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Edited by Dr Tzou-Yien Lin, Dr Ben Berkhout and Dr Jen-Ren Wang 

A thematic series in Journal of Biomedical Science

EV-A71 infected cells 2 © Pin-Hwa Kuo, Jen-Ren Wang

In 1998, a mysterious infection after hand-foot-and-mouth disease caused 405 severe cases and 78 deaths in Taiwan. This epidemic caused a lot of panic among parents, children and even clinicians. Most of them were children younger than 5 years of age. Autopsy found that the brain stem was the primary site of infection that caused cardiopulmonary failure. Enterovirus A71 (EV-A71) was cultured from brain, spinal cord and cerebrospinal fluid.

Since the 1998 epidemic, health authority, medical care providers and academia have collaborated for the control, prevention and treatment of EV-A71 infection. During the past 20 years, virologists have worked very hard on the research of virology of EV-A71, including molecular evolution, intra- and intertypic recombination, neurovirulence as well as development of antiviral agents and vaccines. EV-A71 receptors were also identified by Japanese researchers through very delicate and unbreakable work.

Pediatricians have defined the clinical staging and developed a stage-based management. With the implementation of stage-based management, the case-fatality rate had decreased dramatically, but survivors with brainstem encephalitis were found to have a high rate of neurological sequelae through the long-term follow-up studies. There are some possible mechanisms of pathogenesis for severe cases, including direct viral invasion, cytokine storm and epinephrine induced cardiac toxicity.

After 1998, there were several outbreaks with a cycle of every 3 to 5 years in Taiwan. Luckily, no severe outbreaks occurred in terms of number of severe cases and death after 2012. That battle against EV-A71 is not over. According to Prof Tzou-Yien Lin (National Health Research Institutes, Taiwan), an epidemic may recur if the accumulation of susceptible children is over the threshold. Inactivated vaccines are safe and effective, but antivirals with broad spectrum provide an alternative strategy and are desired. In this thematic series, the authors share their experience and understanding on EV-A71 not only just in Taiwan but also other countries in the Asia-Pacific region. Topics covered include EV-A71 epidemiology, pathogenesis, virulence factors, recent advances in antivirals, vaccines, and current knowledge of host factors and cellular receptors. Hopefully this series may provide some helpful insights and strategies against EV-A71 and this ongoing battle.

  1. Enterovirus A71 (EV-A71) is one of the causative pathogens of hand, foot, and mouth disease (HFMD), which may cause severe neurological and cardiopulmonary complications in children. In this review, we discuss...

    Authors: Shao-Hsuan Hsia, Jainn-Jim Lin, Oi-Wa Chan and Tzou-Yien Lin
    Citation: Journal of Biomedical Science 2020 27:53
  2. Enterovirus 71 (EV-A71) is one of the major causative agents of hand, foot, and mouth disease. EV-A71 infection is sometimes associated with severe neurological diseases such as acute encephalitis, acute flacc...

    Authors: Kyousuke Kobayashi and Satoshi Koike
    Citation: Journal of Biomedical Science 2020 27:23
  3. Upon EV-A71 infection of a host cell, EV-A71 RNA is translated into a viral polyprotein. Although EV-A71 can use the cellular translation machinery to produce viral proteins, unlike cellular translation, which...

    Authors: Ming-Chih Lai, Han-Hsiang Chen, Peng Xu and Robert Y. L. Wang
    Citation: Journal of Biomedical Science 2020 27:22
  4. Enterovirus A71 (EV-A71) is one of the common causative pathogens for hand foot and mouth disease (HFMD) affecting young children. HFMD outbreak can result in a substantial pediatric hospitalization and burden...

    Authors: Jiratchaya Puenpa, Nasamon Wanlapakorn, Sompong Vongpunsawad and Yong Poovorawan
    Citation: Journal of Biomedical Science 2019 26:75
  5. Enterovirus A71 (EV-A71) is an important emerging virus posing a threat to children under five years old. EV-A71 infection in infants or young children can cause hand-foot-and-mouth disease, herpangina, or sev...

    Authors: Jing-Yi Lin, Yu-An Kung and Shin-Ru Shih
    Citation: Journal of Biomedical Science 2019 26:65
  6. During recent 20 years, enterovirus A71 (EV-A71) has emerged as a major concern among pediatric infectious diseases, particularly in the Asia-Pacific region. The clinical manifestations of EV-A71 include uncom...

    Authors: Luan-Yin Chang, Hsiang-Yuan Lin, Susan Shur-Fen Gau, Chin-Yu Lu, Shao-Hsuan Hsia, Yhu-Chering Huang, Li-Min Huang and Tzou-Yien Lin
    Citation: Journal of Biomedical Science 2019 26:57