Human Enterovirus Infection Research Articles

Vascular endothelial growth factor receptor 2 as a potential host target for the inhibition of enterovirus replication.

As the first clinical case was identified in the United States, EV-A71, a significant neurotropic enterovirus, has been a common cause of hand, foot, and mouth disease (HFMD) in infants and young children. Developing an effective antiviral agent for EV-A71 and other human enteroviruses is crucial, as these viral pathogens consistently cause outbreaks in humans. In this study, we demonstrated that multiple inhibitors against VEGFRs effectively reduced EV-A71 replication, with Pazopanib emerging as the top candidate. Furthermore, Pazopanib also attenuated the replication of other enteroviruses, including CVA10, CVB1, EV-D70, and HRV-A, displaying broad-spectrum anti-enterovirus activity. Given that Pazopanib targets various VEGFRs, we narrowed the focus to VEGFR2 using knockdown and overexpression experiments. Transcriptomic analysis suggests that Pazopanib's potential downstream targets involve the TSAd-Src-PI3K-Akt pathway. Our work may contribute to identifying targets for antiviral inhibitors and advancing treatments for human enterovirus infections.

Tanomastat exerts multi-targeted inhibitory effects on viral capsid dissociation and RNA replication in human enteroviruses

Global cyclical outbreaks of human enterovirus infections has positioned human enterovirus A71 (EV-A71) as a neurotropic virus of clinical importance. However, there remains a scarcity of internationally approved antivirals and vaccines. In pursuit of repurposing drugs for combating human enteroviruses, we employed a comprehensive pharmacophore- and molecular docking-based virtual screen targeting EV-A71 capsid protein VP1-4, 3C protease, and 3D polymerase proteins. Among 15 shortlisted ligand candidates, we dissected the inhibitory mechanism of Tanomastat in cell-based studies and evaluated its invivo efficacy in an EV-A71-infected murine model. We demonstrated that Tanomastat exerts dose-dependent inhibition on EV-A71 replication, with comparable efficacy profiles in enterovirus species A, B, C, and D invitro. Time-course studies suggested that Tanomastat predominantly disrupts early process(es) of the EV-A71 replication cycle. Mechanistically, live virus particle tracking and docking predictions revealed that Tanomastat specifically impedes viral capsid dissociation, potentially via VP1 hydrophobic pocket binding. Bypassing its inhibition on entry stages, we utilized EV-A71 replication-competent, 3Dpol replication-defective, and bicistronic IRES reporter replicons to show that Tanomastat also inhibits viral RNA replication, but not viral IRES translation. We further showed that orally administered Tanomastat achieved 85% protective therapeutic effect and alleviated clinical symptoms in EV-A71-infected neonatal mice. Our study establishes Tanomastat as a broad-spectrum anti-enterovirus candidate with promising pre-clinical efficacy, warranting further testing for potential therapeutic application. MOE Tier 2 grants (MOE-T2EP30221-0005, R571-000-068-592, R571-000-076-515, R571-000-074-733) and A∗STARBiomedical Research Council (BMRC).

Temporal regulation of MDA5 inactivation by Caspase-3 dependent cleavage of 14-3-3η.

The kinetics of type I interferon (IFN) induction versus the virus replication compete, and the result of the competition determines the outcome of the infection. Chaperone proteins that involved in promoting the activation kinetics of PRRs rapidly trigger antiviral innate immunity. We have previously shown that prior to the interaction with MAVS to induce type I IFN, 14-3-3η facilitates the oligomerization and intracellular redistribution of activated MDA5. Here we report that the cleavage of 14-3-3η upon MDA5 activation, and we identified Caspase-3 activated by MDA5-dependent signaling was essential to produce sub-14-3-3η lacking the C-terminal helix (αI) and tail. The cleaved form of 14-3-3η (sub-14-3-3η) could strongly interact with MDA5 but could not support MDA5-dependent type I IFN induction, indicating the opposite functions between the full-length 14-3-3η and sub-14-3-3η. During human coronavirus or enterovirus infections, the accumulation of sub-14-3-3η was observed along with the activation of Caspase-3, suggesting that RNA viruses may antagonize 14-3-3η by promoting the formation of sub-14-3-3η to impair antiviral innate immunity. In conclusion, sub-14-3-3η, which could not promote MDA5 activation, may serve as a negative feedback to return to homeostasis to prevent excessive type I IFN production and unnecessary inflammation.

