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Relevance. Non-polio enteroviruses are widespread worldwide, with millions of cases being reported each year, but limited data exist on the true burden of enterovirus (non-polio) infections (EVnI) worldwide due to a lack of standardized surveillance. Considering the absence of specific prevention of EnVI and the difficulty of predicting the epidemic situation due to the diversity of types of enteroviruses, there is an obvious need for substantiating and supplementing the existing parameters of epidemiological monitoring, identifying additional indicators of morbidity risk for the purpose of timely implementing preventive and anti-epidemic measures. Aim. Rationale of necessity of additional measures of the EVnI observation for early discovery of the activation of the epidemic process. Materials and methods. The research was held during the year 2023 and included the following three components: 1. The prospective continuous observation of the patients ranging from 0 to 18 years old who received medical help in ambulatory conditions. Possible symptoms of EVnI were studied using the ambulatory diseased person’s medical cards (f. № 0/25у). 2. The research of biological material, which belonged to the healthy people and people with signs of probable EVnI. 3. The study of epidemiological connection of dew point temperature with the manifestations of the EVnI epidemic process. Results. Probable clinical symptoms of EVnI are found among 511 observed children. Positive correlational connection with EVnI is visible among exanthems (0,43, p < 0,001) and acute nasopharyngitis (0,13, p < 0,001). The maximal incidence rate of EVnI is discovered in a period from 27th to 36th week (54,35 ‰), which coincides with maximal incidence rate of acute nasopharyngitis (434,78 ‰). The rise in incidence rate of EVnI in comparison to the last period is 4,45 times (p < 0,001), while in comparison to the rise in incidence rate of acute nasopharyngitis is 2,71 times (p < 0,0001). In planned observation of examined patients with probable symptoms, EVnI disease is found amongst 78 people, the incidence rate made 254,07 ‰ and that aligns with the results of active observation of health center appeals (267,68 ‰, p > 0,99). Clinical diagnosis of EVnI is made only in 51,28 %% of all cases. As a result of ill and healthy people’s observation, their relation is found to be 6:1 respectively. The activation of the epidemic process started in concurrence with dew point temperature +4,85 °C and continued until the dew point temperature +20,33 °C. Conclusion. The existing system of epidemiological supervision over EVnI has to be enhanced by adding the research on NPEV among the people who have acute nasopharyngitis during the stable rise in dew point temperature from +5,0 °C. Taking into account the rise in the incidence rate of EVnI, it is reasonable to expand the microbiological observation of biological material which belongs to the people who have exanthems, diarrheal syndrome and healthy people more...

Objective: to identify the clinical and epidemiological features of enteroviral meningitis (EVM) in children during the seasonal rise in incidence in 2023.Materials and methods: a retrospective analysis of 171 medical histories of children aged 1 month to 17 years, hospitalized in the infectious diseases hospital of the RSBHI «KICCH № 1» from June to October 2023, is presented.Results. The bulk of patients, 77.9 ± 3.2% (133/171), were hospitalized between August and October, which indicates the persistence of the summer-autumn seasonality of incidence. The clinical picture of EVM is characterized by acute development, persistent fever, intoxication, against which headache and repeated vomiting appear, indicating the development of hypertensive-hydrocephalic syndrome. Dissociation of meningeal signs requires liquorological studies to confirm the diagnosis of enteroviral meningitis. Clinical recovery at the time of discharge occurred only in 64.3 ± 3.7% of convalescents; in the remaining children, 35.7 ± ± 3.7% (61/171) residual effects persisted, which required continued observation. more...

Purpose: To compare the clinical characteristics, virus serotype, and outcome in cases of mild and severe enteroviral infection at a tertiary neonatal intensive care unit in China. Methods: A retrospective analysis of cases hospitalized between June and August 2019. Samples (stool or throat swabs) were examined using reverse transcription polymerase chain reaction. Positive cases were divided into two groups: mild infection and severe infection. Results: A total of 149 cases were assigned to one of two groups: mild infection (n = 104) and severe infection (n = 45). There were no significant differences between the groups in terms of sex, gestational age, birth weight, mode of delivery, and onset within 7 days. Clinical symptoms in both groups mostly resembled sepsis (fever, rash, poor feeding, and lethargy); however, there were significant variations in concomitant symptoms such as hepatitis, thrombocytopenia, encephalitis, coagulopathy, and myocarditis. Severe cases were more likely to have abnormal complete blood counts, biochemical parameters, and cerebrospinal fluid markers. The predominant serotypes implicated in neonatal enterovirus infections were echoviruses and Coxsackievirus B. Invasive ventilation, intravenous immunoglobulin, vasoactive medications, and blood product transfusions were often required, with high mortality rates among severe cases. Conclusion: We found significant differences between mild and severe cases of neonatal enterovirus infection with respect to complications, laboratory findings, and enterovirus serotypes. It is crucial to exercise caution when newborns exhibit symptoms of sepsis, during an enterovirus outbreak. Anemia, thrombocytopenia, abnormal liver function, and coagulation dysfunction should be monitored closely as they could indicate the presence of a severe enteroviral infection. [ABSTRACT FROM AUTHOR] more...

Enteroviruses (EVs) are the main cause of a number of neurological diseases. Growing evidence has revealed that successful infection with enteroviruses is highly dependent on the host machinery, therefore, host proteins play a pivotal role in viral infections. Both host and viral proteins can undergo posttranslational modification (PTM) which can regulate protein activity, stability, solubility and interactions with other proteins; thereby influencing various biological processes, including cell metabolism, metabolic, signaling pathways, cell death, and cancer development. During viral infection, both host and viral proteins regulate the viral life cycle through various PTMs and different mechanisms, including the regulation of host cell entry, viral protein synthesis, genome replication, and the antiviral immune response. Therefore, protein PTMs play important roles in EV infections. Here, we review the role of various host- and virus-associated PTMs during enterovirus infection. [ABSTRACT FROM AUTHOR] more...

Clinical swabs with suspected viral infection are usually transported in virus transport medium (VMT). During epidemics/pandemics, tampons without VTM would be more suitable for saving space and cost. This study was conducted to verify the applicability of throat swabs without VTM in the diagnosis/screening of enteroviral infections by polymerase chain reaction (PCR) in a volunteer study group. Three different swab types were used in 40 volunteers: swabs with two different tips (cotton- or synthetic-tipped) without VTM and standard synthetic tips with VTM. The swabs were processed immediately or after 12 days of storage at either -80°C or +4°C. The molecular analysis included viral RNA extraction, and combination of reverse transcriptase PCR and nested PCR. Enteroviral RNA was detected in 15% (6/40) of the studied volunteers. When processed immediately, the results for all three swab types were compatible. Swabs without VTM may be used for collection of clinical samples in the diagnosis of suspected enteroviral infections or as potential screening tools for enteroviruses. [ABSTRACT FROM AUTHOR] more...

Introduction. Molecular epidemiological monitoring of enterovirus infection (EVI) in the territories of the Russian Federation showed that coxsackievirus A6 (CVA-6) had been one of the most prevalent types of enteroviruses that circulated among the country population during last years and had caused majority of EVI outbreaks. Objective — to evaluate coxsackievirus A6 circulation in the territories of the Far Eastern Federal district (FEFD) in 2014–2019 utilizing methods of molecular genetics. Materials and methods. RT-PCR was employed to detect enterovirus RNA in biological material collected in 9 territories of the FEFD . In order to establish enterovirus types, amplification of positive samples was carried out to detect nucleotide sequence fragments of the VP1 and VP2 genes. Molecular genetic analysis of the Far Eastern CVA-6 strains was based on detection of nucleotide sequences of VP1 and 3Dpol gene fragments. Phylogenetic trees were constructed by the means of Bayesian phylogenetic methods. Results. Total 1773 nucleotide sequences of 43 types of non-polio enteroviruses were obtained in 2014-2019. Majority of the sequences belonged to coxsackievirus A6 (524; 29.5%). In the years of the highest CVA-6 detection an increase in EVI incidence as well as EVI outbreaks were observed in the territories of FEFD. The most prevalent manifestations of EVI caused by CVA-6 in FEFD were herpangina and exanthemic forms. Phylogenetic analysis showed that Far Eastern strains of CVA-6 during in the analyzed period of time belonged to D3 subgenotype that is dominant in the world. The circulation of several recombinant forms of CVA-6 (RF-A, -H, -L, -N, -R) was also registered. Conclusion. The genetic diversity of CVA-6 strains circulating in the territories of the FEFD in 2014–2019 revealed in this study requires further investigation in order to obtain new knowledge about the CVA-6 molecular epidemiology and improve the enterovirus surveillance system. more...

