scholarly journals Response of Severe EV71-Infected Patients to Hyperimmune Plasma Treatment: A Pilot Study

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 625
Author(s):  
Chonnamet Techasaensiri ◽  
Artit Wongsa ◽  
Thanyawee Puthanakit ◽  
Kulkanya Chokephaibulkit ◽  
Tawee Chotpitayasunondh ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Antibody Therapy ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Neurological Involvement ◽  
Healthy Donors ◽  
Enterovirus A71 ◽  
Number Of Patients ◽  
Causative Agents ◽  
East And Southeast Asia

Hand, foot, and mouth disease (HFMD) is highly prevalent in East and Southeast Asia. It particularly affects children under five years of age. The most common causative agents are coxsackieviruses A6 and A16, and enterovirus A71 (EV71). The clinical presentation is usually mild and self-limited, but, in some cases, severe and fatal complications develop. To date, no specific therapy or worldwide vaccine is available. In general, viral infection invokes both antibody and cell-mediated immune responses. Passive immunity transfer can ameliorate the severe symptoms of diseases such as COVID-19, influenza, MERS, and SARS. Hyperimmune plasma (HIP) from healthy donors with high anti-EV71 neutralizing titer were used to transfuse confirmed EV71-infected children with neurological involvement (n = 6). It resulted in recovery within three days, with no neurological sequelae apparent upon examination 14 days later. Following HIP treatment, plasma chemokines were decreased, whereas anti-inflammatory and pro-inflammatory cytokines gradually increased. Interestingly, IL-6 and G-CSF levels in cerebrospinal fluid declined sharply within three days. These findings indicate that HIP has therapeutic potential for HFMD with neurological complications. However, given the small number of patients who have been treated, a larger cohort study should be undertaken. Successful outcomes would stimulate the development of anti-EV71 monoclonal antibody therapy.

scholarly journals Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016

2019 ◽  
Vol 24 (7) ◽  
Author(s):  
Rubén González-Sanz ◽  
Didac Casas-Alba ◽  
Cristian Launes ◽  
Carmen Muñoz-Almagro ◽  
María Montserrat Ruiz-García ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Phylogenetic Analyses ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Asia Pacific ◽  
Enterovirus A71 ◽  
Hospitalised Patients ◽  
Wide Range ◽  
Large Outbreak

Introduction Enterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, however, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions. Aim Our objective was to investigate the epidemiology and clinical characteristics of the outbreak. Methods We carried out a retrospective study which included 233 EV-A71-positive samples collected during 2016 from hospitalised patients. We analysed the clinical manifestations associated with EV-A71 infections and performed phylogenetic analyses of the 3’-VP1 and 3Dpol regions from all Spanish strains and a set of EV-A71 from other countries. Results Most EV-A71 infections were reported in children (mean age: 2.6 years) and the highest incidence was between May and July 2016 (83%). Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Moreover, we found a clear association of EV-A71-C1 infection with severe neurological disorders, brainstem encephalitis being the most commonly reported. Conclusion An emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases.

scholarly journals RSAD2 and AIM2 Modulate Coxsackievirus A16 and Enterovirus A71 Replication in Neuronal Cells in Different Ways That May Be Associated with Their 5′ Nontranslated Regions

2017 ◽  
Vol 92 (6) ◽  
Author(s):  
Thinesshwary Yogarajah ◽  
Kien Chai Ong ◽  
David Perera ◽  
Kum Thong Wong
Keyword(s):  
Viral Replication ◽  
Neuronal Cells ◽  
Neuroblastoma Cells ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Mouth Disease ◽  
Host Responses ◽  
Coxsackievirus A16 ◽  
Enterovirus A71 ◽  
Foot And Mouth

