Background Acute encephalitis is an important and severe disease in children in Vietnam. However, little is known about the etiology while such knowledge is essential for optimal prevention and treatment. To identify viral causes of encephalitis, in 2004 we conducted a one-year descriptive study at Children's Hospital Number One, a referral hospital for children in southern Vietnam including Ho Chi Minh City. Methodology/Principal Findings Children less than 16 years of age presenting with acute encephalitis of presumed viral etiology were enrolled. Diagnostic efforts included viral culture, serology and real time (RT)-PCRs. A confirmed or probable viral causative agent was established in 41% of 194 enrolled patients. The most commonly diagnosed causative agent was Japanese encephalitis virus (n = 50, 26%), followed by enteroviruses (n = 18, 9.3%), dengue virus (n = 9, 4.6%), herpes simplex virus (n = 1), cytomegalovirus (n = 1) and influenza A virus (n = 1). Fifty-seven (29%) children died acutely. Fatal outcome was independently associated with patient age and Glasgow Coma Scale (GCS) on admission. Conclusions/Significance Acute encephalitis in children in southern Vietnam is associated with high mortality. Although the etiology remains unknown in a majority of the patients, the result from the present study may be useful for future design of treatment and prevention strategies of the disease. The recognition of GCS and age as predictive factors may be helpful for clinicians in managing the patient.
References
[1]
Granerod J, Crowcroft NS (2007) The epidemiology of acute encephalitis. Neuropsychol Rehabil 17: 406–428. doi: 10.1080/09602010600989620
[2]
Davison KL, Crowcroft NS, Ramsay ME, Brown DW, Andrews NJ (2003) Viral encephalitis in England, 1989–1998: what did we miss? Emerg Infect Dis 9: 234–240. doi: 10.3201/eid0902.020218
[3]
Glaser CA, Honarmand S, Anderson LJ, Schnurr DP, Forghani B, et al. (2006) Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis 43: 1565–1577. doi: 10.1086/509330
[4]
Srey VH, Sadones H, Ong S, Mam M, Yim C, et al. (2002) Etiology of encephalitis syndrome among hospitalized children and adults in Takeo, Cambodia, 1999–2000. Am J Trop Med Hyg 66: 200–207.
[5]
Solomon T, Dung NM, Kneen R, Thao le TT, Gainsborough M, et al. (2002) Seizures and raised intracranial pressure in Vietnamese patients with Japanese encephalitis. Brain 125: 1084–1093. doi: 10.1093/brain/awf116
[6]
Boom R, Sol C, Beld M, Weel J, Goudsmit J, et al. (1999) Improved silica-guanidiniumthiocyanate DNA isolation procedure based on selective binding of bovine alpha-casein to silica particles. J Clin Microbiol 37: 615–619.
[7]
Boom R, Sol J, Salimans MM, Jansen CL, Wertheim-van Dillen PM, et al. (1990) Rapid and simple method for purification of nucleic acids. J Clin Microbiol 28: 495–503.
[8]
Mai NT, Hoa NT, Nga TV, Linh LD, Chau TT, et al. (2008) Streptococcus suis Meningitis in Adults in Vietnam. Clin Infect Dis.
[9]
Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, et al. (2001) Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 39: 1553–1558. doi: 10.1128/JCM.39.4.1553-1558.2001
[10]
Tan le V, Ha do Q, Hien VM, van der Hoek L, Farrar J, et al. (2008) Me Tri virus: a Semliki Forest virus strain from Vietnam? J Gen Virol 89: 2132–2135. doi: 10.1099/vir.0.2008/002121-0
[11]
Cardosa MJ, Wang SM, Sum MS, Tio PH (2002) Antibodies against prM protein distinguish between previous infection with dengue and Japanese encephalitis viruses. BMC Microbiol 2: 9. doi: 10.1186/1471-2180-2-9
[12]
de Jong MD, Bach VC, Phan TQ, Vo MH, Tran TT, et al. (2005) Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med 352: 686–691. doi: 10.1056/NEJMoa044307
[13]
Kolski H, Ford-Jones EL, Richardson S, Petric M, Nelson S, et al. (1998) Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994–1995. Clin Infect Dis 26: 398–409. doi: 10.1086/516301
[14]
Klein SK, Hom DL, Anderson MR, Latrizza AT, Toltzis P (1994) Predictive factors of short-term neurologic outcome in children with encephalitis. Pediatr Neurol 11: 308–312. doi: 10.1016/0887-8994(94)90007-8
[15]
Rautonen J, Koskiniemi M, Vaheri A (1991) Prognostic factors in childhood acute encephalitis. Pediatr Infect Dis J 10: 441–446. doi: 10.1097/00006454-199106000-00005
[16]
Wang IJ, Lee PI, Huang LM, Chen CJ, Chen CL, et al. (2007) The correlation between neurological evaluations and neurological outcome in acute encephalitis: a hospital-based study. Eur J Paediatr Neurol 11: 63–69. doi: 10.1016/j.ejpn.2006.09.010
[17]
Rayamajhi A, Singh R, Prasad R, Khanal B, Singhi S (2007) Study of Japanese encephalitis and other viral encephalitis in Nepali children. Pediatr Int 49: 978–984. doi: 10.1111/j.1442-200X.2007.02495.x
[18]
Cizman M, Jazbec J (1993) Etiology of acute encephalitis in childhood in Slovenia. Pediatr Infect Dis J 12: 903–908. doi: 10.1097/00006454-199311000-00002
