An outbreak of enterovirus 71 infection in Taiwan 1998: A comprehensive pathological, virological, and molecular study on a case of fulminant encephalitis
Introduction
Enterovirus 71 (EV71) has been associated with an array of clinical diseases including hand, foot and mouth disease (HFMD), aseptic meningitis, encephalitis, and poliomyelitis-like paralysis (Alexander et al., 1994, Melnick, 1996). There have been two EV71 outbreaks resulting in rapid clinical deterioration and death among young children; one outbreak occurred in Bulgaria during May–September 1975 (Shindarov et al., 1979), and another in Malaysia during April–June 1997 (Lum et al., 1998a). However, knowledge of the mechanisms of the viral neurovirulence is still limited.
Between April and October 1998 in Taiwan, an EV71 outbreak characterized by rapid onset of central nervous system disease and fatal outcome occurred (Centers for Disease Control and Prevention, 1998, Chang et al., 1998). In this outbreak, more than 90 000 children with HFMD have been reported. Among these patients, more than 320 children have been hospitalized with suspected meningitis, encephalitis, or acute flaccid paralysis, and at least 55 died, suggesting neurovirulence of the pathogen.
In the present report, we describe a case of EV71 infection with CNS involvement and rapidly fatal course. Comprehensive pathological, virological, and molecular studies have been performed on this case in order to unearth the pathogenesis of the virus.
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Patient and clinical course
On October 26 1998, fever and oral ulcers developed in a 3-year-old boy from Tainan County. On October 28, he had a vesicular rash on his hands and feet, and several episodes of myoclonus seizures. He was admitted to a local hospital for suspected HFMD on October 29. It was not long after this admission when vomiting, cold sweating, ataxia, dyspnea, and hypotension occurred. He was immediately transferred to the National Cheng Kung University Hospital on the same day. On physical examination,
Autopsy findings and immunohistochemistry
The brain appeared normal grossly. On microscopic examination, typical features of acute encephalitis, including perivascular cuffing by mixed inflammatory cells (Fig. 1A) and neuronophagia or inflammatory nodules (Fig. 1B), were noticed. Mixed inflammatory infiltrates in the brain substance and histological evidence of acute neuron injury were observed extensively. Occasionally, devastated and cavitary appearance can be found in the areas with notable inflammation. The most prominent
Discussion
The EV71 epidemic in 1998 in Taiwan is the third known EV71 outbreak resulting in rapid clinical deterioration and death among young children (Shindarov et al., 1979, Centers for Disease Control and Prevention, 1998, Chang et al., 1998, Lum et al., 1998a). The autopsy findings of this case, together with those reported elsewhere (Shindarov et al., 1979, Centers for Disease Control and Prevention, 1998, Chang et al., 1998, Lurn et al., 1998b, Komatsu et al., 1999), indicate that the brain stem
Acknowledgements
The study was supported by the grant NHRI-CN-CR8804 from the National Health Research Institute, Taiwan.
References (19)
- et al.
Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus
Virus Res.
(1995) - et al.
Outbreak of severe neurologic involvement associated with enterovirus 71 infection
Pediatr. Neurol.
(1999) - et al.
Fatal enterovirus 71 encephalomyelitis
J. Pediatr.
(1998) - et al.
Preparation and characterization of encephalomyocarditis (EMC) virus
- et al.
Enterovirus 71 infection and neurologic disease — United States, 1977–1991
J. Infect. Dis.
(1994) - Centers for Disease Control and Prevention. Deaths among children during an outbreak of hand, foot, and mouth disease —...
- et al.
Fulminant neurogenic pulmonary oedema with hand, foot, and mouth disease
Lancet
(1998) - et al.
Rapid production of full-length eDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer
Proc. Natl. Acad. Sci. USA
(1988) - et al.
Reemergence of an epidemic coxsackievirus B5 genotype
J. Infect. Dis.
(1987)
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