Publications

an outbreak of enterovirus 71 infection in taiwan 1998: a comprehensive pathological, virological, and molecular study on a case of fulminant encephalitis.	in a recent enterovirus outbreak in taiwan, serotype 71 was the culprit of encephalitis causing rapid clinical deterioration and death among young children.	2000	10814934
an outbreak of enterovirus 71 infection in taiwan, 1998: epidemiologic and clinical manifestations.	an outbreak of enterovirus infections occurred throughout taiwan in 1998. the diseases were manifectated with hand, foot, and mouth disease (hfmd), some associated with meningitis, encephalitis, or acute flaccid paralysis (afp).	2000	10814935
antiviral therapy for neurological manifestations of enterovirus 71 infection.		2000	10880332
emerging and re-emerging epidemic encephalitis: a tale of two viruses.	two major epidemics of viral encephalitis occurred in asia in 1997 and 1998. the first was a re-emergence of neurovirulent strains of enterovirus 71, which caused severe encephalomyelitis in children in malaysia, taiwan and japan, on a background of hand, foot and mouth disease. necropsy studies of patients who died of enterovirus 71 infection showed severe perivascular cuffing, parenchymal inflammation and neuronophagia in the spinal cord, brainstem and diencephalon, and in focal areas in the c ...	2000	10931364
an outbreak of enterovirus 71 infection in taiwan, 1998. ii. laboratory diagnosis and genetic analysis.	an epidemic of enterovirus 71 (ev71) occurred in taiwan from april to december of 1998, with two peaks, one in june and the other in october. many enteroviruses were isolated in our laboratory from 258 cases during this outbreak. approximately half of the enteroviruses isolated were ev71 and one fifth were coxsackievirus a16.	2000	10942089
genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in taiwan, 1998.	a large scale outbreak of hand-foot-and-mouth disease (hfmd) occurred in taiwan in 1998, in which more than 80 children died of shock syndrome with pulmonary edema/hemorrhage. enterovirus 71 was implicated as the cause of this outbreak. in order to understand the virological basis responsible for mortality on this scale, nucleotide sequences of vp1 that is important for serotypic specificity, and the 5'-non-coding region (5'-ncr) that is important for replication efficiency, were analyzed compar ...	2000	10958984
enterovirus 71 infections at a canadian center.		2000	10959747
rt-pcr, nucleotide, amino acid and phylogenetic analyses of enterovirus type 71 strains from asia.	a specific and sensitive method based on rt-pcr was developed to detect enterovirus 71 (ev71) from patients with hand, foot and mouth disease, myocarditis, aseptic meningitis and acute flaccid paralysis. rt-pcr primers from conserved parts of the vp1 capsid gene were designed on the basis of good correlation with sequences of ev71 strains. these primers successfully amplified 44 strains of ev71 including 34 strains isolated from singapore in 1997 and 1998, eight strains from malaysia isolated in ...	2000	10960707
congenital enterovirus 71 infection: a case study with virology and immunohistochemistry.	previously reported enterovirus 71 (ev71) infections associated with hand-foot-mouth disease, aseptic meningitis, encephalitis, polio-like myelitis, and paralysis all have involved young children. we report a 28-year-old woman who possibly contracted ev71 infection during pregnancy. obstetric ultrasonograms at 25 weeks of gestation revealed an abnormal placenta, as well as hepatosplenomegaly, liver calcification, excessive ascites, and mild hydrocephalus of the fetus. presence of ev71 was determ ...	2000	10987713
light-independent inactivation of dengue-2 virus by carboxyfullerene c3 isomer.	carboxyfullerene (c60) is known as a photosensitizer for virus inactivation. its regioisomer with c3 symmetry, named the c3 isomer, could also inactivate the dengue-2 virus without light when the dose of c3 isomer was increased to 40 microm, indicating the possible involvement of a light-independent mechanism. further analysis showed that the c3 isomer blocked viral replication at the attachment and penetration stages, suggesting that a direct interaction between the c3 isomer and the virion is ...	2000	10998325
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 seizu ...	2000	11017815
neutralizing antibody provided protection against enterovirus type 71 lethal challenge in neonatal mice.	experimental infection with enterovirus type 71 (ev71) induced death in neonatal mice in an age- and dose-dependent manner. the mortality rate was 100% following intraperitoneal inoculation 1-day-old icr mice and this gradually decreased as the age at the time of inoculation increased (60% in 3-day-old mice and no deaths occurred in mice older than 6 days of age). a lethal dose greater than 10(8) pfu was necessary. lethargy, failure to gain weight, rear limb tremors and paralysis were observed i ...	2000	11060501
rapid diagnosis and quantification of herpes simplex virus with a green fluorescent protein reporter system.	a genetically modified cell line (vero-icp10-egfp) was constructed for detection of herpes simplex virus (hsv) by a simple, rapid and direct method. the cell line was developed by stable transfection of vero cell with a plasmid encoding the green fluorescent protein (gfp) driven by the promoter of the hsv-2 icp10 gene. as early as 6 h after infection with hsv, fluorescence-emitting cells can be observed under a fluorescence microscope. a single infected cell emitting fluorescence can be observed ...	2000	11064120
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 hemor ...	2000	11106077
outbreaks of enterovirus 71 infection.		2000	10660400
enterovirus 71 infection and neurologic complications.		2000	10660401
mri of enterovirus 71 myelitis with monoplegia.	we report two boys diagnosed as having herpangina and hand-foot-mouth disease complicated by monoplegia during the outbreak enterovirus infection in taiwan in 1998. enterovirus 71 was identified in the stool and throat swab; neither polio nor coxsackie viruses was identified. mri showed unilateral lesions in the anterior horns of the spinal cord at t11-12 and c2-5. although the mri findings and sites of these lesions were similar to those of poliovirus-associated poliomyelitis, the virological d ...	2000	10663490
