Molecular epidemiology and phylodynamic analysis of enterovirus 71 in Beijing, China, 2009-2019.

BACKGROUND: Enterovirus 71(EV71)-associated hand, foot and mouth disease (HFMD) decreased dramatically in Beijing from 2009 to 2019. This study was to investigate the epidemiological characteristics, evolutionary dynamics, geographic diffusion pathway, and other features of EV71 in Beijing, China. METHODS: We conducted a retrospective study of EV71-associated HFMD and its causative agent in Beijing, China, from 2009 to 2019. Phylogenetic and phylogeographic methods based on the EV71 genome were used to determine the evolution features, origin, and spatiotemporal dynamics. Positive selection sites in the VP1 gene were identified and exhibited in the tertiary structure. Bayesian birth-death skyline model was used to estimate the effective reproductive number (Re). RESULTS: EV71-associated HFMD decreased greatly in Beijing. From 2009 to 2019, EV71 strains prevalent in Beijing shared high homology in each gene segment and evolved with a rate of 4.99*10- 3 substitutions per site per year. The genetic diversity of EV71 first increased and peaked in 2012 and then decreased with fluctuations. The time to the most recent common ancestor (TMRCA) of EV71 in Beijing was estimated around 2003 when the EV71 strains were transmitted to Beijing from east China. Beijing played a crucial role in seeding EV71 to central China as well. Two residues (E145Q/G, A293S) under positive selection were detected from both the VP1 dataset and the P1 dataset. They were embedded within the loop of the VP1 capsid and were exposed externally. Mean Re estimate of EV71 in Beijing was about 1.007. CONCLUSION: In recent years, EV71 was not the primary causative agent of HFMD in Beijing. The low Re estimate of EV71 in Beijing implied that strategies for preventing and controlling HFMD were performed effectively. Beijing and east China played a crucial role in disseminating EV71 to other regions in China.

Clinico Virological Characterization of Hand, Foot and Mouth Disease in a Tertiary Care Hospital, South India.

Introduction: Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease, caused by enteroviruses (EVs) which can present with typical or atypical lesions. Although the disease is self-limiting, it can also lead to serious complications. In the era of polio eradication, it is important to understand the population dynamics of enteroviruses causing HFMD as one of the circulating strains may become dominant. Methods: It was a collaborative study carried out in the Department of Dermatology and Microbiology of a tertiary care teaching hospital. The throat swabs were collected from 132 suspected HFMD cases. Real-time polymerase chain reaction (PCR) was performed to detect the presence of pan enteroviruses, followed by genotype-specific PCR targeting Human Enterovirus 71 (HEV-71) and Coxsackie virus A16 (CVA-16) and CVA-6 for pan Enterovirus-positive samples. Follow-up samples were collected from 14 children in the 2nd week and subjected to molecular testing to detect enteroviruses. Results: Among 132 children suspected to have HFMD, 44 were girls and 88 were boys, and the majority of them 76.5% (101/132) were under 2 years of age. A history of exposure to a similar clinical presentation was present in 15 children. Of 132 suspected cases, 60 samples (45.5%) were positive for pan Enterovirus. The predominantly circulating genotype was found to be CVA-6 (31.6% [19/60]). There were about 10 cases (16.6%) which had co-infection with both HEV71 and CVA-6. Rash with fever was the most common presentation (57%). In most of the cases with HEV 71, 92.3% (12/13) presented within 3 days of illness to the health-care facility. Of 60 positive cases, 25% (15/60) of children had the atypical distribution of rashes in the face, trunk, genitalia, thigh, neck, and axilla and 16.7% of children (10/60) had the atypical type of lesion either only papular lesions or erythema multiforme. Out of 14 follow-up samples, 13 were negative for EVs; one was positive for pan EV in the 2nd week, however, the patient lost to follow-up after that. Conclusion: HFMD outbreaks in our region were caused by various genotypes of enteroviruses. No severe complications were seen in the affected children. Nearly 30% had atypical presentation either in the form of lesion or site. Robust molecular epidemiological surveillance of HFMD is required to know the strain variations and other emerging genotypes in our setup.

Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action.

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Hand, Foot and Mouth Disease: A Single Centre Retrospective Study of 403 New Cases and Brief Review of Relevant Indian Literature to Understand Clinical, Epidemiological, and Virological Attributes of a Long-Lasting Indian Epidemic.

