Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the cr...Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.展开更多
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...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 CCID50 perμL and copies perμL,and the newly established methods were tested in clinical specimens collected in recent years.Results The sensitivity of RT-nPCR assays for amplifying partial VP1 gene of HEVs was 0.1 CCID50 perμL and 10 virus copies perμL,and for the complete VP1 gene was 1 CCID50 perμL and 100 virus copies perμL,using serially-diluted virus stocks of five serotypes.As a proof-of-concept,25 serotypes were identified and complete VP1 sequences of 23 serotypes were obtained by this system among 858 clinical specimens positive for HEVs during the past eight surveillance seasons.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.展开更多
Human enterovirus 71(HEV71) is the cause of hand,foot and mouth disease and associated neurological complications in children under five years of age.There has been an increase in HEV71 epidemic activity throughout th...Human enterovirus 71(HEV71) is the cause of hand,foot and mouth disease and associated neurological complications in children under five years of age.There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade,and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved.展开更多
We report a case of virus-induced acute respiratory distress syndrome(ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first...We report a case of virus-induced acute respiratory distress syndrome(ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth Universitywith vitamin C and with the very positive results of a previously performed phase Ⅰ safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation(ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient's recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes.展开更多
BACKGROUND Hand,foot,and mouth disease(HFMD)has become one of the most common infectious diseases in China.Before 2016,the primary causal serotypes were enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16).Following ...BACKGROUND Hand,foot,and mouth disease(HFMD)has become one of the most common infectious diseases in China.Before 2016,the primary causal serotypes were enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16).Following the introduction of EV-A71 vaccines in China since 2016,the situation could change.CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China.However,the epidemiological characteristics of central China remain unknown.AIM To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City,central China,in recent years.METHODS The epidemiological,clinical,and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed.196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020.To detect and genotype enteroviruses,real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used.In Shiyan,168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes.Based on the logistic regression model,the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan.RESULTS From 2016 to 2020,35840 HFMD cases were reported in Shiyan.The number of cases decreased by 48.4%from 2016 to 2017.Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year,respectively.In 2020,a decrease of about 85.5%was reported when compared to 2019.The most common serotypes shifted from EV-A71 and CV-A16(about 60%-80%in 2016 and 2018)to others(more than 80.0%in 2017,2019,and 2020).EV-A71 lost its dominance in 2017 in Shiyan.Among 196 confirmed HFMD cases,85.7%tested positive for enterovirus,with CV-A6 being the most common serotype(121/168,72.0%).The positive rates for CV-A16 and CVA10 were 4.8%and 3.0%,respectively.There was no EV-A71 discovered.Infection with CV-A6 was linked to fever,myocardial damage,increased creatine kinase MB isoenzyme,and lactate dehydrogenase levels.CONCLUSION CV-A6 was the most common enterovirus serotype in Shiyan City,replacing EV-A71 and CV-A16 as the HFMD pathogen.Developing vaccines against CV-A6 or multiple pathogens,as well as rising CV-A6 surveillance,will help prevent HFMD in central China.展开更多
A sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for human enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) infection was further evaluated. The one step reaction was perfor...A sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for human enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) infection was further evaluated. The one step reaction was performed in a single tube at 65?C for 45 min for EV71 and 35 min for CVA16. The detection limits of RT-LAMP assays for both EV71 and CVA16 were 0.1 of a 50% tissue culture infective dose (TCID50) per reaction, based on 10—Fold dilutions of a titrated EV71 or CVA16 strain. The specific assay showed there were no cross-reactions with Coxsackievirus A (CVA) viruses (CVA 2, 4, 5, 7, 9, 10, 14, and 25), Coxsackievirus B (CVB) viruses (CVB 1, 2, 3, 4, and 5) or ECHO viruses (ECHO 3, 6, 11, and 19). In parallel with commercial quantitative real-time polymerase chain reaction (qRT-PCR) diagnostic kits for EV71 and CVA16, the RT-LAMP assay was evaluated with 515 clinical specimens, the results showed the RT-LAMP assay and the qRT-PCR assay were in complete agreement for 513/515 (99.6%) of the specimens. Two samples with discrepant results from two methods were further verified by nested reverse transcription polymerase chain reaction (nRT-PCR) assay and sequencing to be true positives for CVA16. In conclusion, RT-LAMP assay is demonstrated to be a sensitive and specific assay and have a great potential for the rapid and visual screening of EV71 and CVA16 in China, especially in those resource-limited hospitals and rural clinics of provincial and municipal regions.展开更多
Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71(EV71) associated with pancreatitis has b...Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71(EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease(HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient's symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.展开更多
Recent improvement in the technologies for efficient delivery of DNA vaccines has renewed interest in the DNA-based vaccines. Several DNA-based vaccines against human enterovirus 71 (EV71), the causative agent for han...Recent improvement in the technologies for efficient delivery of DNA vaccines has renewed interest in the DNA-based vaccines. Several DNA-based vaccines against human enterovirus 71 (EV71), the causative agent for hand, foot and mouth disease (HFMD) have been developed. Here we examined the potential of improving the vaccines by inserting the EV71 5’ untranslated region (5’ UTR) containing the full length internal ribosome entry site (IRES) sequence to the EV71 VP1-based DNA vaccine constructs. Four vaccine constructs designated as 5’ UTR-VP1/EGFP, VP1/EGFP, 5’ UTR-VP1/pVAX and VP1/pVAX, were designed using the pEGFP-N1 and pVAX-1 expression vectors, respectively. Transfection of Vero cells with the vaccine constructs with the 5’-UTR (5’-UTR-VP1/EGFP and 5’ UTR-VP1/pVAX) resulted in higher percentages of cells expressing the recombinant protein in comparison to cells transfected with vectors without the 5’-UTR (67% and 57%, respectively). Higher IgG responses (29%) were obtained from mice immunized with the DNA vaccine construct with the full length 5’ UTR. The same group of mice when challenged with life EV71 produced significantly higher neutralizing antibody (NAb) titers (>5-fold). These results suggest that insertion of the EV71 5’ UTR sequence consisting of the full length IRES to the EV71 DNA vaccine constructs improved the efficacy of the constructs with enhanced elicitation of the neutralizing antibody responses.展开更多
After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evid...After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evidence of mild chronic inflammation are often considered as normal findings since no etiology could be found other than H. Pylori. Enteroviruses infect the gastrointestinal tract and have been shown to persist in the stomach of symptomatic patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we evaluated FD patients with and without the diagnosis of ME/CFS, and were able to support the viral protein staining with finding of double-stranded RNA in 63% of the same stomach biopsies by immunoperoxidase staining. Furthermore, we clarified the possible cross-reaction with creatine kinase brain subtype (CKB), present in parietal cells, using antibody competition experiments and western blot analysis of stomach proteins. Viral protein+ and dsRNA+ biopsies were infectious in SCID mice. More research is needed to elucidate the mechanism of enterovirus infection of the stomach associated with FD and chronic gastritis.展开更多
Hand, foot, and mouth disease (HFMD) is a common infectious disease in children, occurring primarily in preschool children[1_3] with infants under three years old being gen erally susceptible. The disease is caused by...Hand, foot, and mouth disease (HFMD) is a common infectious disease in children, occurring primarily in preschool children[1_3] with infants under three years old being gen erally susceptible. The disease is caused by various enteroviruses, among which EV71 and Coxsackievirus A group 16 (Cox A16) are the most comm on ⑷.According to in formation released by the Chinese Center for Disease Control and Prevention on June 8, 2016, EV71 infection- related HFMD has been prevalent among infants and young children in China since 2007, with a high incidenee and many deaths.展开更多
For rapid diagnosis of enteroviral infection in clinic practice, we developed a reverse transcription and polymerase chain reaction (RT-PCR) assay.Primers homologous to the conserved 5’ non-coding region were designe...For rapid diagnosis of enteroviral infection in clinic practice, we developed a reverse transcription and polymerase chain reaction (RT-PCR) assay.Primers homologous to the conserved 5’ non-coding region were designed by analyzing enteroviral genomes, and then they were used to enzymatically amplify RNA from 31 prototype enteroviral strains and enteroviruses (EV) in cerebrospinal fluid (CSF) of 34 cases of aseptic meningitis and 11 cases of aseptic encephalitis. The RT-PCR products generated with these enteroviral primers were analyzed by agar gel electrophoresis and dot blot hybridization analysis. 31 EV strains showed an obvious monoclonal amplification band, and all dot blot hybridization results were positive. Four other viruses and cells cultured were all negative. The study of sensitivity of the RT-PCR showed that amplification production were positive to 10(-2)- 10(-3) 50% tissue culture infective doses. With this assay, 21(61.8%) of 34 aseptic meningitis and 8 (72. 7%) of 11 aseptic encephalitis contained EV RNA in CSF samples. Two cases of meningitis and one of encephalitis with EV infection were still positive during convalescence. Our results suggest that this RT-PCR method was a fast, sensitive and specific technique for detection of common EV infection.展开更多
