ENTEROVIRUS INFECTION: OVERVIEW OF THE CURRENT GLOBAL SITUATION IN THE CONTEXT OF INTENSIFIED MIGRATION FLOWS

2018 ◽  
pp. 55-60
Author(s):  
L.V. Butakova ◽  
O.E. Trotsenko ◽  
E.Yu. Sapega
Keyword(s):  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Scientific Data ◽  
Enterovirus Infection ◽  
Coxsackievirus A6 ◽  
Golden Standard ◽  
Enterovirus D68 ◽  
Genetic Techniques ◽  
Migration Flows

The review presents data on epidemiological risks concerning worldwide spread of enterovirus infection due to intensified migration flows. Outbreak incidence of the most frequently registered forms of enterovirus infection – hand, foot and mouth disease (HFMD) –was analyzed. At the present time, Coxsackievirus A6 plays ever-greater significance in HFMD incidence. The article summarizes currently available scientific data on atypical Coxsackievirus A6-infection clinical manifestations. Details on the tense epidemiological situation concerning Enterovirus D68 that can be the cause of acute flaccid paralysis/myelitis are presented. According to latest recommendations, the molecular genetic techniques are the «golden standard» in diagnostics of enterovirus infection.

Molecular Epidemiological Monitoring of Circulation of Coxsackievirus A10

2021 ◽  
pp. 43-49
Author(s):  
LN Golitsyna ◽  
VV Zverev ◽  
NV Ponomareva ◽  
NI Romanenkova ◽  
Thao Thanh Thi Nguyen ◽  
...  
Keyword(s):  
Russian Federation ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Sewage Water ◽  
Epidemiological Surveillance ◽  
Molecular Monitoring ◽  
South Vietnam ◽  
Epidemiological Monitoring ◽  
The Russian Federation

Background: Coxsackievirus A10 (CV-A10) is currently one of the most common etiological agents of enterovirus infection (EVI). Over the past decade, severe and fatal cases of CV-A10 infection have become more frequent while clinical manifestations of the disease are similar to those of Enterovirus A71 infection. The objective of our study was to characterize circulation of Coxsackievirus A10 in the Russian Federation in 2008–2019 and to study the phylogenetic relationships of strains isolated in Russia and Vietnam. Materials and methods: In 2008–2019, 220 CV-A10 strains were isolated from patients with various clinical manifestations of EVI and from sewage water samples taken in the Russian Federation and then studied using molecular genetic methods. In addition to that, we analyzed 26 CV-A10 strains isolated from patients with hand, foot, and mouth disease (HFMD) and acute flaccid paralysis in South Vietnam in 2018–2019. Results: We established a two-year periodicity of CV-A10 active circulation in Russia. In the structure of clinical forms of CV-A10 infection, herpetic angina prevailed (30.8 %), followed by minor illness (25.25 %), respiratory diseases (15.66 %), exanthema (14.65 %), gastrointestinal disorders (8.08 %), and asymptomatic infections (2.02 %). Symptoms of CNS damage (meningitis, meningoencephalitis) were observed in 3.53 % of cases. Most CV-A10 strains from Vietnam were isolated from patients with CNS affection of varying degrees of severity. During the study period, CV-A10 strains of genotypes C, E, and F3 circulated in the territory of the Russian Federation whereas the strains from South Vietnam were represented by genotypes F3 and F1. The studied strains showed a genetic relationship with those of CV-A10 circulating in different countries. Vietnamese and some Russian strains of the F3 genotype were genetically close to the strains isolated from severe cases. Conclusions: Molecular monitoring of CV-A10 circulation is an important component of the global epidemiological surveillance of EVI.

scholarly journals Genetic recombination in fast-spreading coxsackievirus A6 variants: a potential role in evolution and pathogenicity

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Yang Song ◽  
Yong Zhang ◽  
Zhenzhi Han ◽  
Wen Xu ◽  
Jinbo Xiao ◽  
...  
Keyword(s):  
Large Scale ◽  
Genetic Recombination ◽  
Mainland China ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Capsid Gene ◽  
Global Epidemic ◽  
Public Health Burden ◽  
Coxsackievirus A6 ◽  
Fast Spreading