serotype-specific identification of enterovirus 71 by pcr.	enterovirus 71 and coxsackievirus a16 are closely related genetically and are causative agents of hand foot and mouth disease. because enterovirus 71 is more often associated with severe neurological disease, there is a need to rapidly discriminate between enterovirus 71 and coxsackievirus a16 during hand, foot, and mouth disease outbreaks.	2000	10720814
expression of capsid [correction of caspid] protein vp1 for use as antigen for the diagnosis of enterovirus 71 infection.	to produce enterovirus 71 antigen for diagnostic purposes, the gene encoding the entire capsid protein vp1 was amplified by reverse transcription-polymerase chain reaction (rt-pcr), cloned and expressed in escherichia coli as a poly-histidine fusion protein. western blotting experiments with sera from patients with enterovirus 71 infection indicated that immunoglobulin g (igg) and igm antibodies bound to a single polypeptide vp1. according to these results, igm anti-vp1 appeared in sera of patie ...	2000	10797379
enterovirus infections with special reference to enterovirus 71.	the enteroviruses comprise a large group of immunologically distinct serotypes of viruses belonging to the family of picornaviridae. many enteroviruses cause diseases in human, but the infections are generally mild as asymptomatic, therefore, enteroviruses are considered to be unimportant as human pathogens. however, enteroviruses may also result in serious or even fatal disease (as shown in the enterovirus 71 (ev71) epidemic in taiwan in 1998). there are three types of polioviruses, coxsackievi ...	2000	10806956
[detection of viral aetiology in cerebral spinal fluid samples from 580 clinical cases].	to investigate the viral aetiology in cerebral spinal fluid (csf) from 580 cases of cns infection or fuo in yuedong district from 1990 to 1997.	2000	11471031
enterovirus 71: the virus, its infections and outbreaks.	enterovirus 71 (ev71) was first recognized in 1974. since then it has been implicated in 13 small and large outbreaks world-wide. large outbreaks of hand, foot and mouth disease (hfmd), mostly benign, occurred in japan in 1973 and 1978. four outbreaks with brain stem encephalitis and significant numbers of deaths occurred in bulgaria and hungary in the late 1970's and in malaysia and taiwan in 1997 and 1998 respectively. during the latter two epidemics, pulmonary edema and hemorrhage often leadi ...	2000	11269363
neurologic involvement in an outbreak of enterovirus 71 infection: a hospital-based study.	enterovirus (ev) can cause varied clinical manifestations. involvement of the central nervous system (cns) with the nonpolio evs are common and important causes of morbidity in children. to investigate the manifestations of nonpolio enteroviral infections with cns involvement during the ev outbreak, from february 1998 to january 1999, we collected 153 hospitalized patients in our pediatric ward caused by nonpolio ev infections which were diagnosed by history, clinical features, or detected from ...	2001	11270182
neurologic complications of enterovirus 71 infection in children: lessons from this taiwan epidemic.		2001	11270188
type-specific detection of echovirus 30 isolates using degenerate reverse transcriptase pcr primers.	following an approach used to specifically identify polioviruses and enterovirus 71, we have developed reverse transcriptase (rt) pcr primers containing mixed-base residues or deoxyinosine at positions of codon degeneracy. these primers permit specific rt-pcr amplification of echovirus 30 (e30) sequences by targeting sites that encode conserved amino acid motifs within the major capsid protein, vp1. all 221 e30 strains tested, isolated in 16 countries over a 44-year period, yielded the predicted ...	2001	11283045
[emergent viral infections].	the emergence and re-emergence of viral infections is an ongoing process. large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. increased travel is leading to a rise in the importation of exotic infections such as dengue and hepatitis e, but also of hepatitis a, which is no longer endemic. apart from import diseases new viruses have appeared (nipah-virus and transfusion-transmitted virus). existing ...	2001	11305210
molecular epidemiology of enterovirus 71 in taiwan.	taiwan suffered a severe and widespread outbreak of enterovirus infection in 1998. more than 400 children were hospitalized, with seventy-eight fatalities due to central nerve system (cns) involvement and cardiopulmonary collapse. enterovirus 71 (ev71) was incriminated as the causative agent for the fatal cases. to understand the viral molecular epidemiology in this outbreak, fragments of 207-bp length of the vp4 region in 23 taiwanese ev 71 isolates were sequenced. pair-wise comparison revealed ...	2001	11338392
update on viral encephalitis.	over 100 viruses have been associated with acute central nervous system infections. the present review focuses on some of the most common agents of viral encephalitis, as well as important emerging viral encephalitides. in this context, the initial detection of west nile virus in the western hemisphere during the 1999 new york city outbreak, the first description of nipah virus in malaysia, and the appearance in asia of a new neurovirulent enterovirus 71 strain that causes severe neurologic dise ...	2001	11371762
infections of the nervous system: an update on recent developments.	the past decade has seen major changes in the field of infectious diseases. in particular, many new infections of the nervous system have been recognised, including the lethal infections of enterovirus 71, and the nipah and west nile viruses. increased interest in prion diseases has occurred, following the recognition of animal-to-human transmission in europe. familiar bacteria such as the pneumococcus continue to cause problems due to increasing resistance to multiple antibiotics. furthermore, ...	2001	11406678
