An outbreak of hand, foot, and mouth disease (HFMD) included 1149 people in Linyi
City, Shandong Province, China, in 2007: three children died.
To characterize the pathogens responsible for this outbreak and to analyze their genetic
A total of 233 clinical specimens were collected from 105 hospitalized patients, including
11 patients with severe HFMD. Virological investigations (direct RT-PCR, viral isolation
and molecular identification) and phylogenetic analysis were performed.
Human enterovirus 71 (HEV71) was the main pathogen that caused this outbreak, based
on clinical manifestations, epidemiological data, and laboratory results. Phylogenetic
analysis indicated that the Shandong HEV71 isolates belonged to 3 lineages in subgenotype
C4. Subgenotype C4 could be further divided into two clusters (C4a and C4b), which
corresponded to two time periods. Cluster C4a HEV71 has been the predominant virus
circulating in mainland China in the past 5 years.
The 2007 HFMD outbreak was mainly caused by HEV71 subgenotype C4 with 3 transmission
chains. This virus has been continuously circulating in China since 1998. The Shandong
strains co-evolved with isolates from other provinces in mainland China and neighboring