Human enteroviral infection in fibromyalgia: a case-control blinded study

SUMMARY OBJECTIVE: This study aimed to test the hypothesis that fibromyalgia is associated with a human enteroviral infection. METHODS: Venous peripheral blood samples from 27 patients fulfilling the American College of Rheumatology revised diagnostic criteria for fibromyalgia and from 26 age- and sex-matched controls, who underwent immunofluorescence assays for coxsackievirus A7 IgG, coxsackievirus B1 IgG, coxsackievirus A7 IgA, coxsackievirus B1 IgA, echovirus IgG, and echovirus IgA. These immunological tests were performed blind to group status. RESULTS: There were no significant differences between the patient and control groups in respect of positive results for coxsackievirus A7 IgG (p=0.467), coxsackievirus B1 IgG (p=0.491), coxsackievirus A7 IgA (p=0.586), coxsackievirus B1 IgA (p=0.467), echovirus IgG (p=0.236), and echovirus IgA (p=1). CONCLUSIONS: The results of this systematic study do not support the hypothesis that fibromyalgia is associated with infection by a human enterovirus.

RT-nPCR Assays for Amplification and Sequencing of VP1 Genes in Human Enterovirus A-D from Clinical Specimens / 生物医学与环境科学（英文）

Objective@#To develop RT-nPCR assays for amplifying partial and complete VP1 genes of human enteroviruses (HEVs) from clinical samples and to contribute to etiological surveillance of HEV-related diseases.@*Methods@#A panel of RT-nPCR assays, consisting of published combined primer pairs for VP1 genes of HEV A-C and in-house designed primers for HEV-D, was established in this study. The sensitivity of each RT-nPCR assay was evaluated with serially diluted virus stocks of five serotypes expressed as CCID @*Results@#The sensitivity of RT-nPCR assays for amplifying partial VP1 gene of HEVs was 0.1 CCID @*Conclusion@#This RT-nPCR system is capable of amplifying the partial and complete VP1 gene of HEV A-D, providing rapid, sensitive, and reliable options for molecular typing and molecular epidemiology of HEVs in clinical specimens.

Prevalence of latent infection of pathogens of hand, foot and mouth disease in healthy people in China: A meta-analysis / 预防医学

Objective@#To analyze the prevalence of latent infection of pathogens of hand,foot and mouth disease (HFMD) in Chinese healthy population and its influencing factors,so as to provide reference for the prevention and control of HFMD.@*Methods @#Literature on the latent infection of HFMD was searched in Chinese and English databases,such as CNKI,Wanfang,CBMd,PubMed,Web of Science and ScienceDirect,from January 1,2000 to December 31,2019. The pooled rate and its 95% confidence interval(95%CI)were used to assess the latent infection rate of HFMD pathogens in healthy Chinese population.@*Results@#A total of 442 articles were retrieved,and 31 articles were finally included in the quantitative meta-analysis. The results showed that the latent infection rate of human enteroviruses in healthy Chinese population was 18.8%(95%CI:16.1%-21.6%),and the latent infection rates of EV71,CV-A16 and other HEVs were 3.7%(95%CI:2.5%-4.9%),1.9%(95%CI:1.0%-2.9%) and 15.1%(95%CI:11.9%-18.3%),respectively. The latent infection rates of HEVs in healthy men and women in China were 16.7%(95%CI:12.9%-20.4%) and 14.4%(95%CI:10.8%-18.0%),respectively. The latent infection rates of human enterovirues HEVs in the healthy population aged 0-5 years and over 5 years were 24.4%(95%CI:20.4%-28.5%) and 9.4%(95%CI:6.5%-12.2%),respectively. Meta regression analysis showed that the associated factors for the latent infection rate of HEVs in Chinese healthy population included sampling period,sampling area and study population.Sensitivity analysis showed that there was no significant change on meta results after the exclusion of individual studies one by one(p>0.05). Begg's tests,Egger's tests and funnel plots all indicated the existence of publication bias. Trim and fill method showed that the recessive infection rate was reduced after adjustment(p<0.05). @*Conclusions@#The latent infection rate of HFMD pathogens is high in healthy people in China,and it is mainly caused by other HEVs. Males and children aged under 5 years are at high risk of latent infection of HEVs.