phylogenetic analysis of enterovirus 71 strains isolated during linked epidemics in malaysia, singapore, and western australia.	enterovirus 71 (ev71) is a frequent cause of hand, foot, and mouth disease (hfmd) epidemics associated with severe neurological sequelae in a small proportion of cases. there has been a significant increase in ev71 epidemic activity throughout the asia-pacific region since 1997. recent hfmd epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case fatality rates. in this study, we show that four genetic lineages of ev ...	2001	11462047
emerging viral diseases of southeast asia and the western pacific.	over the past 6 years, a number of zoonotic and vectorborne viral diseases have emerged in southeast asia and the western pacific. vectorborne disease agents discussed in this article include japanese encephalitis, barmah forest, ross river, and chikungunya viruses. however, most emerging viruses have been zoonotic, with fruit bats, including flying fox species as the probable wildlife hosts, and these will be discussed as well. the first of these disease agents to emerge was hendra virus, forme ...	2001	11485641
[characterization of enterovirus type 71 isolated in saitama prefecture in 2000].	coxsackievirus a16 (ca16) has been isolated mainly from hand, foot and mouth disease patients for the past several years in saitama prefecture, japan, but in 2000, enterovirus 71 (ev71) was isolated with high frequency. also, many cases with aseptic meningitis were reported unusually. we determined partial nucleotide sequences of ev71 isolated in this year and compared them with those of the viruses isolated previously. eighteen strains of ev71 were isolated from may to september in 2000. the se ...	2001	11494567
first fatal case of enterovirus 71 infection in hong kong.	enteroviruses are a common cause of childhood infections, from hand, foot and mouth disease, to lethal brainstem encephalitis. enterovirus 71 was first isolated in 1969. brainstem encephalomyelitis and pulmonary oedema are postulated to be causally related and have been found to be a common feature of fatal enterovirus 71 cases. a fatal case of enterovirus 71 infection in a 2-year-old, previously healthy boy is reported. he presented to the department of paediatrics with clinical features of sep ...	2001	11514756
complete genome analysis of enterovirus 71 isolated from an outbreak in taiwan and rapid identification of enterovirus 71 and coxsackievirus a16 by rt-pcr.	hand, foot, and mouth disease (hfmd) and encephalomyelitis were two major clinical manifestations during the 1998 enterovirus 71 (ev71) epidemic in taiwan. to investigate whether different clinical patterns were caused by alterations in ev71 genomes, the complete nucleotide sequences of four ev71 strains associated with hfmd or encephalomyelitis were compared. among these viral strains, two or three nucleotide differences were found within the 5'-noncoding region, and two or four amino acid diff ...	2001	11536241
duration of enterovirus shedding in stool.	excretion of enterovirus (ev) may persist for months after an ev infection; the exact duration of excretion, however, is not yet known. twelve children who were infected with ev between september 1998 and june 1999 were enrolled into this study. the patients included 4 boys and 8 girls, aged from 1 month to 5 years. six patients were asked to join this virus isolation program, and the other 6 were followed-up regularly. only 2 of the patients were infected with ev 71. to delineate the duration o ...	2001	11605806
protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit vp1 vaccines and inactivated virus.	enterovirus 71 (ev71), the newest member of enteroviridae, is notable for its etiological role in epidemics of severe neurological diseases in children. developing effective vaccines is considered a top choice among all control measures. we compared the inactivated virus vaccine (10 microg protein/mouse) with subunit vaccines--vp1 dna vaccine (100 microg/mouse) or recombinant vp1 protein (10 microg/mouse)--in its ability to elicit maternal antibody and to provide protection against lethal infect ...	2001	11738755
[genetic diagnosis and molecular epidemiological analyses of hand, foot and mouth disease which prevailed in osaka prefecture in 2000].	direct rapid genetic diagnosis by rt-pcr as well as virus isolation was performed on the 122 patients with hand, foot and mouth disease (hfmd) in osaka prefecture in 2000, followed by molecular epidemiological analyses of the isolated viruses. mrc-5 cells showed the highest sensitivity for virus isolation, recovering 59 strains of viruses from 80 virus-positive patients. by rt-pcr using newly designed primers spanning vp4 and vp2, corresponding genome regions of coxsackievirus type a16 (ca16) an ...	2001	11766373
respiratory viral infections among pediatric inpatients and outpatients in taiwan from 1997 to 1999.	the present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. a total of 2,295 virus infections were detected in 6,986 patients between 1997 and 1999, including infections caused by respiratory syncytial virus (rsv) (1.7%), parainfluenza virus (2.0%), influenza b virus (2.6%), adenovirus (4.0%), herpes simplex virus type 1 (4. 4%), influenza a virus (5.5%), and enterovirus (12.7 ...	2001	11136758
acute flaccid paralysis in infants and young children with enterovirus 71 infection: mr imaging findings and clinical correlates.	enterovirus 71 (ev71) infection is now considered an important cause of childhood acute flaccid paralysis. the purpose of our study was to determine whether ev71-infection-related acute flaccid paralysis in infants and young children has characteristic mr imaging patterns.	2001	11158910
neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in western australia.	enterovirus 71 (ev71) causes epidemics of hand, foot, and mouth disease associated with neurological complications in young children. we report an outbreak of ev71-associated neurological disease that occurred from february through september 1999 in perth, western australia. fourteen children with culture-proven, ev71-induced neurological disease were identified. nine patients (64%) developed severe neurological disease; 4 of these patients developed long-term neurological sequelae. neurological ...	2001	11170913
