Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity

Wang, Shih-Min; Ho, Tzong Shiann; Lin, Hui-Chen; Lei, Huan Yao; Wang, Jen Ren; Liu, Ching-Chuan

doi:10.1007/s10096-011-1432-6

Cited by 42 publications

(27 citation statements)

References 28 publications

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“…Relative sparing of infants younger than six months was most likely due to protection by maternal antibodies. 23,24 Infection with the causative viruses appears to confer lifelong immunity at least to disease and possibly infection given the virtual absence of adult cases.…”

Section: Discussionmentioning

confidence: 99%

Hand, foot, and mouth disease in China, 2008–12: an epidemiological study

Xing

Liao

Viboud

et al. 2014

The Lancet Infectious Diseases

808

935

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Summary Background Hand–foot–and–mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Increasingly it imposes a substantial disease burden throughout East and Southeast Asia. To better inform vaccine and other interventions, we characterized the epidemiology of HFMD in China based on enhanced surveillance. Methods We extracted epidemiological, clinical and laboratory data from reported HFMD cases during 2008–2012 and compiled climatic, geographic and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status and enterovirus subtype. Findings The surveillance registry captured 7,200,092 probable HFMD cases (annualized incidence, 1·2 per 1,000), of whom 3·7% were laboratory–confirmed and 0·03% died. Incidence and mortality were highest in children aged 12–23 months (in 2012: 38·2 cases per 1,000 and 1·5 death per 100,000). Median durations from onset to diagnosis and death were 1·5 days and 3·5 days respectively. The risk of cardiopulmonary or neurological complications was 1·1% and the severe-case fatality risk was 3·0%, with >90% of deaths associated with enterovirus 71. HFMD peaked annually in June in the North, whereas Southern China experienced semi-annual outbreaks in May and September/October. Geographic differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8-23% and 3–19%, respectively). Interpretation This is the largest population-based study to date of the epidemiology of HFMD. Future mitigation policies should take full account of the heterogeneities of disease burden identified. Additional epidemiologic and serologic studies are warranted to elucidate local HFMD dynamics and immunity patterns and optimize interventions. Funding China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; World Health Organization; The Li Ka Shing Oxford Global Health Programme and Wellcome Trust; Harvard Center for Communicable Disease Dynamics; Health and Medical Research Fund, Government of the Hong Kong Special Administrative Region.

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Section: Discussionmentioning

confidence: 99%

Hand, foot, and mouth disease in China, 2008–12: an epidemiological study

Xing

Liao

Viboud

et al. 2014

The Lancet Infectious Diseases

808

935

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“…Previous studies demonstrate that subneutralizing Abs may be correlated with Ab-dependent enhancement in EV71 infection (44)(45)(46). Thus, T cells that are essential in the selection and maturation of high-affinity Abs deserve more attention for immunological investigation, and a comprehensive knowledge of EV71 T cell immunity would benefit our understanding of host protection mechanisms against EV71 (47).…”

Section: Discussionmentioning

confidence: 99%

VP2 Dominated CD4+ T Cell Responses against Enterovirus 71 and Cross-Reactivity against Coxsackievirus A16 and Polioviruses in a Healthy Population

Tan

Sun

et al. 2013

The Journal of Immunology

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Enterovirus 71 (EV71)–associated hand-foot-mouth disease has become a major threat to public health in the Asia–Pacific region. Although T cell immunity is closely correlated with clinical outcomes of EV71 infection, little is known about T cell immunity baseline against EV71 and T cell immunogenecity of EV71 Ags in the population, which has restricted our understanding of immunoprotection mechanisms. In this study, we investigated the cellular immune responses against the four structural Ags of EV71 and determined the immunohierarchy of these Ags in healthy adults. A low frequency of EV71-responsive T cells was detected circulating in peripheral blood, and broad T cell immune responses could be identified in most of the subjects after in vitro expansion. We demonstrated that the VP2 Ag with broad distribution of immunogenic peptides dominates T cell responses against EV71 compared with VP1, VP3, and VP4. Furthermore, the responses were illuminated to be mainly single IFN-γ–secreting CD4+ T cell dependent, indicating the previous natural acute viral infection of the adult population. Conservancy analysis of the immunogenic peptides revealed that moderately variant peptides were in the majority in coxsackievirus A16 (CV-A16) whereas most of the peptides were highly variant in polioviruses. Less efficient cross-reactivity against CV-A16 might broadly exist among individuals, whereas influences derived from poliovirus vaccination would be limited. Our findings suggest that the significance of VP2 Ag should be addressed in the future EV71-responsive immunological investigations. And the findings concerning the less efficient cross-reactivity against CV-A16 and limited influences from poliovirus vaccination in EV71-contacted population would contribute to a better understanding of immunoprotection mechanisms against enteroviruses.

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“…73 The annual fatality rate in Taiwan over the last decade has been between 0 to 25%, with an average of 13%. 74 Survivors from brainstem encephalitis often suffer from neurological sequelae including long-term motor deficits and cognitive impairment. 75 EV-A71 elicits humoral responses, but there is no correlation between neutralizing antibody levels and disease severity indicating that altered cellular responses such as an imbalance in Th1/Th2 and Th17/Treg subset ratios play a significant role in disease outcome and may have potential prognostic value.…”

Section: Clinical Presentationmentioning

confidence: 99%

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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Keywords: bivalent and multivalent vaccines, coxsackievirus A16, coxsackieviruses B3 and B5, echovirus 30, epidemiology, enterovirus A (EV-A), enterovirus A71, hand, foot and mouth diseases, inactivated whole virion vaccines, monovalent, EV-A71 vaccine Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed.

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Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity

Cited by 42 publications

References 28 publications

Hand, foot, and mouth disease in China, 2008–12: an epidemiological study

Hand, foot, and mouth disease in China, 2008–12: an epidemiological study

VP2 Dominated CD4+ T Cell Responses against Enterovirus 71 and Cross-Reactivity against Coxsackievirus A16 and Polioviruses in a Healthy Population

Is a multivalent hand, foot, and mouth disease vaccine feasible?

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