A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus(T1DM) establishment. Environmental factors may initiate and possibly sustai...A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus(T1DM) establishment. Environmental factors may initiate and possibly sustain, accelerate, or retard damage to β-cells. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of human enterovirus in the pathogenesis of T1 DM. The genetic risk of T1 DM and particular innate and acquired immune responses to enterovirus infection contribute to a tolerance to T1DM-related autoantigens. However, the frequency, mechanisms, and pathways of virally induced autoimmunity and β-cell destruction in T1 DM remain to be determined. It is difficult to investigate the role of enterovirus infection in T1 DM because of several concomitant mechanisms by which the virus damages pancreatic β-cells, which, consequently, may lead to T1 DM establishment. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective.展开更多
Objective:To study the recombination events among enterovirus strains and the development of specific primers for the detection of enteroviruses in environmental samples.Methods: Nucleotide sequence analysis of entero...Objective:To study the recombination events among enterovirus strains and the development of specific primers for the detection of enteroviruses in environmental samples.Methods: Nucleotide sequence analysis of enteroviruses deposited in the international database GenBank （www.ncbi.nlm.nih.gov/Genbank） was conducted to develop specific primers for the detection of these viruses.The specificity and sensitivity of the method were tested using coxackicvirus B3 strain Nancy,environmental isolate of human hepatitis A virus and human rotavirus strain WA.Seventy sewage samples were analyzed.Results:Enterovirus genome was detected in all positive samples.The genome of enterovirus was not detected in negative samples.The level of detection of these viruses was 10<sup>2</sup> TCID<sub>50</sub>mI..Conclusions:The development of new primers is an important issue for the detection of enteroviruses in the environment and the assessment of risk factors to human health.展开更多
BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in children.At the end of 2018,some children with such symptoms were admitted to our hospital.In this study,we aimed to assess two...BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in children.At the end of 2018,some children with such symptoms were admitted to our hospital.In this study,we aimed to assess two children with AFP and neurogenic respiratory failure associated with enterovirus D68(EV-D68).CASE SUMMARY Two children admitted to our hospital presented with symptoms and imaging results different from those of acute disseminated encephalomyelitis and hand,foot,and mouth disease.Their main symptoms were AFP and neurogenic respiratory failure.Magnetic resonance imaging showed severe inflammatory injury mainly to the anterior horn cells of the spinal cord.Blood and cerebrospinal fluid samples were collected to assess for pathogens,including bacteria,tuberculosis,cryptococcus,herpes virus,and coxsackie virus,and the results were negative.At the beginning,the two cases were not assessed for EV-D68 in the nasopharyngeal,blood,and cerebrospinal fluid specimens.About 2 mo later,EVD68 was detected in the stool sample of one of the cases.The symptom of AFP was caused by injury to the anterior horn cells at levels C5-L5 of the spinal cord,while neurogenic respiratory failure was at levels C3-C5.CONCLUSION We should pay attention to the detection and diagnosis of EV-D68 and make efforts to develop antivirus drugs and vaccines.展开更多
Background: While we are inching towards global eradication of polio, the paralysis due to non-polio viruses (NPEV) poses greater challenge. Factors responsible for causing Acute Flaccid Paralysis (AFP) were studied i...Background: While we are inching towards global eradication of polio, the paralysis due to non-polio viruses (NPEV) poses greater challenge. Factors responsible for causing Acute Flaccid Paralysis (AFP) were studied in 3596 AFP patients in 64 districts of Uttar-Pradesh, India, to observe indirect relationship of AFP with wild polio as well as NPEV. A recent study suggests the need to investigate polio virus negative but NPEV positive AFP cases. Methods: The lab results of the stool samples of these children were line listed and analysed to observe the association of various factors with respect to presence of paralysis on 60 follow-up days. Taking zero OPV dose AFP cases as a biological base, we studied the relationship of presence of paralysis at 60 follow-up days to that of presence of NPEV in stool samples while polio virus was present or absent. Results: 70 of the 86 AFP cases (81%) with zero OPV dose and having only NPEV isolated in stool samples were having paralysis at 60 follow-up days. There were 4.54% (162) AFP