Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study.
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.
Ooi
Mong How
MH
Department of Paediatrics, Sibu Hospital, Sibu, Malaysia.
Wong
See Chang
SC
Podin
Yuwana
Y
Akin
Winnie
W
del Sel
Syvia
S
Mohan
Anand
A
Chieng
Chae Hee
CH
Perera
David
D
Clear
Daniela
D
Wong
Darin
D
Blake
Emma
E
Cardosa
Jane
J
Solomon
Tom
T
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