人类肠病毒EV71文献汇编（更新中）
现在凡事都得讲循证医学，感控也不例外哦:lol实验诊断篇
J Clin Virol. 2008 Feb 25 Links
Rapid detection of Enterovirus 71 by real-time TaqMan RT-PCR.
用real-time TaqMan RT-PCR快速检测肠病毒EV71
Tan EL, Yong LL, Quak SH, Yeo WC, Chow VT, Poh CL.
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; School of Chemical and Life Sciences, Singapore Polytechnic, Singapore 139651, Singapore.
BACKGROUND: Enterovirus 71 (EV71) is the main etiological agent of Hand, Foot and Mouth Disease (HFMD) and has been associated with neurological complications which resulted in fatalities during recent outbreaks in Asia Pacific region. OBJECTIVE: Develop a real-time TaqMan RT-PCR for rapid detection of EV71. STUDY DESIGN: Specific primers and probe were designed based on highly conserved VP1 region of EV71. The sensitivity of the real-time RT-PCR was evaluated with 67 clinical specimens collected from pediatric patients with suspected HFMD. RESULTS: Our real-time TaqMan RT-PCR showed 100% specificity in detecting EV71 and showed an analytical sensitivity of 5 viral copies. High sensitivity was also achieved in detecting EV71 directly from clinical specimens. CONCLUSIONS: Real-time TaqMan RT-PCR offers a rapid and sensitive method to detect EV71 from clinical specimens, and will allow quarantine measures to be taken more effectively during outbreaks.
Microbiol Immunol. 2002;46(11):801-8. Links
Complete sequence analyses of enterovirus 71 strains from fatal and non-fatal cases of the hand, foot and mouth disease outbreak in Singapore (2000).
新加坡手足口病暴发的肠病毒EV71全序列分析
Singh S, Poh CL, Chow VT.
Programme in Infectious Diseases, Department of Microbiology, Faculty of Medicine, National University of Singapore, 5 Science Drive 2, Kent Ridge, Singapore 117597.
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 amino acid sequences compared with known EV71 strains. The two outbreak strains were classified under genogroup B, together with those previously isolated in Singapore, Malaysia and Japan. Comparative sequence analysis of the two Singapore strains revealed 99% nucleotide similarity, while their deduced amino acid sequences were almost identical except for residue 1506 in the 3A non-structural region. Given that the outbreak involved closely related genetic variants of EV71, the broad spectrum of disease severity may be attributed to critical factors such as varying viral inoculation doses or differing host immune responses following infection, but is less likely to be due to the emergence of EV71 strains with heightened virulence.
J Clin Microbiol. 2002 Aug;40(8):2823-7.Links
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.
用RT-PCR直接检测临床标本中的肠病毒EV71
Singh S, Chow VT, Phoon MC, Chan KP, Poh CL.
Programme in Infectious Diseases, Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore 117597.
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 direct sequencing in 71% of positive specimens. Three pairs of EV71 type-specific primers were evaluated for rapid detection of EV71 directly from clinical specimens and cell culture isolates. By using a seminested RT-PCR strategy, specific identification of EV71 sequences directly in clinical specimens was achieved, with a detection rate of 53%. In contrast, cell culture could isolate EV71 in only 20% of positive specimens. EV71 was detected directly from brain, heart, and lung specimens of two deceased siblings. Although more than one type of enterovirus was identified in clinical specimens from this outbreak, 90% of the enteroviruses were confirmed as EV71. The data demonstrate the clinical applicability of pan-enterovirus and seminested RT-PCR for the detection of EV71 RNA directly from clinical specimens in an outbreak situation.
Scand J Infect Dis. 2002;34(2):104-9.Links
Clinical manifestations and laboratory assessment in an enterovirus 71 outbreak in southern Taiwan.
台湾南部肠病毒EV71暴发后的临床表现和实验室评估
Li CC, Yang MY, Chen RF, Lin TY, Tsao KC, Ning HC, Liu HC, Lin SF, Yeh WT, Chu YT, Yang KD.
Division of Pediatric Infectious Diseases, Chang Gung Children's Hospital, Kaohsiung, 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 (23/33), vomiting (10/33), ataxia (7/33), lethargy (6/33), seizure (4/33) and tremor (2/33). Patients with CNS involvement had longer durations of fever (4.6+/-0.2 vs. 3.1+/-0.3 d; p <0.01) and a higher white blood cell count (12,512+/-658 vs. 10,607+/-409 cells/mm3; p = 0.01) than patients without CNS involvement. The case fatality rate in patients with CNS involvement was 4/33 (12%), whereas no fatalities (0/57) occurred in patients without CNS involvement. Six of 11 patients subjected to MRI showed a high intensity T2-weighted signal in the brainstem. A nested fluorescent RT-PCR for detection of virus in throat and stool specimens showed higher sensitivity than viral culture. Viremia was detectable using RT-PCR in 20% of cases (3/15), whereas no virus was isolated from culture or detected by RT-PCR in cerebrospinal fluid.
J Clin Virol. 2000 Aug;17(2):91-9. Links
An outbreak of enterovirus 71 infection in Taiwan, 1998. II. Laboratory diagnosis and genetic analysis.
1998年台湾肠病毒暴发感染：实验室诊断和基因型分析
Wang JR, Tsai HP, Chen PF, Lai YJ, Yan JJ, Kiang D, Lin KH, Liu CC, Su IJ.
Department of Medical Technology, National Cheng Kung University, Tainan, Taiwan, ROC. jrwang@mail.ncku.edu.tw
BACKGROUND: 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. OBJECTIVES: To analyze laboratory findings in the EV71 epidemic of 1998 in Taiwan, various EV71 specimens in different cell lines were examined. In addition, genetic analysis of 5' non-coding region (NCR) was performed to analyze the strain variation in this outbreak. RESULTS: The cytopathic effect induced by EV71 was observed 2-13 (mean of 4.5) days post-inoculation in Vero cells and 4-15 (mean of 6.6) days in green monkey kidney (GMK) cells inoculated with throat swabs. Of the total positive EV71 cases, virus was most frequently obtained from throat swabs (91.7%), less from stools (64.8%), and none from cerebral spinal fluid (CSF). Molecular analyses of EV71 by sequencing the 5' NCR of 34 strains obtained from different clinical categories and various geographic areas showed that their sequences differed (0-13 bp in 681 bp sequenced) by approximately 0-2%. The sequences of these isolates differed from EV71 prototype BrCr or MS strain by 17.5-19%, with the exception of two samples which exhibited nucleotide variation by only 8.9 and 8.2%, when compared to the MS strain. CONCLUSION: EV71 was most frequently isolated from throat swab specimens in Vero cells. The molecular analyses of the 5' NCR of EV71 revealed that most isolates from this epidemic belonged to a group of closely related clones and only two were in a different group which was clustered with the EV71 MS strain.
Virus Res. 2000 Jul;68(2):127-36. Links
Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998.
1998年台湾肠病毒EV71暴发基因型分析
Shih SR, Ho MS, Lin KH, Wu SL, Chen YT, Wu CN, Lin TY, Chang LY, Tsao KC, Ning HC, Chang PY, Jung SM, Hsueh C, Chang KS.
School of Medical Technology, Chang Gung University, 259, Wen-Hua 1st Road, Kwei-Shan, 333, Tao-Yuan, Taiwan, ROC.
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 comparatively. Phylogenetic analysis of both VP1 and 5'-NCR of nine EV71 isolates derived from specimens of fatal patients and seven isolates derived from uncomplicated HFMD patients showed that all but one isolate fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD belonged to genotype C that was clustered along with one isolate from Taiwan in 1986. Complete sequence analysis of two selected isolates, one from the spinal cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD, confirmed a high degree (97-100%) of identity in nucleotide sequence throughout the entire genome, except focal regions of 3C and 3'-NCR where the nucleotide homology was 90-91%. The identity of the deduced amino acid sequence in the 3C region that encodes viral proteinase dropped further to 86%, a result of missense mutations at the first nucleotide position of many codons.
Scand J Infect Dis. 1999;31(4):331-5.Links
Molecular detection of enteroviruses from an outbreak of hand, foot and mouth disease in Malaysia in 1997.
1997年马来西亚手足口病暴发相关的肠病毒分子检测
Abubakar S, Chee HY, Shafee N, Chua KB, Lam SK.
Department of Medical Microbiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
Enterovirus 5'UTR sequences were detected by RT-PCR in 22 out of 47 suspected hand, foot and mouth disease (HFMD) patients during an outbreak of the disease with incidences of fatal brainstem encephalomyelitis in Malaysia in 1997. Genetic and phylogenetic analyses of the isolates 5'UTR sequences suggest the presence of predominantly enteroviruses with high sequence similarities to Echovirus 1 and Coxsackievirus A9 in the Malaysian peninsula. No fatal cases, however, were associated with these isolates. The remaining isolates, including all (4/4) isolates of the fatal cases from the Malaysian peninsula and Sarawak shared very high sequence identity with enterovirus 71MS (EV71). These findings suggest that several enteroviruses were circulating in Malaysia during the outbreak period, with only EV71 causing fatal infections.