cases, which did not carry any polio virus but were having NPEV isolated in the stool samples and paralysis at 60 follow-up days. 79% (75/95) of zero OPV dose children, who were having residual weakness at 60 follow-up days, were carrying both polio virus as well as NPEV in their stool samples. Total AFP cases, having residual weakness at 60 follow-up days and having NPEV in stool samples, decreased with increase in OPV doses;a behavior similar to what wild polio viruses (WPV) have to OPV. Conclusions: Maybe polio like NPEV is active for causing severe paralysis in children and is responding to the OPV. As is evident in the studies by M. Margalith, B. Fattal et al. [1] that there is an antibody response to the enteroviruses, we can think of coming out with a vaccine against the enteroviruses. Therefore, enterovirus vaccine can be produced on similar lines to that of OPV, as now we have enough isolates of NPEV. Effective NPEV surveillance system also needs to be in place.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">Enteroviruses are responsible for emerging diseases which cause diverse symptoms and may result in neurological comp...<div style="text-align:justify;"> <span style="font-family:Verdana;">Enteroviruses are responsible for emerging diseases which cause diverse symptoms and may result in neurological complications. An antiviral with multiple mechanisms of action can help prevent enterovirus mediated disease despite differences in the pathogenesis between enteroviruses, including the recently identified enterovirus 69 (EV-69) for which pathogenesis is not well understood. This study investigated the efficacy of epigallocatechin-3-gallate stearate (EGCG-S), a modified form of the antioxidant green tea catechin epigallocatechin-3-gallate (EGCG), in inhibiting EV-69 infection of lung fibroblast cells </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;">. Treatment with EGCG-S resulted in moderate protection from EV-69 mediated cytotoxicity as demonstrated by increased metabolic activity as well as maintenance of cell morphology and mitochondrial function. These effects were correlated with reduced hydrogen peroxide production in infected cells following EGCG-S treatment with concentrations less than 100 μM, suggesting a role for inhibition of EV-69 mediated oxidative stress. This study provides insight into characteristics of EV-69 infection as well as the efficacy of EGCG-S mediated inhibition of EV-69 infection.</span> </div>展开更多
Human enteroviruses are less well-known causes of acute bronchiolitis. In recent years, Enterovirus D68 [EV D68] has emerged as significant cause of epidemic viral bronchiolitis and pneumonia in the United States and ...Human enteroviruses are less well-known causes of acute bronchiolitis. In recent years, Enterovirus D68 [EV D68] has emerged as significant cause of epidemic viral bronchiolitis and pneumonia in the United States and other countries. Chronic bronchiolitis has not been previously attributed to EV D68. We documented EV D68 in open lung biopsies of a young adult patient who was frequently admitted to the hospital for severe exacerbation of respiratory infections and subsequently developed progressive respiratory insufficiency. The difficulty of diagnosis and potential economic impact of this illness is discussed.展开更多
Environmental surveillance (ES) is a useful approach for monitoring circulating viruses, including polioviruses (PVs) and non-polio enteroviruses (NPEVs). In this study, the results of nine years of ES from 2013 to 20...Environmental surveillance (ES) is a useful approach for monitoring circulating viruses, including polioviruses (PVs) and non-polio enteroviruses (NPEVs). In this study, the results of nine years of ES from 2013 to 2021 at six sampling sites in three cities in Fujian Province, China, were summarized. It showed that the sewage samples contained abundant viruses, but the positive rate was affected by different sampling sites. From the 520 samples, 431 PVs, 1,713 NPEVs, and 281 human adenoviruses (HAdVs) were isolated. PV isolates had been markedly affected following the adjustment of the immunization strategy. All but one PV isolate were Sabin-like strains without wild PVs. One isolate was vaccine-derived PV type 3 with 10 variation points in theVP1 region. After May 2016, PV type 2 was no longer detected, and PV type 3 became a superior serotype. Of 1,713 NPEVs, 24 serotypes were identified, including echovirus11 (E11), E6, coxsackievirus B3 (CVB3), CVB5, E7, and E3 were the predominant serotypes (37.65%, 20.96%, 11.50%, 8.87%, 8.23%, and 7.06%, respectively). The temporal dynamic of the six common serotypes was inconsistent. E3 was frequently isolated, but the number of isolates was low, with no obvious peaks. E6, E7, and CVB3 exhibited periodic changes with a high peak every three to four years, and E11 only had one high peak lasting four years. Summer-fall peaks of the echoviruses and spring-winter peaks of CVB were observed in the monthly distribution of virus isolation. The infectious isolates of various serotypes of different species identified from the sewage samples showed that ES is an essential part of pathogen surveillance.展开更多
基金funded by the Hainan Natural Science Foundation 310119Haiman Health Institution Project(No 2011-22)
文摘Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.
