Epidemiology Of Hand, Foot, And Mouth Disease And Genetic Characterization Of Enterovirus A71:A Survey From 2007 To 2012 In Linyi Of Shandong Province, China

Background Hand, foot, and mouth disease (HFMD) is an acute viral disease caused by enterovirus (EV). HFMD is a common disease in recent years in our country, three times of the local outbreaks of HFMD occurred in Shandong province in 2000,2003 and 2005, respectively, and after that, HFMD widespread in Shandong province during 2007-2012. From May 2007, HFMD outbreak occured in Linyi City, Shandong province, and total 39,606 cases were reported, which was 47.5% of the national total reported cases (83,344 cases), and 17 cases were died. On May 2,2008, HFMD was classified as Class C infectious diseases by the Ministry of Health. The trend of HFMD epidemic intensity increased since 2007, and it aroused great attention of the government and society.Ojective 1. To illustrate of the epidemiological characteristics of HFMD in Linyi City and Shandong Province during 2007-2012, including population incidence characteristics, time and geographic distribution, etc.2. To illustrate the disease incidence, pathogen spectrum of HFMD cases in Linyi City, Shandong Province,2007-2012, and to analysis the relationship between the dynamic changes of the etiological constitute and the proportion of severe cases and deaths.3. To analyze the genetic characterizations and the changes in variation patterns based on the entire VP1 coding region nucleotide sequence of enterovirus A71 (EV-A71) in Linyi City of Shandong Province during 2007-2012.4. To provide a scientific basis for the diagnosis, prevention and control of the HFMD for Linyi and other regions through these studies.Methods Collect the case information of HFMD cases in Linyi City of Shandong Province that reported to the China Disease Prevention and Control Information System, and study the clinical characteristics of HFMD by descriptive analysis by using Microsoft Excel (2007 edition) and Maplnfo Professional softwares. Clinical specimens collected from HFMD cases were inoculated onto RD and HEp-2 cells and viral isolation was performed. Real-time PCR method was used for serotype identification of the positive EV isolates. Entire VP1 region of EV-A71 was amplified by using reverse transcript polymerase chain reaction (RT-PCR), and nucleotide sequencing was performed with the amplicons. Phylogenetic tree was constructed among Linyi EV-A71 sequences and EV-A71 doenloaded from the GenBank database, and the nucleotide and amino acid homology analysis were also perormed.Result (1) A large-scale outbreak of HFMD was reported in Shandong Province in 2007, the incidence is mainly concentrated in Linyi and Qingdao cities, and the number of HFMD cases in other cities were small; While from 2007 to 2008, it was the local epidemic period in Shandong Province because HFMD cases were reported in part region of each cities; From 2009 to 2010, a major outbreak of HFMD occurred in various cities of Shandong province; And after 2011, the number of HFMD became somewhat lower, and the case distribution is more dispersed.(2) HFMD in Shandong province showed a seasonal distribution pattern. During 2007 to 2012, the incidence of HFMD in Shandong Province peaked in spring and summer every year, with a single peak incidence. Most cases are under 5 years of age, while children under the age of 2.5 are at high risk of severe and death HFMD, the gender ratio of male and female is 1.69:1. In all the reported cases, the careers of the patients are scattered children, kindergarten children and students.(3) HFMD incidence increased year by year in Linyi City of Shandong Province during 2007-2010, and the peak age of onset of HFMD patients was 2.5 years old. And the peak age of onset of HFMD patients moved to 1.5 years old during 2011-2012.(4) The main pathogens that cause HFMD cases is EV-A71 and CVA16, and two pathogens prevalent alternatively in Linyi City of Shandong Province. The larger number of deaths cases and higher incidence of HFMD in 2009 may account for the higher proportion of EV-A71 in the entire pathogens spectrum of HFMD in that year.(5) C4a evolutionary branch of EV-A71 sustained transmit in Linyi City of Shandong Provinc during 2007-2012, which was the main pathogens in severe and death HFMD cases.Conclusions (1) In this study, through six consecutive years (2007-2012) research on the epidemiological characteristics of Shandong province, and the pathogenic spetrum of HFMD and genetic characterizations of EV-A71 in Linyi city of Shandong province, we found that the peak age of onset was moved from 2.5 years to 1.5 years along with the different time periods; EV-A71 and CVA16 alternating as predominant pathogen of HFMD during this period; C4a evolutionary branch of EV-A71 sustained transmit in Linyi City of Shandong Provinc during 2007-2012, and VP1 region is in constant mutation and evolution(2) This study clarifies the pattern of HFMD epidemic, the dynamic changes and molecular epidemiology of EV-A71 in one city model, which will provide an important scientific basis data for HFMD diagnosis, prevention strategies and future use of the EV-A71 vaccine.(3) HFMD pathogen monitoring should be strengthened, and the severe cases of early screening and treatment and reduce mortality should aldo be strengthened when the EV-A71 accounted for the dominant pathogen in the HFMD pathogen spectrum, and early discovery, early reporting, early diagnosis and early treatment are also needed.