altered cellular but not humoral reactions in children with complicated enterovirus 71 infections in taiwan.	enterovirus 71 (ev 71) infections have high neurovirulence and fatality. immune responses were assessed in 78 patients with ev 71 infection. ev 71 meningoencephalitis occurred more frequently in younger children and in boys. c-reactive protein levels were not elevated, although total leukocyte counts were increased in these patients. the cd40-ligand expression on t cells significantly decreased in children with meningoencephalitis (p=.041). polymorphism of the cytotoxic t lymphocyte antigen-4 (c ...	2001	11237800
pathologic studies of fatal cases in outbreak of hand, foot, and mouth disease, taiwan.	in 1998, an outbreak of enterovirus 71-associated hand, foot, and mouth disease occurred in taiwan. pathologic studies of two fatal cases with similar clinical features revealed two different causative agents, emphasizing the need for postmortem examinations and modern pathologic techniques in an outbreak investigation.	2001	11266307
ciguatera poisoning: a global issue with common management problems.	ciguatera poisoning, a toxinological syndrome comprising an enigmatic mixture of gastrointestinal, neurocutaneous and constitutional symptoms, is a common food-borne illness related to contaminated fish consumption. as many as 50000 cases worldwide are reported annually, and the condition is endemic in tropical and subtropical regions of the pacific basin, indian ocean and caribbean. isolated outbreaks occur sporadically but with increasing frequency in temperate areas such as europe and north a ...	2001	11785597
the complete genome of enterovirus 71 china strain.	five overlapping clones covering the full genome of enterovirus 71 china strain shzh98 were obtained and then the sequences were determined by the chain termination method. it showed that the full length of ev71 shzh98 genome (not including poly a tail) is 7408 bp. there are some diversities on the lengths and sequences of 5' utr and 3' utr between shzh98 and the other ev71 strains. in p1 capsid region, which is closely associated with viral immunogenicity, ev71 strain shzh98 shares the highest ...	2001	18726435
cardiopulmonary manifestations of fulminant enterovirus 71 infection.	the pathogenesis of acute pulmonary edema and cardiac collapse after enterovirus 71 (ev71) infection are not completely understood.	2002	11826236
emerging viral infections in australia.	emerging viruses include known viruses that have increased in incidence or geographic range (such as enteroviruses and japanese encephalitis virus), new viruses associated with known diseases (australian bat lyssavirus) and new viruses associated with previously unrecognized diseases (hendra and nipah viruses). some may have a predilection for children (japanese encephalitis, influenza viruses and enterovirus 71) and vigilance is essential to ensure early recognition of these agents.	2002	11869391
use of molecular assay in diagnosis of hand, foot and mouth disease caused by enterovirus 71 or coxsackievirus a 16.	hand, foot and mouth disease is a common illness in children and is usually caused by coxsackievirus a 16 and enterovirus 71. it has been noted that enterovirus 71 infection is more severe with significantly greater frequency of serious complications and fatality than coxsackievirus a 16. therefore, it is important to develop a rapid and specific assay for discriminating coxsackievirus a 16 and enterovirus 71 in hand, foot and mouth disease outbreaks. in this study we designed two sets of rt-pcr ...	2002	11879688
left ventricular dysfunction in children with fulminant enterovirus 71 infection: an evaluation of the clinical course.	we describe 2 children with typical hand, foot, and mouth disease due to enterovirus 71 infection, 1 of whom died. both cases were complicated by acute fulminant shock syndrome; the patients had remarkable acute left ventricular dysfunction. the clinical experience indicates that the rapid death associated with fulminant enterovirus rhombencephalitis is the result of rapid cardiogenic shock rather than neurogenic pulmonary edema.	2002	11880970
the 3c protease activity of enterovirus 71 induces human neural cell apoptosis.	the human glioblastoma sf268 cell line was used to investigate the induction of apoptosis by the 3c protease of enterovirus 71 (ev71). transient expression in these cells of the wild-type 3c protein encoded by ev71 induced morphological alterations typical of apoptosis, including generation of apoptotic bodies. degradation of cellular dna in nucleosomes was also observed. when two of the amino acids in the catalytic motif of 3c were changed by mutagenesis, the 3c protein not only lost its proteo ...	2002	11886259
molecular classification of enteroviruses not identified by neutralization tests.	we isolated six viruses from patients diagnosed with aseptic meningitis or hand, foot, and mouth disease. the cytopathic effect of these viruses on cultured cells was like that of enteroviruses. however, viral neutralization tests against standard antisera were negative. phylogenetic analysis with the complete vp4 nucleotide sequences of these 6 viruses and 29 serotypes of enteroviruses classified 3 of the viruses as serotype echovirus type 18 (ev18) and 3 as serotype human enterovirus 71 (hev71 ...	2002	11927028
clinical manifestations and laboratory assessment in an enterovirus 71 outbreak in southern taiwan.	an epidemic of enterovirus 71 (ev71) infection compatible with hand, foot and mouth disease and associated with high morbidity and mortality occurred in taiwan in 1998. we recruited 90 patients (50 males, 40 females) with definite ev71 infections for clinical and laboratory analysis. the neurological signs and symptoms, all of which occurred during the febrile period, in patients with central nervous system (cns) involvement (aseptic meningitis, encephalitis or myelitis) were myoclonic jerks (23 ...	2002	11928838