Vigilancia epidemiológica para la identificación de casos de infección respiratoria aguda por enterovirus D68 en niños en un hospital de tercer nivel de atención durante 2014-2016 / Surveillance for the identification of cases of acute respiratory infection by enterovirus D68 in children in a tertiary level care hospital during 2014-2016

Resumen Introducción: La reemergencia de las infecciones por Enterovirus D68 (EV-D68) se reportó en los EE.UU. desde agosto-octubre de 2014 (691 casos). En México, un brote se reportó en el Instituto Nacional de Enfermedades Respiratorias (24 casos). Se presentan los resultados de la vigilancia epidemiológica en un hospital pediátrico nacional de tercer nivel para Enterovirus sp. (EV) y otros virus respiratorios. Método: Tras la alerta emitida por la reemergencia del EV-D68 en 2014, la vigilancia epidemiológica -que solo detectaba virus respiratorios mediante PCR en pacientes con enfermedad tipo influenza mediante toma de hisopados nasofaríngeos- se expandió para incluir niños con exacerbación de asma o dificultad respiratoria aguda. Las muestras positivas para EV fueron confirmadas y tipificadas por secuenciación. Posteriormente, se utilizó secuenciación de siguiente generación para obtener el genoma viral completo. Resultados: De 1705 muestras, 13 fueron positivas para EV. Los pacientes con EV presentaron la siguiente comorbilidad: enfermedad pulmonar crónica (7.7%), enfermedad neoplásica (15.4%), asma/rinitis alérgica (23%), neumonías de repetición (23%), y otras (23%). De las 13 muestras positivas para EV, tres resultaron positivas para EV-D68. Dichos casos requirieron ventilación mecánica invasiva, no tuvieron afectación neurológica y sobrevivieron. Conclusiones: La afectación por EV-D68 de la población estudiada fue menor que lo reportado en México durante el mismo periodo. Los casos de infección por EV-D68 presentan diversa comorbilidad, aunque escasas enfermedades pulmonares, lo cual pudiera explicar la baja tasa de ataque. La presencia del sistema de vigilancia epidemiológica establecido y la prevención de infecciones pudieron haber contenido el brote.

Abstract Background: The reemergence of enterovirus D68 (EV-D68) infections in the United States was reported from August-October 2014 (691 cases). In Mexico, an outbreak at the National Institute of Respiratory Diseases was reported (24 cases). The results of epidemiological surveillance of Enterovirus sp. (EV) and other respiratory viruses in a national pediatric tertiary care level hospital are presented. Methods: Following the alert issued by the reemergence of EV-D68 in 2014, epidemiological surveillance -which only detected respiratory viruses by PCR in patients with influenza-like illness using nasopharyngeal swabs- expanded to include children with asthma exacerbation or acute respiratory distress. Positive samples to EV were confirmed and typed by sequencing. Subsequent sequencing was used to obtain the complete viral genome. Results: Of 1705 samples, 13 were positive to EV. Patients with EV presented the following comorbidities: chronic lung disease (7.7%), neoplastic disease (15.4%), allergic asthma/rhinitis (23%), recurrent pneumonia (23%), and other (23%). Of the 13 samples positive for EV, three were positive for EV-D68. These cases required invasive mechanical ventilation, presented no neurological involvement and survived. Conclusions: The impact of the population studied by EV-D68 was lower than that reported in Mexico during the same period. Cases of EV-D68 infection had multiple comorbidities, but few pulmonary comorbidities, which could explain the low attack rate. The epidemiological surveillance and infection prevention system may have contained the outbreak.

Genetic characteristics of human enterovirus A type 71 in Qinghai province during 2016-2017 / 中华实验和临床病毒学杂志

Objective@#To investigate the genetic characteristics of enterovirus A 71 (EV-A71) and etiological features of hand, foot and mouth disease (HFMD) in Qinghai province from 2016 to 2017.@*Methods@#Specimens were collected from HFMD patients in Qinghai province, and detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). For EV-A71 positive samples, virus was isolated and RNA was extracted, and then VP1 coding region was amplified by RT-PCR. The phylogenetic tree was constructed by comparing with other genotypes and sub-genotypes strains of EV-A71.@*Results@#It was shown that 114 strains of EV-A71 were isolated in Qinghai province from 2016 to 2017, which all belonged to genotype C4a, and could be divided to two different lineages by phylogenetic analysis. From 2016 to 2017, the epidemic strains of EV-A71 in the different transmission chains of Qinghai province was closely related to other provinces of China.@*Conclusions@#C4a was the dominant genotype of EV-A71 in Qinghai province from 2016 to 2017, and no other genotype was detected. In addition, EV-A71 isolated from Qinghai province co-evolved with EV-A71 in other provinces of China.