J Clin Microbiol. 2006 Nov;44(11):4095-100. Epub 2006 Aug 30.Links
High prevalence of human enterovirus a infections in natural circulation of human enteroviruses.
人类肠病毒高致病流行株是哪些
Witsø E, Palacios G, Cinek O, Stene LC, Grinde B, Janowitz D, Lipkin WI, Rønningen KS.
Norwegian Institute of Public Health, Oslo, Norway. elisabet.witso@fhi.no
Human enterovirus (HEV) infections can be asymptomatic or cause only mild illness; recent evidence may implicate HEV infection in type 1 diabetes mellitus and myocarditis. Here, we report the molecular characterization of HEV obtained in serial monthly collections from healthy Norwegian infants. A total of 1,255 fecal samples were collected from 113 healthy infants beginning at age 3 months and continuing to 28 months. The samples were analyzed for HEV nucleic acid by real-time PCR. Fifty-eight children (51.3%) had HEV infections. One hundred forty-five positive samples were typed directly by nucleotide sequencing of the VP1 region. HEV-A was detected most frequently, with an overall prevalence of 6.8%. HEV-B was present in 4.8% of the samples and HEV-C in only 0.2% of the samples. No poliovirus or HEV-D group viruses were detected. Twenty-two different serotypes were detected in the study period: the most common were EV71 (14.5%), CAV6 (10.5%), CAV4 (8.9%), E18 (8.9%), and CBV3 (7.3%). These findings suggest that the prevalence of HEV infections in general, and HEV-A infections in particular, has been underestimated in epidemiological studies based on virus culture.
Diagn Microbiol Infect Dis. 2008 Apr 2 Links
Development of multiplex real-time hybridization probe reverse transcriptase polymerase chain reaction for specific detection and differentiation of Enterovirus 71 and Coxsackievirus A16.
实时多重RT-PCR检测肠病毒EV71
Tan EL, Tak Kwong Chow V, Quak SH, Yeo WC, Poh CL.
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597; School of Chemical and Life Sciences, Singapore Polytechnic, Singapore 139651.
Large outbreaks of hand, foot, and mouth disease have been reported in the Asia Pacific region over the last few years and resulted in significant fatalities. The 2 main etiologic agents are Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16). Both viruses are closely related genetically and show similar clinical symptoms. However, EV71 are associated with neurologic complications and can lead to fatalities. In this study, we developed a multiplex real-time hybridization probe reverse transcriptase polymerase chain reaction to detect and differentiate EV71 from CA16 using the LightCycler (Roche Molecular Biochemicals). Specific primers and hybridization probes were designed based on highly conserved VP1 region of EV71 or CA16. Our results showed high specificity and sensitivities in detecting EV71 or CA16 from 67 clinical specimens, and no other enterovirus serotype was detected. Rapid diagnosis to differentiate EV71 from CA16 in outbreak situations will enable pediatricians to identify and manage the patients more effectively.
J Clin Microbiol. 2007 Jun;45(6):1858-66. Epub 2007 Apr 19.Links
Evaluation of different clinical sample types in diagnosis of human enterovirus 71-associated hand-foot-and-mouth disease.
诊断人类肠病毒EV71时不同临床标本的评价
Ooi MH, Solomon T, Podin Y, Mohan A, Akin W, Yusuf MA, del Sel S, Kontol KM, Lai BF, Clear D, Chieng CH, Blake E, Perera D, Wong SC, Cardosa J.
Department of Paediatrics, Sibu Hospital, Ulu Oya Road, 96000 Sibu, Sarawak, Malaysia. monghow@pd.jaring.my
Human enterovirus 71 and coxsackievirus A16 are important causes of hand-foot-and-mouth disease (HFMD). Like other enteroviruses, they can be isolated from a range of sterile and nonsterile sites, but which clinical sample, or combination of samples, is the most useful for laboratory diagnosis of HFMD is not clear. We attempted virus culture for 2,916 samples from 628 of 725 children with HFMD studied over a 3 1/2-year period, which included two large outbreaks. Overall, throat swabs were the single most useful specimen, being positive for any enterovirus for 288 (49%) of 592 patients with a full set of samples. Vesicle swabs were positive for 169 (48%) of 333 patients with vesicles, the yield being greater if two or more vesicles were swabbed. The combination of throat plus vesicle swabs enabled the identification of virus for 224 (67%) of the 333 patients with vesicles; for this patient group, just 27 (8%) extra patients were diagnosed when rectal and ulcer swabs were added. Of 259 patients without vesicles, use of the combination of throat plus rectal swab identified virus for 138 (53%). For 60 patients, virus was isolated from both vesicle and rectal swabs, but for 12 (20%) of these, the isolates differed. Such discordance occurred for just 11 (10%) of 112 patients with virus isolated from vesicle and throat swabs. During large HFMD outbreaks, we suggest collecting swabs from the throat plus one other site: vesicles, if these are present (at least two should be swabbed), or the rectum if there are no vesicles. Vesicle swabs give a high diagnostic yield, with the added advantage of being from a sterile site.
[ 本帖最后由 David 于 2008-4-29 14:19 编辑 ]
以往暴发案例篇
Emerg Infect Dis. 2003 Mar;9(3):291-3. Links
Enterovirus 71 outbreaks, Taiwan: occurrence and recognition.
台湾肠病毒EV71暴发
Lin TY, Twu SJ, Ho MS, Chang LY, Lee CY.
Chang Gung University, Taoyuan, Taiwan.
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 resulting from fulminant EV71 infection. Seroepidemiologic study suggested that EV71 had circulated for at least 16 years and that the accumulation of susceptible hosts might have triggered the 1998 outbreak. However, a change in EV71 neurovirulence and host genetic susceptibility may also have affected the clinical outcome. The Taiwan outbreak shows that worldwide attention should be paid to such outbreaks, new antiviral drugs should be developed, and that vaccination of children under 5 years of age may be warranted.
Microbiol Immunol. 2002;46(9):621-7. Links
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.
日本肠病毒EV71 暴发
Fujimoto T, Chikahira M, Yoshida S, Ebira H, Hasegawa A, Totsuka A, Nishio O.
Infectious Disease Research Division, Hyogo Prefectural Institute of Public Health and Environmental Sciences, Kobe, Japan. fujimo@iph.pref.hyogo.jp
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.
Clin Infect Dis. 2002 May 1;34 Suppl 2:S52-7. Links
The 1998 enterovirus 71 outbreak in Taiwan: pathogenesis and management.
1998年台湾肠病毒EV71暴发
Lin TY, Chang LY, Hsia SH, Huang YC, Chiu CH, Hsueh C, Shih SR, Liu CC, Wu MH.
Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan. pidlin@adm.cgmh.org.tw
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 the central nervous system and causes neurogenic pulmonary edema and cardiac decompensation through the mechanism of sympathetic hyperactivity and inflammatory responses. Early recognition of risk factors and intensive care are crucial to successful treatment of this fulminant infection. After poliovirus is eradicated, EV71 will become the most important enterovirus that affects children, and development of a vaccine may be the only effective measure against it.
J Clin Virol. 2000 Jun;17(1):23-30. Links
An outbreak of enterovirus 71 infection in Taiwan, 1998: epidemiologic and clinical manifestations.
1998年台湾肠病毒EV71感染暴发：流行病学和临床特征
Liu CC, Tseng HW, Wang SM, Wang JR, Su IJ.
Department of Pediatrics, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan, Taiwan, ROC. liucc@mail.ncku.edu.tw
BACKGROUND: 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). OBJECTIVES: This study is aimed to characterize and analyze the epidermologic and clinical features during the outbreak. STUDY DESIGN: The epidemiologic information was collected from the Ministry of Health on passive surveillance; clinical and virological investigations were carried out at National Cheng Kung University Medical Center. RESULTS: Between April and December 1998, 405 children were hospitalized, and 78 patients died during this outbreak in Taiwan. There were 119 cases identified to be EV71 infection in Tainan and Chiayi areas; 105 cases by virus isolation and 14 by serological assay. The outbreak had a biphasic curve with peak in June and October, especially in the southern Taiwan. Seventy-two percent of patients were below 3 years of age. The spectrum of disease included HFMD in 54, HFMD with central nerve system (CNS) involvement in 37, herpangina in 12, aseptic meningitis in three, encephalitis/ meningoencephalitis in ten, acute flaccid paralysis in three. There was nine fatal cases complicated with neurogenic pulmonary edema. Myoclonus with sleep disturbance was the most important early sign of EV71 infection with CNS involvement. CONCLUSION: Our experience demonstrated that the EV71 isolated in Taiwan had strong dermatotropic as well as neurotropic tendencies. Early detecting CNS involvement and commencing aggressive therapy may reduce the mortality.
J Clin Virol. 2000 Jun;17(1):13-22. Links
An outbreak of enterovirus 71 infection in Taiwan 1998: a comprehensive pathological, virological, and molecular study on a case of fulminant encephalitis.
