Abstract: Objective To clarify the composition and changes of enterovirus spectrum in hand, foot and mouth disease in Jinan, China, from Jan. 2012 to Dec. 2017, further to analyze the epidemiological characteristics of different types of enterovirus. Methods A total of 4 929 specimens were collected from clinically diagnosed hand, foot and mouth disease cases in Jinan from 2012 to 2017. All specimens were detected for Enterovirus A71(EV-A71), Coxsackievirus(CV)-A16, CV-A6 and CV-A10 by real-time reverse transcription-polymerase chain reaction(RT-PCR). For unclassified specimens, reverse transcription nested PCR based on the 5'-untranslated region(5'-UTR)sequence was performed and the types of enterovirus were determined by nucleotide sequencing. Results A total of 27 types of enterovirus were identified in 4 929 specimens, including not only EV-A71, CV-A16, CV-A6 and CV-A10, but also CV-A2, 4, 5, 9, 12, 13, 21, 22, 24, CV-B1-5 and E3, 6, 7, 9, 11, 18, 24, 25, 30. The constituent ratios were different between 山 东 大 学 学 报 (医 学 版)57卷11期 -关恒云,等.济南市2012~2017年手足口病肠道病毒谱变化及流行特征 \=-mild and severe cases. The top four types of enterovirus for mile cases were CV-A16(29.03%), EV-A71(25.67%), CV-A6(17.58%)and CV-A10(3.10%), and for severe cases were EV-A71(77.64%), CV-A16(5.59%), CV-A6(1.86%)and CV-A10(1.24%). The cases with CV-A6 and CV-A10 infections were younger than EV-A71 and CV-A16 infections(F=3.659, P=0.003), and they were(3.02±2.43),(2.87±1.67),(3.29±2.34)and(3.36±2.18)years, respectively. The incidence peak of EV-A71 and CV-A16 appeared usually in the second or fourth quarter, CV-A6 mostly occurred from June to December, and CV-A10 from June to August. The positive detection rate of enteroviruses was higher in Pingyin county and Zhangqiu district(93.49% and 91.99%, respectively). Conclusion EV-A71, CV-A16, CV-A6 and CV-A10 were the dominant types of enteroviruses associated with hand, foot and mouth disease in Jinan, and 27 types of enteroviruses coexisted from 2012 to 2017. The epidemiological characteristics of non-EV-A71 and non-CV-A16 enterovirus should be monitored year-by-year. To clarify the changes of enterovirus spectrum clearly will help health authorities to early provide prevention and control measures for epidemics.

Key words: Hand, foot and mouth disease, Enterovirus, Pathogenic spectrum, Epidemic characteristic