Aumento inusual de casos de mielitis en un hospital pediátrico en Argentina / Unusual increase of cases of myelitis in a pediatric hospital in Argentina

Introducción: La asociación entre enterovirus D68 y cuadros de mielitis aguda fláccida ha sido descrita en Estados Unidos, en 2014. Desde ese año, se han reportado casos esporádicamente en Canadá y Europa. Se describe, en este estudio, una serie de casos con mielitis aguda fláccida en el Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" en Buenos Aires, Argentina, en 2016. Métodos: Estudio descriptivo, retrospectivo. Se incluyeron todos los pacientes internados desde el 1/04/2016 al 1/07/2016 con mielitis fláccida aguda con lesiones en la médula espinal que comprometieran la sustancia gris en la resonancia magnética nuclear. Se procesaron, para la búsqueda etiológica, muestras de secreciones nasofaríngeas, hisopados de materia fecal y líquido cefalorraquídeo. Resultados: Se incluyeron 10 pacientes. La mediana de edad fue 4 años (rango de 3 meses a 5 años). Ocho pacientes tuvieron una enfermedad febril autolimitada antes del inicio de los síntomas neurológicos. Los hallazgos neurológicos fueron debilidad fláccida de, al menos, un miembro, cervicoplejia (n= 2) y parálisis facial (n= 2). Todos los pacientes presentaron lesiones longitudinales en la médula espinal, con compromiso de sustancia gris, predominantemente, en el asta anterior. En todos los casos, se realizó una punción lumbar. En 7 pacientes, se observó pleocitosis. En cuatro niños, se identificó enterovirus D68 en secreciones nasofaríngeas y, en uno, se identificó el enterovirusD68 en el líquido cefalorraquídeo. Todos los pacientes persistieron con déficits neurológicos al momento del alta. Conclusiones: Se reporta el primer brote de mielitis aguda fláccida asociada a enterovirusD68 en Argentina. La vigilancia epidemiológica activa permitirá conocer la verdadera incidencia, epidemiología y etiología de esta enfermedad.

Introduction: The association between enterovirus D68 and acute flaccid myelitis was first described in the United States in 2014. Since then, sporadic cases have been reported in Canada and Europe. This study describes a series of cases of acute flaccid myelitis at Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," in Buenos Aires, Argentina, during 2016. Methods: Descriptive, retrospective study. All patients with acute flaccid myelitis and lesions in the spinal cord involving the gray matter, as observed in the magnetic resonance imaging (MRI) scan, hospitalized from 04/01/2016 to 07/01/2016, were included in the study. Samples of nasopharyngeal secretions, fecal swabs and cerebrospinal fluid were collected and processed to look for the causative agent. Results: Ten patients were included. The median age was 4 years old (range from 3 months to 5 years old). Eight patients had a self-limiting febrile condition before the onset of neurological symptoms. Neurological findings were flaccid weakness in, at least, one limb, cervical paralysis (n= 2) and facial paralysis (n= 2). All patients had longitudinal lesions in the spinal cord, with gray matter involvement, mainly in the anterior horn. In all cases, a lumbar puncture (spinal tap) was performed. Pleocytosis was observed in 7 patients. In four children, enterovirus D68 was identified in nasopharyngeal secretions, and in one, it was detected in the cerebrospinal fluid. Neurological deficit persisted in all patients at the time of discharge. Conclusions: The first outbreak of acute flaccid myelitis associated to enterovirus D68 is reported in Argentina. Active epidemiological surveillance will help to determine the true incidence, epidemiology and etiology of this disease.

Epidemic and etiological characteristics of hand, foot and mouth disease in Gansu province during 2013—2015 / 中华实验和临床病毒学杂志

