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An atypical winter outbreak of hand, foot, and mouth disease associated with human enterovirus 71, 2010

Nan Liu1, Jing Xie1, Xiaoli Qiu2, Leili Jia1, Zhihao Wu1, Yuhua Ma2, Zhongqiang Wang1, Peng Li1, Xingbin Ren2, Rongzhang Hao1, Ligui Wang1, Yong Wang1, Shaofu Qiu1* and Hongbin Song1*

Author Affiliations

1 Academy of Military Medical Sciences, Institute of Disease Control and Prevention, 20 Dongda Street, Fengtai District, Beijing 100071, China

2 Department of Clinical Laboratory Sciences, Linyi People’s Hospital, Linyi 276000, China

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BMC Infectious Diseases 2014, 14:123  doi:10.1186/1471-2334-14-123

Published: 4 March 2014



To analyze the epidemiological characteristics and pathogenic molecular characteristics of an hand, foot, and mouth disease (HFMD) outbreak caused by enterovirus 71 in Linyi City, Shandong Province, China during November 30 to December 28, 2010.


One hundred and seventy three stool specimens and 40 throat samples were collected from 173 hospitalized cases. Epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak.


Among the 173 cases reported in December 2010, the male–female ratio was 1.88: 1; 23 cases (13.3%) were severe. The majority of patients were children aged < 5 years (95.4%). Some patients developed respiratory symptoms including runny nose (38.2%), cough (20.2%), and sore throat (14.5%). One hundred and thirty eight EV71 positive cases were identified based on real time reverse-transcription PCR detection and 107 isolates were sequenced with the VP1 region. Phylogenetic analysis of full-length VP1 sequences of 107 Linyi EV71 isolates showed that they belonged to the C4a cluster of the C4 subgenotype and were divided into 3 lineages (Lineage I, II and III). The two amino acid substitutions (Gly and Gln for Glu) at position 145 within the VP1 region are more likely to appear in EV71 isolates from severe cases (52.2%) than those recovered from mild cases (8.3%).


This outbreak of HMFD was caused by EV71 in an atypical winter. EV71 strains associated with this outbreak represented three separate chains of transmission. Substitution at amino acid position 145 of the VP1 region of EV71 might be an important virulence marker for severe cases. These findings suggest that continued surveillance for EV71 variants has the potential to greatly impact HFMD prevention and control.

Hand; Foot; and mouth disease; HFMD; Enterovirus 71; Phylogenetic analysis; Subgenotype C4