Human Enterovirus B Is a Significant Cause of Aseptic Meningitis and Sepsis-Like Illness in Young Infants in Thailand.

Human enterovirus (EV) and Parechovirus (PeV) infections are major causes of sepsis-like illness in infants < 90 days of age. Enterovirus species B (EV-B) was found to be the leading cause of aseptic meningitis in young infants. In Thailand, EV and PeV are not part of the routine screening of blood or cerebrospinal fluid (CSF) of children with suspected aseptic meningitis and sepsis-like illness. Consequently, data on EV and PeV epidemiology are limited. This study tested clinical samples from hospitalized young infants with suspected aseptic meningitis or sepsis-like illness between 2013 and 2022 for EV, PeV, and Herpes simplex virus (HSV). Of 95 specimens, 10 were positive for EV, representing 10.5%. These positive samples included eight CSF and two stool samples. No samples were positive for PeV and HSV. Of these positive cases, EV-B was detected in eight, and EV-A was detected in two cases. The species of EV-B detected include echovirus-18 (E18) (n=2), E21 (n=2), E4(n=1), E5 (n=1), E9 (n=1), and E11 (n=1). Ourreport demonstrates the significant role of EV-B, and less frequently EV-A, in Thai infants with aseptic meningitis and sepsis-like illness.

Study on the epidemiological characteristics of enterovirus among pediatric patients in Hangzhou, China: A comparison between the pre-COVID-19, COVID-19 pandemic, and post-COVID-19 periods.

Nonpharmaceutical interventions (NPIs) for coronavirus disease 2019 (COVID-19) not only reduce the prevalence of this disease among children but also influence the transmission of other viruses. This retrospective study investigated the impact of NPIs on human enterovirus (HEV) infection in children diagnosed with hand, foot, and mouth disease (HFMD) or herpangina (HA) in Hangzhou, China. We collected and analyzed the laboratory results and clinical data of children diagnosed with HFMD or HA during the following periods: pre-COVID-19 (January 2019 to December 2019), the COVID-19 pandemic (January 2020 to December 2022), and post-COVID-19 (January to December 2023). A total of 41 742 specimens that met the inclusion criteria were obtained, of which 1998 (4.79%) tested positive for enterovirus. In comparison to those in the pre-COVID-19 period, which had 695 (5.63%) HEV-positive specimens, the numbers dramatically decreased to 69 (1.19%), 398 (5.12%), and 112 (1.58%) in 2020, 2021, and 2022, respectively, but significantly increased to 724 (8.27%) in 2023. Seasonal peaks of infections occurred in May, June, July, and August each year, with the total detection rate ranging from 2019 to 2023 being 9.41% in May, 22.47% in June, 28.23% in July, and 12.16% in August, respectively. The difference in the detection rates of HEV infection between males and females was statistically significant (p < 0.005), with 5.11% (1221/23 898) of males and 4.35% (777/17 844) of females testing positive, resulting in a male-to-female positive ratio of 1.57:1. Among the age groups, 11.25% (378/3360) of the children aged 3-5 years had the highest detection rate, which steadily decreased with increasing or decreasing age. The detection of HEV indicated that >95% of the viruses were other types than the previously commonly reported enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16). In conclusion, NPIs for COVID-19 may be effective at reducing the transmission of HEV. However, with the relaxation of NPIs, the detection rate of HEVs increased slowly to a certain extent. Active awareness and surveillance of the epidemiological characteristics of HEV are essential for preventing, controlling, and managing the development of HFMD and HA, as well as contributing to the development of a multivalent HFMD vaccine.

Differential traits between microvesicles and exosomes in enterovirus infection.

Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), are released by most cell types into the extracellular space and represent the pathophysiological condition of their source cells. Recent studies demonstrate that EVs derived from infected cells and tumors contribute to disease pathogenesis. However, very few studies have rigorously characterized exosomes and microvesicles in infectious diseases. In this study, we focused on subpopulations of EVs during the human enterovirus infection and explored the distinct traits and functions of EVs. We construct an effective immunomagnetic method to isolate exosomes and MVs from enterovirus-infected cells excluding virion. The morphology and sizes of exosomes and MVs have no significant alteration after enterovirus infection. Meanwhile, our study observed that the enterovirus infection could induce exosome secretion but not MVs. In vivo study showed that there was differential biodistribution between exosomes and MVs. Using deep RNA sequencing, we found that the cargo information in MVs rather than in exosomes could accurately reflect pathological condition of original cells. Our study demonstrated that it should be considered to use MVs as clinical diagnostics during in enterovirus infection because their composition is reflective of pathological changes.

Non-hepatotropic viral hepatitis and its causative pathogens: The ongoing need for monitoring in children with severe acute hepatitis of unknown etiology.

Non-hepatotropic viral hepatitis and its causative pathogens: The ongoing need for monitoring in children with severe acute hepatitis of unknown etiology.

Dynamic alterations of the mice gut virome after Coxsackievirus B3 infection.

The gut microbiome plays an essential role in the human health and dysbiosis has been implicated in numerous diseases. Coxsackievirus B3 infects millions of humans yearly and yet limited research has explored dynamic alterations of the gut virome after infection. Here, we established the mouse model of Coxsackievirus B3 infection and collected fecal samples at several time points to investigate alterations of the gut virome using viral metagenomic analysis. We found that the mice virome was dominated by Caudovirales and Microviridae, and phylogenetic analyses showed that both Caudovirales and Microviridae had high diversity. The gut virome had significant variations with the increase of Caudovirales and the decrease of Microviridae after infection. We proposed that Caudovirales and Microviridae may be biomarkers for the Coxsackievirus infection process. This study provides a reference for the dynamic changes of the gut virome after human Enterovirus infection, which may help guide the rational drug use in clinical treatment and provide new ideas for preventing Enterovirus infection.

Structure Prediction and Potential Inhibitors Docking of Enterovirus 2C Proteins

Human enterovirus infections are mostly asymptomatic and occasionally could be severe and life-threatening. The conserved non-structural 2C from enteroviruses protein is a promising target in antiviral therapies against human enteroviruses. Understanding of 2C-drug interactions is crucial for developing the potential antiviral agents. While functions of enterovirus 2C proteins have been widely studied, three-dimensional structure information of 2C is limited. In this study, the structures of 2C proteins from 20 enteroviruses were simulated and reconstructed using I-TASSER programs. Subsequent docking studies of the known 22 antiviral inhibitors for 2C proteins were performed to uncover the inhibitor-binding characteristics of 2C. Among the potential inhibitors, the compound hydantoin exhibited the highest broad-spectrum antiviral activities with binding to 2C protein. The anti-enteroviral activity of GuaHCL, compound 19b, R523062, compound 12a, compound 12b, quinoline analogs 12a, compound 19d, N6-benzyladenosine, dibucaine derivatives 6i, TBZE-029, fluoxetine analogs 2b, dibucaine, 2-(α-hydroxybenzyl)-benzimidazole (HBB), metrifudil, pirlindole, MRL-1237, quinoline analogs 10a, zuclopenthixol, fluoxetine, fluoxetine HCl, and quinoline analogs 12c showed a trend of gradual decrease. In addition, the free energy with 22 compounds binding to EV 2C ranged from −0.35 to −88.18 kcal/mol. Our in silico studies will provide important information for the development of pan-enterovirus antiviral agents based on 2C.

The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine.