Objective: the study of molecular epidemiological and clinical aspects of EVI in the Rostov region for the period 2006-2020. to improve the disease surveillance system. Research methods: epidemiological, virological, molecular biological (PCR, sequencing, phylogenetic analysis), microbiological, statistical. Materials and methods: the analysis of medical records of 139 patients with EVI was carried out. Samples of biomaterial (feces, throat swab) from 17293 people, samples from environmental objects (2710 samples), strains of enteroviruses (EV) in the amount of 142 specimens were studied. Results: in the Rostov region until 2013. sporadic incidence of EVI prevailed with registration from 1 to 38 cases per year. June 2013 there was a sharp increase in the incidence of EVI with the formation of local foci in organized groups, associated with the circulation of a new genotype — EV 71 type of subgenotype C4 of “Chinese” origin (622 patients with EVI were registered, one death). The clinical features of the disease were determined: acute onset with manifestations of intoxication, foot and mouth disease-like syndromes, followed by the development of CNS pathology in 37.4% of patients. According to the results of sequencing of biomaterial samples from patients and virus carriers for the period 2006-2020. EVs of 22 types were detected. Conclusions: EVs are subject to intense genetic variability, due to which new genovariants pathogenic for humans may appear. The change in EV genotypes, which dominated the circulation among the population of the Rostov region, determined the rise in the incidence of EVI in 2013. A significant diversity of non-polio EV genotypes was revealed, while the structure of EV genovariants changed in different years. more...

Purpose: This study aimed to evaluate whether vitamin D supplementation can reduce the incidence of influenza and enterovirus infection in Taiwanese children. Methods: This randomized, double-blind, controlled trial included children aged two to five years between April 2018 and October 2019 from daycare centers. All the participants were randomly assigned to a vitamin D supplementation group (2000 IU/day) or placebo group for one month. The primary outcome was the incidence of influenza and enterovirus infection in the following six months, and the secondary outcome was the incidence of influenza and enterovirus infection in the children's household members. Results: Two hundred and forty-eight children participated. The vitamin D group showed a relative risk reduction of 84% against influenza compared to the placebo group but did not reach statistical significance. Kaplan–Meier curves revealed that the placebo group had a higher probability of influenza infection than the vitamin D group (log-rank test, p = 0.055), but the incidence of enterovirus infection was similar between the two groups (p = 0.946) among children. Among children's household members, the incidence of influenza (p = 0.586) and enterovirus infection (p = 0.528) were both similar between the two groups. All children who were tested for serum 25(OH)D levels after vitamin D intervention had 25(OH)D levels above 30 ng/ml Conclusion: Vitamin D supplementation may have a small preventative effect against influenza infection but does not affect enterovirus infection among preschool children. A high-dose short-term vitamin D intervention might be a way to elevate children's serum vitamin D levels in the first month of starting kindergarten. more...

Non-polio enteroviruses (NPEVs) are ubiquitous and are one of the main causative agents of viral infections in children. NPEVs most commonly infect newborns and young children, due to their lack of antibodies. In children, clinical manifestations can range from acute febrile illness to severe complications that require hospitalization and lead in some cases to disability or death. NPEV infections can have severe consequences, such as polio-like diseases, serous meningitis, meningoencephalitis, myocarditis, etc. The most promising strategy for preventing such diseases is vaccination. No less than 53 types of NPEVs have been found to circulate in Russia. However, of epidemic importance are the causative agents of exanthemic forms of the disease, aseptic meningitis and myocarditis. At the same time, the frequency of NPEV detection in the constituent entities of the Russian Federation is characterized by uneven distribution and seasonal upsurges. The review discusses the epidemic significance of different types of enteroviruses, including those relevant to the Russian Federation, as well as current technologies used to create enterovirus vaccines for the prevention of serious diseases. more...

Background: The aim of this study was to evaluate the long-term sequelae and cognitive profiles resulting from severe hand, foot, and mouth disease (HFMD) with central nervous system (CNS) involvement. Methods: 294 HFMD cases were included in a retrospective follow-up study. Physical examinations were conducted. The Chinese Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to assess intelligence. Results: 58 mild HFMD cases and 99 severe HFMD cases with mild CNS involvement did not present any neurological sequelae. In comparison, the sequelae incidence for severe HFMD with more severe CNS complications was 50.0%. The proportion of full-scale intelligence quotient (FSIQ) impairment was 45.0%. In the 2:6–3:11 age group, severe HFMD with more severe CNS complications and lower maternal education level were risk factors for verbal comprehension disorder. Urban–rural residence and lower paternal education level were risk factors for FSIQ disorder. Furthermore, in the 4:0–6:11 age group, severe HFMD with more severe CNS complication was a risk factor for visual spatial disorder and fluid reasoning disorder. Lower paternal education level was a risk factor for FSIQ disorder. Conclusion: Early assessment and intervention among severe HFMD patients with more severe CNS involvement at a very young age will prove beneficial for their future performance. more...

Due to the increasing water crisis, the reuse of wastewater deserves attention as a method to reduce the pressure of the water crisis, especially in developing countries. The application of health risk assessment models is a way to estimate disease burdens associated with crop irrigation by wastewater effluents. In this study, a quantitative microbial risk assessment (QMRA) with probabilistic Monte-Carlo simulation was used to estimate the annual risk of enteroviruses (EVs) infection and disease burden for consumers of effluent-irrigated raw vegetables in Tehran, the capital of Iran. Wastewater effluent samples were collected over two seasons: summer and winter. EVs were analyzed in three stages, concentration and separation, cell culture, and real-time PCR (RT-PCR). A questionnaire was used to determine the dominant patterns of vegetable washing by consumers. There were 4 vegetable washing steps: wiping away mud (A), rinsing (B), using detergents (C), using disinfectants (D). 5 patterns of washing were examined in the laboratory and the concentration of enteroviruses was measured in every pattern. pattern 1: just wiping away mud (A), pattern 2: wiping away mud and rinsing (AB), pattern 3: wiping away mud by using detergents and rinsing (ABCB), pattern 4: wiping away mud by using disinfectants and rinsing (ABDB), and pattern 5: wiping away mud by using detergents and disinfectants and rinsing (ABCBDB). For washing pattern 1, pattern 2, and pattern 3, the estimated annual infection risk of EVs was estimated to be 5.6 × 10–1, 3.6 × 10–1, 1.7 × 10–1 (risk/per.day), and burden of disease was calculated as 3 × 10–2, 2 × 10–2, and 9 × 10–3 (burden/year), respectively. The results showed that if vegetables are washed according to method 5, the microbial risk will be minimized and the excess prevalence of viral infections will be eliminated. [ABSTRACT FROM AUTHOR] more...