1998年台湾肠病毒EV71感染暴发：对一个爆发性脑炎的病理学，病毒学和分子生物学研究
Yan JJ, Wang JR, Liu CC, Yang HB, Su IJ.
Department of Pathology, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan, Taiwan.
BACKGROUND: In a recent enterovirus outbreak in Taiwan, serotype 71 was the culprit of encephalitis causing rapid clinical deterioration and death among young children. OBJECTIVES: Since knowledge of enterovirus 71 (EV71) infection in the central nervous system is still limited, the purpose of the present case study was attempted to uncover the pathogenesis of the virus. STUDY DESIGN: We performed a detailed pathological examination, virological and molecular studies on a case of EV71 infection with a rapidly fatal outcome. In addition, the whole genome of the virus was sequenced to determine the genetic relationships to other enteroviruses and two other EV71 strains (a prototype BrCr and a neurovirulent MS strain), and to provide the genetic basis of its neurovirulence of the new isolate, NCKU9822 strain. RESULTS: Characteristic features of acute encephalomyelitis were observed, with most prominent lesions in the spinal cord and brain stem. Mild myocarditis and pancreatitis were also noticed. EV71 antigen was localized to neurons on immunohistochemical staining. EV71 was recovered from all organs with inflammatory reaction. Sequence analysis showed that overall NCKU9822 and the two EV71 strains shared 80% nucleotide identity and 95% amino acid identity. It had only 45% amino acid and 52% nucleotide identities with polioviral P1 capsid region. CONCLUSION: The spinal cord and brain stem were the main targets of EV71 in the fatal cases in this outbreak, however, heart and pancreas might also be involved. Since the amino acid sequences in the P1 region are conserved (97% identity) among the three EV71 strains as compared to other enteroviruses and polioviruses, these EV71 neurovirulent strains might share the same mechanisms of neurovirulence, and the mechanisms might be different from those in polioviruses.
Emerg Infect Dis. 2007 Nov;13(11):1733-41.Links
Epidemiologic and virologic investigation of hand, foot, and mouth disease, southern Vietnam, 2005.
2005年越南南部手足口病的流行病学和病毒学调查
Tu PV, Thao NT, Perera D, Huu TK, Tien NT, Thuong TC, How OM, Cardosa MJ, McMinn PC.
Pasteur Institute, Ho Chi Minh City, Vietnam.
During 2005, 764 children were brought to a large children's hospital in Ho Chi Minh City, Vietnam, with a diagnosis of hand, foot, and mouth disease. All enrolled children had specimens (vesicle fluid, stool, throat swab) collected for enterovirus isolation by cell culture. An enterovirus was isolated from 411 (53.8%) of the specimens: 173 (42.1%) isolates were identified as human enterovirus 71 (HEV71) and 214 (52.1%) as coxsackievirus A16. Of the identified HEV71 infections, 51 (29.5%) were complicated by acute neurologic disease and 3 (1.7%) were fatal. HEV71 was isolated throughout the year, with a period of higher prevalence in October-November. Phylogenetic analysis of 23 HEV71 isolates showed that during the first half of 2005, viruses belonging to 3 subgenogroups, C1, C4, and a previously undescribed subgenogroup, C5, cocirculated in southern Vietnam. In the second half of the year, viruses belonging to subgenogroup C5 predominated during a period of higher HEV71 activity.
[ 本帖最后由 David 于 2008-4-29 13:03 编辑 ]
分子流行病学分型篇
Arch Virol. 2003 Jul;148(7):1369-85. Links
Molecular epidemiology of enterovirus 71 in peninsular Malaysia, 1997-2000.
马来西亚1997-2000年肠病毒EV71分子流行病学分型统计
Herrero LJ, Lee CS, Hurrelbrink RJ, Chua BH, Chua KB, McMinn PC.
Division of Virology, Telethon Institute for Child Health Research, Subiaco, WA, Australia. larah@ichr.uwa.edu.au
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 1997, and again in 2000, EV71 outbreaks occurred in peninsular Malaysia. Variations in VP1 gene sequences have been shown to divide all known EV71 field isolates into three distinct genogroups (A, B and C). Consequently we examined the VP1 gene sequences of 43 EV71 strains isolated in peninsular Malaysia between 1997 and 2000 in order to determine the genogroup prevalence over the period. In this study we show that four subgenogroups (B3, B4, C1 and C2) of EV71 circulated in peninsular Malaysia between 1997 and 2000. Subgenogroups B3, B4 and C1 have been identified as the primary cause of the outbreaks of EV71 in peninsular Malaysia. Subgenogroup C1 also displayed endemic circulation from 1997 to 2000 and subgenogroup C2 was present at a low level during the 1997 outbreak.
J Clin Microbiol. 2005 Dec;43(12):6171-5.Links
Frequent importation of enterovirus 71 from surrounding countries into the local community of Yamagata, Japan, between 1998 and 2003.
1998-2003年期间日本肠病毒EV71流行情况
Mizuta K, Abiko C, Murata T, Matsuzaki Y, Itagaki T, Sanjoh K, Sakamoto M, Hongo S, Murayama S, Hayasaka K.
Department of Microbiology, Yamagata Prefectural Institute of Public Health, Tokamachi 1-6-6, Yamagata, 990-0031 Japan. mizutak@pref.yamagata.jp
Phylogenetic analysis of 45 enterovirus 71 (EV71) isolates for 6 years in Yamagata, Japan, clarified that the annual outbreak of hand-foot-and-mouth disease was due to four genetically distinct subgenogroups, including a novel "B5." Our results suggest that the importation of EV71 from surrounding countries has had a major epidemiological impact on the local community used in our study.
J Med Virol. 2006 Feb;78(2):254-62. Links
Evolution of EV71 genogroup in Taiwan from 1998 to 2005: an emerging of subgenogroup C4 of EV71.
台湾1998-2005年肠病毒EV71基因型进化研究
Lin KH, Hwang KP, Ke GM, Wang CF, Ke LY, Hsu YT, Tung YC, Chu PY, Chen BH, Chen HL, Kao CL, Wang JR, Eng HL, Wang SY, Hsu LC, Chen HY.
Department of Clinical Laboratory, Kaohsiung Medical University, Kaohsiung City, Taiwan. kuhsli@ms3.hinet.net
In Taiwan, enterovirus 71 (EV71) has played an important role in severe enterovirus-related cases every year since the devastating outbreak in 1998. Three genogroups A, B, C occur worldwide; with the B and C genogroups being subdivided into B1-B4 and C1-C4 subgenogroups respectively. To understand the mutation of the EV71 genogroup in Taiwan before and after 1998, a total of 54 worldwide strains were studied including 41 Taiwanese strains obtained in 1986 and 1998-2004. A fragment of 207 bp of the VP4 region was amplified and sequenced. Genetic analysis was performed using MEGA software (version 3.0) for the nucleotide sequence alignment and phylogenetic analysis. In Taiwan, the subgenogroup B1 was predominant before 1998 while subgenogroup C2 was the major etiologic group in 1998 outbreak. A minor etiologic group outbreak in 1998, subgenogroup B4, became predominant during the period from 1999 to 2003. In this study, subgenogroup C4 emerged and became predominant in 2004 in Taiwan. The nucleotide differences between B1 and C2, C2 and B4, B4 and C4 were 20%-26%, 19%-27%, 18%-22%, respectively. Nucleotide sequence alignment revealed 67 substitutions. Most of the substitutions (62/67) were silent mutations. This is the first report about the emergence of EV71 subgenogroup C4 in Taiwan. Copyright 2005 Wiley-Liss, Inc.
Pediatr Infect Dis J. 2006 Aug;25(8):691-4. Links
Genetic diversity of enterovirus 71 associated with hand, foot and mouth disease epidemics in Japan from 1983 to 2003.
1983-2003年日本手足口病相关的肠病毒EV71基因多样性分析
Hosoya M, Kawasaki Y, Sato M, Honzumi K, Kato A, Hiroshima T, Ishiko H, Suzuki H.
Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan. mhosoya@fmu.ac.jp
BACKGROUND: Enterovirus 71 (EV71) is one of the major etiologic agents of hand, foot and mouth disease (HFMD). The surveillance data indicate that EV71 infection follows an epidemic mode of transmission, causing large outbreaks and then becoming quiescent for a few years. METHODS: We investigated the genetic diversity of a total of 121 EV71 strains isolated from patients with HFMD in Fukushima, Japan, from 1983 to 2003 and compared their genetic relation with the 164 EV71 strains isolated in the world using phylogenetic analysis based on the VP4 sequence. RESULTS: We observed EV71-related HFMD outbreaks in Fukushima in 1984, 1987, 1990, 1993, 1997, 2000 and 2003. Phylogenetic reconstruction of EV71 strains isolated in Fukushima demonstrated 8 genetically distinct clusters, including 6 subgroups previously designated as B-1, B-2 and 3, B-4, C-1, C-2, and C-3 and 2 subgroups newly designated as B-5 and C-4. Additional 2 indistinct clusters belonged to genogroup C and were named C-U1 and C-U2. Of those subgroups, B-1, C-U1, C-U2, C-2, B4, and C-4 and B-5 dominantly related to epidemics that occurred in the years 1984, 1987 and 1990, 1993, 1997, 2000 and 2003, respectively. EV71 strains derived from each outbreak in Fukushima formed a single cluster with those isolated during almost the same time period in other area of Japan and in other countries. CONCLUSIONS: Our results suggested that the repeated EV71 outbreaks might be the result of the worldwide transmission of the newly introduced genetically divergent EV71 strains.
