Enterovirus 71 (EV71) is a non-polio enterovirus (NPEV) and a known cause of severe poliomyelitis-like illness, often resulting in large outbreaks worldwide. EV serotypes have traditionally been grouped according to neutralization serotype, gradually replaced by genomic sequencing and thus, revised recently into four species. Phylogenetically, EV71 is closely related to Coxsackie virus A16 (CAV16).

EV71-associated severe neurological disease has been observed in many outbreaks throughout the world since first reported in California, USA in 1969. During the last 8–10 years, a shift in geographic location and frequency of reported EV71-associated brain stem encephalitis fatalities was observed, in particular during outbreaks in Malaysia in 1997 and Taiwan in 1998. Several smaller scale outbreaks have been recorded from Western Australia, Korea, Japan and Singapore. During 2006, large-scale HFMD outbreaks in India, Thailand, Hong Kong, Malaysia and Brunei were reported and in China during 2008. Since 1998, EV71 epidemics with more than 10 fatal cases occurred during 2000~2002, 2005 and 2008. 

EV71 is in constant evolution with an estimated variation rate of 1.35 × 10-2 substitutions per nucleotide. For phylogenetic analysis, the capsid protein VP1 is considered most robust for evolutionary study and three distinct EV71 genotypes (A, B and C) were identified by Brown et al. The original prototype (BrCr strain) is the sole representative of genotype A, and genotypes B or C can be further sub-divided into genogroups B1–B4 and C1–C4. During the past decade, genotypes B3, B4, C1, and B5 were reported in Malaysia, B3, B4 and C1 in Singapore, B3, C2 and C1 in Australia and C4 in China. In Japan, genotypes B3~B5, C2 and C4 were identified. In Taiwan the longitudinal surveillance showed that genotype C2 was the major strain in 1998 epidemic, B4 dominated between 1999 and 2003, C4 during 2004 and 2005, C5 during 2006 and 2007, and B5 in 2008. No apparent outbreak was observed in 2009. The observations, when taken collectively, suggest that recombination and mutation may benefit the spread of EV71 in the human population.

The Hand, Foot and Mouth Disease (HFMD) was epidemic in China mainland between 2007 and 2009. Enterovirus 71 was the most common pathogen in severe and death cases. According to the primary statistics, 61.43% of the cases confirmed by laboratory network were EV71 (genotype C4), and it was found in 81.59% of the severe cases and more than 95% of the death cases. The prevalence of HFMD challenge both the garvement and medical institution on how to better respond to the public health events.

In order to monitor the prevalance of HFMD, the Ministry of Health defined HFMD as category B communicable disease on May 2, 2008, and all the clinical cases were required to be registered in the Report Cards System. A series of measures were taken on control of the HFMD epidemic and spread, such as the patients were isolated and treated in designated hospitals in epidemic area. According to our data, no rashes or blisters were found in 8% of the death cases in 2008. In 2009, only 2% of the death cases had the same phenomenon, which may be the result of more careful physical examination and increased awareness of the disease. There is no specific antiviral agent or therapy for HFMD. The principles of therapy were symptomatic treatment, supportive therapy. IVIG had some effects on controlling the progress of the disease by immunomodulation. It was still controversial on the use of steroids. The primary clinical study demonstrated that most critical patients with neurological complication or neurogenic pulmonary edema show insufficiency adrenocortical function. The mortality was high when the disease initially broke out, but the survival rate increased after expert teams were dispatched by the Minister of Health to the primary hospitals for expertise support. The government and public realized the importance of PICU after the prevalence of HFMD. Many PICUs were established, and the capabilities of early recognition and treatment of critical cases were improved. So far, the vaccine of HFMD is being developed in the laboratories.

In 1998, there was an outbreak of enteroviral 71 infection in Taiwan. The outbr4ak has caused hundreds of critical illness and significant mortality. Since then, there would be almost yearly interchanging small scale and large scale epidemic.

Initially shocked by the serious epidemic of eenteroviral 71 infection in 1998, the pediatricians in Taiwan soon established a management system to combat the fearsome illness. The accumulation of experience in caring the children with critical enterovitral 71 infection has shed light on the natural course of the illness. Then through the understanding of the natural course of this illness, a practical intervention plan was deducted.

Presently, it is the consensus in Taiwan that there 4 stages for the centeroviral 71 infection. Initially, the victims with enteroviral infection present with symptoms/signs of hand-foot-mouth disease/Herpangina or even suual acute viral illness (Stage I). Some of them then will progress to develop neurological symptoms/signs of neurologic involvement, such as limb weakness, ataxia, myoclonic jerks, ... etc (Stage II). Further then, within a short period of time (usually a few hours to 2-3 days), some patients will develop sympathetic activation syndromes such as hypertension and tachycardia (Stage IIIA). Specifically, the degree of hypertension/tachycardia usually presents well beyond the ordinary range attributed to fever or agitation. Tragically, some of the victims will further progress to sudden collapse with rapid onset of pulmonary edema and circulatory failure (Stage IIIB). Recovery may occur among the survivors with the progress lasting from a few days to the occurrence of long-term sequelae (Stage IV). The sequelae usually consists of neurological ones (including drooling, swallowing difficulty, limb weakness) while some are due to the critical care interventions.

The management of critical enteroviral 71 infection depends on the stage of the illness. For stage I patients (or for almost every patient with acute viral-like illness during epidemic season), general alertness should be made for both parents and pediatricians. For patients at Stage II, admission with appropriate monitoring is strongly considered or closely followed up at least. Once sympathetic activation occurs, immediate admission to the pediatric Intensive Care Unit should be highly considered and then direct intervention toward reversing the sympathetic activation should be immediately given. During this stage, depending on the severity and progress of the illness, artificial support for heart-lung function may be considered. The final stage needs supportive care including a well organized rehabilitative care system for those with long term sequelae.

Up to now, there is consensus regarding the care of victims with critical enertoviral 71 infection. But there are also some unsolved issues. Further effort is now undertaken to maximize the consensus so that the critical enteroviral 71 infection could be optimally managed.