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1/4. Deaths of children during an outbreak of hand, foot, and mouth disease in sarawak, malaysia: clinical and pathological characteristics of the disease. For the Outbreak Study Group.

    From April through June 1997, 29 previously healthy children aged <6 years (median, 1.5 years) in Sarawak, malaysia, died of rapidly progressive cardiorespiratory failure during an outbreak of hand, foot, and mouth disease caused primarily by enterovirus 71 (EV71). The case children were hospitalized after a short illness (median duration, 2 days) that usually included fever (in 100% of case children), oral ulcers (66%), and extremity rashes (62%). The illness rapidly progressed to include seizures (28%), flaccid limb weakness (17%), or cardiopulmonary symptoms (of 24 children, 17 had chest radiographs showing pulmonary edema, and 24 had echocardiograms showing left ventricular dysfunction), resulting in cardiopulmonary arrest soon after hospitalization (median time, 9 h). Cardiac tissue from 10 patients showed normal myocardium, but central nervous system tissue from 5 patients showed inflammatory changes. Brain-stem specimens from 2 patients were available, and both specimens showed extensive neuronal degeneration, inflammation, and necrosis, suggesting that a central nervous system infection was responsible for the disease, with the cardiopulmonary dysfunction being neurogenic in origin. EV71 and possibly an adenovirus, other enteroviruses, or unknown cofactors are likely responsible for this rapidly fatal disease.
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ranking = 1
keywords = central nervous system, nervous system
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2/4. Acute encephalomyelitis during an outbreak of enterovirus type 71 infection in taiwan: report of an autopsy case with pathologic, immunofluorescence, and molecular studies.

    We report a fatal case of enterovirus type 71 (EV 71) infection in an 8-year-old girl during a summer outbreak of hand, foot, and mouth disease in 1998 in taiwan. The clinical course was rapidly progressive, with manifestations of hand, foot, and mouth disease, aseptic meningitis, encephalomyelitis, and pulmonary edema. The patient died 24 hours after admission. Postmortem study revealed extensive inflammation in the meninges and central nervous system and marked pulmonary edema with focal hemorrhage. brain stem and spinal cord were most severely involved. The inflammatory infiltrates consisted largely of neutrophils involving primarily the gray matter with perivascular lymphocytic cuffing, and neuronophagia. The lungs and heart showed no evidence of inflammation. EV 71 was isolated from the fresh brain tissues and identified by immunofluorescence method with type-specific EV 71 monoclonal antibody. It was also confirmed by neutralization test and reverse-transcriptase polymerase chain reaction with sequence analysis. The present case was the first example in which EV 71 was demonstrated to be the causative agent of fatal encephalomyelitis during its epidemic in taiwan.
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ranking = 0.5
keywords = central nervous system, nervous system
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3/4. Echovirus 7 associated encephalomyelitis.

    BACKGROUND: hand, foot, and mouth disease (HFMD) is endemic in malaysia. In 1997, a large outbreak of enterovirus 71 (EV-71) associated HFMD resulted in 41 deaths due to severe left ventricular dysfunction and central nervous system infection with extensive damage to the medulla and pons. The clinical presentation in all these patients were rapid cardio-respiratory decompensation leading to cardiac arrest. Another large outbreak of HFMD with 55 fatal cases and a similar clinical picture was reported in taiwan in 1998. In 2000, an outbreak of HFMD resulted in the deaths of three children who had rapid cardio-respiratory decompensation and one child who survived a central nervous system infection. OBJECTIVES: We set out to study the etiologic agent and mechanism involved in three children who presented to our hospital, two of whom died and one survived a central nervous system infection. STUDY DESIGN: The clinical course of the disease was described. Throat, rectal swab and cerebrospinal fluid samples were subjected to viral isolation and viral isolates were identified by immunofluorescence, micro-neutralisation using human rhabdomyosarcoma (RD) cells, and reverse transcritpase polymerase chain reaction. magnetic resonance imaging was performed on two of the patients. RESULTS: Echovirus 7 was the sole pathogen isolated from three cases of acute encephalomyelitis, two of which were fatal due to severe left ventricular dysfunction resistant to inotropic support. The survivor had residual bulbar palsy, but is considered to have had a good neurological outcome. CONCLUSION: Echovirus 7 infection associated with encephalomyelitis could be fatal due to indirect involvement of the heart resulting in severe left ventricular dysfunction. In addition one of the children presented with hand, foot, and mouth disease, a syndrome that has not been previously associated with echovirus 7 infection.
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ranking = 1.5
keywords = central nervous system, nervous system
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4/4. Outbreak of central nervous system disease associated with hand, foot, and mouth disease in japan during the summer of 2000: detection and molecular epidemiology of enterovirus 71.

    Few outbreaks of the serious enterovirus 71 (EV71) infections, which affect the central nervous system (CNS), had been reported in japan before 2000. During June through August 2000, a patient died of pulmonary edema caused by brainstem encephalitis accompanied by EV71-induced hand, foot, and mouth disease (HFMD), and many patients complicated by serious CNS disease, including paralysis, were hospitalized in a restricted area in Hyogo Prefecture, japan (K-area). During the same period, endemics of HFMD were reported in other areas in Hyogo Prefecture, where EV71 was isolated from HFMD patients, but few patients developed aseptic meningitis. The isolations of EV71 from K-area patients were difficult with the use of vero cells, so the strains were isolated by use of GL37 cells; vero cells, however, could isolate EV71 strains from other areas in Hyogo Prefecture. We sequenced VP4 coding regions of these EV71 isolates and found that the isolates from K-area had the same sequence, which, except for one isolate, was different from the sequences of EV71 strains isolated from other areas of Hyogo Prefecture. Although these results were not enough to state that EV71 from K-area was a virulent strain, it seemed reasonable to conclude that serious CNS diseases in K-area were caused by EV71 because it was the only infectious agent detected in the inpatients of K-area.
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ranking = 2.5
keywords = central nervous system, nervous system
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