design, synthesis, and structure-activity relationship of pyridyl imidazolidinones: a novel class of potent and selective human enterovirus 71 inhibitors.	when skeletons of win compounds were used as templates, computer-assisted drug design led to the identification of a novel series of imidazolidinone derivatives with significant antiviral activity against enterovirus 71 (ev 71), the infection of which had resulted in about 80 fatalities during the 1998 epidemic outbreak in taiwan. in addition to inhibiting all the genotypes (a, b, and c) of ev 71 in the submicromolar to low micromolar range, compounds 1 and 8 were extensively evaluated against a ...	2002	11931618
the 1998 enterovirus 71 outbreak in taiwan: pathogenesis and management.	the most recently discovered enterovirus, enterovirus 71 (ev71), is neurotropic and may cause severe disease and sudden death in children. in 1998, a large outbreak of enterovirus infection occurred in taiwan that resulted in 405 severe cases in children and 78 deaths. of the 78 children who died, 71 (91%) were <5 years old. ev71 was the primary agent in fatal cases of infection. most of these patients died within 1-2 days of admission to the hospital. we hypothesize that ev71 directly attacks t ...	2002	11938497
neutralizing antibodies to enterovirus 71 in belém, brazil.	non-polio enteroviruses (coxsackievirus a, coxsackievirus b, echovirus and ev 68-72) which belong to the enterovirus (ev) genus, picornaviridae family, may be responsible for acute flaccid paralysis, aseptic meningitis, myocarditis, hepatitis, pleurodinia, neonatal sepsis, hand, foot and mouth disease (hfmd) even though 50-80% of infections are asymptomatic. ev 71 has been responsible for outbreaks and epidemics of hfmd and acute neurologic disease justifying its study in our country. the aim of ...	2002	11992146
pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71.	among the enteroviruses, polioviruses and enterovirus 71 (ev71) are two major neurotropic viruses causing serious neurological manifestations. while polioviruses are being eradicated globally by vaccination, ev71 still has the potential to cause a large outbreak such as that in taiwan in 1998, in which there were many fatalities. in this study, we determined the neurovirulence of ev71 by neuropathological analysis of cynomolgus monkeys after experimental infection with five ev71 strains, which w ...	2002	11992581
incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak in taiwan.	in 1998, an epidemic of hand-foot-and-mouth disease and herpangina caused by enterovirus 71 occurred in taiwan, leaving many fatalities and severely handicapped survivors in its wake. the reasons this rather common pathogen would cause such a large-scale epidemic remain unknown. a seroepidemiological survey to elucidate the epidemiological characteristics of this outbreak, including its incidence and case-fatality rates was undertaken. microneutralization tests for antibodies against enterovirus ...	2002	11992582
an overview of the evolution of enterovirus 71 and its clinical and public health significance.	since its discovery in 1969, enterovirus 71 (ev71) has been recognised as a frequent cause of epidemics of hand-foot-and-mouth disease (hfmd) associated with severe neurological sequelae in a small proportion of cases. there has been a significant increase in ev71 epidemic activity throughout the asia-pacific region since 1997. recent hfmd epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary oedema and high case-fatality rates. the ...	2002	12007645
[aseptic meningitis syndrome due to enterovirus and leptospira sp in children of salvador, bahia].	for the purpose of identifying the frequency that enterovirus, leptospires, arbovirus cause aseptic meningitis syndrome (ams) during non-epidemic periods and comparing patients with and without laboratory evidence for an etiologic agent, 112 patients were selected aged between 3 months and 15 years and a clinical suspicion of ams and were referred to couto maia hospital, the infectious and parasitic disease reference center for salvador, bahia. in 44.6% (n=50), the etiologic agent for the diagno ...	2002	12011925
pulmonary oedema, encephalitis and retroauricular vesicular rash in a 9-month-old infant. enterovirus 71 infection complicated by pulmonary oedema and encephalitis.		2002	12014399
infection with enterovirus 71 or expression of its 2a protease induces apoptotic cell death.	enterovirus 71 (ev71) is the causative agent of human diseases with distinct severity, from mild hand-foot-and-mouth disease to severe neurological syndromes, such as encephalitis and meningitis. infection of several different cell lines with ev71 causes extensive cytopathic effect, leading to destruction of the entire monolayer and the death of infected cells. in this study, cell death processes during ev71 infection and the underlying mechanisms of them were investigated. the hallmarks of apop ...	2002	12029152
differential display rt-pcr analysis of enterovirus-71-infected rhabdomyosarcoma cells reveals mrna expression responses of multiple human genes with known and novel functions.	in order to better understand cellular responses to viral infection at the transcriptional level, we employed differential display rt-pcr to analyze mrnas from rd rhabdomyosarcoma cells following infection with a neurovirulent enterovirus 71 (ev71) strain, compared with mrnas from uninfected cells. of 250 expressed sequence tags (ests) isolated, sequenced, and identified, all were of cellular origin except 1 that was of viral origin. of these, 156 were individual distinctive clones, comprising 4 ...	2002	12033773
risk factors of enterovirus 71 infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in taiwan.	in 1998, an enterovirus 71 (ev71) epidemic in taiwan was associated with hand, foot, and mouth disease (hfmd)/herpangina and involved 78 fatal cases. we measured ev71 seroprevalence rates before and after the epidemic and investigated risk factors associated with ev71 infection and illness.	2002	12042582
characterization of a vero cell-adapted virulent strain of enterovirus 71 suitable for use as a vaccine candidate.	enterovirus 71 (ev71) is a neurotrophic virus that causes seasonal morbidity and mortality in children throughout the world with increasing frequency in recent years. because of the lack of an effective antiviral agent, primary prevention, including the development of effective vaccines, is a top priority in terms of control strategies. poliovirus vaccine technology, both live attenuated and inactivated, killed virus vaccines, can be adopted for use with ev71 because of their relatedness. in thi ...	2002	12057603
