Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by enteroviruses. We analyzed the pathogenic characteristics of HFMD in Shaanxi province, China, during 2010-2016. Clinical samples were collected from HFMD cases. Real-time PCR and RT-PCR were used to identify the enterovirus(EVs) serotypes. Viral RNA sequences were amplified using RT-PCR and compared by phylogenetic analysis. Descriptive epidemiological methods were used to analyze. A total of 16,832 HFMD positive cases were confirmed in the laboratory. EV-A71 and CV-A16 were the main pathogens in 2010. EV-A71 was the dominant pathogen in the periods of 2011 to 2012 and 2014, 2016. In 2013 and 2015, other EVs increased greatly, in which CV-A6 was the predominant pathogen. EV-A71 was more frequently detected in deaths and severe cases. Phylogenetic analysis revealed that EV-A71 belonged to the C4a evolution branch of C4 sub-genotype and CV-A16 belonged to the B1a or B1b evolution branch of B1 sub-genotype, whereas CV-A6 strains were assigned to D2 or D3 sub-genotype. The pathogen spectrum of HFMD has changed in 7 years, and the major serotypes EV-A71, CV- A16 and CV- A6 alternated or co-circulated. Long-term surveillance and research of EVs should be strengthened for the prevention and control of HFMD.

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