ABSTRACT Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are closely related enteroviruses that cause the same hand, foot, and mouth disease (HFMD), but neurological complications occur only very rarely in CV-A16 compared to EV-A71 infections. To elucidate host responses that may be able to explain these differences, we performed transcriptomic analysis and real-time quantitative PCR (RT-qPCR) in CV-A16-infected neuroblastoma cells (SK-N-SH), and the results showed that the radical S -adenosylmethionine domain containing 2 (RSAD2) was the highest upregulated gene in the antimicrobial pathway. Increased RSAD2 expression was correlated with reduced viral replication, while RSAD2 knockdown cells were correlated with increased replication. EV-A71 replication showed no apparent correlation to RSAD2 expressions. Absent in melanoma 2 (AIM2), which is associated with pyroptotic cell death, was upregulated in EV-A71-infected neurons but not in CV-A16 infection, suggesting that the AIM2 inflammasome played a significant role in suppressing EV-A71 replication. Chimeric viruses derived from CV-A16 and EV-A71 but containing swapped 5′ nontranslated regions (5′ NTRs) showed that RSAD2 expression/viral replication and AIM2 expression/viral replication patterns may be linked to the 5′ NTRs of parental viruses. Differences in secondary structure of internal ribosomal entry sites within the 5′ NTR may be responsible for these findings. Overall, our results suggest that CV-A16 and EV-A71 elicit different host responses to infection, which may help explain the apparent lower incidence of CV-A16-associated neurovirulence in HFMD outbreaks compared to EV-A71 infection. IMPORTANCE Although coxsackievirus A16 (CV-A16) and enterovirus A17 (EV-A71) both cause hand, foot, and mouth disease, EV-A71 has emerged as a leading cause of nonpolio, enteroviral fatal encephalomyelitis among young children. The significance of our research is in the identification of the possible differing and novel mechanisms of CV-A16 and EV-A71 inhibition in neuronal cells that may impact viral neuropathogenesis. We further showed that viral 5′ NTRs may play significant roles in eliciting different host response mechanisms.

scholarly journals Functional Insights into Silymarin as an Antiviral Agent against Enterovirus A71 (EV-A71)

2021 ◽  
Vol 22 (16) ◽  
pp. 8757
Author(s):  
Salima Lalani ◽  
Malihe Masomian ◽  
Chit Laa Poh
Keyword(s):  
Foot And Mouth Disease ◽  
Antiviral Agent ◽  
Underlying Mechanism ◽  
Neurological Complications ◽  
In Vivo Evaluation ◽  
Competitive Binding Assay ◽  
Enterovirus A71 ◽  
Viral Protein 1

Enterovirus A71 (EV-A71) is a major neurovirulent agent capable of causing severe hand, foot and mouth disease (HFMD) associated with neurological complications and death. Currently, no FDA-approved antiviral is available for the treatment of EV-A71 infections. The flavonoid silymarin was shown to exert virucidal effects, but the binding site on the capsid was unknown. In this study, the ligand interacting site of silymarin was determined in silico and validated in vitro. Moreover, the potential of EV-A71 to develop resistance against silymarin was further evaluated. Molecular docking of silymarin with the capsid of EV-A71 indicated that silymarin binds to viral protein 1 (VP1) of EV-A71, specifically at the GH loop of VP1. The in vitro binding of silymarin with VP1 of EV-A71 was validated using recombinant VP1 through ELISA competitive binding assay. Continuous passaging of EV-A71 in the presence of silymarin resulted in the emergence of a mutant carrying a substitution of isoleucine by threonine (I97T) at position 97 of the BC loop of EV-A71. The mutation was speculated to overcome the inhibitory effects of silymarin. This study provides functional insights into the underlying mechanism of EV-A71 inhibition by silymarin, but warrants further in vivo evaluation before being developed as a potential therapeutic agent.

scholarly journals Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 184 ◽  
Author(s):  
Salima Lalani ◽  
Chit Laa Poh
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Level ◽  
Rna Virus ◽  
Antiviral Treatment ◽  
Antiviral Agents ◽  
Foot And Mouth Disease ◽  
Dna Viruses ◽  
Enterovirus A71 ◽  
Causative Agents ◽  
Rna And Dna

