Epidemiological and aetiological characteristics of hand, foot, and mouth disease in Shijiazhuang City, Hebei province, China, 2009-2012

May Epidemiological and aetiological characteristics of hand, foot, and mouth disease in Shijiazhuang City, Hebei province, China, 2009-2012 Huifang Tian 0 1 2 3 Yong Zhang 0 1 3 Yan Shi 0 1 2 3 Xiujuan Li 0 1 2 3 Qiang Sun 0 1 3 Li Liu 0 1 2 3 Dong Zhao 0 1 2 3 Baohong Xu 0 1 2 3 0 Current address: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of sciences , Beijing , People's Republic of China 1 Funding: The study was supported by the National Natural Science Foundation of China, project no. 81672070 2 Shijiazhuang Center for Disease Control and Prevention , Shijiazhuang City, Hebei Province , People's Republic of China, 2 WHO WPRO Regional Polio Reference Laboratory and Key Laboratory for Medical Virology, National Health and Family Planning Commission of China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing , People's Republic of China 3 Editor: Oliver Schildgen, Kliniken der Stadt KoÈln gGmbH , GERMANY Large outbreaks of hand, foot, and mouth disease (HFMD) have repeatedly occurred in mainland of China since 2007. In this study, we investigated the epidemiological and aetiological characteristics of HFMD in Shijiazhuang City, one of the biggest northern cities of China. A total of 57,173 clinical HFMD cases, including 911 severe and 32 fatal cases, were reported in Shijiazhuang City during 2009±2012. The disease incidence peaked during March±July, with a small increase in the number of cases observed in November of each year. Seventeen potential HFMD-causing enterovirus serotypes were detected, with the most frequent serotypes being EV-A71 and CV-A16. CV-A10 was also a frequently detected causative serotype, and was associated with the second largest number of severe HFMD cases, following EV-A71. Phylogenetic analysis revealed that all EV-A71, CV-A16 and CVA10 strains from Shijiazhuang City had co-evolved and co-circulated with those from other Chinese provinces. Our findings underscore the need for enhanced surveillance and molecular detection for HFMD, and suggest that EV-A71 vaccination may be an effective intervention strategy for HFMD prevention and vaccines against CV-A10 and CV-A16 are also urgently needed. - Data Availability Statement: All relevant data are within the paper. Competing interests: The authors have declared that no competing interests exist. Introduction Hand, foot, and mouth disease (HFMD) is a common infectious disease in young children, particularly those aged <5 years, and the disease is more prevalent during the warm season (May to July)[1±4]. HFMD is usually caused by human enteroviruses (EV) that are members of the genus Enterovirus within the family Picornaviridae, order Picornavirales, consisting of four species: EV-A, EV-B, EV-C, and EV-D. Till date, EV comprises more than 100 serotypes that are the most common pathogens infecting humans, especially children, worldwide. Most EV infections are asymptomatic or present with benign symptoms; are characterised by a brief febrile illness, typical vesicular rashes (on the palms, soles or buttocks), and oropharyngeal ulcers; and can usually resolve spontaneously. Occasionally, however, they may also lead to serious neurological complications such as acute flaccid paralysis, encephalitis, myocarditis, and encephalomyelitis[5±7]. HFMD can be transmitted by direct person-to-person contact through nasal discharge, saliva, faeces, and fluid from blisters of infected persons. Additionally, it can spread through EV-contaminated water and food[ 8, 9 ]. As is well established, EV-A and EV-B account for most of the HFMD cases. The most common aetiological agents of HFMD are two members of the EV-A speciesÐenterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), with varying incidence rates attributed to each [8, 10±13]. The first CV-A16 infection was reported in Canada, and it is one of the most widely prevalent EV serotypes in the world. The first reported EV-A71 infection occurred in the United States, and the serotype has been a recurrent feature in the Asia-Pacific region since the first reported outbreak in Sarawak, Malaysia in 1997[14±17]. Besides these two serotypes, other EV-A and EV-B serotypes may also co-circulate and account for a sizeable proportion of the pathogen spectrum of HFMD; the clinical features of the resultant infections are usually indistinguishable from those caused by the two predominant EV serotypes [18±21]. Among these other serotypes, CV-A6 is especially important as it is known to have circulated in mainland of China and was the predominant HFMD-causing EV in 2013 and 2015[22±25]. Large outbreaks of HFMD have repeatedly occurred in mainland of China since 2007, and the disease has become a serious public health concern[ 9, 26 ]. Over the past few years, some studies on the epidemiological characteristics of HFMD have been carried out in mainland (...truncated)