618 KH Kim • Enterovirus 71 infection: An experience in Korea, 2009 rectal swabs in the patients. Viruses in throat through the saliva or respiratory droplets of patients may be transmitted during the acute stage of the disease17). Although hand-washing precaution is important for the period of virus excretion through feces, it is not sufficient to limit the spread and transmission of the virus and to prevent further epidemics. Therefore, isolation of infected patients within single rooms with masks should be considered during hospitalization of patients14). It is not clear why a certain region has experienced an increased incidence of EV71 infection. A change in clinical presentation could coincide with a change in the viral transmission pathway. An epidemiological parameters like crowding, lack of sanitation, and climate, could enhance virus transmission. An increased susceptibility of the population to EV71 infection could be another explanation. Pathogenesis Infants and young children are very susceptible to EV71 infection. Immature immunity is therefore suspected to associate with increased morbidity and mortality. Moreover individual host genetic factors may affect clinical severity Lymphopenia, depletion of CD4 and CD8 T lymphocytes, and decreased cellular immunity in the peripheral blood were noted in patients with brain stem encephalitis and pulmonary edema18). However, some clinical studies showed that elevated cellular immunity was linked with unfavorable outcomes19). The clinical manifestations are reflecting the contribution of immunopathological process in addition to cytopathic damage to neuronal cells12, 20, 21). Cytokines in the central nervous system and systemic inflammatory responses play important roles in the pathogenesis of EV71-associated encephalomyelitis. Destruction of vasomotor in the brainstem by EV71 produces autonomic nervous system dysregulation prior to the pulmonary edema. The pulmonary edema is the result of increased pulmonary vascular permeability caused by the direct brainstem lesions and/or a systemic inflammatory response syndrome produced by the release of cytokines and chemokines. Clinical Manifestations Enterovirus serotypes are distinguished by antigenic and genetic sequence differences. Although no enterovirus disease is uniquely associated with any specific serotype, certain manifestations are preferentially associated with specific serotypes. About half of EV71 infections are asymptomatic22). Most symptomatic EV71 infections commonly result in HFMD or herpangina. EV71 infections can cause pharyngitis, herpangina, stomatitis, gastrointestinal complaints, pericarditis, ventricular dysfunction, macular, maculopapular, vesicular or exanthema22). These clinical manifestations can be associated with neurologic syndromes frequently. Children having only febrile illness without mucocutaneous manifestations may have neurologic complications23). HEV71 is closely related to coxsackie virus A16 (CA16), the other major causative agent of HFMD, but unlike CA16, HEV71 is also associated with cases of acute neurologic disease including poliomyelitis-like paralysis, encephalitis, and aseptic meningitis. Neurologic syndromes observed in EV71 include meningitis, meningoencephalomyelitis, poliomyelitis-like paralytic disease, Guillain-Barré syndrome, transverse myelitis, cerebellar ataxia, opsoclonus-myoclonus syndrome, benign intracranial hypertension, and brainstem encephalitis3, 12) (Table 1). Neurologic disorders have been prominent in recent epidemics of EV71 disease. In the outbreaks in Taiwan in 1998 and in Australia in 1999, virological studies found that HFMD and herpangina epidemics were caused by EV71 and coxsackievirus A16 but the cases presenting with acute pulmonary edema and other neurological diseases were caused by brainstem encephalitis resulting from acute EV71 infection16, 24, 25). HFMD with EV71-associated neurological syndrome has increased continually in many countries during the last 10 years, especially in the Asia- Pacific region8, 26). In some countries, outbreaks occur in a cyclical pattern every three years, Table 1. Outbreak of EV71 Infection and Major Clinical Manifestations in Worldwide Country USA USA USA USA Australia Sweden Bulgaria Hungary France Year Clinical manifestation 1969 aseptic meningitis, encephalitis 1972 aseptic meningitis, encephalitis, HFMD 1977 aseptic meningitis 1995 neurologic HFMD 1972 aseptic meningitis, rash 1973 HFMD, aseptic meningitis 1975 aseptic meningitis, encephalitis 1978 aseptic meningitis, encephalitis 1979 acute respiratory infection with CNS involvement Japan 1973 aseptic meningitis, HFMD Hong King 1985 aseptic meningitis China 1987 HFMD Singapore, Malaysia 1997 HFMD, aseptic meningitis Taiwan 1998 HFMD, encephalitis China 2008-9 HFMD, meningitis, encephalitis, pulmonary edema Korea 2009 aseptic meningitis, encephalitis, HFMD Abbreviation: HFMD, hand foot mouth disease