Background: There have been sporadic and periodic large-scale epidemics of hand, foot, and mouth disease (HFMD) with cases at risk for significant morbidity and mortality particularly in Southeast Asia since 1997 and in India since early 2003. Method: We retrospectively studied 403 cases recorded from 2009 to 2019 and reviewed relevant Indian literature published between 2004 and 2019 to understand clinical, epidemiological, and virological attributes of this long-lasting Indian epidemic. Result: There were 96.8% children and adolescents (M:F 1.6:1) aged 2 months to 18 years and 84% were aged <5 years. Adult family contacts comprised 3.2%. Only 12 sporadic cases occurred during 2009-2011 followed by increased number from 2012 to 2015 peaking with 30.8% cases in 2013 and declining slowly until the year 2019 with small resurge in 2018. The major peaks occurred during summers with small peaks in autumns. Literature review showed 3332 cases presenting between 2004 and 2019 across Indian states with similar epidemiological trends whereas serotyping identified Coxsackievirus A16 (CV A16) in 83%, Coxsackievirus A6 (CV A6) in 17%, Enterovirus 71 in 4.1%, and multiple strains in 11.7% samples, respectively. Conclusion: The overall features of this long-lasting HFMD epidemic; affecting children aged <5 years more often than adults, none or minimum neurological or pulmonary complications in few patients, peaks occurring during summer and autumn months, and identity of the pathogenic virus coincide with global trends. However, the continuous spread of the disease across the country appears in sync with pre-epidemic periods of China and Taiwan. It calls for a continuous surveillance and making HFMD a notifiable disease in India.

First seroepidemiological investigation of human enterovirus 71 in Iran.

BACKGROUND AND OBJECTIVES: Human Enterovirus 71 (EV-A71) is the causative agent for many dermal to neurological diseases especially polio-like paralysis outbreaks around the world. This study, the first of this kind in Iran, aimed to find neutralizing antibodies against EV-A71 in serum of healthy individuals in different age groups based on neutralization test (NT). MATERIALS AND METHODS: In this cross-sectional study, 547 serum samples were collected from healthy individuals who were referring for routine checkup tests (aged from under 6 months to over 31 years old) to Imam-Khomeini Hospital in Tehran during January-December 2015. Serum samples were examined by NT in cell culture to detect neutralizing antibodies against EV-A71. In the next step, some of the positive samples were subjected to complete titration to determine the exact titer of anti-EV-A71 antibodies. RESULTS: Of 547 samples, 310 (56.7%) were positive for EV-A71 neutralizing antibody. The presence of the antibody increased with age (p<0.001), and there was a significant statistical relationship between sex and the presence of antibody (p=0.009). CONCLUSION: Our results demonstrated an apparent but limited circulation of EV-A71 in our society. After the worldwide eradication of poliovirus, EV-A71 which can cause polio-likes syndrome, might be the new challenge for our health care system as regard more in depth research is however needed.

Electrochemical investigations for COVID-19 detection-A comparison with other viral detection methods.

Virus-induced infection such as SARS-CoV-2 is a serious threat to human health and the economic setback of the world. Continued advances in the development of technologies are required before the viruses undergo mutation. The low concentration of viruses in environmental samples makes the detection extremely challenging; simple, accurate and rapid detection methods are in urgent need. Of all the analytical techniques, electrochemical methods have the established capabilities to address the issues. Particularly, the integration of nanotechnology would allow miniature devices to be made available at the point-of-care. This review outlines the capabilities of electrochemical methods in conjunction with nanotechnology for the detection of SARS-CoV-2. Future directions and challenges of the electrochemical biosensors for pathogen detection are covered including wearable and conformal biosensors, detection of plant pathogens, multiplexed detection, and reusable biosensors for on-site monitoring, thereby providing low-cost and disposable biosensors.

Prevalence and Management of Severe Hand, Foot, and Mouth Disease in Xiangyang, China, From 2008 to 2013.

Therapeutic strategies for severe hand, foot, and mouth disease (HFMD) are currently either inconsequent or deficient in evidence. We retrospectively surveyed HFMD outbreaks in Xiangyang from June 2008 to December 2013. HFMD is staged from I to V according to clinical severity. Severe HFMD is defined as a case involving the central nervous system (CNS). We analyzed risk factors for fatality of severe cases and compared the efficiency and outcome of some therapies by binary logistic regression. The overall HFMD cases included 637 (1.26%) severe cases and 38 fatalities (0.075%). Analyses indicate that age (<3 years), enterovirus 71 (+), autonomic nervous system dysregulation, pulmonary edema/hemorrhage, C-reactive protein (CRP) (>40 mg/L), and cardiac troponin I (>0.04 ng/ml) are risk factors for fatality (all P < 0.05). Intravenous immunoglobulin (IVIG) and mechanical ventilation applied only in early stage IV significantly improved HFMD progression (both P < 0.05) with odds ratios of 0.24 (95% CI: 0.10-0.57) and 0.01 (95% CI: 0.00-0.10), respectively. Neither methylprednisolone nor milrinone administered in any stage made any significant difference on mortality (all P > 0.05). Precise recognition of the severe HFMD cases in early stage IV and prompt IVIG and mechanical ventilation application may reduce mortality. Mechanical ventilation training programs and dispatch of specialists to hospitals where there is no chance of transferring critical cases to the severe HFMD designated hospitals are two key measures to reduce fatality.