基金funded by Natural Science Foundation of Zhejiang(LQ14C010006)National Natural Science Foundation of China(81501363)Planned Science and Technology Project of Zhejiang(2014C33261)
文摘在现在的学习，完全的染色体四普通(4/EV71/Wenzhou/CHN/2014， 15/EV71/Wenzhou/CHN/2014， 116/EV71/Wenzhou/CHN/2014，和 120/EV71/Wenzhou/CHN/2014 ) 并且二剧毒(11/EV71/Wenzhou/CHN/2014 和 109/EV71/Wenzhou/CHN/2014 ) enterovirus (EV71 ) 71 孤立被定序并且描述。他们是在长度的 7405 bp 并且属于 EV71 亚遗传型 C4 (C4a 簇) 。核苷酸顺序排列揭示了六个核苷酸变化( G <sup > P151 </sup > T <sup > P151 </sup>, G <sup > P199 </sup > <sup > P199 </sup>, G <sup > P261 </sup > T <sup > P261 </sup>, A <sup > P328 </sup > C <sup > P328 </sup>, G <sup > P422 </sup > <sup > P422 </sup>,和 G <sup > P437 </sup > T <sup > P437 </sup>)在二剧毒在 IRES 元素的 5UTR 以内孤立。怒火和 FCE 的 RNA 第二等的结构预言显示普通孤立分享的类似的结构，它与那些不同剧毒孤立。而且， G <sup > P114 </sup > C <sup > P114 </sup> 和 G <sup > P151 </sup > T <sup > P151 </sup> 变化在剧毒孤立在 SL II 贡献了唯一的 RNA 第二等的结构的形成。而且， EV71 孤立的 82 的 nucleotide/amino 酸顺序排列显示了那六个地点(T <sup > P488 </sup> 和 C <sup > 在 5UTR 的 P577 </sup> ；Asn <sup > 在 2A 的 P57 </sup> ；Ile <sup > 在 3C 的 P56 </sup> ；C <sup > P10 </sup> 和 A <sup > 在 3UTR 的 P47 </sup>) 潜在地与 EV71 的 neurovirulence 被联系。最后， 2A 的 3D 结构是类似的，而 VP1 和 3C 的结构是可变的。
基金National Science and Technology Major Projects[No.2017ZX10104001 and No.2017ZX10103008]Fujian Provincial Natural Science Foundation[No.2016J01350]。
文摘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 CCID50 perμL and copies perμL,and the newly established methods were tested in clinical specimens collected in recent years.Results The sensitivity of RT-nPCR assays for amplifying partial VP1 gene of HEVs was 0.1 CCID50 perμL and 10 virus copies perμL,and for the complete VP1 gene was 1 CCID50 perμL and 100 virus copies perμL,using serially-diluted virus stocks of five serotypes.As a proof-of-concept,25 serotypes were identified and complete VP1 sequences of 23 serotypes were obtained by this system among 858 clinical specimens positive for HEVs during the past eight surveillance seasons.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.
文摘Human enterovirus 71(HEV71) is the cause of hand,foot and mouth disease and associated neurological complications in children under five years of age.There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade,and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved.
基金supported by the Aubrey Sage McF arlane acute lung injury fund, the VCU Johnson Center for Critical Care and Pulmonary Research
文摘We report a case of virus-induced acute respiratory distress syndrome(ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth Universitywith vitamin C and with the very positive results of a previously performed phase Ⅰ safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation(ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient's recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes.
基金Supported by the Hubei Province Health and Family Planning A Scientific Research Project,No.WJ2017M220the Wuhan Health Bureau Scientific Research Fund,No.WX19C11+2 种基金the Joint Precision Medical Research Fund From Taihe Hospital,No.2016JZ10the Shiyan COVID-19 Pilot Emergency Scientific Research Project,No.20Y19the Wuhan Children's Hospital Research Project,No.2017FE007.
文摘BACKGROUND Hand,foot,and mouth disease(HFMD)has become one of the most common infectious diseases in China.Before 2016,the primary causal serotypes were enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16).Following the introduction of EV-A71 vaccines in China since 2016,the situation could change.CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China.However,the epidemiological characteristics of central China remain unknown.AIM To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City,central China,in recent years.METHODS The epidemiological,clinical,and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed.196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020.To detect and genotype enteroviruses,real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used.In Shiyan,168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes.Based on the logistic regression model,the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan.RESULTS From 2016 to 2020,35840 HFMD cases were reported in Shiyan.The number of cases decreased by 48.4%from 2016 to 2017.Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year,respectively.In 2020,a decrease of about 85.5%was reported when compared to 2019.The most common serotypes shifted from EV-A71 and CV-A16(about 60%-80%in 2016 and 2018)to others(more than 80.0%in 2017,2019,and 2020).EV-A71 lost its dominance in 2017 in Shiyan.Among 196 confirmed HFMD cases,85.7%tested positive for enterovirus,with CV-A6 being the most common serotype(121/168,72.0%).The positive rates for CV-A16 and CVA10 were 4.8%and 3.0%,respectively.There was no EV-A71 discovered.Infection with CV-A6 was linked to fever,myocardial damage,increased creatine kinase MB isoenzyme,and lactate dehydrogenase levels.CONCLUSION CV-A6 was the most common enterovirus serotype in Shiyan City,replacing EV-A71 and CV-A16 as the HFMD pathogen.Developing vaccines against CV-A6 or multiple pathogens,as well as rising CV-A6 surveillance,will help prevent HFMD in central China.
