New Tricks for an Old Enterovirus

abstracts & Commentary

Synopsis: An outbreak of enterovirus 71 in Taiwan in 1998 resulted in more than 1 million cases of hand-foot-and-mouth disease or herpangina. Severe disease, especially rhombencephalitis, and fatalities from pulmonary edema and hemorrhage were observed, especially in young children.

Sources: Ho M, et al. An epidemic of enterovirus 71 infection in Taiwan. N Engl J Med 1999;341:929-935; Huang CC, et al. Neurologic complications in children with enterovirus 71 infection. N Engl J Med 1999;341:936-942.

In 1998, an epidemic in taiwan of enteroviruses caused 129,106 cases of hand-foot-and-mouth disease or herpangina, which was estimated to represent less than 10% of the total number of cases. There were 405 cases of severe disease: aseptic meningitis, encephalitis, acute flaccid paralysis, pulmonary edema or hemorrhage, and myocarditis. There were 78 deaths, including 71 (91%) in children younger than 5 years of age, primarily resulting from pulmonary edema or hemorrhage. Enterovirus was isolated from 49% of outpatients with uncompleted hand-foot-and-mouth disease or herpangina, 75% of hospitalized patients who survived, and 92% of patients who died.

During the 1998 enterovirus epidemic in Taiwan, 41 children were hospitalized with culture-confirmed enterovirus infection and acute neurologic manifestations. The mean age of the patients was 2.5 years (range, 3 months to 8.2 years). Twenty-eight patients (68%) had hand-foot-and-mouth disease and six (15%) had herpangina. Three neurologic syndromes were observed: aseptic meningitis in three patients, rhombencephalitis (brain-stem encephalitis) in 37 patients, and acute flaccid paralysis in four patients, which followed rhombencephalitis in three patients. The most common symptoms were myoclonic jerks, and T2-weighted magnetic resonance imaging (MRI) showed high-intensity lesions in the brain stem in 17 of 24 (71%) patients. Five patients with rhombencephalitis died.

Comment by Hal B. Jenson, MD, FAAP

Since enterovirus 71 was isolated in 1969, it has been recognized to cause sporadic cases and several large outbreaks in many parts of the world. Enteroviruses, as their name implies, are spread primarily by the fecal-oral route but the characteristics of this outbreak indicate potential respiratory spread.

The unusual complications of rhombencephalitis suggest that this enterovirus could represent a particularly virulent strain, with tropism for the rhombencephalon. Rhombencephalitis was manifest by: myoclonic jerks with tremor, ataxia, or both (Grade I); myoclonus with cranial nerve involvement, including ocular disturbances such as nystagmus, strabismus, or gaze paresis (Grade II); or transient myoclonus rapidly followed by loss of doll’s eye reflex, and apnea (Grade III). This outbreak was also characterized by pulmonary edema and hemorrhage, another uncommon although recognized complication of enterovirus 71 infection, which was responsible for the majority of deaths.

We tend to consider enterovirus encephalitis as sporadic, self-limited, and generally without serious morbidity and with low mortality. This outbreak showed the epidemic and fatal aspects of enterovirus 71 infections. Patients with neurologic symptoms following hand-foot-and-mouth syndrome or herpangina, or with encephalitis of uncertain etiology, should be cultured for enteroviruses. This may hasten the diagnosis in sentinel patients and lead to earlier recognition of enteroviral outbreaks complicated by neurologic involvement.

True statements concerning enterovirus 71 include all of the following except:

a. it is an etiologic agent in some cases of herpangina and hand-foot-and-mouth disease.

b. severe complications occur more in young children than in adults.

c. it may produce lesions in the brain stem demonstrated by MRI.

d. they are exclusively spread by the fecal-oral route.