The epidemic situation and etiological factors of enterovirus infection in Russia and Vietnam were analysed and compared. The identified strains of enteroviruses of 47 types, which circulated in Russia in 2018–2019, belonged to different species: Enterovirus species A (CV-A2, CV-A4, CV-A6, CV-A8, CV-A10, CV-A16, EV-A71), as well as Enterovirus species B and Enterovirus species C. The strains isolated from 87 children from southern Vietnam hospitalised in 2018–2019 into infectious hospitals while having enterovirus infection with exanthema were also studied. All identified strains were represented by Enterovirus species A: EV-A71 — 59 strains, CV-A10 — 20 strains, CV-A16 — 5 strains, CV-A6 — two strains and CV-A2 — one strain. Out of 59 viruses EV-A71, 53 strains belonged to genotype C4 and 6 strains belonged to genotype B5. The sequences of EV-A71 strains of genotype C4 from South Vietnam formed a monophyletic cluster with the sequences of EV-A71 viruses which circulated during 2016–2018 in different provinces of China, and they were very close to EV-A71 strains of the same genotype from the Yunnan Province. These strains were genetically different from Russian viruses and Vietnamese viruses identified in the years 2003–2005 and 2011– 2012. Most of the cases of enterovirus infection from southern Vietnam (78%) caused by EV-A71 virus of genotype C4 were reported in three provinces located in southern Vietnam in the Mekong Delta. The epidemic process and the etiology of enterovirus infection in Russia and Vietnam have common features. At the same time, the epidemic situation in these countries is not the same. The incidence of enterovirus infection is influenced by geographic, climatic, economic and demographic factors that differ in two countries. In the majority of territories of Russia, the climate is temperate or cold, seasonal rises in the incidence rates of enterovirus infection usually occur in the summer, when people go on vacation, spend a lot of time outdoors and swim in open reservoirs. In Vietnam, a constant high-level temperature, a high population density and a large proportion of children determine the higher incidence of enterovirus infection, especially in the southern provinces of Vietnam, compared to Russia. The fact that more than 20% of the Vietnamese population lives in the Mekong Delta, which is the largest river in Indochina, has a significant impact on the epidemic process of enterovirus infection in South Vietnam. The Mekong River which flows through China, Laos, Thailand, Cambodia and Vietnam, and carries huge streams of water, including rainstorm waters and sewages, from all of these countries into the southern provinces of Vietnam, which have the highest incidence rates of enterovirus infection in the country. The results of the research underline the importance of active epidemiological and virological surveillance of enterovirus infection, which plays the key role in informing the public health authorities about the changes in the epidemic situation in order to take appropriate measures and develop the prevention strategies. The goal of anti-epidemic and preventive measures is to reduce the incidence of enterovirus infection and the economic burden of this infection for Russia and Vietnam. more...

Coxsackieviruses B (CV-B) (Picornaviridae) are a common infectious cause of acute myocarditis in children and young adults, a disease, which is a precursor to 10-20% of chronic myocarditis and dilated cardiomyopathy (DCM) cases. The mechanisms involved in the disease progression from acute to chronic myocarditis phase and toward the DCM clinical stage are not fully understood but are influenced by both viral and host factors. Subgenomic replicons of CV-B can be used to assess viral replication mechanisms in human cardiac cells and evaluate the effects of potential antiviral drugs on viral replication activities. Our objectives were to generate a reporter replicon from a cardiotropic prototype CV-B3/28 strain and to characterize its replication properties into human cardiac primary cells. To obtain this replicon, a cDNA plasmid containing the full CV-B3/28 genome flanked by a hammerhead ribozyme sequence and an MluI restriction site was generated and used as a platform for the insertion of sequences encoding emerald green fluorescent protein (EmGFP) in place of those encoding VP3. In vitro transcribed RNA from this plasmid was transfected into HeLa cells and human primary cardiac cells and was able to produce EmGFP and VP1-containing polypeptides. Moreover, non-structural protein biological activity was assessed by the specific cleavage of eIF4G1 by viral 2A(pro). Viral RNA replication was indirectly demonstrated by inhibition assays, fluoxetine was added to cell culture and prevented the EmGFP synthesis. Our results indicated that the EmGFP CV-B3 replicon was able to replicate and translate as well as the CV-B3/28 prototype strain. Our EmGFP CV-B3 replicon will be a valuable tool to readily investigate CV-B3 replication activities in human target cell models. more...

Abstract Background Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high lethality. This review systematically summarized the clinical characteristics of neonates with severe enteroviral infection to provide evidence for the identification and treatment of severe neonatal EV infection. Methods PubMed, Embase, and Web of Science were searched for original studies on neonates with severe EV infections from January 1, 2000, to November 27, 2020. Two reviewers independently screened the literature, extracted the data, and performed a descriptive analysis. Results In total, 66 articles with 237 cases of severe neonatal enterovirus infection were included. All neonates developed severe complications. Among them, 46.0% neonates had hepatitis or coagulopathy, 37.1% had myocarditis, 11.0% had meningoencephalitis, and 5.9% had other complications such as hemophagocytic lymphohistiocytosis and pulmonary hemorrhage. The lethality rate of neonates with severe infection was 30.4%. The highest lethality rate was 38.6%, which was observed in neonates with myocarditis. In 70.5% neonates, the age at the onset of symptoms was less than 7 days. Coxsackievirus B infection was seen in 52.3% neonates. The most common symptoms included temperature abnormalities (127, 53.6%), rash (88, 37.1%), poor feeding (58, 24.5%), and respiratory symptoms (52, 21.9%). The main treatment included transfusion of empirical antibiotics (127, 53.6%), blood components (100, 42.2%), intravenous immunoglobulin (IVIG; 97, 40.9%), mechanical ventilation (51, 21.5%), and extracorporeal membrane oxygenation (ECMO; 43, 18.1%). Additionally, antiviral medications pleconaril (14, 5.9%) and pocapavir (3, 1.3%) were administered. Conclusions Lethality was high in neonates with severe enterovirus infection, especially in those complicated with myocarditis. The most common symptoms included temperature abnormalities, rash, and poor feeding. The chief supportive treatment consisted of transfusion of blood components, mechanical ventilation, and ECMO. Empirical antibiotics and IVIG were widely used. Antiviral medications included pocapavir and pleconaril; however, more clinical evidence regarding their efficacy is needed. more...

Aim: Analysis of enterovirus infection morbidity and characteristics of the etiological agents of this infection on some territories of Russia in 2017.Materials and methods: We investigated 7858 samples of the biological material from the patients suffering from enterovirus infection. The isolation and identification of enteroviruses were conducted by virological and molecular methods.Results: The epidemic process and the clinical picture of enterovirus infection on different territories had some peculiarities. On some territories enterovirus meningitis was the predominant form of infection, on other territories enterovirus infection with exanthema prevailed. In Saint-Petersburg, Archangel and Saratov regions the percentage of enterovirus infection cases with the clinical picture of enterovirus meningitis was significantly higher than the percentage of enterovirus infection with exanthema. In the Komi Republic, Leningrad and Murmansk regions the percentage of infection with exanthema was statistically higher than the enterovirus meningitis portion. Enteroviruses of 30 serotypes were detected in the samples of patients suffering from enterovirus infection. We determined the etiology of sporadic and epidemic cases of enterovirus infection represented by different clinical forms. On some territories the epidemic foci of enterovirus infection among children were revealed. The etiological agents of enterovirus meningitis foci in Saint-Petersburg, Murmansk and Saratov regions were Coxsackievirus B5, Coxsackievirus B4 and Echovirus 30. The foci of enterovirus infection with exanthema in Archangel, Leningrad, Murmansk and Novgorod regions were caused by Coxsackieviruses A10, A16 and A6.Conclusion: The clinical forms of enterovirus infection on some territories were provoked by enteroviruses which dominated in the circulation on one or other territory. Enteroviruses of species B, mainly Echovirus 30, Echovirus 6 and Coxsackieviruses B1–6 were the etiological agents of enterovirus meningitis. The etiological factors of enterovirus infection with exanthema were Enteroviruses of species A, mainly Coxsackieviruses of different serotypes as well as Enterovirus 71. more...

Objectives – to identify the clinical and epidemiological features of enterovirus infection in the adult population in the Oryol region, to track the seasonality of the disease, distribution in different age groups, and to assess the main clinical forms, symptoms, and complications.Objects and methods of research. The object of investigation was 24 medical histories of patients who gave informed consent, with a confirmed diagnosis of “enterovirus infection”, the 2 nd infectious diseases Department of Department of Oryol region “City hospital. S.P. Botkin”.Results. For the period from 2009 to 2019 was gospitalizirovany 24 patients with laboratory-confirmed diagnosis “enterovirus infection”. The most patients with this diagnosis were in 2017 – 33,5 %, the least – in 2012 – 4,1 %. In 2013 and 2019, there were no patients. Women were sick more often than men – 55 % of the total number of subjects. After analyzing statistical data, it was found that young people (aged 20–29 years) were sick more often – 58,3 %. There is a summer-autumn seasonality: 45,8 % and 54,2 %, respectively. 37,5 % of the subjects were in contact with infectious SARS patients. 37,5 % also left the Oryol region the day before.Most often, enterovirus exanthema was observed in patients – 58,3 %.. The onset of the disease in 100 % of cases was acute. All patients had fever, most often subfebrile – 54,2 %. The studied patients complained of body aches – 100 %, headaches of various localization and intensity – 96 %, sore throat – 12,5 %, vesicular-papular rash on the skin of the trunk, limbs, and head – 58,3 %, and enanthema on the oropharyngeal mucosa – 12,5 %. In 100 % of cases, the diagnosis was confirmed by a positive polymerase chain reaction response to the presence of enterovirus RNA.Conclusion. The study revealed that over the past 10 years, enterovirus infection in the Oryol region has a consistently low level. It is more common in young people. The disease is characterized by summer and autumn seasonality. In this area, the more common form is enterovirus exanthema. more...

Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is believed to be transmitted through respiratory droplets, aerosols, and contact. During the COVID-19 pandemic, Taiwan has implemented timely and accurate non-pharmaceutical intervention (NPI) measures on a national level (i.e., border control, quarantine and isolation, contact tracing, delay of school opening, and suspension of mass gatherings), and promoted personal hygiene habits to the public (i.e., frequent hand washing with soap, face masks wearing). Consequently, as of July 27, Taiwan has had relatively low number of confirmed cases (458) and deaths (7), and no locally transmitted cases for more than 30 consecutive days. We observed from data collected via Taiwan National Infectious Disease Statistics System that during the COVID-19 pandemic, outpatient visits for other infectious diseases such as influenza, which is also transmitted through droplets, aerosols, and contact, and enterovirus infections, transmitted via faecal-oral route or respiratory transmissions, have reduced significantly compared to previous two years. Epidemic trend for both diseases have also changed, with seasonal influenza activities ending weeks earlier than it did in 2018 and 2019, and lack of increase in enterovirus infections that is usually witnessed at the end of March. Our observation suggest the NPI measures and personal hygiene habits enforced against the COVID-19 pandemic may have inadvertently “flattened the curve” for influenza and enterovirus infections as well. This may indirectly relieve the stress on Taiwan’s health system and healthcare workers during the COVID-19 crisis. More information will be needed to verify this hypothesis. more...

ABSTRACT Enterovirus infections are known to cause a diverse range of illnesses, even in healthy individuals. However, information detailing enterovirus infections and their severity in immunocompromised patients, such as transplant recipients, is limited. We compared enterovirus infections in terms of genotypes, clinical presentation, and severity between transplant and nontransplant patients. A total of 264 patients (38 transplant recipients) with 283 enterovirus infection episodes were identified in our hospital between 2014 and 2018. We explored the following factors associated with enterovirus infections: clinical presentation and diagnosis on discharge, length of hospital stay, symptom persistence, and infection episodes in both children and adults. We observed some differences in genotypes between patients, with enterovirus group C occurring mainly in transplant recipients (P < 0.05). EV-associated gastrointestinal infections were more common in patients with a transplant (children [71%] and adults [46%]), compared to nontransplant patients (P < 0.05). Additionally, nontransplant patients had a higher number of hospital stays (P < 0.05), potentially reflecting more severe disease. However, transplant patients were more likely to have symptom persistence after discharge (P < 0.05). Finally, children and adults with a transplant were more likely to have additional enterovirus infection episodes (P < 0.05). In our cohort, enterovirus infections did not seem to be more severe after transplantation; however, patients tended to present with different clinical symptoms and had genotypes rarely found in nontransplant recipients. IMPORTANCE Despite the high prevalence of enteroviruses in the community and the increasing demand for transplants from an aging population, knowledge on enteroviruses in solid organ transplant recipients is currently limited. Transplant recipients represent a significant patient population and require additional considerations in patient management, particularly as they have an increased risk of disease severity. Enteroviruses are known to cause significant morbidity, with a diverse range of clinical presentation from over 100 different genotypes. In this study, we aimed to provide a more comprehensive overview of enteroviral infections in transplant recipients, compared to nontransplant patients, and to bridge some gaps in our current knowledge. Identifying potential clinical manifestation patterns can help improve patient management following enterovirus infections. more...

In order to effectively respond to outbreaks of enterovirus infection, to prevent its spread and due to the need to increase doctors’ awareness for timely diagnosis of the disease, timely informing the authorities monitoring the formation and spread of epidemic variants of viruses, an algorithm was created of the primary care physician actions in identifying a sick child with enterovirus infection. The primary task of the doctor is to suspect enterovirus infection on time. Next step is to provide clear instructions to parents with determination of “red flags” — the symptoms for the need for immediate medical attention if they occur. And also, it is necessary to detect a severe form of the disease for timely hospitalization of the patient, to choose a reasonable treatment approach at the outpatient stage, and to eliminate the source of the threat of infection spread. We propose an algorithm for the diagnosis and treatment of enterovirus infection at the outpatient stage of pediatric care, based on the international consensus “A Guide to Clinical Management and Public Health Response for Hand, Foot and Mouth Disease” (2011). The development of a unified treatment and diagnostic approach for patients with enterovirus infection and their contacts is a prerequisite for the effectiveness of providing assistance to this category of people in the context of the reorganization of the national medical industry, and the proposed algorithm which should help primary care physician in identifying a sick child with suspicion of enterovirus infection. more...

In recent years, enterovirus infection (EVI) retains its cyclical nature with an increase in the incidence rate in the Russian Federation in 2000, 2006, 2009, 2013 and 2017. Observation of 41 patients with laboratory-confirmed enteroviral meningitis (EVM) in 2000, 54 children in 2013, and 56 patients in 2018 revealed the clinical and laboratory features of this clinical form of the disease, mainly concerning changes in hemo- and liquorogram parameters, which allowed to trace the evolutionary changes during this infection in children. more...

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. more...

Relevance. Annual elevation of enterovirus infection (EVI) incidence in the Russian Federation as well as in the Sakhalin region determine a necessity of continuous surveillance involving molecular-genetic methods and phylogenetic analysis. Objective: to highlight epidemiological and molecular-genetic peculiarities of EVI in the Sakhalin region during 2016-2018 years. Materials and methods. Analysis of enterovirus incidence were based on official statistical reporting forms. The structure of enterovirus types was evaluated by means of molecular methods and followed by phylogenetic analysis. Results and discussion. A deterioration of epidemic situation concerning EVI that began in 2016 in the Sakhalin region included elevation of incidence and registration of enterovirus outbreaks in childcare facilities triggered by introduction of new enterovirus types or those that were not circulating for a long time suchas Coxsackievirus A-6, Coxsackievirus A-10, Coxsackievirus A-16, ECHO-9. The phylogenetic analysis of Coxsackievirus A-16 detected in the Sakhalin region revealed their similarities with two genovariants of B genogroup (В1а и В1b) that were continuously circulating in Russia and China. In addition, enterovirus ECHO-9 that was also circulating in other constituent entities of the Russian Federation was isolated in Sakhalin region from patients suffering from viral meningitis including two children from two different infection cites of EVI group incidence. Conclusion. An unfavorable epidemic situation concerning EVI was revealed in the Sakhalin region during the last three years of surveillance. It was caused by introduction and further spread among population of Coxsackieviruses A-6, 10, 16 and ECHO-9 that presumably have Russian or foreign origin. more...

The article describes two intrafamilial foci of enterovirus infection (EVI), caused by ECHO-3 and ECHO-6 viruses. In the first group, 6 children aged from 3 months to 4 years were found (average age — 18.0 ± 4.3 months), 3 boys (50 %) and 3 girls (50 %) with various clinical manifestations of EVI associated between themselves epidemiologically (siblings of one fami­ly, who used water from one draw-well and had close household contact). ECHO-3 virus was detected in the clinical material of the examined children. The second outbreak involved two children from the same family, who simultaneously suffered from aseptic meningitis in 2017. Cerebrospinal fluid of both children was examined by reverse transcription polymerase chain reaction (RT-PCR) (Republican Research and Practical Center for Epidemiology and Microbiology, Minsk), RNA EV was detected in both samples. After RNA sequencing, ECHO 6 was detected in both samples. The verification in both cases was performed by various clinical and laboratory methods (general clinical methods, enzyme-linked immunosorbent assay with detection of antibo­dies to EV and antigens of EV in feces, RT-PCR with subsequent EV RNA sequencing and determination of virus serotype). In two cases of the disease, the diagnosis of EVI was made epidemiologically without laboratory detection of RNA EV. PCR with the determination of EV RNA in feces and cerebrospinal fluid showed the greatest effectiveness. In the described outbreaks, RNA of enteroviruses was not detected in the blood in any sample. more...