Rev Med Virol. 2007 Nov-Dec;17(6):371-9. Links
Genetic evolution of enterovirus 71: epidemiological and pathological implications.
香港肠病毒EV71基因进化分析（中大微生物系做的哦）
Bible JM, Pantelidis P, Chan PK, Tong CY.
Infection and Immunology Delivery Unit, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Since its discovery in the 1970s, enterovirus 71 (EV71) has become one of the most pathogenic enterovirus serotypes causing recurrent outbreaks in different parts of the world. Three waves of outbreaks globally have been recorded over the last three decades and more recently active circulation of EV71 is evident amongst countries in South East Asia and beyond. There is evidence of a continuous evolution in its genetic make up which is likely to impact on its epidemiology and pathological potential. This review examines the molecular genetics and evolution of EV71 in relation to its epidemiological and pathological properties. A thorough understanding of the relationship between the genetic changes and the resulting host-virus interaction is essential for successful control. (c) 2007 John Wiley & Sons, Ltd.
J Clin Microbiol. 2002 Jan;40(1):10-5.Links
Change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in Taiwan between 1998 and 2000.
1998-2000年台湾肠病毒EV71的主要基因型改变
Wang JR, Tuan YC, Tsai HP, Yan JJ, Liu CC, Su IJ.
Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. jrwang@mail.ncku.edu.tw
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 the diversity of EV71 in these outbreaks of HFMD. Most EV71 isolates from the 1998 epidemic belonged to genotype C, while only one-tenth of the isolates were genotype B. Interestingly, all EV71 isolates tested from 1999 to 2000 belonged to genotype B. This study indicated that two genogroups of EV71 capable of inducing severe clinical illness have been circulating in Taiwan. Furthermore, the predominant EV71 genotypes responsible for each of the two major HFMD outbreaks within the 3-year period in Taiwan were different.
J Virol. 1999 Dec;73(12):9969-75.Links
Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998.
1970-1998年澳大利亚肠病毒EV71分子流行病学和基因进化分析
Brown BA, Oberste MS, Alexander JP Jr, Kennett ML, Pallansch MA.
Division of Viral Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333, USA. bzb2@cdc.gov
Enterovirus 71 (EV71) (genus Enterovirus, family Picornaviridae), a common cause of hand, foot, and mouth disease (HFMD), may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity and rate of evolution of EV71, we have determined and analyzed complete VP1 sequences (891 nucleotides) for 113 EV71 strains isolated in the United States and five other countries from 1970 to 1998. Nucleotide sequence comparisons demonstrated three distinct EV71 genotypes, designated A, B, and C. The genetic variation within genotypes (12% or fewer nucleotide differences) was less than the variation between genotypes (16.5 to 19.7%). Strains of all three genotypes were at least 94% identical to one another in deduced amino acid sequence. The EV71 prototype strain, BrCr-CA-70, isolated in California in 1970, is the sole member of genotype A. Strains isolated in the United States and Australia during the period from 1972 to 1988, a 1994 Colombian isolate, and isolates from a large HFMD outbreak in Malaysia in 1997 are all members of genotype B. Although strains of genotype B continue to circulate in other parts of the world, none have been isolated in the United States since 1988. Genotype C contains strains isolated in 1985 or later in the United States, Canada, Australia, and the Republic of China. The annual rate of evolution within both the B and C genotypes was estimated to be approximately 1.35 x 10(-2) substitutions per nucleotide and is similar to the rate observed for poliovirus. The results indicate that EV71 is a genetically diverse, rapidly evolving virus. Its worldwide circulation and potential to cause severe disease underscore the need for additional surveillance and improved methods to identify EV71 in human disease.
Pediatr Int. 2004 Apr;46(2):231-5. Links
Molecular epidemiology of enterovirus 71 infection in the Western Pacific Region.
西太平洋地区肠病毒EV71感染的分子流行病学分析
Shimizu H, Utama A, Onnimala N, Li C, Li-Bi Z, Yu-Jie M, Pongsuwanna Y, Miyamura T.
Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan. hshimizu@nih.go.jp
BACKGROUND: Recently, there have been large outbreaks of hand, foot and mouth disease (HFMD) mainly caused by enterovirus 71 (EV71) associated with severe neurological diseases in the Western Pacific Region (WPR). To monitor the realtime trend of EV71 transmission throughout the WPR, the authors conducted a molecular epidemiological analysis of EV71 infection. METHODS: Viruses were isolated from clinical samples from patients with HFMD or those with neurological complications. The EV71 isolates were identified by microneutralization assay. The VP4 and/or VP1 regions of recent EV71 isolates were sequenced and subjected to phylogenetic analysis using reference EV71 strains. RESULTS: The phylogenetic analysis of EV71 isolates from the WPR revealed two major genogroups, B and C, based on the nucleotide sequence alignment of the VP1 or VP4 region. These two major genogroups were further divided into subgenogroups, B1, B2, B3, and B4 and C1, C2, C3 and C4, respectively. CONCLUSIONS: The molecular epidemiological analyses of recent and previous EV71 isolates in the WPR indicated that two major genogroups of EV71 are co-circulating in Australia, Malaysia, Singapore, Taiwan and Japan. Recent EV71 isolates in Mainland China constitute a new distinct genetic cluster, subgenogroup C4. Two major lineages of EV71 are the major causative agents of the present HFMD epidemics in the WPR and both are considered to be neurovirulent.
Emerg Infect Dis. 2003 Apr;9(4):461-8. Links
Molecular epidemiology of human enterovirus 71 strains and recent outbreaks in the Asia-Pacific region: comparative analysis of the VP1 and VP4 genes.
亚太地区肠病毒EV71的分子流行病学
Cardosa MJ, Perera D, Brown BA, Cheon D, Chan HM, Chan KP, Cho H, McMinn P.
Universiti Malaysia Sarawak, Sarawak, Malaysia. janecardosa@yahoo.co.uk
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 Taiwan in 1998, caused by genogroup C2, and in Perth (Western Australia) in 1999, where viruses belonging to genogroups B3 and C2 cocirculated. Singapore, Taiwan, and Sarawak had HEV71 epidemics in 2000, caused predominantly by viruses belonging to genogroup B4; however, large numbers of fatalities were observed only in Taiwan. HEV71 was identified during an epidemic of hand, foot and mouth disease in Korea; that epidemic was found to be due to viruses constituting a new genogroup, C3.
BMC Microbiol. 2006 Aug 30;6:74.Links
Phylogenetic evidence for inter-typic recombination in the emergence of human enterovirus 71 subgenotypes.
人类肠病毒EV71亚型基因重组的进化证据
Yoke-Fun C, AbuBakar S.
Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. yokefunchan@gmail.com
BACKGROUND: Human enterovirus 71 (EV-71) is a common causative agent of hand, foot and mouth disease (HFMD). In recent years, the virus has caused several outbreaks with high numbers of deaths and severe neurological complications. Several new EV-71 subgenotypes were identified from these outbreaks. The mechanisms that contributed to the emergence of these subgenotypes are unknown. RESULTS: Six EV-71 isolates from an outbreak in Malaysia, in 1997, were sequenced completely. These isolates were identified as EV-71 subgenotypes, B3, B4 and C2. A phylogenetic tree that correlated well with the present enterovirus classification scheme was established using these full genome sequences and all other available full genome sequences of EV-71 and human enterovirus A (HEV-A). Using the 5' UTR, P2 and P3 genomic regions, however, isolates of EV-71 subgenotypes B3 and C4 segregated away from other EV-71 subgenotypes into a cluster together with coxsackievirus A16 (CV-A16/G10) and EV-71 subgenotype C2 clustered with CV-A8. Results from the similarity plot analyses supported the clustering of these isolates with other HEV-A. In contrast, at the same genomic regions, a CV-A16 isolate, Tainan5079, clustered with EV-71. This suggests that amongst EV-71 and CV-A16, only the structural genes were conserved. The 3' end of the virus genome varied and consisted of sequences highly similar to various HEV-A viruses. Numerous recombination crossover breakpoints were identified within the non-structural genes of some of these newer EV-71 subgenotypes. CONCLUSION: Phylogenetic evidence obtained from analyses of the full genome sequence supports the possible occurrence of inter-typic recombination involving EV-71 and various HEV-A, including CV-A16, the most common causal agent of HFMD. It is suggested that these recombination events played important roles in the emergence of the various EV-71 subgenotypes.