文摘A sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for human enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) infection was further evaluated. The one step reaction was performed in a single tube at 65?C for 45 min for EV71 and 35 min for CVA16. The detection limits of RT-LAMP assays for both EV71 and CVA16 were 0.1 of a 50% tissue culture infective dose (TCID50) per reaction, based on 10—Fold dilutions of a titrated EV71 or CVA16 strain. The specific assay showed there were no cross-reactions with Coxsackievirus A (CVA) viruses (CVA 2, 4, 5, 7, 9, 10, 14, and 25), Coxsackievirus B (CVB) viruses (CVB 1, 2, 3, 4, and 5) or ECHO viruses (ECHO 3, 6, 11, and 19). In parallel with commercial quantitative real-time polymerase chain reaction (qRT-PCR) diagnostic kits for EV71 and CVA16, the RT-LAMP assay was evaluated with 515 clinical specimens, the results showed the RT-LAMP assay and the qRT-PCR assay were in complete agreement for 513/515 (99.6%) of the specimens. Two samples with discrepant results from two methods were further verified by nested reverse transcription polymerase chain reaction (nRT-PCR) assay and sequencing to be true positives for CVA16. In conclusion, RT-LAMP assay is demonstrated to be a sensitive and specific assay and have a great potential for the rapid and visual screening of EV71 and CVA16 in China, especially in those resource-limited hospitals and rural clinics of provincial and municipal regions.
文摘Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71(EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease(HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient's symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.
文摘Recent improvement in the technologies for efficient delivery of DNA vaccines has renewed interest in the DNA-based vaccines. Several DNA-based vaccines against human enterovirus 71 (EV71), the causative agent for hand, foot and mouth disease (HFMD) have been developed. Here we examined the potential of improving the vaccines by inserting the EV71 5’ untranslated region (5’ UTR) containing the full length internal ribosome entry site (IRES) sequence to the EV71 VP1-based DNA vaccine constructs. Four vaccine constructs designated as 5’ UTR-VP1/EGFP, VP1/EGFP, 5’ UTR-VP1/pVAX and VP1/pVAX, were designed using the pEGFP-N1 and pVAX-1 expression vectors, respectively. Transfection of Vero cells with the vaccine constructs with the 5’-UTR (5’-UTR-VP1/EGFP and 5’ UTR-VP1/pVAX) resulted in higher percentages of cells expressing the recombinant protein in comparison to cells transfected with vectors without the 5’-UTR (67% and 57%, respectively). Higher IgG responses (29%) were obtained from mice immunized with the DNA vaccine construct with the full length 5’ UTR. The same group of mice when challenged with life EV71 produced significantly higher neutralizing antibody (NAb) titers (>5-fold). These results suggest that insertion of the EV71 5’ UTR sequence consisting of the full length IRES to the EV71 DNA vaccine constructs improved the efficacy of the constructs with enhanced elicitation of the neutralizing antibody responses.
基金supported by the Beijing Municipal Science and Technology Commission(Z151100003915140)Capital Medical Development and scientific research fund(2016-2-3011)National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases of China(2016ZX10004206)
文摘After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evidence of mild chronic inflammation are often considered as normal findings since no etiology could be found other than H. Pylori. Enteroviruses infect the gastrointestinal tract and have been shown to persist in the stomach of symptomatic patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we evaluated FD patients with and without the diagnosis of ME/CFS, and were able to support the viral protein staining with finding of double-stranded RNA in 63% of the same stomach biopsies by immunoperoxidase staining. Furthermore, we clarified the possible cross-reaction with creatine kinase brain subtype (CKB), present in parietal cells, using antibody competition experiments and western blot analysis of stomach proteins. Viral protein+ and dsRNA+ biopsies were infectious in SCID mice. More research is needed to elucidate the mechanism of enterovirus infection of the stomach associated with FD and chronic gastritis.
基金supported by the China Mega-Project for Infectious Diseases of the Ministry of Science and Technology and Ministry of Health of the People’s Republic of China [2018ZX10201002]a grant from Science and Technology Department of Hubei Province [2018CFB630]a grant from the ‘ChuTian Scholar’ Project Award,Hubei Province,China
文摘Hand, foot, and mouth disease (HFMD) is a common infectious disease in children, occurring primarily in preschool children[1_3] with infants under three years old being gen erally susceptible. The disease is caused by various enteroviruses, among which EV71 and Coxsackievirus A group 16 (Cox A16) are the most comm on ⑷.According to in formation released by the Chinese Center for Disease Control and Prevention on June 8, 2016, EV71 infection- related HFMD has been prevalent among infants and young children in China since 2007, with a high incidenee and many deaths.