In 2016, an upsurge of neurologic disease associated with infection with multirecombinant enterovirus A71 subgenogroup C1 lineage viruses was reported in France. These viruses emerged in the 2000s; 1 recombinant is widespread. This virus lineage has the potential to be associated with a long-term risk for severe disease among children. more...

ObjectiveThe association between enterovirus infection and type 1 diabetes (T1D) is controversial, and this meta-analysis aimed to explore the correlation.MethodsPubMed, Embase, Web of Science, and Cochrane Database were searched from inception to April 2020. Studies were included if they could provide sufficient information to calculate odds ratios and 95% confidence intervals. All analyses were performed using STATA 15.1.ResultsThirty-eight studies, encompassing 5921 subjects (2841 T1D patients and 3080 controls), were included. The pooled analysis showed that enterovirus infection was associated with T1D (P < 0.001). Enterovirus infection was correlated with T1D in the European (P < 0.001), African (P = 0.002), Asian (P = 0.001), Australian (P = 0.011), and Latin American (P = 0.002) populations, but no conclusion could be reached for North America. The association between enterovirus infection and T1D was detected in blood and tissue samples (both P < 0.001); no association was found in stool samples.ConclusionOur findings suggest that enterovirus infection is associated with T1D. more...

Objective: The association between enterovirus infection and type 1 diabetes (T1D) is controversial, and this meta-analysis aimed to explore the correlation. Methods: PubMed, Embase, Web of Science, and Cochrane Database were searched from inception to April 2020. Studies were included if they could provide sufficient information to calculate odds ratios and 95% confidence intervals. All analyses were performed using STATA 15.1. Results: Thirty-eight studies, encompassing 5921 subjects (2841 T1D patients and 3080 controls), were included. The pooled analysis showed that enterovirus infection was associated with T1D (P < 0.001). Enterovirus infection was correlated with T1D in the European (P < 0.001), African (P = 0.002), Asian (P = 0.001), Australian (P = 0.011), and Latin American (P = 0.002) populations, but no conclusion could be reached for North America. The association between enterovirus infection and T1D was detected in blood and tissue samples (both P < 0.001); no association was found in stool samples. Conclusion: Our findings suggest that enterovirus infection is associated with T1D. [ABSTRACT FROM AUTHOR] more...

Relevance.The urgency of the problem of non-polio enterovirus infection is determined by the wide spread of pathogens, the occurrence of outbreak of morbidity, polymorphism of clinical manifestations and the lack of specific prophylaxis. Most often non-polio enterovirus infection is asymptomatic. Clinically expressed forms can be serous meningitis, herpetic sore throat, eczematous fever, vesicular pharyngitis, gastroenteritis, epidemic myalgia (pleurodynia), tonsillitis, myocarditis, pericarditis, hemorrhagic conjunctivitis, uveitis, etc. The aim of the work is a comparative evaluation of the epidemic process manifestations and the leading factors of serous meningitis (SM) pathogens, enterovirus etiology herpetic angina (HA) transmission and enterovirus etiology gastroenteritis (GE). Materials and methods. Manifestations of the epidemic process of SM and HA were studied according to the official registration of the incidence of the population of Perm for the 2010–2017. In conditions of analytical «case-control» method the epidemiological survey of 350 epidemiological focuses of SM and 142 focuses of HA and 61 focuses of GE were conducted. Results. According to official registration data, the incidence rates of NEVI in the population of Perm during the last 7 years (2010–2017) ranged from 0.3 to 21.5, averaging 5.4 per 100 thousand population. There were mainly three clinical forms registered - serous meningitis, herpetic sore throat, gastroenteritis, the proportion of which was 45.3; 36.6 and 12.4%, respectively. The findings clearly demonstrate that it is similarity between epidemic process manifestations of SM, HA and enterovirus etiology gastroenteritis. Conclusion. In both clinical variants of enterovirus infection the priority role is the water way of transmission of the pathogen by drinking water from centralized and decentralized sources of water system, as well as swimming in surface water. more...

Aim: Characteristics of enterovirus infection morbidity and study of peculiarities of enterovirus circulation on some territories of Russia in 2017. Materials and methods: We investigated more than 5000 samples from the patients with enterovirus infection. The isolation and identification of enteroviruses were conducted by virological method and by partial sequencing of the genome region VP1. Phylogenic trees were constructed according to the method of Bayesian Monte Carlo Markov Chain. Results: Epidemic process and clinical picture of enterovirus infection were not the same on different territories. Peculiarities of the circulation of different types of enteroviruses on the territories were also different. In Saratov region 65% of cases were represented by enterovirus meningitis. In Murmansk region and in the Komi Republic enterovirus infection with exanthema prevailed, 95% and 60% correspondingly. In Saratov region enterovirus ECHO18 was the etiological agent of enterovirus meningitis. In Murmansk region and in the Komi Republic the cases were connected mainly with Coxsackieviruses A6. The strains of enterovirus ECHO18 were distributed to three clusters. The strains which provoked enterovirus meningitis in Saratov region belonged to cluster 3, they were formed separately from other strains of this enterovirus type and differed from the stains of ECHO18 which circulated in the North-West of Russia. The strains of Coxsackieviruses A6 identified in the North-West of Russia belonged to three sub-genotypes 5, 6, 8 of pandemic genotype of CoxsackievirusesA6. The majority of the strains belonged to sub-genotypes 6 and 8 which in 2017 dominated in the structure of Coxsackieviruses A6 in the North-West of Russia and in Russia. Conclusion: Epidemic peaks of enterovirus infection represented by different clinical forms of the disease were provoked by different types of enteroviruses. Enterovirus ECHO18 was the etiological agent of enterovirus meningitis. The main etiological factors of enterovirus infection with exanthema were Coxsackieviruses A6 of different sub-genotypes. more...

Objective. To reveal the clinical and epidemiological features of еnterovirus meningitis (EVM) in 140 children of Krasnoyarsk in the period of seasonal rise of morbidity in 2017.Materials and methods. For the etiological interpretation of the enterovirus infection (EVI), a molecular biological and virological study of the cerebrospinal fluid, two samples of feces, a swab from the oropharynx, the contents of the vesicles was carried out. Statistical processing of data was carried out using the PASW Statistics 17.0 program.Results. In the Krasnoyarsk Territory, an annual increase in the incidence of EVI is registered, exceeding the average for the country. Serous meningitis is traditionally the main clinical form of EVI. Among the observed patients with EVM, the main group consisted of preschool children (32.9%) and school age (30%), mainly organized in children's groups (84.3%), and the summer-autumn seasonality of the disease remains. Meningitis was observed in 82.8% of patients, meningitis combined with exanthema — in 10%, with herpangina — in 2.1%, with myalgia — in isolated cases . Mediastinal forms of the disease predominated (96.4% — 135 people), severe forms of the EVM were diagnosed only in 3.6% (5 patients). The clinical picture is traditionally represented by three leading syndromes: intoxication, cerebral and meningeal. The implementation of the epidemic process in 2017 was mainly represented by enteroviruses Coxackie B, B1, B2, B4. Despite the relatively favorable course of the EVM, residual events were in 10% of patients (14 people) at the time of discharge. more...

The sporadic incidence of tetanus, the identity of symptoms with the clinical picture of a number of common neuroinfections, the high frequency of various background pathologies create difficulties in disease diagnosing in children. On the case history example of a 3 years 9 months old child with two diseases (tetanus, enterovirus infection) that developed against the background of the active form of herpesvirus infection, an algorithm of diagnostic and therapeutic measures is presented.A differential diagnosis was made between the generalized form of tetanus and meningoencephalitis of enteroviral etiology. Lack of vaccination, living in rural areas, violation of the integrity of the skin and soil contamination testified in favor of tetanus. The clinical symptoms of tetanus were revealed: a triad of symptoms (trismus, «sardonic smile», dysphagia), tetanic cramps against a background of clear consciousness, muscle hypertonicity in the interictal period. The patient received complex treatment; 100 thousand IU of anti-tetanus serum and tetanus anatoxin were introduced. Discharged on the 23rd day of illness with recovery. more...