Objective@#To analyze the epidemiological and etiological characters of hand, foot and mouth disease ( HFMD ) in Gansu during 2013 to 2015 and provide evidence for the development of effective prevention and control measures.@*Methods@#The descriptive epidemiological analysis was used to analyze the data of HFMD, and the specimens were collected from hospitals to detect the pathogens by RT- PCR or Real-time RT-PCR. The nucleotide sequences of VP1 encoding region of virus strains were amplified by RT-PCR method, and determined and analyzed.@*Results@#Total of 29 934 HFMD cases were reported in Gansu from 2013 to 2015, including 81 severe cases and 2 deaths; the largest number occurred in Lanzhou was 7 053, accounting for 23.56% of the cases in the province. HFMD cases were mostly reported during May to July, accounted for 61.69% in total cases; the male to female ratio was 1.5: 1, and most cases were under the age of five and accounted for 83.02%. A total of 5 251 laboratory confirmed cases were reported, of which the number of cases caused by human enterovirus (HEV) were 2 972, the positive rate was 56.60%. Among the severe 81 cases, the positive rate of HEV was 67.90%, and both of the 2 death cases were infected by EV71. 341 strains of viruses were isolated, the genotyping of VP1 encoding region showed that all the 133 EV71 were C4a; among the 134 CVA16 isolates, 6 were B1a and 128 were B1b.@*Conclusions@#In Gansu province, there is a high infection rate of HFMD in children under the age of five, the proportion of other HEV is more and more, and the incidence is related to the difference of pathogens that showed alternant epidemic characteristics. CVA16 and EV71 viruses have the phenomenon of alternating.

The association between toll-like receptor 7 single nucleotide polymorphisms and severity of hand, foot and mouth disease caused by enterovirus 71 infection / 中华传染病杂志

Objective To explore the association between toll-like receptor 7 (TLR7) single nucleotide polymorphisms (SNP) and susceptibility of hand, foot and mouth disease caused by enterovirus (EV)71 infection.Methods The genotype of SNP (rs179019 and rs3853839) was determined in 775 EV7l-infected cases (including 439 mild cases and 336 severe cases) and 748 healthy control cases with TaqMan assay.The difference of allele frequencies was compared.The difference of TLR7 mRNA expression in peripheral blood mononuclear cells (PBMCs) derived from different SNP genotype carriers was detected.PBMCs derived from different SNP genotype carriers were stimulated by imiquimod and the TLR7-specific interferon-α(IFN-α) and interleukin-6 (IL-6) secretions were detected.Logistic regression was used to analyze for genotype frequency.Results The frequencies of rs3853839 genotype CC and CG in female patients of severe group were significantly higher than mild group (rs3853839 GC: OR=0.36,95%CI:0.14-0.82, P=0.01;rs3853839 CC: OR=0.19,95%CI:0.11-0.69,P=0.01).In addition, the frequency of rs3853839 genotype C in severe male group was significantly higher compared with that in mild group (OR=0.35,95%CI:0.19-0.63, P=0.01).Female carriers with rs3853839 genotype CC had significantly lower TLR7 mRNA expression than genotype GC and GG (CC vs GG: P=0.005;CC vs GC: P=0.016).Male carriers with rs3853839 genotype C also had significantly lower TLR7 mRNA expression than genotype G (C vs G: P=0.004).After stimulation of imiquimod, the expression of IFN-α (CC vs GG, P=0.001;CC vs GC: P=0.026) and IL-6 productions (CC vs GG: P=0.001;CC vs GC: P=0.011) were significantly lower in female carriers with rs3853839 genotype CC.The same patterns were observed in male carriers with rs3853839 genotype CC (IFN-α: P=0.003;IL-6: P=0.018).Conclusions The rs3853839C allele is the risk factor of severe infection of EV71, which may be due to specific cytokine profiles in rs3853839C allele carriers in children.

Clinical significance of inflammatory factors in severe EV71 hand-foot-and-mouth disease / 中国感染控制杂志

Objective To investigate the clinical significance of 5 kinds of inflammatory factors (MCP 1,IL 1β,IL-18,HMGB1,and IL-10) in severe EV71 hand-foot-and-mouth disease (HFMD).Methods Hospitalized children who were diagnosed with severe EV71 HFMD in a hospital in March August,2014 were as HFMD group,healthy children who underwent physical examination in outpatient department of the same hospital during the sameperiod were as control group,changes in expression levels of peripheral blood MCP-1,IL-1β,IL-18,HMGB1,and IL-10 of both groups were dynamically observed,clinical data of HFMD group were collected.Results There were 102 children in HFMD group,the average age was (2.18 ± 0.91) years old,80.39％ of whom were ≤3 years old;there were 77,16,and 9 cases in HFMD group at stage 2,3,and 4 respectively at admission.77,52,21,and 88 cases went through stage 2,3,4,and 5 respectively.Expression levels of 5 kinds of inflammatory factors at stage 2,3,and 4 in HFMD group were compared respectively with control group,differences were all statistically significant(all P＜0.05);expression levels of IL-10 at stage 3 and 4 in HFMD group were not significantly different (P＞0.05).In HFMD group,the expression levels of HMGB1 of stage 2,3 progression groups were both higher than recovery group(both P＜0.05).The expression levels of 5 kinds of inflammatory factors in the death group and survival group at admission were all significantly different (all P＜0.05).Conclusion The expression levels of MCP 1,HMGB1,IL-1β,IL-10,and IL-18 are closely related to the severity of HFMD,and has certain clinical significance for the prognosis of children.HMBG1 has certain predictive value in the prognosis of HFMD.