[the usefulness of human lung embryonal fibroblast cells (mrc-5) for isolation of enteroviruses and adenoviruses].	although various cell lines have been used for virus isolation, few study of virus isolation using mrc-5 cell, a human embryonic lung fibroblasts, have been reported in japan. mrc-5 and other cell lines (caco-2, vero, rd-18s, llc-mk2, hela, mdck, fl, b95a and hmv-ii), and suckling mouse were compared for isolation of viruses from clinical specimens. a total of 3,284 specimens, collected from clinics and hospitals in saitama prefecture between july 1997 and august 2001, were inoculated in these c ...	2002	12136651
direct detection of enterovirus 71 (ev71) in clinical specimens from a hand, foot, and mouth disease outbreak in singapore by reverse transcription-pcr with universal enterovirus and ev71-specific primers.	a recent outbreak of hand, foot, and mouth disease in singapore in 2000 affected several thousand children and resulted in four deaths. the aim of this study was to determine the applicability of reverse transcription-pcr (rt-pcr) with universal pan-enterovirus primers and enterovirus 71 (ev71) type-specific primers for the direct detection of enteroviruses in clinical specimens derived from this outbreak. with the universal primers, ev71 rna sequences were successfully detected by rt-pcr and di ...	2002	12149336
different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy.	the mechanism of pulmonary oedema, a life-threatening manifestation of enterovirus 71 (ev71) encephalitis, is unclear. our aim was to assess the relationship of proinflammatory cytokines to ev71-related pulmonary oedema.	2002	12162592
seroepidemiology of human enterovirus 71, singapore.	human enterovirus 71 has caused outbreaks in many parts of the world, especially southeast asia, with some fatal cases. the epidemiology of this viral infection is not well understood. we conducted a serologic survey in singapore children, and the results indicate that infection occurs largely in preschool settings.	2002	12194783
lactoferrin inhibits enterovirus 71 infection of human embryonal rhabdomyosarcoma cells in vitro.	enterovirus 71 (ev71), the newest member of enterovirudae, is notable for its etiological role in epidemics of severe neurological diseases in children. it appears to be emerging as an important virulent neurotropic enterovirus in the upcoming era of poliomyelitis eradication, whereas no effective vaccine or antiviral agents are available at this moment. human and bovine lactoferrins, iron-binding proteins belonging to the nonimmune defense system, were assayed in vitro to assess their inhibitin ...	2002	12355368
responses of igm for enterovirus 71 infection.	a rapid serological assay was developed for detection of specific igm to enterovirus 71, a human picornavirus that is usually associated with severe central nervous system complications. the sensitivity and specificity of this "in-house" mu-capture enzyme linked-immunosorbent assay was assessed by testing 213 serum samples. with the conventional virus culture as a standard method, the sensitivity and specificity were 91.5 and 93.1%, respectively, for this newly developed immunoassay. this method ...	2002	12376966
favorable outcome in a case of perinatal enterovirus 71 infection.	a 5-day-old newborn baby presented with skin eruption, oral vesicles, and fever. his mother developed skin eruption at the same time, and his four-year-old sister was diagnosed with hand-foot-mouth disease 1 week before his delivery. enterovirus 71 was isolated from cerebrospinal fluid that showed mild pleocytosis. this rare case of virology documented perinatal enterovirus 71 infection recovered without sequelae.	2002	12380593
rapid serological diagnosis of enterovirus 71 infection by igm elisa.		2002	12403913
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 ...	2002	12437029
left ventricular dysfunction and treatment of fulminant enterovirus 71 infection.		2002	12439812
molecular identification and typing of enteroviruses isolated from clinical specimens.	enterovirus characterization and typing require an integrated technological approach, using both immunological and molecular methods. the seventy-nine enteroviruses included in this study were isolated from cell cultures and classified as enteroviruses on the basis of an indirect immunofluorescence assay (ifa) against common enterovirus antigens and a neutralization test based on the lim benyesh-melnick (lbm) pool. the final identification was carried out using a number of different molecular ap ...	2002	12454151
complete sequence analyses of enterovirus 71 strains from fatal and non-fatal cases of the hand, foot and mouth disease outbreak in singapore (2000).	enterovirus 71 (ev71) is a major aetiological agent of hand, foot and mouth disease (hfmd). in recent years, several outbreaks in east asia were associated with neurological complications and numerous deaths. an outbreak in singapore in october 2000 afflicted thousands of children, resulting in four fatal cases from three of whom ev71 was isolated. the genomes of two representative ev71 strains isolated from a fatal case and a surviving patient were completely sequenced, and their nucleotide and ...	2002	12516778
change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in taiwan between 1998 and 2000.	two outbreaks of hand-foot-and-mouth disease (hfmd) occurred in taiwan between 1998 and 2000. enteroviruses were isolated from a total of 1,892 patients in this laboratory during this period. of the virus isolates, enterovirus 71 (ev71) was diagnosed in 44.4% of the patients (132 of 297) in 1998, 2% (13 of 646) in 1999, and 20.5% (195 of 949) in 2000. genetic analyses of the 5'-untranslated and vp1 regions of ev71 isolates by reverse transcription-pcr and sequencing were performed to understand ...	2002	11773085