文摘For rapid diagnosis of enteroviral infection in clinic practice, we developed a reverse transcription and polymerase chain reaction (RT-PCR) assay.Primers homologous to the conserved 5’ non-coding region were designed by analyzing enteroviral genomes, and then they were used to enzymatically amplify RNA from 31 prototype enteroviral strains and enteroviruses (EV) in cerebrospinal fluid (CSF) of 34 cases of aseptic meningitis and 11 cases of aseptic encephalitis. The RT-PCR products generated with these enteroviral primers were analyzed by agar gel electrophoresis and dot blot hybridization analysis. 31 EV strains showed an obvious monoclonal amplification band, and all dot blot hybridization results were positive. Four other viruses and cells cultured were all negative. The study of sensitivity of the RT-PCR showed that amplification production were positive to 10(-2)- 10(-3) 50% tissue culture infective doses. With this assay, 21(61.8%) of 34 aseptic meningitis and 8 (72. 7%) of 11 aseptic encephalitis contained EV RNA in CSF samples. Two cases of meningitis and one of encephalitis with EV infection were still positive during convalescence. Our results suggest that this RT-PCR method was a fast, sensitive and specific technique for detection of common EV infection.
文摘A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus(T1DM) establishment. Environmental factors may initiate and possibly sustain, accelerate, or retard damage to β-cells. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of human enterovirus in the pathogenesis of T1 DM. The genetic risk of T1 DM and particular innate and acquired immune responses to enterovirus infection contribute to a tolerance to T1DM-related autoantigens. However, the frequency, mechanisms, and pathways of virally induced autoimmunity and β-cell destruction in T1 DM remain to be determined. It is difficult to investigate the role of enterovirus infection in T1 DM because of several concomitant mechanisms by which the virus damages pancreatic β-cells, which, consequently, may lead to T1 DM establishment. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective.
文摘Objective:To study the recombination events among enterovirus strains and the development of specific primers for the detection of enteroviruses in environmental samples.Methods: Nucleotide sequence analysis of enteroviruses deposited in the international database GenBank （www.ncbi.nlm.nih.gov/Genbank） was conducted to develop specific primers for the detection of these viruses.The specificity and sensitivity of the method were tested using coxackicvirus B3 strain Nancy,environmental isolate of human hepatitis A virus and human rotavirus strain WA.Seventy sewage samples were analyzed.Results:Enterovirus genome was detected in all positive samples.The genome of enterovirus was not detected in negative samples.The level of detection of these viruses was 10<sup>2</sup> TCID<sub>50</sub>mI..Conclusions:The development of new primers is an important issue for the detection of enteroviruses in the environment and the assessment of risk factors to human health.
文摘BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in children.At the end of 2018,some children with such symptoms were admitted to our hospital.In this study,we aimed to assess two children with AFP and neurogenic respiratory failure associated with enterovirus D68(EV-D68).CASE SUMMARY Two children admitted to our hospital presented with symptoms and imaging results different from those of acute disseminated encephalomyelitis and hand,foot,and mouth disease.Their main symptoms were AFP and neurogenic respiratory failure.Magnetic resonance imaging showed severe inflammatory injury mainly to the anterior horn cells of the spinal cord.Blood and cerebrospinal fluid samples were collected to assess for pathogens,including bacteria,tuberculosis,cryptococcus,herpes virus,and coxsackie virus,and the results were negative.At the beginning,the two cases were not assessed for EV-D68 in the nasopharyngeal,blood,and cerebrospinal fluid specimens.About 2 mo later,EVD68 was detected in the stool sample of one of the cases.The symptom of AFP was caused by injury to the anterior horn cells at levels C5-L5 of the spinal cord,while neurogenic respiratory failure was at levels C3-C5.CONCLUSION We should pay attention to the detection and diagnosis of EV-D68 and make efforts to develop antivirus drugs and vaccines.