Enteroviruses infect gastrointestinal epithelium cells, cause multiple human diseases, and present public health risks worldwide. However, the mechanisms underlying host immune responses in intestinal mucosa against the early enterovirus infections remain elusive. Here, we showed that human enteroviruses including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1) predominantly induce type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), in cultured human normal and cancerous intestine epithelial cells (IECs), mouse intestine tissues, and human clinical intestine specimens. Mechanistic studies demonstrated that IFN-λ production is induced upon enterovirus infection through the Toll-like receptor 3/interferon regulatory factor 1 (TLR3/IRF1) signaling pathway in IECs. In turn, the supplementation of IFN-λ subsequently induces intrinsically antiviral responses against enterovirus replication. Notably, intraperitoneal injection in neonatal C57BL/6J mice with mouse recombinant IFN-λ2 protein represses EV71 replication and protects mice from viral lethal effects. Altogether, these results revealed a distinct mechanism by which the host elicited immune responses against enterovirus infections in intestine through activating the TLR3/IRF1/type III IFN axis. The new findings would provide an antiviral strategy for the prevention and treatment of enterovirus infections and associated diseases.IMPORTANCE Enterovirus infections are significant sources of human diseases and public health risks worldwide, but little is known about the mechanism of innate immune response in host intestine epithelial surface during the viral replication. We reported the epithelial immune response in cultured human normal and cancerous cells (IECs), mouse tissues, and human clinical intestine specimens following infection with enterovirus 71. The results mechanistically revealed type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), as the dominant production through TLR3/IRF1 signaling upon multiple human enterovirus infection, including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1). IFN-λ subsequently induced antiviral activity against enterovirus replication in vitro and in vivo. These studies uncovered the role of the novel process of type III IFN production involved in the TLR3/IRF1 pathway in host intestine upon enterovirus infection, which highlighted a regulatory manner of antiviral defense in intestine during enterovirus infection.

Molecular Evaluation of Human Enterovirus-Related Aseptic Meningitis in Isfahan, Iran 2017

Background: Human enteroviruses (HEVs) cause various infections, especially in children. These viruses are common causes of aseptic meningitis worldwide. Objectives: Limited information about HEV-related aseptic meningitis is available in Isfahan/Iran. Therefore, this study was designed to evaluate HEV-related meningitis in this city. Methods: In this cross-sectional study, 70 patients with the diagnosis of aseptic meningitis were enrolled and divided into 2 groups, including children and adults, in 2 centers of Alzahra and Imam Hossein hospitals from December 2016 to December 2017. Diagnosis of meningitis was made on clinical symptoms and lumbar puncture samples. The RNA of HEV was extracted with Roch extraction Kit and enteroviral infection was detected by real-time PCR test. Chi-square and descriptive statistics were used for data analysis. Results: Enteroviruses were detected in 2 cases out of 70 patients (2.8%). Two cases were in the children group (9.5%). The relationship between gender and prevalence was not significant. Two cases were found in summer and winter. Conclusions: We found that the positive test results of enterovirus in lumbar puncture (LP) samples were significant in the children patients (9.5%, P value = 0.026) but the positive test results in adult patients were zero. So it makes sense to do PCR tests in children with signs or symptoms of meningitis. A well-designed study with more samples is recommended for better evaluation of HEV-related infections, especially aseptic meningitis in Iran. These types of studies help to find a good strategy for the management of HEV infections in Iran and, thereby reducing hospitalization and overuse of antibiotics.

Villitis of unknown etiology and chronic deciduitis are not associated with human papilloma virus and enterovirus infection.

Villitis of unknown etiology (VUE) and chronic deciduitis with plasma cells (CD) are supposed to be non infectious placental lesions caused by a pathologic immune reaction similar to a host versus graft mechanism. In some investigations, infection of human trophoblastic cells with human papilloma virus (HPV) has been described, and a relationship with miscarriage, preeclampsia, and chronic inflammatory placental lesions has been suspected. Infection with enterovirus, especially Coxsackievirus, has been observed in cases with spontaneous abortion and adverse perinatal outcome, respectively. We investigated 20 cases with VUE and 30 cases with chronic deciduitis with plasma cells. The placenta specimens were analyzed for expression of HPV capsid protein by immunohistochemistry, for presence of HPV DNA via polymerase chain reaction (PCR), and for presence of enterovirus mRNA using RT-PCR, respectively. VUE was associated with maternal diseases: atopic lesions in 21%, other autoimmune diseases in 15.5%, and obesity in 31.5%, respectively. Birth weight below the 10th percentile was detected in 63% of the cases with VUE. Chronic deciduitis was associated with preterm labor and preterm premature rupture of membranes (26%). Intrauterine fetal demise occurred in 5 cases with CD (18.5%). HPV DNA, HPV capsid protein, and enterovirus mRNA were not detected in all investigated VUE or CD cases. Our investigations show that a causal role for enterovirus and human papilloma virus in the development of VUE and CD is unlikely. Therefore, HPV vaccination is unlikely to reduce the incidence of VUE and CD in the future.