Abstract Hand, foot, and mouth disease (HFMD) is a common global epidemic. From 2008 onwards, many HFMD outbreaks caused by coxsackievirus A6 (CV-A6) have been reported worldwide. Since 2013, with a dramatically increasing number of CV-A6-related HFMD cases, CV-A6 has become the predominant HFMD pathogen in mainland China. Phylogenetic analysis based on the VP1 capsid gene revealed that subtype D3 dominated the CV-A6 outbreaks. Here, we performed a large-scale (near) full-length genetic analysis of global and Chinese CV-A6 variants, including 158 newly sequenced samples collected extensively in mainland China between 2010 and 2018. During the global transmission of subtype D3 of CV-A6, the noncapsid gene continued recombining, giving rise to a series of viable recombinant hybrids designated evolutionary lineages, and each lineage displayed internal consistency in both genetic and epidemiological features. The emergence of lineage –A since 2005 has triggered CV-A6 outbreaks worldwide, with a rate of evolution estimated at 4.17 × 10−3 substitutions site-1 year−1 based on a large number of monophyletic open reading frame sequences, and created a series of lineages chronologically through varied noncapsid recombination events. In mainland China, lineage –A has generated another two novel widespread lineages (–J and –L) through recombination within the enterovirus A gene pool, with robust estimates of occurrence time. Lineage –A, –J, and –L infections presented dissimilar clinical manifestations, indicating that the conservation of the CV-A6 capsid gene resulted in high transmissibility, but the lineage-specific noncapsid gene might influence pathogenicity. Potentially important amino acid substitutions were further predicted among CV-A6 variants. The evolutionary phenomenon of noncapsid polymorphism within the same subtype observed in CV-A6 was uncommon in other leading HFMD pathogens; such frequent recombination happened in fast-spreading CV-A6, indicating that the recovery of deleterious genomes may still be ongoing within CV-A6 quasispecies. CV-A6-related HFMD outbreaks have caused a significant public health burden and pose a great threat to children’s health; therefore, further surveillance is greatly needed to understand the full genetic diversity of CV-A6 in mainland China.

scholarly journals Clinical Manifestations of Coxsackievirus A6 Infection Associated with a Major Outbreak of Hand, Foot, and Mouth Disease in Japan

2013 ◽  
Vol 66 (3) ◽  
pp. 260-261 ◽  
Author(s):  
Masaaki Kobayashi ◽  
Tomohiko Makino ◽  
Nozomu Hanaoka ◽  
Hiroyuki Shimizu ◽  
Miki Enomoto ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Coxsackievirus A6 ◽  
Foot And Mouth ◽  
Major Outbreak

scholarly journals Identification and Characterization of DM1 Patients by a New Diagnostic Certified Assay: Neuromuscular and Cardiac Assessments

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Rea Valaperta ◽  
Valeria Sansone ◽  
Fortunata Lombardi ◽  
Chiara Verdelli ◽  
Alessio Colombo ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Molecular Method ◽  
High Reproducibility ◽  
Pathological Mechanism ◽  
Genetic Techniques ◽  
Identification And Characterization ◽  
Very High ◽  
Unambiguous Interpretation

The expansion of the specific trinucleotide sequence, [CTG], is the molecular pathological mechanism responsible for the clinical manifestations of DM1. Many studies have described different molecular genetic techniques to detect DM1, but as yet there is no data on the analytical performances of techniques used so far in this disease. We therefore developed and validated a molecular method, “Myotonic Dystrophy SB kit,” to better characterize our DM1 population. 113 patients were examined: 20 DM1-positive, 11 DM1/DM2-negative, and13 DM1-negative/DM2-positive, who had a previous molecular diagnosis, while 69 were new cases. This assay correctly identified 113/113 patients, and all were confirmed by different homemade assays. Comparative analysis revealed that the sensitivity and the specificity of the new kit were very high (>99%). Same results were obtained using several extraction procedures and different concentrations of DNA. The distribution of pathologic alleles showed a prevalence of the “classical” form, while of the 96 nonexpanded alleles 19 different allelic types were observed. Cardiac and neuromuscular parameters were used to clinically characterize our patients and support the new genetic analysis. Our findings suggest that this assay appears to be a very robust and reliable molecular test, showing high reproducibility and giving an unambiguous interpretation of results.

scholarly journals Characterization of oral virome and microbiome revealed distinctive microbiome disruptions in paediatric patients with hand, foot and mouth disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Si Xian Ho ◽  
Nyo Min ◽  
Emmerie Phaik Yen Wong ◽  
Chia Yin Chong ◽  
Justin Jang Hann Chu
Keyword(s):  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Human Microbiome ◽  
Foot And Mouth Disease ◽  
Critical Factor ◽  
Mouth Disease ◽  
Oral Microbiome ◽  
Coxsackievirus A6 ◽  
Foot And Mouth

