Clinical Characteristics and Functional Motor Outcomes of Enterovirus 71 Neurological Disease in Children

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 CV-A10 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.

Interleukin (IL)-22+CD4+T (Th22) cells play crucial roles in the pathogenesis of autoimmune diseases and infectious diseases, although the role of Th22 cells remains largely unclear in children with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71). This study aims to explore the role of circulating IL-22+IL-17A−CD4+T (cTh22) cells in children with EV71-associated HFMD. We found that during the acute stage of illness, the frequencies of cTh22 and circulating IL-22+IL-17A+CD4+T (IL-22+cTh17) cells in CD4+T cells infrom affected patients, and especially in severely affected patients, were significantly higher than in healthy controls (HC). The major source of IL-22 production was cTh22 cells, partially from cTh17 cells. Moreover, the protein and mRNA levels of IL-22, IL-17A, IL-23, IL-6, and TNF-α were significantly different among the mild patients, severe patients and HC, as well as AHR and RORγt mRNA levels. A positive correlation was found between plasma IL-22 levels and cTh22 cell frequencies, and cTh17 cell and IL-22+ cTh17 cell frequencies. Furthermore, the frequencies of cTh22 were significantly decreased in the convalescent patients. Our findings indicated that cTh22 cells could play critical roles in the pathogenesis of EV71 infection, and are potential therapeutic targets for patients with EV71-associated HFMD.

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