molecular phylogeny and proposed classification of the simian picornaviruses.	the simian picornaviruses were isolated from various primate tissues during the development of general tissue culture methods in the 1950s to 1970s or from specimens derived from primates used in biomedical research. twenty simian picornavirus serotypes are recognized, and all are presently classified within the enterovirus genus. to determine the phylogenetic relationships among all of the simian picornaviruses and to evaluate their classification, we have determined complete vp1 sequences for ...	2002	11773400
hand, foot and mouth disease: university malaya medical centre experience.	the prevalence of hfmd as well as the causative agents was unknown in peninsular malaysia prior to may 1997. from may 1997 to june 2001, 585 patients suspected to have enterovirus infections, with 467 patients clinically diagnosed as having hfmd, were investigated in the diagnostic virology unit of the university malaya medical centre. data from this study showed that hfmd is endemic in malaysia with the occurrence of two outbreaks during the study period. in each outbreak, a number of viruses w ...	2002	14569723
the hand, foot and mouth disease virus capsid: sequence analysis and prediction of antigenic sites from homology modelling.	enterovirus 71 (ev71) is the most common aetiological agent detected in cases of hand, foot and mouth disease (hfmd) resulting in incidences of neurological complications and fatality in recent years. a comparison of the capsid proteins implicated in the pathogenicity of the fatal and non-fatal strains of ev71, reveals a high degree of homology (93%-100% identity). to facilitate diagnostic immunoassays and vaccine development, a consensus structural model for the ev71 coat protein has been devel ...	2002	15130856
evaluation of a one-tube rt-pcr system for detection of enteroviruses.	a highly sensitive pcr assay for early and rapid detection of enteroviral (ev) rna in csf is necessary to investigate the role of ev in acute neurological illnesses.	2002	11744425
echovirus 7 associated encephalomyelitis.	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 taiw ...	2002	11595594
emerging and re-emerging diseases in malaysia.	emerging and re-emerging infectious diseases have become a major global problem. malaysia appears to be an epicenter for such infections and in recent years, several outbreaks have occurred resulting in loss of lives and economic hardships. in this paper, we discussed the outbreaks of leptospirosis, enterovirus 71 encephalitis, chikungunya polyarthritis and nipah encephalitis and how a developing country such as malaysia managed the situation with the help of international agencies and organisat ...	2002	12597511
pulmonary edema of enterovirus 71 encephalomyelitis is associated with left ventricular failure: implications for treatment.	epidemics of enterovirus 71 infections caused the rapid death of many children in malaysia in 1997 and in taiwan in 1998. pulmonary edema occurred in most of the fatal cases and was considered to be neurogenic. the role of the heart was rarely investigated before. between january 1998-january 2001, 34 consecutive patients who were admitted to the intensive care unit due to enterovirus infection were studied prospectively. patients were divided into two groups: group i with pulmonary edema, and g ...	2003	12629622
comparative study of enterovirus 71 infection of human cell lines.	the cell tropism of enterovirus 71 (enteroviridae) in neuronal, glial and laryngeal cells. the 4643 strain, an enterovirus 71 isolate from a patient in taiwan, was used to infect three human cell lines representing neuronal cells (sk-n-sh, neuroblastoma), glial cells (u373mg, glioblastoma), and laryngeal cells (hep-2, larynx epidermoid carcinoma). immunofluorescent staining and transmission electron microscopy (tem) were used to detect mature enterovirus 71 4643 virions in these cell lines. the ...	2003	12629651
inhibition of enterovirus 71-induced apoptosis by allophycocyanin isolated from a blue-green alga spirulina platensis.	enterovirus 71 infection causes significant morbidity and mortality in children, yet there is no effective treatment. in this study, a protein-bound pigment, allophycocyanin purified from blue-green algae is first reported to exhibit anti-enterovirus 71 activity. allophycocyanin neutralized the enterovirus 71-induced cytopathic effect in both human rhabdomyosarcoma cells and african green monkey kidney cells. the 50% inhibitory concentration of allophycocyanin for neutralizing the enterovirus 71 ...	2003	12629652
enterovirus 71 outbreaks, taiwan: occurrence and recognition.	enterovirus 71 (ev71) caused a large outbreak in taiwan in 1998 with 78 deaths, and smaller outbreaks recurred in 2000 and 2001. the outbreak was recognized because of a large number of hand, foot, and mouth disease cases and the rapid deaths of children with the disease. virologic and pathologic studies indicated that ev71 was the most important agent related to severe and fatal cases and that a neurogenic inflammatory response was involved in the pathogenesis of cardiopulmonary collapse result ...	2003	12643822
sequencing of 'untypable' enteroviruses reveals two new types, ev-77 and ev-78, within human enterovirus type b and substitutions in the bc loop of the vp1 protein for known types.	the n-terminal part of vp1 was sequenced for 43 enterovirus isolates that could not initially be neutralized with lbm pools or in-house antisera. most isolates were found to belong to human enterovirus type a (hev-a) and hev-b (18 isolates of each). all hev-a isolates could be typed by sequencing, with cv (coxsackievirus)-a16 and ev (enterovirus)-71 being dominant (nine and seven isolates, respectively). these types thus seem to have diverged more from their prototypes than the other types. amon ...	2003	12655083
molecular epidemiology of human enterovirus 71 strains and recent outbreaks in the asia-pacific region: comparative analysis of the vp1 and vp4 genes.	this study provides a comprehensive overview of the molecular epidemiology of human enterovirus 71 (hev71) in the asia-pacific region from 1997 through 2002. phylogenetic analysis of the vp4 and vp1 genes of recent hev71 strains indicates that several genogroups of the virus have been circulating in the asia-pacific region since 1997. the first of these recent outbreaks, described in sarawak (malaysian borneo) in 1997, was caused by genogroup b3. this outbreak was followed by large outbreaks in ...	2003	12702227