Background: Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high lethality. This review systematically summarized the clinical characteristics of neonates with severe enteroviral infection to provide evidence for the identification and treatment of severe neonatal EV infection.Methods: PubMed, Embase, and Web of Science were searched for original studies on neonates with severe EV infections from January 1, 2000, to November 27, 2020. Two reviewers independently screened the literature, extracted the data, and performed a descriptive analysis.Results: In total, 66 articles with 237 cases of severe neonatal enterovirus infection were included. All neonates developed severe complications. Among them, 46.0% neonates had hepatitis or coagulopathy, 37.1% had myocarditis, 11.0% had meningoencephalitis, and 5.9% had other complications such as hemophagocytic lymphohistiocytosis and pulmonary hemorrhage. The lethality rate of neonates with severe infection was 30.4%. The highest lethality rate was 38.6%, which was observed in neonates with myocarditis. In 70.5% neonates, the age at the onset of symptoms was less than 7 days. Coxsackievirus B infection was seen in 52.3% neonates. The most common symptoms included temperature abnormalities (127, 53.6%), rash (88, 37.1%), poor feeding (58, 24.5%), and respiratory symptoms (52, 21.9%). The main treatment included transfusion of empirical antibiotics (127, 53.6%), blood components (100, 42.2%), intravenous immunoglobulin (IVIG; 97, 40.9%), mechanical ventilation (51, 21.5%), and extracorporeal membrane oxygenation (ECMO; 43, 18.1%). Additionally, antiviral medications pleconaril (14, 5.9%) and pocapavir (3, 1.3%) were administered.Conclusions: Lethality was high in neonates with severe enterovirus infection, especially in those complicated with myocarditis. The most common symptoms included temperature abnormalities, rash, and poor feeding. The chief supportive treatment consisted of transfusion of blood components, mechanical ventilation, and ECMO. Empirical antibiotics and IVIG were widely used. Antiviral medications included pocapavir and pleconaril; however, more clinical evidence regarding their efficacy is needed. [ABSTRACT FROM AUTHOR] more...

Objective To study the clinical features of neonatal enterovirus infection, especially severe enterovirus infection. Methods A retrospective analysis was performed for the clinical data of 244 neonates with enterovirus infection. According to the severity of infection, they were divided into a common infection group with 231 neonates and a severe infection group with 13 neonates. Clinical features were compared between the two groups. Results Of the 244 neonates, 207 (84.8%) developed the disease in May to October, with the highest number of patients in June to July. Compared with the common infection group, the severe infection group had a significantly lower gestational age at birth and a significantly higher proportion of preterm infants (P<0.05). Compared with the common infection group, the severe infection group had a significantly earlier onset time (P<0.05) and significantly higher incidence rates of skin petechiae and ecchymosis, respiratory symptoms, sepsis-like manifestations (poor appetite, crying less, and less movement), concomitant diseases (such as pneumonia, myocarditis, necrotic hepatitis, and coagulation disorder), thrombocytopenia, prolonged prothrombin time, elevated creatine kinase-MB, and elevated alanine aminotransferase (P<0.05). The severe infection group had a significantly higher mortality rate than the common infection group (P<0.05). Conclusions There are significant differences in onset time, common clinical manifestations, and concomitant diseases between the neonates with common and severe enterovirus infection. In the enterovirus epidemic season, if the neonates have rashes and/or sepsis-like manifestations such as poor appetite and less movement, especially if the laboratory tests suggest liver damage and coagulation dysfunction, it is necessary to pay particular attention to the possibility of severe enterovirus infection. [ABSTRACT FROM AUTHOR] more...

In the infectious pathology of childhood, viral diarrhea becomes increasingly important. In the present work, the clinical and epidemiological features of rotavirus, adenovirus, norovirus and enterovirus enteric infections in children have been analyzed. It was found that viral intestinal infections are one of the leading causes of infectious gastroenteritis in infants. Viral diarrhea is most severe in children with unfavorable premorbid background. Infant patients are characterized by the development of water-deficient excoxicosis. The absence of specific prevention, ease introduction of infection creates the prerequisites for the growth of morbidity. more...

Aim: Characteristics of the peculiarities and the etiological factor of enterovirus infection on some territories of Russia in 2016. Materials and methods: We investigated 2138 samples from the patients with enterovirus infection. The isolation and identification of enteroviruses were conducted by the virological method and by partial sequencing of the genome region VP1. Phylogenic trees were constructed according to the method of Bayesian Monte Carlo Markov Chain. Results: Epidemic peaks of enterovirus infection were fixed on some territories of Russia. In Saratov region the morbidity index of enterovirus infection in 2016 was twice as high as the median morbidity index over previous years. The morbidity level of enterovirus meningitis – 3, 21 for 100000 of the population (77% from all the cases of enterovirus infection) was higher than on the other territories. In Kostroma region the morbidity index of enterovirus infection in 2016 was 11 times higher than the index of the previous year. On both territories the rise of morbidity depends on the active circulation of enterovirus ЕСНО30. Enteroviruses ECHO30 from Saratov region belonged to two phylogenic groups of genotype h. To one of them belonged viruses ECHO30 from Kostroma region. In Murmansk and Leningrad regions in 2016 most cases of enterovirus infection were represented by hand, foot and mouth disease (HFMD). The grouped foci of infection were registered in some preschool institutions. The etiological factor of this clinical form was Coxsackieviruses A6 belonging to different genetic variants. Conclusion: Epidemic peaks of enterovirus infection with the prevalence of different clinical forms of the disease were provoked by different etiological factors. On territories where enterovirus meningitis prevailed strains of enterovirus ECHO30 belonging to different variants of genotype h were detected. In patients with clinical picture of HFMD from territories where this form was leading the etiological factor of infection was Coxsackievirus A6 of different genetic variants. more...

Every year, an increase in the incidence of enterovirus infection is registered everywhere, including Coxsackie viruses. Parents of sick children are often very uneasy considering these viruses to be extremely dangerous and the disease to be severe one, with possible adverse consequences. The situation is exacerbated by many mass media that inform about the epidemic of Coxsackie virus, which causes a terrible disease. The article gives main characteristics of microorganisms, modes of infection, clinical manifestations of enterovirus infections as well as measures for prevention and treatment. more...

Objective – to determine the frequency of serous meningitis of enteroviral etiology and find out their clinical and laboratory features. Materials and Methods. The study included 51 patients with serous meningitis. To confirm the serous meningitis of enteroviral etiology the method of polymerase chain reaction with enteroviruses RNA identification in feces and cerebrospinal fluid and subsequent identification of the enterovirus type 71. The study has been carried out as a part of an open cohort study of the Small Grants Joint Programme WHO/HHWS focused on the programs of the communicable disease control implementation. Results. Enterovirus etiology of serous meningitis was confirmed in 27 (52.9 %) patients, but the genotype of enterovirus type 71 was not detected in any case. The risk group of serous meningitis of enteroviral etiology development were children aged 8–11 years, as the frequency of serous meningitis of enteroviral etiology among them was 40.8 % against 12.5 % (χ2 = 5.09, p < 0.02) of cases serous meningitis of unknown etiology in the same age group. Serous meningitis of enteroviral etiology, which was not caused by virus type 71, was characterized by acute onset, less pronounced cerebral symptomatology, dissociation of meningeal signs (48.1 %), neutrophilic pleocytosis (25.9 %) at the beginning of the disease and benign course of the disease due to faster regress in the clinical manifestations of the disease such as headache and meningeal signs. Conclusions. Enterovirus etiology of serous meningitis was confirmed in 52.9 % of patients but there was not identification of enterovirus genotype 71. Mostly serous meningitis had enterovirus etiology in children of 8–11 years old. Serous meningitis of enteroviral etiology was not caused by virus type 71, and was characterized by acute onset, less severe cerebral symptoms, dissociation of meningeal signs, neutrophilic pleocytosis at the beginning of the disease and benign course of the disease. more...

