Reflecting on the 1998 enterovirus outbreak: A 25-year retrospective and learned lessons.

Enterovirus A71 (EV-A71) infections pose a significant public health concern in the Asia-Pacific region. EV-A71 is primarily responsible for causing hand, foot, and mouth disease (HFMD) in children. However, this virus can also lead to severe and potentially fatal neurological consequences in affected individuals. This review aims to provide a comprehensive understanding of the molecular virology, epidemiology, and recombination events associated with EV-A71. The literature extensively covers the clinical manifestations and neurological symptoms that accompany EV-A71 infections. One of the complications explored in this review is brainstem encephalitis, which can arise as a result of EV-A71 infections. Brainstem encephalitis refers to inflammation of the brainstem, a critical region responsible for various bodily functions. The review examines the underlying mechanisms, diagnostic criteria, treatment options, and prognosis for central nervous system infections involving EV-A71. Neurological complications associated with EV-A71 infections are diverse and can have severe consequences. These complications may include aseptic meningitis, acute flaccid paralysis, and acute transverse myelitis. The review delves into the pathophysiology of these complications, shedding light on the molecular mechanisms through which EV-A71 affects the central nervous system. Accurate diagnosis of EV-A71 infections is crucial for appropriate management and treatment. Treatment options for EV-A71 infections primarily focus on supportive care, as there are currently no specific antiviral drugs available for this virus. The review highlights the importance of managing symptoms, such as fever, dehydration, and pain relief, to alleviate the burden on affected individuals. Prognosis for individuals with central nervous system (CNS) infections involving EV-A71 can vary depending on the severity of the complications. The review provides insights into the long-term outcomes and potential neurological sequelae associated with EV-A71 infections. In conclusion, EV-A71 infections have emerged as a major public health concern in the Asia-Pacific region. This review aims to enhance our understanding of the molecular virology, epidemiology, and neurological complications associated with EV-A71. By examining the underlying mechanisms, diagnostic criteria, treatment options, and prognosis, this review contributes to the development of effective strategies for the prevention, diagnosis, and management of EV-A71 infections. The paper presents a comprehensive analysis of worldwide data pertaining to outbreaks of EV-A71 and HFMD. The subsequent discourse delves into the advancement and strategic formulation pertaining to the creation of vaccines targeting EV-A71. In summary, this study provides a comprehensive examination of the potential obstacles and considerations involved in the management and treatment of EV-A71 infections. Additionally, it proposes suggestions for future research and development endeavors with the objective of formulating efficacious treatment approaches for this viral infection.

The secular trend of enterovirus A71 after the implementation of preventive measures in Taiwan.

BACKGROUND: Enterovirus A71 (EV A71) is one of the most important enteroviruses related to morbidity and mortality in children worldwide. This study aimed to analyse the secular trend of EV A71 in Taiwan from 1998 to 2020 and to evaluate the effectiveness of infection control measures. METHODS: We collected the epidemiological data of EV A71 from disease surveillance systems in Taiwan. We analysed the association between the secular trend of EV A71 and preventive measures such as hand washing, case isolation, and suspension of classes. RESULTS: The incidence of enterovirus infections with severe complications (EVSC) decreased from 16.25 per 100,000 children under six in 1998 to less than 9.73 per 100,000 children under six after 2012 (P = 0.0022). The mortality rate also decreased significantly, from 3.52 per 100,000 children under six in 1998 to 0 per 100,000 children under six in 2020 (P < 0.0001). The numbers of EVSC and fatalities were significantly higher in the years when EV A71 accounted for more than 10% of the annual predominant serotypes (p < 0.05). After the implementation of many non-pharmaceutical interventions in 2012, the incidence of EVSC and mortality rate decreased significantly (p < 0.001). CONCLUSIONS: After implementing active enterovirus surveillance and preventive measures, we found that the incidence of EVSC and fatalities due to EV A71 in Taiwan decreased significantly from 1998 to 2020. Continuous surveillance and strengthened infection control policies are still needed in the future.

Successful Control of Streptococcus pneumoniae 19A Replacement With a Catch-up Primary Vaccination Program in Taiwan.

BACKGROUND: Streptococcus pneumoniae infections in Taiwan mostly occur in children aged 2-4 years. Because of a significant increase in the incidence of serotype 19A-related infections, the 13-valent pneumococcal conjugate vaccine (PCV13) was initially introduced in the national immunization program for children 2-5 years of age, prior to the national programs for infants. We have assessed the impact of such vaccination programs in reducing the incidence of invasive pneumococcal disease (IPD) in Taiwanese children. METHODS: We analyzed the national data on IPDs from the Taiwan Centers for Disease Control between 2008 and 2017. We calculated the incidence rates of IPD and incidence rate ratios (IRRs) between years for different serotypes to estimate the effectiveness of the vaccination programs. RESULTS: The national catch-up primary vaccination schedule successfully reduced the incidence rate of IPD from 17.8/100 000 in 2012 to 5.5/100 000 in 2017 among children aged 0-5 years. The IRR (2017 over 2012) was 0.31, corresponding to a 69% reduction. A modest herd effect was also observed, with a 37% reduction in the incidence of IPD in elderly people (≥70 years) from 2012 to 2017. The incidence of IPD caused by serotype 19A in children aged 0-5 years was reduced by 32.6-44.3% yearly from 2012 to 2017. In 2015, serogroup 15 outnumbered 19A, to become the leading serotypes in children 0-5 years old. CONCLUSIONS: Special catch-up vaccination programs starting from children 2-5 years of age with PCV13 have been highly effective in reducing the incidence of IPD, especially as caused by serotype 19A, in Taiwanese children.

Disease burden of enterovirus infection in Taiwan: Implications for vaccination policy.

OBJECTIVES: This study aimed to assess the disease burden and economic impacts of human nonpolio enteroviruses (NPEV) and enterovirus A71 (EV-A71) infection in Taiwan. MATERIALS AND METHODS: We included children under five years old (n=983,127-1,118,649) with ICD-9-CM codes 0740 (herpangina) or 0743 (hand-foot-and-mouth disease) from the 2006 to 2010 National Health Insurance Database. Severity of enterovirus infection was assessed from outpatient/emergency visits, hospitalization (with/without intensive care unit [ICU] admission), infection with severe complications, and death. We estimated medical costs and indirect costs from the societal perspective. RESULTS: The annual rates of NPEV events for children under five years old ranged from 13.9% to 38.4%, of which 5.1-8.8% were hospitalized. EV-A71 accounted for 7.8% of all NPEV medical costs, but 79.1% of NPEV ICU costs. Travel costs and productivity loss of caregivers were $37.1 (range: $24.5-$64.7) million per year. These costs were not higher in the EV-A71 dominant year ($34.4 million) compared with those in the other years. Productivity losses resulting from premature mortality by NPEV infection were $0.8 (range: $0.0-$2.9) million per year, of which 96.3% were caused by EV-A71. CONCLUSIONS: Diseases associated with NPEV other than EV-A71 were responsible for most of the medical expenses. In addition, caregiver productivity loss by high rates of NPEV infection impacted the society much more than medical costs. A multi-valent vaccine that includes EV-A71 and other serotypes, for example coxsackievirus A16, may be beneficial to the health of children in Taiwan.

Imported measles and implications for its elimination in Taiwan.

During November 2008-May 2009, an outbreak of 53 measles cases occurred in Taiwan. Of these, 3 cases were sporadic, and the other 50 cases could be grouped into 8 clusters by genetic analysis. We determined 7 H1 genotypes linked to importation and 1 G3 genotype linked to an untraceable source.