[ 本帖最后由 David 于 2008-4-29 14:51 编辑 ]
临床识别诊断篇
Ann Acad Med Singapore. 2003 May;32(3):381-7.Links
Clinical characteristics of an outbreak of hand, foot and mouth disease in Singapore.
新加坡一起手足口病暴发的临床特征
Shah VA, Chong CY, Chan KP, Ng W, Ling AE.
Department of Neonatology, Singapore General Hospital, Outram Road, Singapore 169608. gnevas@sgh.com.sg
BACKGROUND: 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. OBJECTIVE OF THE STUDY: To study the clinical profile and virologic isolates of children admitted with HFMD during the outbreak. STUDY DESIGN: A prospective observational study. METHODS: Analysis of clinical features and virologic studies of 129 selected cases of HFMD and herpangina. RESULTS: The median age was 25 months with a range of between 4 months and 11 years. The majority were less than 5 years old (87%). The male-to-female ratio was 1.3:1. The median numbers of day of illness to presentation to the hospital was 3 days. Poor feeding and loss of appetite accounted for 76.7% of the admissions. Symptoms of vomiting were present in 37.2% of the cases. Oral ulcers were found in 96.1%, rashes over hands in 87.6%, over feet in 86.8% and over buttocks in 54.3%. Only 4.7% exhibited no rashes other than oral ulcers and were labelled as herpangina. The median duration of fever was 3 days, ranging from 2 to 7 days. An intravenous drip was required in 68.2% due to poor feeding. Viral cultures were sent in 89.1% of patients of whom 61.7% of patients were positive for viruses. Of the positive cultures, types of viruses isolated were EV71 (enterovirus 71) in 59/71 (83%), Coxsackievirus (A16, A24, A2 B3, B4) in 6/71 (8.4%), EV Untypable in 4/71 (5.6%) and mixed in 2/71 (2.8%). EV71 was isolated mostly from stool samples followed by vesicle fluid culture and throat swabs. Two siblings aged 14 months and 2.5 years died during this period at day 5 of illness, their post-mortem examinations showed interstitial pneumonitis of the lungs. EV71 was isolated from the brain, heart, tonsils, intestines, throat and rectal swabs. A raised total white cell count of 14,000/L versus 12,000/L was significantly associated with complicated HFMD (P = 0.04). There was no difference in clinical characteristics of EV71 versus non-EV71 infections. Other viral illnesses, e.g. measles and CMV, may be mistaken for HFMD in the outbreak setting. CONCLUSIONS: HFMD tends to occur in younger children less than 5 years old due to low herd immunity. Poor feeding due to mouth ulcers accounts for admission to hospital requiring intravenous drip. EV71 accounted for the majority (75%) of the positive isolations, followed by coxsackievirus and untypable EV, mixed infection of echovirus or CMV. The yield of virus isolation was highest from stool, followed by vesicles and throat swabs. There is no difference in clinical characteristics of EV71 and non-EV71 virus infections. Enterovirus can cause mild symptoms to fatal death. Two infants died of interstitial pneumonitis and encephalitis.
Clin Infect Dis. 2007 Oct 15;45(8):950-7. Epub 2007 Sep 13. Links
Outbreak of neurologic enterovirus type 71 disease: a diagnostic challenge.
肠病毒EV71暴发：临床诊断的挑战
Pérez-Vélez CM, Anderson MS, Robinson CC, McFarland EJ, Nix WA, Pallansch MA, Oberste MS, Glodé MP.
Department of Pediatrics, Section of Infectious Diseases, University of Colorado School of Medicine, and The Children's Hospital, Denver, Colorado 80218, USA. anderson.marsha@tchden.org
BACKGROUND: Similar to poliovirus, enterovirus type 71 (EV71) causes severe disease, including aseptic meningitis, encephalitis, acute flaccid paralysis, and acute cardiopulmonary dysfunction. Large epidemics of EV71 infection have been reported worldwide. METHODS: After recognition of a cluster of cases of EV71 disease, we reviewed records of patients with EV71 disease who required hospitalization at The Children's Hospital in Denver, Colorado, from 2003 through 2005. The presence of enterovirus was detected by reverse-transcriptase polymerase chain reaction (PCR) and/or viral culture of specimens from multiple sources, and the virus was typed as EV71 using genetic sequencing. RESULTS: Eight cases of EV71 disease were identified in both 2003 and 2005. Fifty-six percent of patients with EV71 disease were < or = 6 months of age (range, 4 weeks to 9 years). All 16 patients had EV71 central nervous system infection. Enterovirus PCR (EV-PCR) of cerebrospinal fluid specimens yielded positive results for only 5 (31.2%) of the 16 patients; all of these patients were < 4 months of age and had less severe disease. However, EV-PCR of upper respiratory tract specimens yielded positive results for 8 (100%) of 8 patients, and EV-PCR of lower gastrointestinal tract specimens yielded positive results for 7 (87.5%) of 8 patients. CONCLUSIONS: An outbreak of neurologic EV71 disease occurred in Denver, Colorado, during 2003 and 2005. Likely, EV71 disease remains unrecognized in other parts of the United States, because EV-PCR of cerebrospinal fluid frequently yields negative results. EV-PCR of specimens from the respiratory and gastrointestinal tracts had higher diagnostic yields than did EV-PCR of cerebrospinal fluid. EV71 infection should be considered in young children presenting with aseptic meningitis, encephalitis, acute flaccid paralysis, or acute cardiopulmonary collapse. EV71 infection may be an underrecognized emerging disease in the United States.
Clin Infect Dis. 2000 Sep;31(3):678-83. Epub 2000 Oct 4. Links
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.
马来西亚儿童手足口病暴发的临床和病理特征
Chan LG, Parashar UD, Lye MS, Ong FG, Zaki SR, Alexander JP, Ho KK, Han LL, Pallansch MA, Suleiman AB, Jegathesan M, Anderson LJ.
Department of Pediatrics, Sarawak General Hospital, Sarawak, Malaysia.
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.
Clin Infect Dis. 1999 Jul;29(1):184-90.Links
Comment in:
Clin Infect Dis. 2000 Jun;30(6):988.
Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications.
台湾南部肠病毒EV71感染的临床特征，强调神经性并发症状
Wang SM, Liu CC, Tseng HW, Wang JR, Huang CC, Chen YJ, Yang YJ, Lin SJ, Yeh TF.
Department of Emergency Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
An outbreak of enterovirus 71 (EV71) infection occurred in Taiwan in 1998. The clinical spectrums and laboratory findings for 97 patients with virus culture-proven EV71 infections were analyzed. Eighty-seven percent of the patients were younger than age 5 years. Hand-foot-and-mouth syndrome occurred in 79% of the children and central nervous system (CNS) involvement in 35%, including nine fatal cases. The predominant neurological presentations were myoclonus (68%), vomiting (53%), and ataxia (35%). Brain stem encephalitis was the cardinal feature of EV71 CNS involvement during this outbreak. Magnetic resonance imaging and pathological findings illustrated that the midbrain, pons, and medulla were the target areas. EV71 brain stem encephalitis can present either with cerebellar signs and an initially mild, reversible course or with overwhelming neurogenic shock and neurogenic pulmonary edema (NPE) resulting in a fatal outcome. Brain stem encephalitis that progressed abruptly to neurogenic shock and NPE was indicative of poor prognosis in this epidemic. Early aggressive treatment and close monitoring of the neurological signs are mandatory to improve the chance of survival.
Int J Pediatr Otorhinolaryngol. 2008 Jan;72(1):41-7. Epub 2007 Oct 29. Links
Upper aerodigestive tract sequelae in severe enterovirus 71 infection: predictors and outcome.
严重肠病毒EV71感染的上呼吸消化道后遗症：预报因子和结果
Tsou YA, Cheng YK, Chung HK, Yeh YC, Lin CD, Tsai MH, Chang JS.
Department of Otolaryngology, China Medical University Hospital, Taichung, Taiwan, ROC.
OBJECTIVE: Enterovirus 71 (EV71) infection sequelae can be severe and life-threatening, and long-term follow-up outcomes remain unknown. Therefore, we conducted a retrospective follow-up study to review airway and neurological sequelae development in patients with severe EV71 infection. We also studied the incidence and risk factors for tracheotomy and gastrostomy requirement. PATIENTS AND METHODS: We investigated 202 EV71-infected children according to their disease stage. Seventy-two of them were diagnosed to have EV71 encephalitis, which was characterized by myoclonus, ataxia, nystagmus, oculomotor palsy and bulbar palsy or combinations of these conditions. All the 72 patients required endotracheal intubation due to respiratory failure or ventilator dependence; among these, 14 underwent tracheostomy and 10 underwent gastrostomy. All patients were followed-up for at least 3 years after discharge. Predictors of tracheostomy and gastrostomy requirement were age <2 years, body weight <10th percentile, pulmonary hemorrhage or edema, meningeal symptoms and magnetic resonance imaging (MRI) findings of upper spinal cord and brainstem. We determined outcome based on persistent tracheostomy or gastrostomy requirement and whether patients developed positive neurological sequelae. RESULTS: Significant tracheostomy and gastrostomy predictors were age <2 years, pulmonary edema or hemorrhage, hypotension, hemiparesis and positive MRI findings. Statistical analysis revealed pulmonary edema and hypotension as index predictors of tracheostomy requirement and pulmonary edema as the significant risk factor for gastrostomy. CONCLUSIONS: Long-term neuropsychological impact was observed on children who present the signs of the pulmonary edema or hypotension in the early onset of the EV71 infection. EV71-infected patients who develop neurological pulmonary edema or hypotension should be hemodynamically stabilized and undergo early tracheostomy to prevent further complications. This may improve the decannulation success rate after the brainstem function recovers.