Prevalence and Management of Severe Hand, Foot, and Mouth Disease in Xiangyang, China from 2008-2013.

Therapeutic strategies for severe hand, foot, and mouth disease (HFMD) are currently either inconsequent or deficient in evidence. We retrospectively surveyed HFMD outbreaks in Xiangyang from June 2008 to December 2013. HFMD is staged form I to V according to clinical severity and the case with central nervous system involvement is defined as a severe one. We analyzed risk factors for fatality of severe cases and compared the efficiency and outcome of some therapies by binary logistic regression. The overall HFMD cases included 637 (1.26%) severe cases, 38 fatalities (0.75‰). Analysis indicates that age (<3 y), enterovirus 71 (+), autonomic nervous system dysregulation, pulmonary edema/hemorrhage, CRP (>40 mg/L) and cardiac troponin I (>0.04 ng/mL) are risk factors for fatality (all P < 0.05). Intravenous immunoglobulin (IVIG) and mechanical ventilation applied only in early stage IV significantly improved HFMD progression (both P < 0.05) with odds ratios of 0.24 (95% CI: 0.10-0.57) and 0.01 (95% CI: 0.00-0.10), respectively. Neither methylprednisolone nor milrinone administered in any stage made any significant difference on mortality (all P > 0.05). Precise recognition of the severe HFMD cases in early stage IV and prompt IVIG and mechanical ventilation application may decrease mortality. Mechanical ventilation training programs and dispatching specialists to county-level or district hospitals when there is no chance of transfer critical HFMD cases to a superior hospital are two key successful administrative initiatives. This article is protected by copyright. All rights reserved.

Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections.

BACKGROUND: Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection. METHODS: To evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured. RESULTS: The high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization. CONCLUSIONS: The present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections.

Analysis of an Imported Subgenotype C2 Strain of Human Enterovirus 71 in Beijing, China, 2015.

Background: Subgenotype C4 of enterovirus 71 (EV71) is the predominant agent of Hand Foot and Mouth disease (HFMD) circulating in the mainland of China. For the first time, a subgenotype C2 of EV71 named SY30-2 was isolated from a HFMD case in Beijing, China. Since it is uncertain whether antibodies raised against subgenotype C4 of EV71 can protect C2 EV71, it is important to monitor and check the presence of cross-reactive antibodies against new EV71 subgenotypes. To find out the causes for the different NtAb, this study is to investigate the relationships between amino acid residue variations and cross-reactive antibodies against EV71 subgenotypes C2 and C4. Methods: Nucleotide and amino acid sequences from full-length genome sequence of SY30-2 were compared to EV71 reference strains. A microneutralization test was used to detect neutralizing antibody (NTAb) in the sera of subgenotype C4 of EV71 infected cases against SY30-2 and FY17 (a C4 isolate). The 3D structure of the viral capsid protein of SY30-2 was constructed. Results: Genome sequence and similarity plot analyses showed that SY30-2 shared the highest identity with subgenotype C2 of EV71 strains in every fragment of the genome. While the microneutralization test result showed that children infected with subgenotype C4 of EV71 had higher NTAb titers against FY17 than SY30-2 (p < 0.001). The amino acid sequence comparison revealed that four amino acid residues VP1-22, VP1-31, VP1-249 and VP3-93 were highly conserved in subgenotype C4 of EV71 compared with the corresponding amino acid residues on subgenotype C2 of EV71 (p < 0.05). Furthermore, the 3D-structure of viral capsid protein showed that VP1-22, VP1-31 and VP3-93 were located on the surface of virion. Conclusion: This is the first report of an EV71 subgenotype C2 isolated from HFMD in Beijing, China. Only a few antigenic variations on subgenotype C2 of EV71 could have led to a great decrease in NTAb titer. Thus, imported new genotypes and subgenotypes of EV71 should be closely monitored. The efficacy of available vaccines against new viruses should be evaluated as well.

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.

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.

Enterovirus 71 infection and neurological complications.

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.