AbstractWhile the underlying determinants are unclear, hand, foot and mouth disease (HFMD) presents a wide spectrum of clinical manifestations with varying severity in different individuals. Recently, many studies identified the human microbiome as a critical factor in the pathogenesis of various diseases. Therefore, we here investigated the ecological dynamics of the oral microbiome changes during the HFMD infection. After targeted enrichment of all known vertebrate viruses, the virome profiles of symptomatic and asymptomatic HFMD patients were examined and revealed to be significantly altered from those of healthy individuals, with nine discriminative viruses detected. Further characterization of the prokaryotic microbiome revealed an elevated level of Streptococcus sp. as the most important signature of the symptomatic HFMD cohort, positively correlating to the level of enterovirus A RNA. In addition, we found that while coxsackievirus A5 is detected in saliva RNA of all asymptomatic cases, coxsackievirus A6 dominates the majority of the symptomatic cohort.

scholarly journals SAMHD1 inhibits multiple Enteroviruses by interfering with the interaction between VP1 and VP2 proteins

2021 ◽  
Author(s):  
Zhilei Zhao ◽  
Zhaolong Li ◽  
Chen Huan ◽  
Xin Liu ◽  
Wenyan Zhang
Keyword(s):  
Binding Site ◽  
Biological Activities ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Viral Assembly ◽  
Inhibitory Effect ◽  
Coxsackievirus A6 ◽  
Enterovirus D68 ◽  
Acid Domain ◽  
Underlying Mechanisms

Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) possess multiple biological activities such as virus restriction, innate immunity regulation, and autoimmunity. Our previous study demonstrated that SAMHD1 potently inhibits the replication of enterovirus 71 (EV71). In this study, we observed that SAMHD1 also restricts multiple enteroviruses (EVs) including Coxsackievirus A16 (CA16) and Enterovirus D68 (EVD68), but not Coxsackievirus A6 (CA6). Mechanistically, SAMHD1 competitively interacted with the same domain in VP1 that binds to VP2 of EV71 and EVD68, thereby interfering with the interaction between VP1 and VP2, and therefore viral assembly. Moreover, we showed that while the SAMHD1 T592A mutant maintained the EV71 inhibitory effect by attenuating the interaction between VP1 and VP2, the T592D mutant failed to. We also demonstrated that SAMHD1 could not inhibit CA6 because a different binding site is required for the SAMHD1 and VP1 interaction. Our findings reveal the mechanism of SAMHD1 inhibition of multiple EVs, and this could potentially be important for developing drugs against a broad range of EVs. Importance Enterovirus cause a wide variety of diseases, such as the hand-foot-and-mouth disease (HFMD), which is a severe public problem threatening children under 5 years. Therefore, identifying essential genes which restrict EV infection and exploring the underlying mechanisms is necessary to develop an effective strategy to inhibit EV infection. In this study, we report that host restrictive factor SAMHD1 has broad-spectrum antiviral activity against EV71, CA16 and EVD68 independent of its well-known dNTPase or RNase activity. Mechanistically, SAMHD1 restricts EVs by competitively interacting with the same domain in VP1 that binds to VP2 of EVs, thereby interfering with the interaction between VP1 and VP2, and therefore viral assembly. In contrast, we also demonstrated that SAMHD1 could not inhibit CA6 because a different binding site is required for the SAMHD1 and CA6 VP1 interaction. Our study reveals a novel mechanism for the SAMHD1 anti-EV replication activity.

A Different Epidemiology of Enterovirus A and Enterovirus B Co-circulating in Korea, 2012–2019

2020 ◽  
Author(s):  
Hae Ji Kang ◽  
Youngsil Yoon ◽  
Young-Pyo Lee ◽  
Hye-Jin Kim ◽  
Deog-Yong Lee ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Clinical Manifestations ◽  
Virus Detection ◽  
Foot And Mouth Disease ◽  
Echovirus 30 ◽  
Health Measures ◽  
Coxsackievirus A6 ◽  
Polymerase Chain ◽  
Respiratory Specimens

