Epidemiological and genetic characteristics of EV71 in hand, foot, and mouth disease in Guangxi, southern China, from 2010 to 2015

December Epidemiological and genetic characteristics of EV71 in hand, foot, and mouth disease in Guangxi, southern China, from 2010 to 2015 Minmei Chen 0 1 Yu Ju☯ 0 1 Min Chen☯ 0 1 Zhenguo Xie 0 1 Kaijiao Zhou 0 1 Yi Tan 0 1 Jianjun Mo 0 1 0 Institute of Acute Infectious Diseases Control and Prevention, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control , Nanning, Guangxi , China 1 Editor: Zhefeng Meng, Fudan University , CHINA Hand, foot, and mouth disease (HFMD) is a significant public health challenge in China. Human enterovirus 71 (EV71) is regarded as the predominant causative pathogen of HFMD. Since 2015, two inactivated EV71 vaccines have been approved in mainland China, and because their use could change the HFMD pathogen spectrum, this should now be monitored. However, the epidemiological and genetic trends of EV71 with respect to HFMD in Guangxi, southern China, are still not clear. In this study, we describe the epidemiological and genetic characterization of this virus in clinically-diagnosed HFMD reported from 2010 to 2015 in Guangxi. Data showed that a two-year epidemic cycle, with a predominance of EV71 infections, contributed to HFMD outbreaks in Guangxi. Furthermore, this virus is a major causative agent of severe and fatal HFMD. Interestingly, in Guangxi, EV71-positive rates tended to decrease over time. In particular, EV71-positive rates were found in Fangchenggang city, which reported very few severe and fatal cases over the six-year period. Phylogenetic analysis of the VP1 gene revealed that the major circulating strains belonged exclusively to genotype C, subtype 4a (C4a), and most clustered with strains circulating in southern China. The most interesting finding was that a strain isolated in 2012 clustered with Vietnamese strains isolated from 2011±2012. The data highlight the importance of pathogen surveillance for HFMD in China, especially Guangxi, which is located on the border of China and the Association of Southeast Asian Nations. - Funding: Key research projects of medical and health care of Guangxi Zhuang Autonomous Region Center (2012051).The Guangxi Zhuang Autonomous Region Health and Familiy Planning Commision.http://www.gxhfpc.gov.cn/.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Introduction Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease that is normally self-limiting; however, in few cases, there can be serious complications with the nervous and respiratory systems, which can lead to death. HFMD is a considerable global public health challenge, especially in the Asia-Pacific region [ 1 ]. Since 2008, the numbers of HFMD cases that have been reported by national disease control and prevention agencies have increased significantly in China, with a total of 344,688 cases, and 25 deaths, recorded from January 1 to May 10 of 2017. Competing interests: The authors have declared that no competing interests exist. HFMD is caused by members of the enterovirus family, among which human enterovirus 71 (EV71) and coxsackievirus A16 are the main pathogens responsible for global outbreaks [ 2, 3 ]. EV71 infection has been reported to be responsible for both severe and fatal HFMD [ 1, 4, 5 ]. On December 3, 2015, the Chinese Food and Drug Administration (CFDA) approved two inactivated EV71 whole-virus vaccines for preventing severe HFMD [ 6, 7 ]. Consequently, EV71 vaccination began in Guangxi from 2016 and continues to date. Because this might change the HFMD pathogen spectrum, monitoring EV71 epidemics at different times and geographical locations remains a high priority. The Guangxi autonomous region is located in the south of China, and is divided into fourteen cities; it is one of the Chinese provinces that is most affected by HFMD [ 8 ]. In Guangxi, the number of reported cases has increased from 2008 to 2015, and since 2008, the incidence and rate of severe and fatal cases has consistently been the highest in China. In addition, from January 1 to May 10 of 2017, the number of reported cases (46,674) and incidence (97/10,000) were highest in Guangxi, among 31 Chinese provinces. Elucidating the epidemiological and evolutionary characteristics of E71 is critical for guiding the development of HFMD prevention and control strategies. This study focused on characterizing the epidemiological profiles and molecular evolution of EV71 in HFMD in the Guangxi autonomous region from January 2010 to December 2015. The results therefore provide information describing the baseline HFMD pathogen profile before vaccination was implemented. Materials and methods Ethics statement This research was approved by the Human Research Ethics Committee of Disease Control and Prevention of Guangxi Zhuang Autonomous Region. Specimens were obtained from sentinel hospitals associated with the Center of Guangxi Zhuang Autonomous for Disease Control and Preve (...truncated)