reduced frequency of hla drb103-dqb102 in children with type 1 diabetes associated with enterovirus rna.	enteroviruses have been associated with type 1 diabetes mellitus (t1dm), but it is unclear whether there is a distinct disease subtype. plasma and stool samples from 206 consecutively diagnosed children and 160 healthy control children were analyzed by reverse-transcription polymerase chain reaction for the rna of 60 enteroviruses. more children with diabetes tested positive for enterovirus rna (30% vs. 4%; odds ratio, 11.1; 95% confidence interval, 4.7-25.7; p<.001). enterovirus 71 was detected ...	2003	12721936
survival after pulmonary edema due to enterovirus 71 encephalitis.	a distinctive pattern of enterovirus 71 (ev71) infection, characterized by fever, exanthem, acute pulmonary edema (pe), brainstem encephalitis, and flaccid paresis, affects infants and young children. most die rapidly owing to respiratory failure and fulminant pe.	2003	12771257
cardiac troponin i: a reliable marker and early myocardial involvement with meningoencephalitis after fatal enterovirus-71 infection.	a major outbreak of enterovirus 71 (ev71) in taiwan in 1998 caused many severe cases and 78 deaths. our purpose was to find reliable markers and early indicators of fatal ev71 central nervous system (cns) infection.	2003	12799149
serotype-specific detection of enterovirus 71 in clinical specimens by dna microchip array.	enterovirus 71 is an important pathogen that causes high morbidity and mortality in children in taiwan. virus isolation in cell cultures has been the standard method for enterovirus 71 identification in clinical virology laboratories. however, virus isolation takes 5-10 days when using cell culture. a microchip for enterovirus 71 detection was developed as an alternative diagnostic method. the novel approach is based on hybridization of amplified dna specimens with oligonucleotide dna probes imm ...	2003	12821197
molecular epidemiology of enterovirus 71 in peninsular malaysia, 1997-2000.	human enterovirus 71 (ev71) (genus enterovirus, family picornaviridae) has been responsible for sporadic cases and outbreaks of hand-foot-and-mouth disease (hfmd), aseptic meningitis, encephalitis and poliomyelitis-like disease in europe, the u.s.a., australia and asia. recently, there has been an increase in ev71 activity in the asia-pacific region, with many outbreaks of hfmd associated with brainstem encephalitis manifesting as neurogenic pulmonary oedema with a high case fatality rate. in 19 ...	2003	12827466
neurogenic pulmonary edema in enterovirus 71 encephalitis is not uniformly fatal but causes severe morbidity in survivors.	during the australian summer of 2000/2001, there was an outbreak of enterovirus 71 infection in sydney. between december 2000 and may 2001, approximately 200 children presented to sydney children's hospital with hand-foot-and-mouth disease and 18 experienced neurologic complications. four presented with acute invasive central nervous system disease and severe pulmonary edema. we describe the cardiorespiratory disturbances and intensive care management of these four consecutive children successfu ...	2003	12831425
hepatic failure in a newborn with maternal peripartum exposure to echovirus 6 and enterovirus 71.		2003	12851816
clinical characteristics of an outbreak of hand, foot and mouth disease in singapore.	we experienced a hand, foot and mouth disease (hfmd) outbreak in late year 2000 in singapore. between 14 september 2000 and 14 november 2000, a total of 3526 cases of hfmd were notified. there were 652 patients clinically suspected to have hfmd, who were seen at the children's emergency department of kk women's and children's hospital of singapore.	2003	12854382
exotic and emerging viral encephalitides.	the exotic and emerging viral encephalitides are caused by animal or human viruses and characterised by sudden unexpected outbreaks of neurological disease, usually in tropical and sub-tropical regions, but sometimes spreading to temperate areas. although a wide range of viruses come within this label, as this review highlights, there are common research questions as to the origin and spread of the viruses, the contribution of viral and host factors to the clinical presentations and outcome, and ...	2003	12858080
frequency, viral loads, and serotype identification of enterovirus infections in scottish blood donors.	enteroviruses are non-enveloped, frequently pathogenic rna viruses infecting humans. infection is potentially transmissible through blood or blood component transfusion from donor in the viremic phase before seroconversion for antibody. to investigate the threat to blood safety from enteroviruses, a large-scale survey of frequency and levels of viremia in blood donors was conducted. study designs and methods: blood donations from scotland over a period of 22 calendar months were screened for ent ...	2003	12869111
formation of enterovirus-like particle aggregates by recombinant baculoviruses co-expressing p1 and 3cd in insect cells.	the assembly of enterovirus requires the cleavage of p1 polyprotein by protease 3cd into individual structural proteins. two recombinant baculoviruses were constructed to encode p1 and 3cd of enterovirus 71 (ev71), respectively. the expressed 3cd successfully cleaved p1 in vitro and in vivo. also, the co-infection in insect cells resulted in crystalline virus-like particle structures morphologically resembling the authentic ev71 aggregates, which are reported for the first time.	2003	12889824
pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema.	taiwan experienced several epidemics of enterovirus 71 (ev71) infections, which were associated with brainstem encephalitis (be) and pulmonary edema (pe). to elucidate the role of immune mechanisms in the pathogenesis of be caused by ev71 and its fatal complication, pe, we analyzed the laboratory findings, cytokine, and immunophenotypes of 73 ev71-infected patients with be. patients were stratified by disease: pe (n=14), autonomic nervous system (ans) dysregulation (n=25), and isolated be (n=34) ...	2003	12898444