60 years and 6.39 ± 3.57 years, respectively. Real-time reverse transcription PCR and multiplex PCR were used to detect human enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and rubella virus in acute serum. The clinical and outcome data were collected during patients' hospitalization.

Results: The etiology of viral encephalitis was confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%) in viral encephalitis. The incidence of sequelae and the fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The etiology of viral meningitis was identified in 42.8% cases. The leading pathogen was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral meningitis was favorable with only 0.7% patients had neurological sequelae.

Conclusions: Human enteroviruses were the leading cause both in acute viral encephalitis and viral meningitis in children. The incidence of sequelae and fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The prognosis of viral meningitis was favorable compared to viral encephalitis.

Keywords: Children; Etiology; Prognosis; Viral encephalitis; Viral meningitis.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by Medical Ethics Committee of Beijing Children’s Hospital, Capital Medical University. Written informed consent was obtained from the patients’ parents.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Seasonal distribution of viral encephalitis and meningitis cases

**Fig. 2**
Percentage of viral pathogens in viral encephalitis cases with confirmed etiology. HSV1: herpes simplex virus 1; HSV2: herpes simplex virus 2; VZV: varicella zoster virus; EBV: Epstein-Barr virus; CMV: cytomegalovirus; HHV6: human herpes virus 6; EVs: human enteroviruses; JEV: Japanese encephalitis virus; mumps: mumps virus; TBEV: tick-borne encephalitis virus; dengue: Dengue virus; rubella: rubella virus

**Fig. 3**
Percentage of viral pathogens in viral meningitis cases with confirmed etiology. HSV1: herpes simplex virus 1; HSV2: herpes simplex virus 2; VZV: varicella zoster virus; EBV: Epstein-Barr virus; CMV: cytomegalovirus; HHV6: human herpes virus 6; EVs: human enteroviruses; JEV: Japanese encephalitis virus; mumps: mumps virus; TBEV: tick-borne encephalitis virus; dengue: Dengue virus; rubella: rubella virus

**Fig. 4**
Seasonal distribution of viral encephalitis cases with confirmed etiology. HSV1: herpes simplex virus 1; HSV2: herpes simplex virus 2; VZV: varicella zoster virus; EBV: Epstein-Barr virus; CMV: cytomegalovirus; HHV6: human herpes virus 6; EVs: human enteroviruses; JEV: Japanese encephalitis virus; mumps: mumps virus; TBEV: tick-borne encephalitis virus; dengue: Dengue virus; rubella: rubella virus

**Fig. 5**
Seasonal distribution of viral meningitis cases with confirmed etiology. HSV1: herpes simplex virus 1; HSV2: herpes simplex virus 2; VZV: varicella zoster virus; EBV: Epstein-Barr virus; CMV: cytomegalovirus; HHV6: human herpes virus 6; EVs: human enteroviruses; JEV: Japanese encephalitis virus; mumps: mumps virus; TBEV: tick-borne encephalitis virus; dengue: Dengue virus; rubella: rubella virus

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References

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[1] Parpia AS, Li Y, Chen C, Dhar B, Crowcroft NS. Encephalitis, Ontario, Canada, 2002–2013. Emerg Infect Dis. 2016;22(3):426–32. doi: 10.3201/eid2203.151545. - DOI - PMC - PubMed

[2] Parpia AS, Li Y, Chen C, Dhar B, Crowcroft NS. Encephalitis, Ontario, Canada, 2002–2013. Emerg Infect Dis. 2016;22(3):426–32. doi: 10.3201/eid2203.151545. - DOI - PMC - PubMed

[3] Barbadoro P, Marigliano A, Ricciardi A, D'Errico MM, Prospero E. Trend of hospital utilization for encephalitis. Epidemiol Infect. 2012;140(4):753–64. doi: 10.1017/S0950268811001002. - DOI - PubMed

[4] Barbadoro P, Marigliano A, Ricciardi A, D'Errico MM, Prospero E. Trend of hospital utilization for encephalitis. Epidemiol Infect. 2012;140(4):753–64. doi: 10.1017/S0950268811001002. - DOI - PubMed

[5] Vora NM, Holman RC, Mehal JM, Steiner CA, Blanton J, Sejvar J. Burden of encephalitis-associated hospitalizations in the United States, 1998–2010. Neurology. 2014;82(5):443–51. doi: 10.1212/WNL.0000000000000086. - DOI - PubMed

[6] Vora NM, Holman RC, Mehal JM, Steiner CA, Blanton J, Sejvar J. Burden of encephalitis-associated hospitalizations in the United States, 1998–2010. Neurology. 2014;82(5):443–51. doi: 10.1212/WNL.0000000000000086. - DOI - PubMed

[7] Huppatz C, Durrheim DN, Levi C, Dalton C, Williams D, Clements MS, Kelly PM. Etiology of encephalitis in Australia, 1990–2007. Emerg Infect Dis. 2009;15(9):1359–65. doi: 10.3201/eid1509.081540. - DOI - PMC - PubMed

[8] Huppatz C, Durrheim DN, Levi C, Dalton C, Williams D, Clements MS, Kelly PM. Etiology of encephalitis in Australia, 1990–2007. Emerg Infect Dis. 2009;15(9):1359–65. doi: 10.3201/eid1509.081540. - DOI - PMC - PubMed

[9] Le VT, Phan TQ, Do QH, Nguyen BH, Lam QB, Bach V, et al. Viral etiology of encephalitis in children in southern Vietnam: results of a one-year prospective descriptive study. PLoS Negl Trop Dis. 2010;4(10):e854. doi: 10.1371/journal.pntd.0000854. - DOI - PMC - PubMed

[10] Le VT, Phan TQ, Do QH, Nguyen BH, Lam QB, Bach V, et al. Viral etiology of encephalitis in children in southern Vietnam: results of a one-year prospective descriptive study. PLoS Negl Trop Dis. 2010;4(10):e854. doi: 10.1371/journal.pntd.0000854. - DOI - PMC - PubMed

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