Enterovirus infection in the Socialist Republic of Vietnam

Human enterovirus infections comprise a group of infectious diseases caused by viruses of Enterovirus A-D species (genus Enterovirus, family Picornaviridae). Enterovirus infections can vary in clinical manifestations and severity, from asymptomatic infection to serious multisystem diseases. During evolution, enterovirus strains with increased neurovirulence or atypical pathogenicity may emerge exhibiting an epidemic potential. Recently, outbreaks of enterovirus infection with an increased rate of neurological manifestations, a significant percentage of severe cases and lethal outcomes have been observed worldwide, which were associated with enteroviruses EV-A71, EV-D68 etc. The World Health Organization has included EV-A71 and EV-D68 enterovirus infection together with some other dangerous viral diseases considered for inclusion in the List of Blueprint Priority Diseases. In connection with this, global enterovirus surveillance is important for controlling emergence and spread of epidemic enterovirus variants, prediction of establishing epidemic situation, timely conduction of preventive measures and vaccine development. A growing multi-field cooperation between Russia and Vietnam leads to increased two-way population migration, which actualizes scientific and practical collaboration in surveillance and control of infectious disease spread, including enterovirus infection. Currently, epidemiological surveillance of enterovirus infection in Vietnam is based on monitoring hand, foot and mouth disease (HFMD) rate, laboratory diagnostics of enterovirus infection and identification of enterovirus strains, mainly detected in severe patients. In 2001–2016, 34 non-polio virus types were identified in patients with enterovirus infection, largely represented by viruses EV-A71, CVA6, CVA10, and CVA16. Moreover, the peak incidence of enterovirus infection and related mortality rate were associated with the increased activity of EV-A71 virus. In Vietnam, EVA71 enterovirus of genotypes C1, C4, C5 and B5 circulated at different times. Over the last years, a new pandemic genotype virus CVA6 has been dominating as a causative agent of enterovirus infection in Vietnam as well as the majority of other countries. The data on phylogenetic relation between Vietnamese epidemic EV-A71 and CVA6 strains allowed to find that they underwent multiple betweencountry spreads, whereas their subsequent in-country dissemination resulted in 2011–2012 enterovirus outbreak and sustained high-level HFMD morbidity.

Neonatal acute liver failure due to enteroviruses: a 14 years single NICU experience

Background: Neonatal acute liver failure (ALF) is a severe condition with a mortality rate up to 70%. Human enterovirus (HEV) infections are associated with serious diseases in newborns, including myocarditis, meningoencephalitis and, more rarely, ALF with a fulminant course.Methods: Cases of neonatal-onset ALF were identified using the institutional clinical database. The history and clinical data of infants with HEV infection were collected by medical record revision. Viral testing by nested real- time PCR (nRT-PCR) was performed by the Bambino Gesù Children’s Hospital Clinical Laboratory and by National Institute of Public Health in Rome.Results: Among ten infants referred to our Institution with neonatal-onset ALF in the 2004–2018 period, we identified five cases due to HEV. In three of these, the mother reported an episode of mild fever and diarrhea during the last trimester of gestation, suggesting fetal-maternal transmission. All were late preterm infants (32–36 weeks). Two infants died as a result of ALF; the other three survived with full normalization of liver function. In four, the causing agents were coxsackie B serotypes 3 (n = 1), 4 (n = 1) and 5 (n = 2), in the fifth case we identified echovirus serotype 11.Conclusions: Human enterovirus (HEV) are a rare but relevant cause of ALF in neonates. HEV testing should be systematically performed in cases of neonatal ALF for diagnostic and management purposes.

