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      The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development


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          Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms “enterovirus 71” and “epidemiology” or “pathogenesis” or “molecular epidemiology” or “vaccine” in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing.

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          An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group.

          Enteroviruses can cause outbreaks of hand-foot-and-mouth disease (characterized by vesicular lesions on the hands, feet, and oral mucosa) or herpangina, usually without life-threatening manifestations. In 1998 an epidemic of enterovirus 71 infection caused hand-foot-and-mouth disease and herpangina in thousands of people in Taiwan, some of whom died. We assessed the epidemiologic aspects of this outbreak. Cases of hand-foot-and-mouth disease or herpangina in ambulatory patients were reported to the Taiwan Department of Health by a mean of 818 sentinel physicians. Severe cases in hospitalized patients were reported by 40 medical centers and regional hospitals. Viruses were isolated by 10 hospital laboratories and the department of health. The sentinel physicians reported 129,106 cases of hand-foot-and-mouth disease or herpangina in two waves of the epidemic, which probably represents less than 10 percent of the estimated total number of cases. There were 405 patients with severe disease, most of whom were five years old or younger; severe disease was seen in all regions of the island. Complications included encephalitis, aseptic meningitis, pulmonary edema or hemorrhage, acute flaccid paralysis, and myocarditis. Seventy-eight patients died, 71 of whom (91 percent) were five years of age or younger. Of the patients who died, 65 (83 percent) had pulmonary edema or pulmonary hemorrhage. Among patients from whom a virus was isolated, enterovirus 71 was present in 48.7 percent of outpatients with uncomplicated hand-foot-and-mouth disease or herpangina, 75 percent of hospitalized patients who survived, and 92 percent of patients who died. Although several enteroviruses were circulating in Taiwan during the 1998 epidemic, enterovirus 71 infection was associated with most of the serious clinical manifestations and with nearly all the deaths. Most of those who died were young, and the majority died of pulmonary edema and pulmonary hemorrhage.
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            An apparently new enterovirus isolated from patients with disease of the central nervous system.

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              Seasonal variation in host susceptibility and cycles of certain infectious diseases.

              S Dowell (2001)
              Seasonal cycles of infectious diseases have been variously attributed to changes in atmospheric conditions, the prevalence or virulence of the pathogen, or the behavior of the host. Some observations about seasonality are difficult to reconcile with these explanations. These include the simultaneous appearance of outbreaks across widespread geographic regions of the same latitude; the detection of pathogens in the off-season without epidemic spread; and the consistency of seasonal changes, despite wide variations in weather and human behavior. In contrast, an increase in susceptibility of the host population, perhaps linked to the annual light/dark cycle and mediated by the pattern of melatonin secretion, might account for many heretofore unexplained features of infectious disease seasonality. Ample evidence indicates that photoperiod-driven physiologic changes are typical in mammalian species, including some in humans. If such physiologic changes underlie human resistance to infectious diseases for large portions of the year and the changes can be identified and modified, the therapeutic and preventive implications may be considerable.

                Author and article information

                Role: Academic Editor
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                International Journal of Environmental Research and Public Health
                09 September 2016
                September 2016
                : 13
                : 9
                : 890
                [1 ]Division of Infectious Disease, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan 736, Taiwan; 2LH101@ 123456TMH.org.tw
                [2 ]Department of Family Medicine, Da-Chien General Hospital, Miaoli 237, Taiwan; scchen818@ 123456gmail.com
                [3 ]General Education Center, Ta Tung University, Taipei 104, Taiwan
                [4 ]Department of Occupational Medicine, Tainan Municipal Hospital, Tainan 701, Taiwan
                [5 ]Department of Public Health, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
                Author notes
                [* ]Correspondence: ktchen@ 123456mail.ncku.edu.tw ; Tel.: +886-6-2609926

                These authors contributed equally to this work.

                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                : 24 June 2016
                : 01 September 2016

                Public health
                hand-foot-mouth disease,herpangina,enterovirus 71,pathogenesis,virology
                Public health
                hand-foot-mouth disease, herpangina, enterovirus 71, pathogenesis, virology


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