Clinical research is a key force to steer the progress of current medicine. From the very beginning, patients have never stopped being our best teachers. However, excellent research can only occur in the context of excellent services. By closely observe the clinical course of the patient and record carefully, pediatrician can conduct excellent clinical studies. I will take our study of enterovirus 71 as an example.

Enterovirus 71 (EV71) was first isolated in 1969. Since then, it has been associated with several outbreaks in Bulgaria(1975), Hungary(1978), Malaysia(1997) and Taiwan(1998). After eradication of poliovirus, EV71 will became the most important enterovirus that causes fatalities and sequelae in children.

A severe outbreak of EV71 infections occurred in Taiwan in 1998. There were 405 severe cases with 78 deaths. The outbreak occurred in Taiwan almost each year since 2000. We have found most children with EV71 infections presented with hand, foot, and mouth disease or herpangina. Some progressed to CNS involvement, and only a few of them further advanced to cardio-pulmonary failure. If they survived, severe neurological sequelae may develop. The risk factors for CNS involvement are lethargy and fever for more than 3 days, and for cardiopulmonary failure after CNS involvement are hyperglycemia, leukocytosis and limb weakness. Those risk factors may alert pediatrician to hospitalize high risk children as early as possible.

We have conducted a long term follow-up study of children with cardiopulmonary failure after CNS involvement. Sixty-four percent had limb weakness and atrophy, 61% needed tube feeding, 57% needed ventilator support, 75% had delayed developmental and 50% had lower intelligence. We also identified HLA-A33 was associated with susceptibility to EV71 infections.

With the development of stage-based management, the mortality rate decreased from 19 % in 1998 to 15 % in 2001, and 3.8 % in 2008. But the neurological sequelae have increased. Vaccination is the only way to control EV71 outbreak. A cohort study in Taiwan showed that seropositive rate of EV 71 in pregnant women was 65%, in neonates was 50%, and the rate decreased to 1.2% in infants age 6 months. This study suggested that the target age for inactivated EV71 immunization would be infants younger than 6 months of age.