Pediatrics. 2002 Feb;109(2):E26-. Links
Cardiopulmonary manifestations of fulminant enterovirus 71 infection.
暴发性肠病毒EV71感染的心肺病变
Wu JM, Wang JN, Tsai YC, Liu CC, Huang CC, Chen YJ, Yeh TF.
Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan. jingming@mail.ncku.edu.tw
BACKGROUND: The pathogenesis of acute pulmonary edema and cardiac collapse after enterovirus 71 (EV71) infection are not completely understood. OBJECTIVE: To determine the hemodynamic features and the mechanism of pulmonary edema (PE) after EV71 infection by direct intracardiac monitoring. DESIGN: Prospective clinical and laboratory study at a tertiary medical center. PARTICIPANTS: Five consecutive infants, ages 2 to 13 months, with EV71 infection-proved by viral isolation in 4 and antibody in 1-with PE were enrolled. The clinical characteristics were systemically assessed. Hemodynamic profiles were determined every 4 hours by simultaneously implanted pulmonary arterial and central venous catheters during the acute stage. RESULTS: Magnetic resonance imaging revealed that all 5 infants had brainstem lesions. All patients had tachycardia and hyperthermia. Transient systolic hypertension was noted in 1 patient, and 1 presented with hypotension. Pulmonary artery pressure in all 5 infants was normal or mildly elevated (26-31 mm Hg), and central venous pressure ranged from 10 to 22 mm Hg. Pulmonary artery occlusion pressures were normal or slightly elevated (13-16 mm Hg). Systemic and pulmonary vascular resistances were transiently increased in only 1 patient. The stroke volume index decreased to 15.3 to 35.7 mL/M2 (normal: 30-60 mL/M2), but because of the elevated heart rate, the cardiac index did not decrease. All hemodynamics normalized within days. CONCLUSION: Fulminant EV71 infection may lead to severe neurologic complications and acute PE. The acute PE and cardiopulmonary decompensation in EV71 infection are not directly caused by viral myocarditis. The mechanism of PE may be related to increased pulmonary vascular permeability caused by brainstem lesions and/or systemic inflammatory response instead of increased pulmonary capillary hydrostatic pressure.
N Engl J Med. 1999 Sep 23;341(13):936-42. Links
Neurologic complications in children with enterovirus 71 infection.
儿童感染肠病毒71的神经并发症
Huang CC, Liu CC, Chang YC, Chen CY, Wang ST, Yeh TF.
Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan. huangped@mail.ncku.edu.tw
BACKGROUND: Enterovirus 71 infection causes hand-foot-and-mouth disease in young children, which is characterized by several days of fever and vomiting, ulcerative lesions in the oral mucosa, and vesicles on the backs of the hands and feet. The initial illness resolves but is sometimes followed by aseptic meningitis, encephalomyelitis, or even acute flaccid paralysis similar to paralytic poliomyelitis. METHODS: We describe the neurologic complications associated with the enterovirus 71 epidemic that occurred in Taiwan in 1998. At three major hospitals we identified 41 children with culture-confirmed enterovirus 71 infection and acute neurologic manifestations. Magnetic resonance imaging (MRI) was performed in 4 patients with acute flaccid paralysis and 24 with rhombencephalitis. RESULTS: The mean age of the patients was 2.5 years (range, 3 months to 8.2 years). Twenty-eight patients had hand-foot-and-mouth disease (68 percent), and 6 had herpangina (15 percent). The other seven patients had no skin or mucosal lesions. Three neurologic syndromes were identified: aseptic meningitis (in 3 patients); brain-stem encephalitis, or rhombencephalitis (in 37); and acute flaccid paralysis (in 4), which followed rhombencephalitis in 3 patients. In 20 patients with rhombencephalitis, the syndrome was characterized by myoclonic jerks and tremor, ataxia, or both (grade I disease). Ten patients had myoclonus and cranial-nerve involvement (grade II disease). In seven patients the brain-stem infection produced transient myoclonus followed by the rapid onset of respiratory distress, cyanosis, poor peripheral perfusion, shock, coma, loss of the doll's eye reflex, and apnea (grade III disease); five of these patients died within 12 hours after admission. In 17 of the 24 patients with rhombencephalitis who underwent MRI, T2-weighted scans showed high-intensity lesions in the brain stem, most commonly in the pontine tegmentum. At follow-up, two of the patients with acute flaccid paralysis had residual limb weakness, and five of the patients with rhombencephalitis had persistent neurologic deficits, including myoclonus (in one child), cranial-nerve deficits (in two), and ventilator-dependent apnea (in two). CONCLUSIONS: In the 1998 enterovirus 71 epidemic in Taiwan, the chief neurologic complication was rhombencephalitis, which had a fatality rate of 14 percent. The most common initial symptoms were myoclonic jerks, and MRI usually showed evidence of brainstem involvement.
N Engl J Med. 2007 Mar 22;356(12):1226-34. Links
Neurodevelopment and cognition in children after enterovirus 71 infection.
儿童感染肠病毒EV71后的神经病变发展和认知（2007年新英格兰医学杂志）
Chang LY, Huang LM, Gau SS, Wu YY, Hsia SH, Fan TY, Lin KL, Huang YC, Lu CY, Lin TY.
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. ly7077@tpts6.seed.net.tw
BACKGROUND: Enterovirus 71 is a common cause of hand, foot, and mouth disease and encephalitis in Asia and elsewhere. The long-term neurologic and psychiatric effects of this viral infection on the central nervous system (CNS) are not well understood. METHODS: We conducted long-term follow-up of 142 children after enterovirus 71 infection with CNS involvement - 61 who had aseptic meningitis, 53 who had severe CNS involvement, and 28 who had cardiopulmonary failure after CNS involvement. At a median follow-up of 2.9 years (range, 1.0 to 7.4) after infection, the children received physical and neurologic examinations. We administered the Denver Developmental Screening Test (DDST II) to children 6 years of age or younger and the Wechsler intelligence test to children 4 years of age or older. RESULTS: Nine of the 16 patients with a poliomyelitis-like syndrome (56%) and 1 of the 5 patients with encephalomyelitis (20%) had sequelae involving limb weakness and atrophy. Eighteen of the 28 patients with cardiopulmonary failure after CNS involvement (64%) had limb weakness and atrophy, 17 (61%) required tube feeding, and 16 (57%) required ventilator support. Among patients who underwent DDST II assessment, delayed neurodevelopment was found in only 1 of 20 patients (5%) with severe CNS involvement and in 21 of 28 patients (75%) with cardiopulmonary failure (P<0.001 for the overall comparison). Children with cardiopulmonary failure after CNS involvement scored lower on intelligence tests than did children with CNS involvement alone (P=0.003). CONCLUSIONS: Enterovirus 71 infection with CNS involvement and cardiopulmonary failure may be associated with neurologic sequelae, delayed neurodevelopment, and reduced cognitive functioning. Children with CNS involvement without cardiopulmonary failure did well on neurodevelopment tests. (ClinicalTrials.gov number, NCT00172393 .). Copyright 2007 Massachusetts Medical Society.
Clin Infect Dis. 2007 Mar 1;44(5):646-56. Epub 2007 Jan 22. Links
Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study.
马来西亚人类肠病毒EV71感染的回顾性临床、病毒学和分子流行病学研究
Ooi MH, Wong SC, Podin Y, Akin W, del Sel S, Mohan A, Chieng CH, Perera D, Clear D, Wong D, Blake E, Cardosa J, Solomon T.
Department of Paediatrics, Sibu Hospital, Sibu, Malaysia.
BACKGROUND: Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear. METHODS: We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates. RESULTS: Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 of 168 vs. 30 of 109; odds ratio , 0.48; 95% confidence interval , 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 of 168 vs. 29 of 109; OR, 0.21; 95% CI, 0.10-0.46; P<.0001); children with HEV-71 genogroup B5 were more likely to be part of a family cluster (OR, 6.26; 95% CI, 2.77-14.18; P<.0001). Children with HEV-71 and coinfected with another enterovirus or adenovirus were no more likely to have CNS disease. CONCLUSIONS: Genogroups of HEV-71 may differ with regard to the risk of causing CNS disease and the association with family clusters. Dual infections are common, and all possible causes should be excluded before accepting that the first virus identified is the causal agent.