Enterovirus 71 infection and neurological complications / 소아과

Since the outbreak of the enterovirus 71 (EV71) infection in Malaysia in 1997, large epidemics of EV71 have occurred in the Asia-Pacific region. Many children and infants have died from serious neurological complications during these epidemics, and EV71 infection has become a serious public health problem in these areas. EV71 infection causes hand, foot and mouth disease (HFMD) in children, and usually resolves spontaneously. However, EV71 occasionally involves the central nervous system (CNS), and induces diverse neurological complications such as brainstem encephalitis, aseptic meningitis, and acute flaccid paralysis. Among those complications, brainstem encephalitis is the most critical neurological manifestation because it can cause neurogenic pulmonary hemorrhage/edema leading to death. The characteristic clinical symptoms such as myoclonus and ataxia, cerebrospinal fluid (CSF) pleocytosis, and brainstem lesions on magnetic resonance imaging, in conjunction with the skin rash of HFMD and the isolation of EV71 from a stool, throat-swab, or CSF sample are typical findings indicating CNS involvement of EV71 infection. Treatment with intravenous immunoglobulin and milrinone are recommended in cases with severe neurological complications from EV71 infection, such as brainstem encephalitis. Despite the recent discovery of receptors for EV71 in human cells, such as the scavenger receptor B2 and P-selection glycoprotein ligand 1, it is not known why EV71 infection predominantly involves the brainstem. Recently, 3 companies in China have completed phase III clinical trials of EV71 vaccines. However, the promotion and approval of these vaccines in various countries are problems yet to be resolved.

Research progress of human enterovirus 71 vaccine / 中华实用儿科临床杂志

Human enterovirus 71 (HEV71) is a major causative agent of hand,foot and mouth disease.Children infection with HEV71 can lead to series of neurological complications including aseptic meningitis,cerebral ataxia and even fatal outcomes.During recent decades,epidemic of hand,foot and mouth disease have occurred in many countries and regions in the world,which has become a major public health problem for children's health.There are no specific antiviral drugs for HEV71 infection,so it is necessary to develop safe and effective vaccine.In recent years,the research on HEV71 vaccine has made a breakthrough,and this article reviews the research progress of the vaccine.

Clinical Profile of Hand, Foot, and Mouth Disease and its Associated Complications among Children in Shimoga City, Southern Karnataka: A Hospital-Based Study.

Hand, foot, and mouth disease (HFMD) is one of the important public health problems. It has become a common childhood illness in our part of the country. In most instances, this is a mild self-limiting illness. The affected children are often given outpatient care. However, over the last decade, HFMD has emerged as a growing health problem in Asian countries following frequent outbreaks of deaths associated with HFMD caused by a more virulent member of human enterovirus (HEV), namely, HEV71. A hospital-based descriptive study about the clinical presentations and complications of HFMD at the hospitals of Shimoga city between March 2013 and August 2013 is documented and presented here. HFMD was more common in the 1-3-year old age group, with aseptic meningitis being the most common complication. Surveillance of HFMD must be maintained as there is no effective chemoprophylaxis or vaccine available.

Systemic antibody response to nano-size calcium phospate biocompatible adjuvant adsorbed HEV-71 killed vaccine