Flavonoids are natural biomolecules that are known to be effective antivirals. These biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth. Enterovirus A71 (EV-A71), a non-enveloped RNA virus, is one of the causative agents of hand, foot and mouth disease (HFMD), which is prevalent in Asia. Despite much effort, no clinically approved antiviral treatment is available for children suffering from HFMD. Flavonoids from plants serve as a vast reservoir of therapeutically active constituents that have been explored as potential antiviral candidates against RNA and DNA viruses. Here, we reviewed flavonoids as evidence-based natural sources of antivirals against non-picornaviruses and picornaviruses. The detailed molecular mechanisms involved in the inhibition of EV-A71 infections are discussed.

scholarly journals A large-scale outbreak of hand, foot and mouth disease, France, as at 28 September 2021

2021 ◽  
Vol 26 (43) ◽  
Author(s):  
Audrey Mirand ◽  
Robert Cohen ◽  
Maxime Bisseux ◽  
Stéphanie Tomba ◽  
Fabienne Cahn Sellem ◽  
...  
Keyword(s):  
Early Detection ◽  
Large Scale ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Mouth Disease ◽  
Clinical Samples ◽  
Enterovirus A71 ◽  
Foot And Mouth ◽  
Virological Surveillance

We report a large-scale outbreak of hand, foot and mouth disease (HFMD) in France. As at 28 September 2021, 3,403 cases have been reported (47% higher than in 2018–19). We prospectively analysed 210 clinical samples; 190 (90.5%) were enterovirus-positive. Most children presented with atypical HFMD. Coxsackievirus (CV)A6 (49.5%; 94/190) was predominant; no enterovirus A71 was detected. Dermatological and neurological complications of HFMD justify prospective syndromic and virological surveillance for early detection of HFMD outbreaks and identification of associated types.

scholarly journals Enterovirus A71 Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 199
Author(s):  
Mei-Ling Li ◽  
Shin-Ru Shih ◽  
Blanton S. Tolbert ◽  
Gary Brewer
Keyword(s):  
Virus Infection ◽  
Capsid Protein ◽  
Causative Agent ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Medical Products ◽  
National Medical ◽  
Enterovirus A71 ◽  
Control Virus ◽  
Vp1 Capsid Protein

Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease (HFMD) and herpangina. Moreover, EV-A71 infection can lead to neurological complications and death. Vaccination is the most efficient way to control virus infection. There are currently three inactivated, whole EV-A71 vaccines licensed by the China NMPA (National Medical Products Administration). Several other types of vaccines, such as virus-like particles and recombinant VP1 (capsid protein), are also under development. In this review, we discuss recent advances in the development of EV-A71 vaccines.

scholarly journals Bioinformatics-based prediction of conformational epitopes for Enterovirus A71 and Coxsackievirus A16

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liping Wang ◽  
Miao Zhu ◽  
Yulu Fang ◽  
Hao Rong ◽  
Liuying Gao ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Distribution Patterns ◽  
Vital Role ◽  
Coxsackievirus A16 ◽  
Essential Information ◽  
Site Distribution ◽  
The North ◽  
Conformational Epitopes ◽  
Enterovirus A71 ◽  
Antigenic Evolution

AbstractEnterovirus A71 (EV-A71), Coxsackievirus A16 (CV-A16) and CV-A10 are the major causative agents of hand, foot and mouth disease (HFMD). The conformational epitopes play a vital role in monitoring the antigenic evolution, predicting dominant strains and preparing vaccines. In this study, we employed a Bioinformatics-based algorithm to predict the conformational epitopes of EV-A71 and CV-A16 and compared with that of CV-A10. Prediction results revealed that the distribution patterns of conformational epitopes of EV-A71 and CV-A16 were similar to that of CV-A10 and their epitopes likewise consisted of three sites: site 1 (on the “north rim” of the canyon around the fivefold vertex), site 2 (on the “puff”) and site 3 (one part was in the “knob” and the other was near the threefold vertex). The reported epitopes highly overlapped with our predicted epitopes indicating the predicted results were reliable. These data suggested that three-site distribution pattern may be the basic distribution role of epitopes on the enteroviruses capsids. Our prediction results of EV-A71 and CV-A16 can provide essential information for monitoring the antigenic evolution of enterovirus.