Abstract Background Enteroviruses (EVs) occur frequently worldwide and are known to be associated with a broad spectrum of clinical manifestations from mild syndromes to neurological disease. To understand the epidemiology of EV in Korea, we characterized EV-infected cases during 2012–2019 based on national surveillance. Methods We collected specimens from patients with suspected EV infections and analyzed the data using real-time reverse-transcription polymerase chain reaction and VP1 gene sequencing. Results Among the 18 261 specimens collected, EVs were detected in 6258 (34.3%) cases. Although the most common EV types changed annually, EV-A71, echovirus 30, coxsackievirus B5, coxsackievirus A6, and coxsackievirus A10 were commonly identified. Among the human EVs, the case numbers associated with the 2 major epidemic species (EV-A and EV-B) peaked in the summer. While EV-A species affected 1-year-old children and were associated with herpangina and hand, foot, and mouth disease, EV-B species were mostly associated with neurologic manifestations. The highest incidence of EV-B species was observed in infants aged <12 months. Feces and respiratory specimens were the most predictive of EV infection. Specimens collected within 5 days of symptom onset allowed for timely virus detection. Conclusions EV-A and EV-B species co-circulating in Korea presented different epidemiologic trends in clinical presentation, affected subjects, and seasonality trends. This study could provide information for the characterization of EVs circulating in Korea to aid the development of EV antivirals and vaccines, as well as public health measures to control enteroviral diseases.

scholarly journals Neonatal hand, foot, and mouth disease due to Coxsackievirus A6 in Shanghai

2020 ◽  
Author(s):  
Shanshan Xu ◽  
Huajun Li ◽  
Peng Qiao ◽  
Guofeng Xu ◽  
Dongying Zhao ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
White Blood Cells ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Nonparametric Test ◽  
Peripheral Blood Lymphocytes ◽  
Mouth Disease ◽  
Logistic Analysis ◽  
Coxsackievirus A6 ◽  
Foot And Mouth

Abstract Background: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. Methods: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings. Results: There were 16 neonates among the 12608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about one week after onset. None of the neonates had sequelae. Conclusions: In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

scholarly journals Enterovirus infection in the Socialist Republic of Vietnam

2019 ◽  
Vol 9 (3-4) ◽  
pp. 467-475
Author(s):  
L. N. Golitsyna ◽  
T. T.T. Nguyen ◽  
N. I. Romanenkova ◽  
M. T. Luong ◽  
L. T. Vu ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
World Health ◽  
Disease Spread ◽  
Epidemiological Surveillance ◽  
Human Enterovirus ◽  
Laboratory Diagnostics ◽  
Enterovirus Infection ◽  
Socialist Republic

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.

scholarly journals State-of-the-art molecular genetic techniques in surveillance over intensity of enterovirus infection epidemic process in some constituent entities of the Siberian Federal District of the Russian Federation

2019 ◽  
pp. 42-50
Author(s):  
E.Yu. Sapega ◽  
L.V. Butakova ◽  
Trotsenko ◽  
Lapa ◽  
Perezhogin ◽  
...  
Keyword(s):  
Russian Federation ◽  
State Of The Art ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Federal District ◽  
Enterovirus Infection ◽  
Siberian Federal District ◽  
Epidemic Process ◽  
Epidemiologic Surveillance ◽  
The Russian Federation

Background. Enterovirus infection is widely spread around the world. It has different epidemiologic and clinical manifestations. However, to date, the amount of accumulated information on the epidemic process of enterovirus infection in different constituent entities of the Siberian Federal district of the Russian Federation is insufficient. Objectives. Our objectives were to investigate characteristics of the enterovirus infection epidemic process in Siberian constituent entities subjected to surveillance using the innovative molecular genetic analysis. Materials and methods. The analysis of long-term enterovirus infection incidence in the investigated constituent entities of Siberia was performed. The total number of 237 enterovirus strains circulating during 2017-2018 epidemic seasons in the analyzed regions were isolated using sequencing technique. A phylogenetic analysis of the obtained nucleotide sequences was performed. Results. The epidemiologic situation related to enterovirus infection was unfavorable in the majority of the Siberian constituent entities in the past two years. A significant increase in incidence rates was registered in the Irkutsk Region, Zabaykalsky Krai and Altai Republic. We distinguished major manifestations of the enterovirus infection epidemic process including a years-long excess of the national average and a rising trend in the annual incidence rate, prevalence of herpangina, exanthema and enterovirus meningitis in the clinical course of the disease among children aged 3–6. Prevalence of Coxsackievirus A-6 and Coxsackievirus A-9 in the landscape of circulation was revealed in a number of Siberian regions. Group incidence and imported cases were also registered. Discussion. Our results demonstrated the importance of molecular genetic monitoring of circulating enteroviruses as part of the epidemiologic surveillance. This state-of-the-art approach can reveal potential epidemiologic links between cases of the disease.

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