Assessment of a swab collection method without virus transport medium for PCR diagnosis of coxsackievirus infections

Classically, detection of human enterovirus (EV) infections is based on virus isolation in tissue culture, proper sample collection and handling that optimizes virus viability. Samples are collected in virus transport medium (VTM) to ensure virus stability. High sensitivity and rapid results have made polymerase chain reaction (PCR) analysis increasingly popular for routine diagnosis. The PCR method enables simple sample collection and storage for EV diagnostics, which may eventually allow self-sampling at home.Our aim was to test a modification of the conventional clinical swab sample collection method for molecular diagnosis of EV infection. We compared swabs (cotton or synthetic) without VTM and the classical standard synthetic swabs with VTM. Effects of storage temperature (+4 °C or −80 °C) and duration were studied. EV-RNA could be detected by reverse transcriptase and nested PCR in both swab types without VTM. Differences depended on the storage duration and temperature. Optimum conditions were immediate processing or storage at −80 °C. Storage without VTM at +4 °C for longer periods is not advisable. We conclude that swabs without VTM can be considered for clinical EV-diagnostics based on PCR, and ultimately for epidemiological sample collection.

Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals

RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates; however, whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner and loaded into AGO, and they were fully active in degrading cognate viral RNAs. Recombinant HEV71 deficient in 3A-mediated RNAi suppression was significantly restricted in human somatic cells and mice, whereas Dicer deficiency rescued HEV71 infection independently of type I interferon response. Thus, RNAi can function as an antiviral immunity, which is induced and suppressed by a human virus, in mammals.

Identifying Novel Antiviral Targets Against Enterovirus 71: Where Are We?

Human enterovirus 71 (HEV71) has been considered as an essential human pathogen, which causes hand, foot and mouth disease in young children. Several HEV71 outbreaks have been observed in many Asia-Pacific countries for the past two decades with significant fatalities. However, there are no competent vaccines or antivirals against HEV71 infection to date. Thus, it is of critical priority to delve into the search for anti-HEV71 agents. Prior to this, there is a need to gain knowledge about the distinct targets of HEV71 that are available and that have been exploited for antiviral therapy. This review aims to provide a better understanding of HEV71 virology and feature potential antivirals for progressive clinical development with respect to their elucidated mechanistic actions.

Molecular detection and genotyping of enteroviruses from CSF samples of patients with suspected sepsis-like illness and/or aseptic meningitis from 2012 to 2015 in West Bank, Palestine.

BackgroundHuman enteroviruses (HEVs) are the most frequently reported cause of aseptic meningitis with or without CSF pleocytosis in childhood. Rapid detection and genotype of HEVs is essential to determine the causative agent and variant causing sepsis-like illness and/or aseptic meningitis.AimTo investigate the molecular epidemiology of enteroviruses (EVs) among patients with sepsis-like illness and/or aseptic meningitis admitted to three major hospitals in West Bank, Palestine from 2012 to 2015.MethodsDuring the study period, 356 CSF samples were collected from patients with sepsis-like illness and/or aseptic meningitis. Two RT-nested PCR assays targeting a partial part of 5'UTR for direct diagnosis and the VP1 region for genotyping by sequence analysis of the viral genome were used.ResultsHEV RNA was detected in 66 of 356 (18.5%) of CSF samples. Age distribution showed that 64% (42/66) were infants (<1 year), 18% were children between 1 and 5 years old, 12% were children between 5 and 10 years old, and 6% were more than 10 years old. Of the 66 EV cases, 12 were successfully genotyped. Five different EV genotypes were identified. All of them belonged to HEV-B species. The study showed that echovirus 6 genotype accounted for 42% of the sequenced cases. The HEV infections in the present study tended to show slight seasonal pattern with more cases occurring during spring and summer, yet still significant numbers were also reported in fall and winter seasons.ConclusionHEV was isolated from a significant number of children with sepsis-like illness and/or aseptic meningitis. In addition, the molecular method utilized for direct diagnosis and genotyping of HEV from CSF revealed that more than one HEV type circulated in the West Bank, Palestine during the study period.