Background: Viral central nervous system (CNS) infections are typically characterized by a cerebrospinal fluid (CSF) lymphocytic pleocytosis. A CSF neutrophilic pleocytosis presentation has been described, but its prognostic and clinical significance is unknown. The objectives of this study were to (1) compare the clinical and laboratory characteristics of viral CNS infections with a CSF neutrophilic pleocytosis to those with a lymphocytic pleocytosis, and (2) evaluate factors associated with an adverse clinical outcome. Methods: A retrospective study of patients with confirmed viral CNS infections was conducted. The patients were divided into those with CSF neutrophilic pleocytosis and those with CSF lymphocytic pleocytosis. Clinical findings and outcomes were compared between the two groups. Results: Of the 182 patients included in the study, 45 (24.7%) had CSF neutrophilic pleocytosis. Enterovirus infections were the cause of 64% of neutrophil-predominant CSF and 33% of lymphocyte-predominant CSF (p more...

Copyright of Zdorov'ye Rebenka is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...

Enteroviruses (EVs) are associated with a broad spectrum of disease manifestations, including aseptic meningitis, encephalitis, hand, foot and mouth disease, acute flaccid paralysis and acute flaccid myelitis with outbreaks being reported frequently world-wide. The aim of this study was the molecular characterization of all enteroviruses detected in Cyprus in the ten-year period from January 2008 and December 2017 as well as a description of the circulation patterns associated with the most frequently encountered genotypes. For this purpose, serum, cerebrospinal fluid, nasal swab, skin swab and/or stool samples from 2666 patients with a suspected EV infection were analysed between January 2008 and December 2017. Enteroviruses were detected in 295 (11.1%) patients, which were then investigated further for epidemiological analysis by VP1 genotyping. Overall, 24 different enterovirus types belonging to three different species were identified. The predominant species was EV-B (209/295, 71%), followed by species EV-A (77/295, 26.1%). Only one virus belonged to species EV-D, whereas EV-C enteroviruses were not identified at all. The most frequent genotypes identified were echovirus 30 (26.1%), echovirus 6 (14.2%) and coxsackievirus A6 (10.9%). While Echovirus 30 and echovirus 6 frequency was significantly higher in patients older than 3 years of age, the opposite was observed for CV-A16 and EV-A71, which dominated in young children less than 3 years. Importantly, for the current study period a significant increase of previously only sporadically observed EV-A types, such as EV-A71 and CV-A16 was noted. A phylogenetic analysis of EV-A71 showed that the majority of the EV-A71 strains from Cyprus belonged to sub-genogroup C1 and C2, with the exception of one C4 strain that was observed in 2011. The data presented provide a comprehensive picture of enteroviruses circulating in Cyprus over the last decade and will be helpful to clinicians and researchers involved in the treatment, prevention and control of enteroviral infections by helping interpret trends in enteroviral diseases by associating them with circulating serotypes, for studying the association of enteroviruses with clinical manifestations and develop strategies for designing future EV vaccines. [ABSTRACT FROM AUTHOR] more...

Enteroviruses, members of the family of picornaviruses, are the most common viral infectious agents in humans causing a broad spectrum of diseases ranging from mild respiratory illnesses to life-threatening infections. To efficiently replicate within the host cell, enteroviruses hijack several host factors, such as ACBD3. ACBD3 facilitates replication of various enterovirus species, however, structural determinants of ACBD3 recruitment to the viral replication sites are poorly understood. Here, we present a structural characterization of the interaction between ACBD3 and the non-structural 3A proteins of four representative enteroviruses (poliovirus, enterovirus A71, enterovirus D68, and rhinovirus B14). In addition, we describe the details of the 3A-3A interaction causing the assembly of the ACBD3-3A heterotetramers and the interaction between the ACBD3-3A complex and the lipid bilayer. Using structure-guided identification of the point mutations disrupting these interactions, we demonstrate their roles in the intracellular localization of these proteins, recruitment of downstream effectors of ACBD3, and facilitation of enterovirus replication. These structures uncovered a striking convergence in the mechanisms of how enteroviruses and kobuviruses, members of a distinct group of picornaviruses that also rely on ACBD3, recruit ACBD3 and its downstream effectors to the sites of viral replication. [ABSTRACT FROM AUTHOR] more...

Copyright of Aktual'naa Infektologia is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...

Background: Limited data is available about the etiology of influenza like illnesses (ILIs) in Qatar. Objectives: This study aimed at providing preliminary estimates of influenza and other respiratory infections circulating among adults in Qatar. Methods: We retrospectively collected data of about 44,000 patients who visited Hamad General Hospital clinics, sentinel sites, and all primary healthcare centers in Qatar between 2012 and 2017. All samples were tested for influenza viruses, whereas about 38,000 samples were tested for influenza and a panel of respiratory viruses using Fast Track Diagnostics (FTD) RT-PCR kit. Results: Among all ILIs cases, 20,278 (46.5%) tested positive for at least one respiratory pathogen. Influenza virus was predominating (22.6%), followed by human rhinoviruses (HRVs) (9.5%), and human coronaviruses (HCoVs) (5%). A detection rate of 2–3% was recorded for mycoplasma pneumonia, adenoviruses, human parainfluenza viruses (HPIVs), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ILIs cases were reported throughout the year, however, influenza, RSV, and HMPV exhibited strong seasonal peaks in the winter, while HRVs circulated more during fall and spring. Elderly (>50 years) had the lowest rates of influenza A (13.9%) and B (4.2%), while presenting the highest rates of RSV (3.4%) and HMPV (3.3%). While males had higher rates of HRVs (11.9%), enteroviruses (1.1%) and MERS CoV (0.2%), females had higher proportions of influenza (26.3%), HPIVs (3.2%) and RSV (3.6%) infections. Conclusion: This report provides a comprehensive insight about the epidemiology of ILIs among adults in the Qatar, as a representative of Gulf States. These results would help in improvement and optimization of diagnostic procedures, as well as control and prevention of the respiratory infections. [ABSTRACT FROM AUTHOR] more...

Hand, foot, and mouth disease (HFMD) is well recognized as one of the major threats to children's health globally. The increasing complexity of the etiology of HFMD still challenges disease control in China. There is little surveillance of the molecular epidemiological characteristics of the enteroviruses (EVs) that cause HFMD in Neijiang city or the Sichuan Basin area in Southwest China. In this study, demographic and epidemiological information for 14,928 probable HFMD cases was extracted and analyzed to describe the epidemic features of HFMD in Neijiang city from Jan 2010 to Dec 2017. The swab samples of select probable HFMD cases from 2012 to 2017 were tested by reverse transcription (RT) real-time PCR to identify the serotype distribution of EVs, and 110 randomly selected RT-real-time PCR positive samples were then amplified and analyzed for the VP1 or VP4 regions of EVs to further analyze the phylogenetic characteristics of the circulating strains in this area. The eight-year average annual incidence was 49.82 per 100,000 in Neijiang. The incidence rates varied between 19.51 and 70.73 per 100,000, demonstrating peaks of incidence in even-number years (2012, 2014 and 2016). The median age of the probable cases was 27 months and the interquartile range (25th to 75th percentile) of ages for the probable HFMD cases was between 14 and 42 months. The male-to-female ratio of the probable HFMD cases was 1.47:1, and scattered children were the major population classification (81.7%). Two epidemic peaks were observed: one major peak between April and July and the other lesser peak between October and December. Of 6513 probable cases tested with RT-real-time PCR, 4015 (61.6%) were positive for enterovirus with the serotype distribution as follows: EV71+, 30.1% (n = 1210); CV-A16+, 28.7% (n = 1154) and a sole pan-enterovirus+, 41.1% (n = 1651). A total of 91 cases (82.7%, 91/110) were successfully amplified and underwent phylogenetic analysis: all EV71+ cases were C4a serotype (n = 23/30); all CV-A16+ cases were B2b serotype (n = 24/30); of 42 sole pan-enterovirus+ samples, 20 were CV-A6, 14 were CV-A10 and the rest within this group were CV-A4 (n = 4), CV-A8 (n = 2), CV-A9 (n = 1) and CV-B3 (n = 1). Our findings provide important evidence that aids the improvement of strategies for vaccination against HFMD and comprehensive disease control in China. [ABSTRACT FROM AUTHOR] more...

