PI Lee, CY Lee

A large epidemic of enterovirus infection occurred in Taiwan starting from April 1998. The number of reported enterovirus infections peaked in early June and had declined gradually thereafter (Fig. 1). The Ministry of Health in Taiwan received approximately 90,000 reports of hand-foot-and-mouth disease (HFMD) or herpangina from sentinel physicians. According to data collected on August 6, a total of 314 cases has been hospitalized because of HPMD or herpangina with complications, including meningitis, encephalitis, acute flaccid paralysis, and/or acute cardiopulmonary failure. Fifty-five of them died.

Fig. 1 Number of death and hospitalization due to severe enterovirus infection in Taiwan. Data were collected on August 6, 1998.

Most of severe cases lived in the northern and central part of Taiwan, especially in rural areas. The age of fatal cases was below 6 months in 4 (7%), between 7 months and 3 years in 42 (76%), and between 4 and 15 years in 9 (16%). The majority of surviving cases who required hospitalization were also younger than 3 years of age (161/259, 62%; Fig. 2). Males accounted for 58% of fatal cases, and 56% of hospitalized surviving cases. Several types of enterovirus had been isolated from the throat and rectal swabs during this epidemic. However, enterovirus 71 was the most common serotype isolated from children with HFMD or herpangina. The same was also true for cases with severe complications or death.

Fig. 2 Age distribution of death and hospitalization due to severe enterovirus in Taiwan. Data were collected on August 6, 1998.

Fatal and near-fatal cases of enterovirus infection usually present with symptoms or signs of encephalitis, pulmonary edema, pulmonary hemorrhage, and acute cardiopulmonary failure. Deterioration of the clinical condition was quite sudden and rapid in fatal cases with an average of 3.2 days between the onset of illness and the time of death. Forty-one of them expired within 24 hours after hospitalization.

Usually there is no an early sign capable of predicting whether or not the infection will endanger the life. Nevertheless, analysis of clinical features in fatal cases showed that three clinical features were frequently noted in the early phase of the illness in the severe cases, including profound sleepiness, myoclonic jerks, and persistent vomiting. All three features might be related to brain involvement. Other clinical manifestations that should be regarded as early signs of severe illness include poor activity, irritability, change of consciousness, coma, neck stiffness, seizures, tachypnea, general weakness, tachycardia and arrhythmia.

There were some debates about the exact cause of death in severe cases. Investigations on clinical history showed that neurological manifestations were usually present in severe cases. Similar to previous observations on severe enterovirus 71 infection in Malaysia, autopsy findings on some fatal cases showed the presence of brain stem involvement and the absence of myocardial inflammation.^1,2 It is tempting to conclude that brain stem encephalitis might be the most important cause of death. Pulmonary edema, pulmonary hemorrhage and circulatory collapse may thus result from a neurogenic mechanism² or a systemic inflammatory response to severe virus infection.

Some recommendations have been made for the management of severe enterovirus infection by Pediatric Association in Taiwan,³ including the followings:

1. Because most severe cases have features of encephalitis and cardiopulmonary failure, thorough evaluations of central nervous system and cardiopulmonary system are mandatory for patients with suspected enterovirus 71 infection.

2. It is important to note that empirical therapy with fluid challenge should be avoided because it may compromise further the brain edema and the heart failure. Institution of fluid therapy should be guided by central venous pressure that should be kept at about 4 mmHg.

3. Inotropic agents and early respiratory support should be the first line of therapy for patients with deteriorated cardiopulmonary function. Glycerol or mannitol and hyperventilation therapy should be given to lessen increased intracranial pressure in cases with signs of encephalitis.

4. Intravenous immunoglobulin may be given to severe enterovirus infections in infants and young children. The recommended dose is 1 gm/kg/day via intravenous infusion for 12 hours daily for 2 days. Indications for the use of intravenous immunoglobulin are cases with HFMD or herpangina and with one of the followings:

   (a) Less than 24 months of age with manifestations of acute encephalitis, polio-like syndrome, acute myocarditis, acute heart failure or tachydyspnea caused by pulmonary edema.

   (b) A grave clinical condition that may endanger the life as judged by attending physician.

References

1. Anonymous. Deaths among children during an outbreak of hand, foot, and mouth disease - Taiwan, Republic of China, April-July 1998. MMWR 1998;47:629-2.

2. Chang LY, Huang YC, Lin TY Fulminant neurogenic pulmonary oedema with hand, foot, and mouth disease. Lancet 1998;352:367.

3. Lee PI, Lee CY, Wang TR. Recommendations for management of severe enterovirus infection in Taiwan. Acta Pediatr Sin 1998;39:217.