title: Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study.
abstract: BACKGROUND
  Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear.
  
  
  METHODS
  We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates.
  
  
  RESULTS
  Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 [15%] of 168 vs. 30 [28%] of 109; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 [7%] of 168 vs. 29 [27%] of 109; OR, 0.21; 95% CI, 0.10-0.46; P<.0001); children with HEV-71 genogroup B5 were more likely to be part of a family cluster (OR, 6.26; 95% CI, 2.77-14.18; P<.0001). Children with HEV-71 and coinfected with another enterovirus or adenovirus were no more likely to have CNS disease.
  
  
  CONCLUSIONS
  Genogroups of HEV-71 may differ with regard to the risk of causing CNS disease and the association with family clusters. Dual infections are common, and all possible causes should be excluded before accepting that the first virus identified is the causal agent.
authors.affiliation: Department of Paediatrics, Sibu Hospital, Sibu, Malaysia.
authors.forename: Mong How
authors.initials: MH
authors.lastname: Ooi
authors.forename: See Chang
authors.initials: SC
authors.lastname: Wong
authors.forename: Yuwana
authors.initials: Y
authors.lastname: Podin
authors.forename: Winnie
authors.initials: W
authors.lastname: Akin
authors.forename: Syvia
authors.initials: S
authors.lastname: del Sel
authors.forename: Anand
authors.initials: A
authors.lastname: Mohan
authors.forename: Chae Hee
authors.initials: CH
authors.lastname: Chieng
authors.forename: David
authors.initials: D
authors.lastname: Perera
authors.forename: Daniela
authors.initials: D
authors.lastname: Clear
authors.forename: Darin
authors.initials: D
authors.lastname: Wong
authors.forename: Emma
authors.initials: E
authors.lastname: Blake
authors.forename: Jane
authors.initials: J
authors.lastname: Cardosa
authors.forename: Tom
authors.initials: T
authors.lastname: Solomon
mesh_terms: D002493:Central Nervous System Diseases / Q000150:complications / Q000453:epidemiology / Q000821:virology; D002648:Child; D002675:Child, Preschool; D004770:Enterovirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D005838:Genotype; D006232:Hand, Foot and Mouth Disease / Q000150:complications / Q000453:epidemiology* / Q000821:virology; D006801:Humans; D007223:Infant; D008296:Malaysia / Q000453:epidemiology; D010802:Phylogeny; D011446:Prospective Studies; D012307:Risk Factors