[ 本帖最后由 David 于 2008-4-29 14:24 编辑 ]
感染控制篇
Pediatrics. 2002 Jun;109(6):e88. Links
Risk factors of enterovirus 71 infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in Taiwan.
台湾肠病毒EV71感染的风险因素
Chang LY, King CC, Hsu KH, Ning HC, Tsao KC, Li CC, Huang YC, Shih SR, Chiou ST, Chen PY, Chang HJ, Lin TY.
Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University, Taoyuan, Taiwan.
OBJECTIVE: 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. METHODS: Neutralizing antibodies to EV71 were assayed for 539 people before the epidemic and 4619 people of similar ages after the epidemic. Questionnaires, which were completed during household interviews after the epidemic, solicited demographic variables, exposure history, and clinical manifestations. RESULTS: A total of 129 106 cases of HFMD were reported during the epidemic. Age-specific pre-epidemic EV71 seroprevalence rates were inversely related to age-specific periepidemic mortality rates (r = -0.82) or severe case rates (r = -0.93). Higher postepidemic EV71 seropositive rates among children who were younger than 3 years positively correlated with higher mortality rates in different areas (r = 0.88). After the epidemic, 51 (56%) of 91 younger siblings of elder siblings who were EV71-seropositive were EV71-seropositive; otherwise, 2.2% (4 of 186) of younger siblings were EV71-seropositive (matched odds ratio : 10; 95% confidence interval : 3.4-29). Stepwise multiple logistic regression revealed other factors associated with EV71 infection to be older age (adjusted OR: 2.5; 95% CI: 1.9-3.4), attendance at kindergartens/child care centers (adjusted OR: 1.8; 95% CI: 1.3-2.5), contact with HFMD/herpangina (adjusted OR: 1.6; 95% CI: 1.2-2.1), greater number of children in a family (adjusted OR: 1.4; 95% CI: 1.1-1.7), and rural residence (adjusted OR: 1.4; 95% CI: 1.2-1.6). Twenty-nine percent of preschool children who were infected with EV71 developed HFMD/herpangina. Younger age and contact with HFMD/herpangina were significant factors for the development of EV71-related HFMD/herpangina in these children. CONCLUSIONS: An increased incidence of EV71 infection in young children occurred more often in geographic areas with increased mortality rates. Intrafamilial and kindergarten transmissions among preschool children were major modes of disease transmission during the widespread EV71 epidemic in Taiwan in 1998.
Pediatr Int. 2006 Jun;48(3):250-6. Links
Critical management in patients with severe enterovirus 71 infection.
严重肠病毒EV71感染的病人监护管理经验
Wang JN, Yao CT, Yeh CN, Huang CC, Wang SM, Liu CC, Wu JM.
Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
OBJECTIVE: The aim of this study was to analyze clinical details occurring in children with severe enterovirus 71 (EV71) infection and synthesize the critical care experience for patients with severe EV71 infection. METHODS: A retrospective clinical, laboratory, and hemodynamic study was performed in a pediatric intensive care unit in a university hospital. From March 1998 to April 2000, seven consecutive pediatric patients with severe EV71 infection were retrospectively analyzed as the comparison group. From May 2000 to March 2003, eight consecutive patients with severe EV71 infection who had received the protocol therapy were enrolled as the study group. Detailed information about clinical treatment and pharmacological therapy was collected for comparison. RESULTS: The clinical presentations and laboratory findings between the comparison and the study groups were not significantly different. The amount of intravenous fluid in the first 24 h was significantly higher in the comparison group (9.2+/-5.0 vs 4.9+/-1.3 mL/kg per h). More patients in the study group received low doses of dopamine infusion, patients in the comparison group received more epinephrine, and none of them received milrinone. The acute-stage and long-term survival rates were higher in the study group (100% vs 43%, 87% vs 29%). CONCLUSION: Early cardiopulmonary support may prevent the vicious cycle of cardiopulmonary failure and improve the clinical outcome of severe EV71 infection. Milrinone may be the ideal inotropic agent for these patients. Echocardiography, a central line, and an arterial line could be an alternate method to replace direct intracardiac hemodynamic monitoring for guiding critical management.
Lancet. 1999 Nov 13;354(9191):1682-6. Links
Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease.
感染肠病毒EV71后肺水肿的临床特征和风险因素
Chang LY, Lin TY, Hsu KH, Huang YC, Lin KL, Hsueh C, Shih SR, Ning HC, Hwang MS, Wang HS, Lee CY.
Department of Pediatrics, Chang Gung Children's Hospital, Kweishan, Taoyuan, Taiwan.
BACKGROUND: In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan. METHODS: We studied 154 children with virus-culture confirmed EV71 infection. Children were divided into three groups: 11 patients with pulmonary oedema; 38 patients with central nervous system (CNS) involvement and no pulmonary oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups. FINDINGS: Nine children with pulmonary oedema had hand, foot, and mouth disease, one had herpangina, and one had febrile illness with eight children with limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complications recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12.4 , p=0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leucocytosis, and limb weakness. Hyperglycaemia was the most significant prognostic factor for pulmonary oedema (odds ratio 21.5 , p=0.003). INTERPRETATION: EV71 can cause hand, foot, and mouth disease, CNS involvement with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the most important prognostic factor.
JAMA. 2004 Jan 14;291(2):222-7. Links
Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan.
家庭接触在台湾肠病毒EV71感染中的传播和临床特征
Chang LY, Tsao KC, Hsia SH, Shih SR, Huang CG, Chan WK, Hsu KH, Fang TY, Huang YC, Lin TY.
Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Kweishan, Taiwan.
CONTEXT: Although enterovirus 71 has caused epidemics associated with significant morbidity and mortality, its transmission has not been thoroughly investigated. OBJECTIVES: To investigate enterovirus 71 transmission and determine clinical outcomes within households. DESIGN, SETTING, AND PARTICIPANTS: Prospective family cohort study to investigate patients at a children's hospital in Taiwan and family members of these patients who had signs and symptoms suggestive of enterovirus 71 between February 2001 and August 2002. Patients and household members underwent clinical evaluations, virological studies, questionnaire-based interviews, and were followed up for 6 months. MAIN OUTCOME MEASURES: Enterovirus 71 infection, defined as a positive viral culture from a throat or rectal swab, or the presence of IgM or a 4-fold increase in neutralizing antibody in serum; and clinical syndromes, defined as asymptomatic; uncomplicated symptomatic; and complicated; with unfavorable outcomes of sequelae or death. RESULTS: Ninety-four families (433 family members) had at least 1 family member with evidence of enterovirus 71 infection. The overall enterovirus 71 transmission rate to household contacts was 52% (176/339 household contacts). Transmission rates were 84% for siblings (70/83); 83%, cousins (19/23); 41%, parents (72/175); 28%, grandparents (10/36); and 26%, uncles and aunts (5/19). Of 183 infected children, 11 (6%) were asymptomatic and 133 (73%) had uncomplicated illnesses (hand, foot, and mouth disease, herpangina, nonspecific febrile illness, upper respiratory tract infection, enteritis, or viral exanthema). Twenty-one percent (39/183) experienced complicated syndromes including the central nervous system or cardiopulmonary failure. During the 6-month follow-up, 10 died and 13 had long-term sequelae consisting of dysfunction in swallowing, cranial nerve palsies, central hypoventilation, or limb weakness and atrophy. Age younger than 3 years was the most significant factor associated with an unfavorable outcome in children (P =.004). Among 87 infected adults, 46 (53%) were asymptomatic, 34 (39%) had nonspecific illnesses of fever, sore throat, or gastrointestinal discomfort, and 7 (8%) had hand, foot, and mouth disease. There were no complicated cases in adults. CONCLUSIONS: Enterovirus 71 household transmission rates were high for children in Taiwan and severe disease with serious complications, sequelae, and death occurred frequently. In contrast, adults had a much lower rate of acquisition of the infection and much less adverse sequelae.
[ 本帖最后由 David 于 2008-4-28 17:28 编辑 ]
综述
J Microbiol Immunol Infect. 2000 Dec;33(4):205-16. Links
Enterovirus 71: the virus, its infections and outbreaks.
肠病毒EV71：病毒学特征，感染与暴发
Ho M.
Division of Clinical Research, National Health Research Institutes, Taipei, Taiwan, ROC.
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 leading to quick deaths in children aged from 0.5 to 3 years old was first recognized. In Taiwan 78 deaths and over 100,000 cases of HFMD occurred. Coxsackie A16 cocirculated with EV 71, without however, causing any severe illnesses. The transmission of EV 71 was related to number of siblings in a household, rural residence and contact with cases of HFMD. Genotype analyses show that genotypes have changed with time in the United States and Japan. Recent isolates from Japan are similar to the isolates from Malaysia and Taiwan in 1997 and 1998, respectively. Even though genotype analysis has not identified specific sequences responsible for neurovirulence, the strains causing brain stem encephalitis and pulmonary edema in the Far East are similar and have arisen since 1997. Seroepidemiological studies in Taiwan suggest that children aged from 0.5 to 4 years old are most susceptible while the rest of the population are over 50% immune. Theoretically there is a pool of such susceptible subjects every few years. In prevention for another major outbreak, a simple, inactivated Salk type vaccine should be immediately prepared and made available.