[19]
Fowler A, Stodberg T, Eriksson M, Wickstrom R (2008) Childhood encephalitis in Sweden: etiology, clinical presentation and outcome. Eur J Paediatr Neurol 12: 484–490. doi: 10.1016/j.ejpn.2007.12.009
[20]
Xu Y, Zhaori G, Vene S, Shen K, Zhou Y, et al. (1996) Viral etiology of acute childhood encephalitis in Beijing diagnosed by analysis of single samples. Pediatr Infect Dis J 15: 1018–1024. doi: 10.1097/00006454-199611000-00017
[21]
Ooi MH, Lewthwaite P, Lai BF, Mohan A, Clear D, et al. (2008) The epidemiology, clinical features, and long-term prognosis of Japanese encephalitis in central sarawak, malaysia, 1997–2005. Clin Infect Dis 47: 458–468. doi: 10.1086/590008
[22]
Kumar R, Tripathi P, Singh S, Bannerji G (2006) Clinical features in children hospitalized during the 2005 epidemic of Japanese encephalitis in Uttar Pradesh, India. Clin Infect Dis 43: 123–131. doi: 10.1086/505121
[23]
Fowlkes AL, Honarmand S, Glaser C, Yagi S, Schnurr D, et al. (2008) Enterovirus-associated encephalitis in the California encephalitis project, 1998–2005. J Infect Dis 198: 1685–1691. doi: 10.1086/592988
[24]
Khetsuriani N, Lamonte A, Oberste MS, Pallansch M (2006) Neonatal enterovirus infections reported to the national enterovirus surveillance system in the United States, 1983–2003. Pediatr Infect Dis J 25: 889–893. doi: 10.1097/01.inf.0000237798.07462.32
[25]
Beig FK, Malik A, Rizvi M, Acharya D, Khare S.Etiology and clinico-epidemiological profile of acute viral encephalitis in children of western Uttar Pradesh, India. Int J Infect Dis. doi: 10.1016/j.ijid.2009.03.035
[26]
Cam BV, Fonsmark L, Hue NB, Phuong NT, Poulsen A, et al. (2001) Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever. Am J Trop Med Hyg 65: 848–851.
Kumar R, Tripathi S, Tambe JJ, Arora V, Srivastava A, et al. (2008) Dengue encephalopathy in children in Northern India: clinical features and comparison with non dengue. J Neurol Sci 269: 41–48. doi: 10.1016/j.jns.2007.12.018
[29]
Gould EA, Solomon T (2008 Feb 9) Pathogenic flaviviruses. Lancet 371: 500–509. doi: 10.1016/S0140-6736(08)60238-X
[30]
Ha DQ, Calisher CH, Tien PH, Karabatsos N, Gubler DJ (1995) Isolation of a newly recognized alphavirus from mosquitoes in Vietnam and evidence for human infection and disease. Am J Trop Med Hyg 53: 100–104.
[31]
Benschop K, Molenkamp R, van der Ham A, Wolthers K, Beld M (2008) Rapid detection of human parechoviruses in clinical samples by real-time PCR. J Clin Virol 41: 69–74. doi: 10.1016/j.jcv.2007.10.004
[32]
Verboon-Maciolek MA, Groenendaal F, Hahn CD, Hellmann J, van Loon AM, et al. (2008) Human parechovirus causes encephalitis with white matter injury in neonates. Ann Neurol 64: 266–273. doi: 10.1002/ana.21445
[33]
Wolthers KC, Benschop KS, Schinkel J, Molenkamp R, Bergevoet RM, et al. (2008) Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children. Clin Infect Dis 47: 358–363. doi: 10.1086/589752
[34]
Solomon T (2004) Flavivirus encephalitis. N Engl J Med 351: 370–378. doi: 10.1056/NEJMra030476
[35]
Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, et al. (2008) Global trends in emerging infectious diseases. Nature 451: 990–993. doi: 10.1038/nature06536
[36]
Jerome KR, Huang ML, Wald A, Selke S, Corey L (2002) Quantitative stability of DNA after extended storage of clinical specimens as determined by real-time PCR. J Clin Microbiol 40: 2609–2611. doi: 10.1128/JCM.40.7.2609-2611.2002
[37]
Beld M, Minnaar R, Weel J, Sol C, Damen M, et al. (2004) Highly sensitive assay for detection of enterovirus in clinical specimens by reverse transcription-PCR with an armored RNA internal control. J Clin Microbiol 42: 3059–3064. doi: 10.1128/JCM.42.7.3059-3064.2004
[38]
Perera D, Podin Y, Akin W, Tan CS, Cardosa MJ (2004) Incorrect identification of recent Asian strains of Coxsackievirus A16 as human enterovirus 71: improved primers for the specific detection of human enterovirus 71 by RT PCR. BMC Infect Dis 4: 11. doi: 10.1186/1471-2334-4-11
[39]
Oberste MS, Maher K, Pallansch MA (1999) Specific detection of echoviruses 22 and 23 in cell culture supernatants by RT-PCR. J Med Virol 58: 178–181. doi: 10.1002/(SICI)1096-9071(199906)58:2<178::AID-JMV13>3.0.CO;2-Q
[40]
Scaramozzino N, Crance JM, Jouan A, DeBriel DA, Stoll F, et al. (2001) Comparison of flavivirus universal primer pairs and development of a rapid, highly sensitive heminested reverse transcription-PCR assay for detection of flaviviruses targeted to a conserved region of the NS5 gene sequences. J Clin Microbiol 39: 1922–1927. doi: 10.1128/JCM.39.5.1922-1927.2001
[41]
Boom R, Sol CJ, Schuurman T, Van Breda A, Weel JF, et al. (2002) Human cytomegalovirus DNA in plasma and serum specimens of renal transplant recipients is highly fragmented. J Clin Microbiol 40: 4105–4113. doi: 10.1128/JCM.40.11.4105-4113.2002