Prediction of Protection against Asian Enterovirus 71 Outbreak Strains by Cross-neutralizing Capacity of Serum from Dutch Donors, The Netherlands.

Outbreaks of human enterovirus 71 (EV-71) in Asia are related to high illness and death rates among children. To gain insight into the potential threat for the population of Europe, we determined the neutralizing activity in intravenous immunoglobulin (IVIg) batches and individual serum samples from donors in the Netherlands against EV-71 strains isolated in Europe and in Asia. All IVIg batches and 41%, 79%, and 65% of serum samples from children ≤5 years of age, women of childbearing age, and HIV-positive men, respectively, showed high neutralizing activity against a Dutch C1 strain, confirming widespread circulation of EV-71 in the Netherlands. Asian B3-4 and C4 strains were efficiently cross-neutralized, predicting possible protection against extensive circulation and associated outbreaks of those types in Europe. However, C2 and C5 strains that had few mutations in the capsid region consistently escaped neutralization, emphasizing the importance of monitoring antigenic diversity among circulating EV-71 strains.

Epidemiology and virologic investigation of human enterovirus 71 infection in the Republic of Korea from 2007 to 2012: a nationwide cross-sectional study.

BACKGROUND: Enterovirus (EV) 71 is the main pathogen associated with hand, foot and mouth disease (HFMD) or herpangina. Outbreaks of HFMD caused by EV71 infection are associated severe neurological disease and high mortality rates in children. Several sporadic cases of EV71 infection occurred in the Republic of Korea (ROK) in 2000, and EV71 infections were not reported thereafter until 2006. In this prospective study, we report the epidemic and virologic characteristics of the EV71 endemic from 2007 to 2012 in the Republic of Korea. METHODS: We analyzed characteristics of the EV71 infection-associated epidemic from collected specimens and clinical information from 9987 patients with suspected EV infection from the National EV Surveillance System in ROK. To identify the EV71 subgenotype, the homology of viral protein 1 sequences obtained using reverse transcription polymerase chain reaction was compared with the sequences on other countries available from GenBank database. RESULTS: EV71 was detected in 585 (16.7 %) specimens (cerebrospinal fluid, stool or rectal swabs, throat swabs and blood) during study period and was most frequently observed during epidemic seasons in 2009-2012. Major manifestations due to EV71 infection were HFMD (62.2 %) and HFMD with severe neurological complications (28.4 %). Five deaths (0.9 %) due to EV71 infection occurred, with an increased mortality rate during the period after 2009. Most patients (476; 81.4 %) were less than 5 years of age. Analysis of the monthly distribution showed that there was an obvious seasonal pattern to the epidemics, with infections appearing from June to August. The major subgenotype of EV71 isolates circulating in ROK was the C4a strain, which has also appeared in China, Japan and Vietnam. CONCLUSIONS: This surveillance provided valuable data on the epidemic characteristics of EV71 infections in ROK during a 6-year period. Our findings provide data to assist during future outbreaks of EV71 and associated acute neurologic disease.

Meteorological factors affect the hand, foot, and mouth disease epidemic in Qingdao, China, 2007-2014.

Hand, foot, and mouth disease (HFMD) has caused public health concerns worldwide. We aimed to investigate the effect of meteorological factors on the HFMD epidemic in Qingdao, a port city in China. A total of 78641 cases were reported in Qingdao between January 2007 and December 2014. Of those, 71084 (90·39%) occurred in children aged 0-5 years, with an incidence of 1691·2/100000. The incidence increased from early spring, peaked between spring and summer, and decreased in late summer. Aetiological agents in all severe cases and selected mild cases were characterized by examining throat swabs. Except for enterovirus 71 (EV71) and coxsackievirus A16 (CA16), other EVs caused >50% of the HFMD cases between 2011 and 2014. EV71 was more frequent in the off-peak months than in the peak months and prone to causing more severe cases compared to CA16 (χ 2 = 46·3, P < 0·001). CA10 caused more severe HFMD than did CA6 (χ 2 = 20·49, P < 0·001) and all non-CA10 EVs (χ 2 = 41·01, P < 0·001). Community-derived HFMD cases accounted for 65·11%. Spearman rank correlation analysis showed that HFMD incidence in children aged 0-5 years was positively correlated with atmospheric temperature (r s = 0·77, P < 0·001), relative humidity (r s = 0·507, P < 0·001), and precipitation (r s = 0·328, P < 0·001). Climate changes and CA10 surveillance in communities should be integrated into the current prophylactic programme.

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.

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.

Therapeutic and prevention strategies against human enterovirus 71 infection.

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.