J Microbiol Immunol Infect. 2000 Mar;33(1):1-8. Links
Enterovirus infections with special reference to enterovirus 71.
肠病毒EV71导致的感染
Hsiung GD, Wang JR.
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.
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, Coxsackievirus group A and group B viruses, and echoviruses group. All together a total of 67 types are available. Starting from enterovirus type 68 to 71, they are named as enterovirus types. Enterovirus type 72 is hepatitis A virus. Paralytic disease of poliomyelitis was recorded in ancient time but characterization of poliovirus was not reported until the turn of the 19th century that poliomyelitis was a viral disease. The major breakthrough for diagnosing and controlling of poliomyelitis was the discovery that poliovirus can be propagated in human embryonic tissues in cultures. As soon as cultures of human and monkey cells began to use for isolating polioviruses in stool specimen of patients, more unknown viruses were isolated which unlike polioviruses nor Coxsackie viruses; they were called "orphan" viruses or human enteric viruses, name later simplified to "echoviruses". Morphologically all enteroviruses are alike. They are small, ether insensitive viruses with an RNA genome. Their nucleic acid is single stranded, and the nucleocapsid has a cubic (icosahedral) symmetry, and is naked. The host ranges of enteroviruses vary greatly from one type to the next and even among strains of the same type. Polioviruses have a very restricted host range among laboratory animals. Virus isolation is the best method for diagnosis of enterovirus infection, but infection in the central nervous system (CNS) may be detected by polymerase chain reaction (PCR). Currently final identification and serotyping of enteroviruses are by indirect immunofluorescent tests using monoclonal antibody or by neutralization test using antiserum pools described by Lim and Benyesh-Melnick. The incidence and prevalence of diseases associated with the enterovirus infections are varied. The circulation of enteroviruses recently in Tainan and the epidemic of EV71 in Taiwan in 1998 are described in this review. Although poliovirus infection may be eradicated from the world due to the efficient vaccination program, there is no specific antiviral agents for either treatment or prevention for other enterovirus infections. In 1991, a new antiviral "pleconaril" which is a novel orally bioavailable and systematically acting small molecule inhibitor for picornaviruses. "Pleconaril" is currently in clinical trials for treatment of enterovirus meningitis and respiratory infections.
FEMS Microbiol Rev. 2002 Mar;26(1):91-107. Links
An overview of the evolution of enterovirus 71 and its clinical and public health significance.
肠病毒EV71基因进化回顾及临床和公共卫生意义
McMinn PC.
Division of Virology, TVW Telethon Institute for Child Health Research, 100 Roberts Road, Subiaco, WA 6008, Australia. peterm@ichr.uwa.edu.au
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 emergence of large-scale epidemic activity in the Asia-Pacific region has been associated with the circulation of three genetic lineages that appear to be undergoing rapid evolutionary change. Two of these lineages (B3 and B4) have not been described previously and appear to have arisen from an endemic focus in equatorial Asia, which has served as a source of virus for HFMD epidemics in Malaysia, Singapore and Australia. The third lineage (C2) has previously been identified and was primarily responsible for the large HFMD epidemic in Taiwan during 1998. As EV71 appears not to be susceptible to newly developed antiviral agents and a vaccine is not currently available, control of EV71 epidemics through high-level surveillance and public health intervention needs to be maintained and extended throughout the Asia-Pacific region. Future research should focus on (1) understanding the molecular genetics of EV71 virulence, (2) identification of the receptor(s) for EV71, (3) development of antiviral agents to ameliorate the severity of neurological disease and (4) vaccine development to control epidemics. Following the successful experience of the poliomyelitis control programme, it may be possible to control EV71 epidemics if an effective live-attenuated vaccine is developed.
[ 本帖最后由 David 于 2008-4-29 12:45 编辑 ]
好厉害！辛苦了！ 环境卫生篇
FEMS Immunol Med Microbiol. 2008 Mar;52(2):253-9. Epub 2008 Jan 22. Links
Prevalence of enteroviruses in hot spring recreation areas of Taiwan.
台湾温泉疗养地肠病毒的流行
Hsu BM, Chen CH, Wan MT.
Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi, Taiwan, ROC. bmhsu@ccu.edu.tw
Enteroviruses can be introduced into the water environment as a result of human activity. Contaminations within hot tubs, spas and public baths are also possible. We investigated the distribution of enteroviruses at six hot spring recreation areas throughout Taiwan. Spring water was collected from 34 sites and enteroviruses were detected in 13 (38.2%). The most frequently detected was coxsackievirus A2, followed by echovirus 11. Enterovirus 71 (EV 71) and porcine enterovirus 9 were detected once. Water quality indicators were not statistically associated with the occurrence of enteroviruses, although the enterovirus-positive samples were positive for a greater number of microbiological indicators and showed a link to pH and water temperature. The results confirm the ubiquity of enteroviruses in Taiwan spring recreation areas. Coxsackievirus A2, echovirus 11 and EV 71, the enteroviruses responsible for disease outbreaks identified at these sites, should be considered a potential public health threat in spring recreation areas of Taiwan.
J Appl Microbiol. 2008 Mar;104(3):817-23. Epub 2008 Jan 14. Links
Molecular detection and prevalence of enterovirus within environmental water in Taiwan.
台湾环境水体中肠病毒的流行和分子检测
Chen CH, Hsu BM, Wan MT.
Department of Bioengineering, Tatung University, Taipei, Taiwan, China. chchen@ttu.edu.tw
AIMS: To investigate the presence of enterovirus RNA in various samples of environmental water collected in Taiwan during 2004-2005, and to characterize the genotypes and distribution of the viruses identified in Taiwan. METHODS AND RESULTS: Total 131 environmental samples were screened using the reverse transcription polymerase chain reaction (RT-PCR) for the highly conserved 5'-nontranslated regions (5'-NTR). Among these enterovirus RNA-positive samples, 32, 15 and 6 of the samples were recovered from surface water, ground water and sewage water respectively. However, the total positive detection rate increased to 40.5% with the application of seminested PCR. Sequencing revealed that the majority of isolates belonged to the following genotypes: coxsackie A2 (35.8%), coxsackie A6 (13.2%) and enterovirus (EV)71 (11.3%); echovirus 11, porcine EV9 and coxsackie A16 isolates were also observed. CONCLUSIONS: This study confirms that the major epidemic genotypes of enterovirus are prevalent in the surface and ground water of Taiwan. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is helpful in understanding the significance and epidemiology of the virus within and beyond the study area. Moreover, it was possible to predict the enterovirus genotype and evaluate possible correlations between water contamination and viral sequences found among clinical samples.
[ 本帖最后由 David 于 2008-4-29 13:01 编辑 ]
自己顶上去！ 拜托来中文的:L :L :L 文献提供很及时！ 好东东，可是看不懂。:'( :'( :'( 翻译要花时间的呀，;P
有谁帮我？:loveliness:
回复
谢谢，你辛苦啦。的确是好东西，可是，咱的外语水平够呛，哪位高人翻译出来吧。
先谢谢啦。 是的，虽是及时雨，但英文需翻译，为便于学习，建议各位版主最好发布中文版。谢谢了！:handshake 原帖由 David 于 2008-5-2 15:18 发表 http://bbs.sific.com.cn/images/common/back.gif
翻译要花时间的呀，;P
有谁帮我？:loveliness:
原来以为高手看英文资料跟看母语差不多，原来也需要花时间，谢谢戴维长久以来的无私奉献。俺们只能先学习，再出力了。 好文章。近日国内关于EV71的宣传已经很多了。深入进行防控，包括政策制定，需要学习国外的文献资料。因为此病不是新发疾病，国际上已经有不少科学的研究结果，我们应该去享用。
文献太多，而我们的英文能力又相对不足，是否请David和其他英文功底比较好的朋友，翻译几篇重要的，尤其是如何预防和控制的内容，可以摘译的形式。这样才能更好地指导我国对此病的防控。 原帖由 icchina 于 2008-5-4 10:24 发表 http://bbs.sific.com.cn/images/common/back.gif
好文章。近日国内关于EV71的宣传已经很多了。深入进行防控，包括政策制定，需要学习国外的文献资料。因为此病不是新发疾病，国际上已经有不少科学的研究结果，我们应该去享用。
文献太多，而我们的英文能力又相 ...
符合国情，支持。:lol :handshake 原帖由 icchina 于 2008-5-4 10:24 发表 http://bbs.sific.com.cn/images/common/back.gif
好文章。近日国内关于EV71的宣传已经很多了。深入进行防控，包括政策制定，需要学习国外的文献资料。因为此病不是新发疾病，国际上已经有不少科学的研究结果，我们应该去享用。
文献太多，而我们的英文能力又相 ...
按icchina的要求办！:lol
好像真的很多:L 光是浏览、下载就花了不少时间，DAVID辛苦了！
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