scholarly journals Characterization of Anti-Bacterial Effect of the Two New Phages against Uropathogenic Escherichia coli

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1348
Author(s):  
Lívia Slobodníková ◽  
Barbora Markusková ◽  
Michal Kajsík ◽  
Michal Andrezál ◽  
Marek Straka ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Therapeutic Potential ◽  
Medical Intervention ◽  
Uropathogenic Escherichia Coli ◽  
E Coli ◽  
Phage Cocktail ◽  
Causative Agents ◽  
Tract Infections

Urinary tract infections (UTIs) are among the events that most frequently need medical intervention. Uropathogenic Escherichia coli are frequently their causative agents and the infections are sometimes complicated by the presence of polyresistant nosocomial strains. Phage therapy is a tool that has good prospects for the treatment of these infections. In the present study, we isolated and characterized two bacteriophages with broad host specificity against a panel of local uropathogenic E. coli strains and combined them into a phage cocktail. According to genome sequencing, these phages were closely related and belonged to the Tequatrovirus genus. The newly isolated phages showed very good activity on a panel of local clinical E. coli strains from urinary tract infections. In the form of a two-phage cocktail, they were active on E. coli strains belonging to phylogroups B2 and D, with relatively lower activity in B1 and no response in phylogroup A. Our study is a preliminary step toward the establishment of a national phage bank containing local, well-characterized phages with therapeutic potential for patients in Slovakia.

Concrescence of the cervical vertebrae and neurological complications

2021 ◽  
pp. 195-201
Author(s):  
Sabiyat Abdulaevna Yakhyaeva ◽  
Naida Isagadzhievna Garabova ◽  
Madina Garunovna Burzhunova
Keyword(s):  
Cervical Spine ◽  
Clinical Practice ◽  
Research Methods ◽  
Neurological Disorders ◽  
Cervical Vertebrae ◽  
Clinical Manifestations ◽  
Neurological Complications ◽  
Timely Diagnosis ◽  
Number Of Patients ◽  
Genetically Determined

In clinical practice, a sufficiently large number of patients complain of neurological disorders caused by osteochondrosis of the cervical spine. Despite this, in some cases, the development and progression of this symptomatology may be due to an anomaly in the structure of the cervical spine (Klippel-Feil syndrome), which is genetically determined. Timely diagnosis of this pathology with the implementation of complex research methods allows you to develop individual tactics for each individual patient, taking into account the severity of clinical manifestations to slow the progression of complications.

Enterovirus Diseases and Vaccines

2021 ◽  
Author(s):  
Heinz-Josef Schmitt
Keyword(s):  
Disease Outbreaks ◽  
Foot And Mouth Disease ◽  
Asia Pacific ◽  
Asia Pacific Region ◽  
Internal Organs ◽  
Enterovirus A71 ◽  
Life Threatening ◽  
Development Pipeline ◽  
The Brain ◽  
Genus Enterovirus

Enterovirus A71 (EV A71) (genus enterovirus, family pircornaviridae) causes benign vesicular lesions on skin (hand, foot and mouth disease, HFMD) and mucous membranes of the mouth (herpangina), and also severe to life-threatening infections of the brain, the heart, and other internal organs. Disease outbreaks in the Asia-Pacific region regularly involve thousands of children <5 years resulting in many deaths. Such outbreaks are caused by specific EV genotypes that vary by time and place. While there are various promising and innovative options for treatment in development, none are licensed to date. Immunoglobulins may be beneficial through virus neutralization and modulation of the inflammatory response by the host. In China, 3 different highly efficacious and safe vaccines are commercially available; however, none are licensed outside the country. Roughly half a dozen vaccines are in the development pipeline, with some using innovative approaches and trying to broaden strain coverage.

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