文摘Background: While we are inching towards global eradication of polio, the paralysis due to non-polio viruses (NPEV) poses greater challenge. Factors responsible for causing Acute Flaccid Paralysis (AFP) were studied in 3596 AFP patients in 64 districts of Uttar-Pradesh, India, to observe indirect relationship of AFP with wild polio as well as NPEV. A recent study suggests the need to investigate polio virus negative but NPEV positive AFP cases. Methods: The lab results of the stool samples of these children were line listed and analysed to observe the association of various factors with respect to presence of paralysis on 60 follow-up days. Taking zero OPV dose AFP cases as a biological base, we studied the relationship of presence of paralysis at 60 follow-up days to that of presence of NPEV in stool samples while polio virus was present or absent. Results: 70 of the 86 AFP cases (81%) with zero OPV dose and having only NPEV isolated in stool samples were having paralysis at 60 follow-up days. There were 4.54% (162) AFP cases, which did not carry any polio virus but were having NPEV isolated in the stool samples and paralysis at 60 follow-up days. 79% (75/95) of zero OPV dose children, who were having residual weakness at 60 follow-up days, were carrying both polio virus as well as NPEV in their stool samples. Total AFP cases, having residual weakness at 60 follow-up days and having NPEV in stool samples, decreased with increase in OPV doses;a behavior similar to what wild polio viruses (WPV) have to OPV. Conclusions: Maybe polio like NPEV is active for causing severe paralysis in children and is responding to the OPV. As is evident in the studies by M. Margalith, B. Fattal et al. [1] that there is an antibody response to the enteroviruses, we can think of coming out with a vaccine against the enteroviruses. Therefore, enterovirus vaccine can be produced on similar lines to that of OPV, as now we have enough isolates of NPEV. Effective NPEV surveillance system also needs to be in place.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">Enteroviruses are responsible for emerging diseases which cause diverse symptoms and may result in neurological complications. An antiviral with multiple mechanisms of action can help prevent enterovirus mediated disease despite differences in the pathogenesis between enteroviruses, including the recently identified enterovirus 69 (EV-69) for which pathogenesis is not well understood. This study investigated the efficacy of epigallocatechin-3-gallate stearate (EGCG-S), a modified form of the antioxidant green tea catechin epigallocatechin-3-gallate (EGCG), in inhibiting EV-69 infection of lung fibroblast cells </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;">. Treatment with EGCG-S resulted in moderate protection from EV-69 mediated cytotoxicity as demonstrated by increased metabolic activity as well as maintenance of cell morphology and mitochondrial function. These effects were correlated with reduced hydrogen peroxide production in infected cells following EGCG-S treatment with concentrations less than 100 μM, suggesting a role for inhibition of EV-69 mediated oxidative stress. This study provides insight into characteristics of EV-69 infection as well as the efficacy of EGCG-S mediated inhibition of EV-69 infection.</span> </div>
文摘Human enteroviruses are less well-known causes of acute bronchiolitis. In recent years, Enterovirus D68 [EV D68] has emerged as significant cause of epidemic viral bronchiolitis and pneumonia in the United States and other countries. Chronic bronchiolitis has not been previously attributed to EV D68. We documented EV D68 in open lung biopsies of a young adult patient who was frequently admitted to the hospital for severe exacerbation of respiratory infections and subsequently developed progressive respiratory insufficiency. The difficulty of diagnosis and potential economic impact of this illness is discussed.
基金funded by Fujian Health System Youth Backbone Talents training project(2013-ZQN-ZD-10)leading(key)project of social development in Fujian Province(2017Y0011)National Key Research and Development Program of China(2021YFC2302003)。
文摘Environmental surveillance (ES) is a useful approach for monitoring circulating viruses, including polioviruses (PVs) and non-polio enteroviruses (NPEVs). In this study, the results of nine years of ES from 2013 to 2021 at six sampling sites in three cities in Fujian Province, China, were summarized. It showed that the sewage samples contained abundant viruses, but the positive rate was affected by different sampling sites. From the 520 samples, 431 PVs, 1,713 NPEVs, and 281 human adenoviruses (HAdVs) were isolated. PV isolates had been markedly affected following the adjustment of the immunization strategy. All but one PV isolate were Sabin-like strains without wild PVs. One isolate was vaccine-derived PV type 3 with 10 variation points in theVP1 region. After May 2016, PV type 2 was no longer detected, and PV type 3 became a superior serotype. Of 1,713 NPEVs, 24 serotypes were identified, including echovirus11 (E11), E6, coxsackievirus B3 (CVB3), CVB5, E7, and E3 were the predominant serotypes (37.65%, 20.96%, 11.50%, 8.87%, 8.23%, and 7.06%, respectively). The temporal dynamic of the six common serotypes was inconsistent. E3 was frequently isolated, but the number of isolates was low, with no obvious peaks. E6, E7, and CVB3 exhibited periodic changes with a high peak every three to four years, and E11 only had one high peak lasting four years. Summer-fall peaks of the echoviruses and spring-winter peaks of CVB were observed in the monthly distribution of virus isolation. The infectious isolates of various serotypes of different species identified from the sewage samples showed that ES is an essential part of pathogen surveillance.