In 2016, an upsurge of neurologic disease associated with infection with multirecombinant enterovirus A71 subgenogroup C1 lineage viruses was reported in France. These viruses emerged in the 2000s; 1 recombinant is widespread. This virus lineage has the potential to be associated with a long-term risk for severe disease among children. [ABSTRACT FROM AUTHOR] more...

Background. The latest 1.5–2 decades were marked by the intensification of enterovirus infection (EI) in all regions of the world. There were sporadic cases and outbreaks with the involvement of several hundreds or thousands of people, and even powerful epidemics. The aim of the investigation was to study the clinical features of EI in season 2016 in children of Ternopil region. Materials and methods. The course of clinically diagnosed EI in 149 children was analyzed. Results. The peculiarities of EI course in season 2016 in Ternopil region were established. Most of EI cases (66.44 %) were registered in autumn. Infection has predominantly mild course, therefore only 36.91 % of the observed persons were hospitalized. The average age of ill children was 3.49 ± 0.78 years, with a slight predominance of boys (56.38 %). The onset of the disease was accompanied by intoxication symptoms in all the patients. 67.79 % patients had a short-term (1.87 ± 0.92 days) increase of body temperature ranged 37.6–40.0 °C; herpangina in 65.10 %; respiratory syndrome in 46.31 %; intestinal syndrome in 38.26 %; rash and hand-foot-and-mouth-disease in 32.21 %; epidermis desquamation on palms and soles in 12.75 %; onichomadesis in 22.82 %. Conclusions. EI in season 2016 in Ternopil region was characterized by considerable polymorphism of clinical symptoms with general intoxication syndrome in all patients observed. The low level (5.34 %) of laboratory verification at the diversity of enteroviruses and the diversity of clinical manifestations of the diseases they cause do not allow receive full clinical experience (although today it is possible to determine the enterovirus serotype by sequestration and phylogenetic analysis), determine the source of infection, determine the links between the probable source of infection and patients, and identify where the virus was transferred from and follow the changes of the clinical course. more...

Type 1 diabetes (T1D) is believed to have complex interplay between several enteroviruses (EVs) and host immune system disturbance induced or accelerated by viral pathogenesis. In the past two decades, there has been global upsurge in the incidence of childhood T1D, especially in those less than 5 years. Because of the ubiquity and persistence of EVs in human bowel and their tropism to pancreatic cells, they tend to express certain viral proteins that have propensity for genetic manipulation and activation of autoimmunity that could be potentially linked to T1D. In view of these, we present this review of existing literature in order to analyze the epidemiology and possible association between EV infections, host immune dysfunction, and development of autoimmunity or T1D with the view to encourage the investigation of EV infections and associated virus-induced islet cells autoimmunity and immunopathy in genetically predisposed children. more...

The aim. To analyse the morbidity of the enterovirus infection (EI) in Novokuznetsk – the major industrial city of Western Siberia and to determine the clinical peculiarities of enterovirus meningitis (EM) in the outbreak period in 2015.The materials and methods. There have been analysed the official statistical data in the period of 2006–2015 and the enterovirus meningitis, clinical manifestations in 148 patients, hospitalized in 2015. Liquor was tested by the method of the polymerase chain reaction (PCR) for presence RNA of the enteroviruses. The C-reactive protein value was tested by the method of the latex test and the procalcitonin value was tested by the method of the immunoenzymatic analysis. The statistical material treatment has been done using InStat programme.The results. There has been registered 3,2 times growth of the enterovirus infection morbidity in 2015, compared to 2014, which 6,2 times exceeds Russia, s average rate. The enteroviruses ECHO 30 have been identified in patients, biological material and in wastewater. In the structure of the clinical forms the share of the enterovirus meningitis makes 92, 91%. The children, s morbidity 4,57 times exceeds the total burden of disease. The age structure accompanying the enterovirus meningitis: children 2–6 years of age – 47,3%, 7–14 years of age – 27,7%, 15–17 years of age – 7,43%, 18–53 years of age – 17,57%. Vomiting and headache in children (under the age of 7) are registered rarely, and the full meningeal syndrome and the neutrophil pleocytosis in liquor in children (under the age of 7) are registered more frequently. The rate of children and adults has increased in 2015, compared to 2005. The alteration in clinical picture relates to degree of meningeal syndrome intensity and catarrhal manifestations. The C-reactive protein value (in 67,21%) and the procalcitonin value (in 100%) don, t exceed the threshold values in patients with leucocytosis and pleocytosis of liquor with neutrophil/mixed character, which enables to differentiate enterovirus meningitis from bacterial meningitis and to exclude antibiotic treatment.The conclusion. The dynamics of the rate of the enterovirus infection morbidity on the territory under investigation differs from Russia, s average rate. The enterovirus meningitis has got clinical and age peculiarities in different epidemic seasons. more...

Participation of hormones in maintaining immune homeostasis is a complicated process as the hormones can have both immunomodulatory and immunosuppressive effect. Changes in the hypothalamic-pituitary-thyroid axis in diseases may appear low triiodothyronine, and is currently being discussed the issue of the state of development, characterized by a decrease in blood levels of thyroid hormone in the absence of pathology of the thyroid gland. In the literature there is the term - (nonthyroidal illness syndrome) «netireoidnyh disease syndrome.» One of the most debated issues related to the pathogenesis of diseases netireoidnyh syndrome - this is the role of proinflammatory cytokines in violation of the secretory activity of the thyroid gland and the hypothalamus-pituitary-thyroid axis in general. However, the exact mechanisms for reducing serum triiodothyronine remain poorly studied, including thyroid status and relationship with objective criteria systemic inflammation in children, especially during viral infection. The paper presents the materials and the results of an open prospective study conducted in the city of Yekaterinburg in 2009-2012. We observed 71 children with enteroviral meningitis at the age of three to fourteen. We studied the levels of thyroid-stimulating hormone, triiodothyronine, thyroxine and intracellular cytokine synthesis in blood lymphocytes. The nature of changes in hormonal status in children with enteroviral meningitis can be treated as a syndrome netireoidnyh diseases. Low level of triiodothyronine correlates with the time of CSF readjustment and control pleocytosis indicators, more long-term liquor rehabilitation is mentioned in children with low initial level of triiodothyronine, the odds ratio (OR = 7,3, 95% CI 0,9: 6,7). This syndrome is secondary and occurs as the result of cytokine system on the thyroid gland exposure. more...

Abstract Background Over recent decades, hand, foot and mouth disease (HFMD) has emerged as a serious public health threat in the Asia-Pacific region because of its high rates of severe complications. Understanding the differences and similarities between mild and severe cases can be helpful in the control of HFMD. In this study, we compared the two types of HFMD cases in their temporal trends. Methods We retrieved the daily series of disease counts of mild and severe HFMD cases reported in mainland China in the period of 2009–2014. We applied a quasi-Poisson regression model to decompose each series into the long-term linear trend, periodic variations, and short-term fluctuations, and then we compared each component between two series separately. Results A total of 11,101,860 clinical HFMD cases together with 115,596 severe cases were included into this analysis. We found a biennial increase of 24.46 % (95 % CI: 22.80–26.14 %) for the baseline of disease incidence of mild cases, whereas a biennial decrease of 8.80 % (95 % CI: 7.26–10.31 %) was seen for that of severe cases. The periodic variations of both two series could be characterized by a mixture of biennial, annual, semi-annual and eight-monthly cycles. However, compared to the mild cases, we found the severe cases vary more widely for the biennial and annual cycle, and started its annual epidemic earlier. We also found the short-term fluctuations between two series were still significantly correlated at the current day with a correlation coefficient of 0.46 (95 % CI: 0.43–0.49). Conclusions We found some noticeable differences and also similarities between the daily series of mild and severe HFMD cases at different time scales. Our findings can help us to deepen the understanding of the transmission of different types of HFMD cases, and also provide evidences for the planning of the associated disease control strategies. more...