PURPOSE: Since 1980s, human enterovirus-71 virus (HEV-71) is one of the common infectious disease in Asian Pacific region since late 1970s without effective commercial antiviral or protective vaccine is unavailable yet. The work examines the role of vaccine adjuvant particle size and the route of administration on postvaccination antibody response towards HEV-71 vaccine adsorbed to calcium phosphate (CaP) adjuvant. MATERIALS AND METHODS: First, CaP nano-particles were compared to a commercial micro-size and vaccine alone. Secondly, intradermal reduced dosage was compared to the conventional intramuscular immunization. Killed HEV-71 vaccines adsorbed to CaP nano-size (73 nm) and commercial one of micro-size (1.7 microm) were administered through intradermal, intramuscular, rabbits received vaccine alone and unvaccinated animals. RESULTS: CaP nano-particles adsorbed HEV-71 vaccine displayed higher antibody than the micro-size or unadsorbed vaccine alone, through both parenteral immunization routes. Moreover, the intradermal route (0.5 microg/mL) of 0.1-mL volume per vaccine dose induced equal IgG antibody level to 1.0-mL intramuscular route (0.5 microg/mL). CONCLUSION: The intradermal vaccine adsorbed CaP nano-adjuvant showed safer and significant antibody response after one-tenth reduced dose quantity (0.5 microg/mL) of only 0.1-mL volume as the most suitable protective, cost effective and affordable formulation not only for HEV-71; but also for developing further effective vaccines toward other human pathogens.

Hand, foot and mouth disease in yangpu district of shanghai: An analysis of epidemiologic characteristics in 2009-2013 / 第二军医大学学报

Objective To analyze the etiological and epidemiological characteristics of hand, foot and mouth disease (HFMD) in Yangpu District of Shanghai from 2009 to 2013, providing evidence for its prevention and control. Methods HFMD surveillance and report were done using the National Disease Supervision Information Management System. Descriptive epidemiological method was used to analyze the 2009-2013 epidemiologic characters and etiological characters (partial patients) of HFMD in Yangpu District, Shanghai. Nucleic acid of enterovirus (EV) genome was detected by real-time PCR in some patients. Results A total of 4 974 cases of HFMD were reported during 2009-2013 in Yangpu District, Shanghai, with the average annual incidence rate of 755.3 per million, with no death cases and 9 (0.18%) severe cases. The peak incidence was observed in the period of April to July. The epidemic peak had an increasing tendency and could be delayed. The incidence rates of HFMD were increased at an annual basis(Ptrend<0.05) in all communities and were significantly different between different communities (P<0.05). Most of the cases were less than 5-year-old scattered and childcare children. The main epidemic strains were EV71 and Cox A16 in 2010, and other enterovirus and Cox A16 in 2011-2013. The proportions of other enterovirus strains were increased, with overlapping phenomenon found in the pathogenic spectrum curves before and after the epidemic peak. Conclusion The 2009-2013 epidemiology of HFMD in Yangpu District of Shanghai had prominent seasonal, regional and population characteristics. Epidemic superiority strains vary annually and influence the epidemic trend and severity.

Hand, foot, and mouth disease: Current scenario and Indian perspective.

Hand, foot, and mouth disease (HFMD), first reported in New Zealand in 1957 is caused by Coxsackievirus A16 (CVA16) and human enterovirus 71 (HEV71) and occasionally by Coxsackievirus A4-A7, A9, A10, B1-B3, and B5. This is characterized by erythematous papulo vesicular eruptions over hand, feet, perioral area, knees, buttocks and also intraorally mostly in the children. HFMD has been known for its self limiting course. Only small scale outbreaks have been reported from United States, Europe, Australia, Japan and Brazil for the first few decades. However, since 1997 the disease has conspicuously changed its behavior as noted in different Southeast Asian countries. There was sharp rise in incidence, severity, complications and even fatal outcomes that were almost unseen before that period. Following the near complete eradication of poliovirus, HEV71, the non-polio enterovirus, may become the greatest threat to cause significant neurological complications. This adds to the fact that effective therapy or vaccine is still a far reaching goal. There are reports of disease activity in different corners of India since 2004. Although of milder degree, continuous progress to affect larger parts of the country may indicate vulnerability of India from possible future fatal outbreaks. Low level of awareness among the health care providers may prove critical.

Etiologic and epidemiologic analysis of hand, foot, and mouth disease in Guangzhou city: a review of 4,753 cases