High prevalence of coxsackievirus A2 in children with herpangina in Thailand in 2015.

Coxsackievirus (CV) is a member of the genus Enterovirus and the family Picornaviridae. CV infection can cause herpangina, a disease characterized by multiple ulcers on the tonsils and soft palate affecting mostly young children. CV strains are categorized by serotypes. Unfortunately, serotypes responsible for infections in patients are often undetermined. This knowledge gap partly contributes to the ineffective prevention and control of CV-associated herpangina in Southeast Asia. To characterize the viral etiology of children presented with herpangina, 295 throat swabs were tested for human enterovirus infection. Using RT-PCR specific for the viral 5'UTR/VP2 and the VP1 regions, two most frequent CV types found in these samples were CV-A2 (33.33%, 40/120) and CV-A4 (15.8%, 19/120). Phylogenetic analysis of the VP1 gene demonstrated that the CV-A2 strains in this study not only were closely related to those previously identified in Asia and Europe, but the majority clustered into a distinct group. Thus, infection predominantly by CV-A2 and CV-A4 caused herpangina in 2015 in Thailand.

Human enterovirus infection status and clinical characteristics of 274 patients with viral encephalitis in Henan Province, 2011-2012

Objective: To investigate human enterovirus (HEV) infection and clinical characteristics of viral encephalitis patients in Pingdingshan, Henan Province. Methods: Cerebrospinal fluid specimens and epidemiological information were collected from 274 viral encephalitis patients in the departments of pediatrics and neurology in hospitals in Pingdingshan, Henan Province, from April 2011 to August 2012. Patients with bacterial infections were excluded from the study. Demographic information was collected by questionnaires and clinical information was mainly obtained from hospital examinations. Viral RNA was extracted using magnetic bead extraction. Real-time RT-PCR was then performed for HEV, CV-A16, and EV-A71 testing. SPSS statistical software was statistical analyses. Significant differences were determined using the chi-squared test (P<0.05). Results: Among 274 cases of viral encephalitis, 180 cases (65.7%) were male and 94 cases were female (34.3%). The median age was 2.17 years. Approximately 61.3% (168) of patients were younger than 3 years of age. A total of 107 (39.1%), 2 (0.7%), and 42 (15.3%) cases were positive for HEV, CV-A16, and EV-A71, respectively. Eleven patients were younger than 6 months of age and one patient was co-infected with HEV and EV-A71. In the<3, 3-5, 6-15, and>15 years old age groups, HEV infections comprised 31.5% (53/168), 52.9% (18/34), 53.0% (35/66), and 16.7% (1/6) (χ(2)=13.10, P=0.003), respectively. The EV-A71 infection rates were 17.9% (30/168), 23.5% (8/34), 6.1% (4/66), and 0 (χ(2)=8.04, P=0.045), respectively. The other enterovirus (OEV) infection rates were 12.5% (21/168), 29.4% (10/34), 48.5% (32/66), and 16.7% (1/6) (χ(2)=35.19, P<0.001), respectively. The rate of vomiting in OEV and EV-A71 infected patients was 73% (44/60) and 26% (11/42), respectively, while the frequency of skin rash in OEV and EV-A71 infected patients was 32% (19/60) and 79% (33/42), respectively. Approximately 95% (99/104) of patients infected with HEV had a fever, and the breathing rhythm change rate was 19% (20/104), which was lower than that of patients without HEV infection (36.8% (60/163)) (χ(2)=9.35, P=0.002). Conclusion: In Pingdingshan, HEV was a major causative agent of viral encephalitis and the rate of OEV infection was high, especially in children aged 3-15 years old. Fever was a common clinical symptom of patients infected with HEV. Patients infected with OEV primarily exhibited vomiting symptoms and EV-A71 infected patients showed skin rash.