OBJECTIVES: This study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (HFMD) cases that occurred between 2008 and 2010 in Guangzhou City, to help develop and implement precautionary measures applicable for future outbreaks. METHODS: The characteristics of 4,753 HFMD episodes were retrospectively reviewed in 4,636 patients reported between 2008 and 2010 by the Guangdong Women and Children's Hospital, which is the national enterovirus monitoring agent and the designated hospital in China for treating severe HFMD. RESULTS: Out of 4,753 incident episodes reviewed, 525 patients were hospitalized; 60% were males. Most patients (93.8%) were children under 5 years old, with a median age at onset of 2.4 years. HFMD incidence peaked in April/May and September/October. From the total, 1,067 (22.4%) infections were positive for human enterovirus 71 (HEV71), 1,094 (23.0%) were positive for coxsackievirus A16 (CA16), and 941 (19.8%) were positive for other common enteroviruses. In contrast, 1,666 (35.0%) cases were negative to HEV71, CA16, and other common enteroviruses. Cross-correlation coefficients demonstrated associations between the number of cases, seasonal temperatures, and humidity. Among hospitalized cases, HEV71 was positive in 261 (24.5%), and 42 (3.9%) critical cases were positive for HEV71. CONCLUSION: Seasonal fluctuations and HEV71 and CA16 were the two key factors influencing the Guangzhou HFMD epidemic. The infection predominantly affected children younger than 5 years old.

A case of Enterovirus 71 Infection Presented with Acute Flaccid Paralysis in Jeju Island

Most human enterovirus 71 (EV71) infections present with mild conditions such as hand-foot-mouth disease or herpangina. However, EV71 can invade the central nervous system, causing neurologic diseases such as brainstem encephalitis, meningitis and acute flaccid paralysis despite the near complete eradication of polioviruses. Neurological complications from EV71 infection occur within a few days and can lead to death even though rare. There is no report for EV71 infection with severe neurological manifestation in Jeju Island so far. We therefore report a case of EV 71 infection with bilateral acute flaccid paralysis for the first time in Jeju Island with review of related articles.

A Case of Enterovirus 71 Infection Presented with Acute Flaccid Paralysis

Hand-foot-mouth disease (HFMD) is characterized by distinctive skin lesions on the hand, foot, and mouth and in general, recovery occurs within one week. However, in cases of HFMD by enterovirus 71 (EV71) infection, the development of neurologic complications such as brainstem encephalitis, acute flaccid paralysis, and aseptic meningitis has been common. Moreover, it has been reported that some patients with neuologic complications have expired in severe cases. Here, we report a case of EV71 infection presented with acute flaccid paralysis of a single similar to paralytic poliomyelitis.

Enterovirus 71-associated hand, foot and mouth diseases with neurologic symptoms, a university hospital experience in Korea, 2009 / 소아과

PURPOSE: Hand-foot-mouth disease (HFMD) is a common viral illness in children, which is usually mild and self-limiting. However, in recent epidemics of HFMD in Asia, enterovirus 71 (EV71) has been recognized as a causative agent with severe neurological symptoms with or without cardiopulmonary involvement. HFMD was epidemic in Korea in the spring of 2009. Severe cases with complications including death have been reported. The clinical characteristics in children with neurologic manifestations of EV71 were studied in Ewha Womans University Mokdong Hospital. METHODS: Examinations for EV71 were performed from the stools, respiratory secretion or CSF of children who presented neurologic symptoms associated with HFMD by realtime PCR. Clinical and radiologic data of the patients were collected and analyzed. RESULTS: EV71 was isolated from the stool of 16 patients but not from respiratory secretion or CSF. Among the 16 patients, meningitis (n=10) was the most common manifestation, followed by Guillain-Barre syndrome (n=3), meningoencephalitis (n=2), poliomyelitis-like paralytic disease (n=1), and myoclonus (n=1). Gene analysis showed that most of them were caused by EV71 subgenotype C4a, which was prevalent in China in 2008. CONCLUSION: Because EV71 causes severe complications and death in children, a surveillance system to predict upcoming outbreaks should be established and maintained and adequate public health measures are needed to control disease.

Positive Selection Analysis of VP1 Genes of Worldwide Human Enterovirus 71 Viruses / 中国病毒学·英文版

Human enterovirus 71 viruses have been long circulating throughout the world. In this study, we performed a positive selection analysis of the VP1 genes of capsid proteins from Enterovirus 71 viruses. Our results showed that although most sites were under negative or neutral evolution, four positions of the VP1 genes were under positive selection pressure. This might account for the spread and frequent outbreaks of the viruses and the enhanced neurovirulence. In particular, position 98 might be involved in neutralizing antibodies, modulating the virus-receptor interaction and enhancing the virulence of the viruses. Moreover, both positions 145 and 241 might correlate to determine the receptor specificity. However, these positions did not display much difference in amino acid polymorphism. In addition, no position in the VP1 genes of viruses isolated from China was under positive selection.