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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.

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.

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.

Aim: Analysis of the morbidity of vaccine-associated paralytic poliomyelitis and acute flaccid paralysis and the results of virological investigation of the patients on 14 territories of the Russian Federation in 1998-2017. Materials and methods: We investigated nearly 3000 stool samples from paralytic patients and contact persons. Isolation and identification of polioviruses were performed according to WHO recommendations with the help of cell lines RD and L20B. We conducted the sequencing of the genome fragments VP3-VP1, VP1-2A and full sequencing of genome region VP1 of 45 poliovirus strains. Results: From 1998 till 2017 1257 cases of acute flaccid paralysis were registered on 14 territories of Russia, 15 cases of which (1,2%) were classified as vaccine-associated paralytic poliomyelitis. From these patients 9 children were non vaccinated and 6 children received from one to four doses of oral poliomyelitis vaccine. The percentage of the detection of polioviruses from the patients and contact persons in different years was not equal and constituted from 3, 4±0,89% to 9, 5±0,79%. All in all from the patients with acute flaccid paralysis and contact persons we isolated 191 polioviruses, 60 of them belonged to type 1, 55 polioviruses were identified as types 2 and 76 as type 3. Some cases of vaccine-associated paralytic poliomyelitis are described in the article; polioviruses were isolated from all these patients. The sequencing of the genome fragments of 45 poliovirus strains showed that the majority of them had the nucleotide substitutions including neurovirulent substitutions. Conclusion: In order to prevent the risk of the appearance of vaccine-associated paralytic poliomyelitis it is necessary to maintain the high quality of surveillance of poliomyelitis and acute flaccid paralysis, to ensure the 95% coverage of children with poliomyelitis vaccine, to minimize the cases of groundless delays of vaccination according to medical recommendations and parents’ refusals to vaccinate children against poliomyelitis and to respect strictly the National calendar of vaccination.

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.

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.

Aim: Study of the role of Coxsackieviruses B in the etiology of enterovirus infection and other forms of neurological pathology and also the frequency of isolation of enteroviruses excreted by children living on the territory of the Russian Federation.Materials and methods: We investigated 1722 samples from children with acute flaccid paralysis, 19030 samples from patients with enterovirus infection and 100 samples from healthy children from institutions of preschool education. Isolation and identification of enteroviruses were conducted according to WHO recommendations.Results: Coxsackieviruses B were detected in patients with acute flaccid paralysis and persons who had contacts with them. In the patients with enterovirus infection Coxsackieviruses B were isolated in 3, 6% of cases, mainly in sporadic cases of enterovirus meningitis. In the structure of all isolated enteroviruses the percentage of Coxsackieviruses B was rather high (26%) and it was only lower than those of enterovirus ECHO 30 (32, 2%) which caused the season’s peaks of enterovirus infection in 2007–2009 and 2013. Coxsackieviruses B were also detected in the samples from children from preschool institutions. These viruses prevailed in the structure of all isolated enteroviruses and they were isolated in the samples from some children in two preschool institutions which served as the proof of the virus propagation after their importation to the institution when children start attending the institutions after summer holidays.Conclusion: Coxsackieviruses B constantly circulated on a great number of territories. They are the etiologic factor of mainly sporadic but also group cases of enterovirus meningitis. In the structure of all isolated enteroviruses these viruses occupied the leading position during almost all the years of 10 years of surveillance. The examination of the children without clinical symptoms of infection revealed that Coxsackieviruses B constituted the majority among isolated enteroviruses. That proves the possibility that healthy children are carriers of Coxsackieviruses B.

Aim: to study of the frequency of isolation and determination of the spectrum of enterovirus serotypes excreted by children living in the North-Western region of Russia and children arriving in this region from unsafe territories.Materials and methods: we investigated 832 samples of children with acute flaccid paralysis and 1153 samples of healthy children from institutions and migrants’ families. Isolation and identification of enteroviruses were conducted according to WHO recommendations.Results: enteroviruses of different serotypes were detected in all categories of children. The percentage of detection of enteroviruses in the samples of children from institutions and from migrants’ families was significantly higher than in those of patients with acute flaccid paralysis. In children living in the North-West of Russia we detected enteroviruses ECHO 6, which were not found in children who arrived in the North-Western region of Russia. Enteroviruses ECHO 30 were revealed in resident children more frequently than in children from migrants’ families. Enteroviruses of serotypes which had not circulated earlier in the North-Western region of Russia were revealed in the samples of children from migrants’ families. They were Coxsackieviruses A 13, 17, 24 and enterovirus 99 (species C), enteroviruses 75 and 120 (species B and A).Conclusion: the difference in the spectrum of enterovirus serotypes excreted by resident children and children who arrived in the North-Western region of Russia from unsafe territories was shown. The obtained data will enlarge the scope of knowledge about enterovirus circulation among various groups of population during different periods of time on different territories.

In 2013 after two previous years when the situation had been calm the incidence rates of enterovirus infection significantly increased on certain territories of the North-West of Russia. In Novgorod and Vologda regions and in Saint-Petersburg enterovirus meningitis group cases were registered. The etiology of enterovirus infection was studied by virological and molecular methods. Enterovirus ECHO30 was identified as the principal etiological agent of the cases. Molecular study revealed that enteroviruses ECHO30 isolated in the North-West of Russia belonged to the genotype H and formed two subtypes inside this genotype. Phylogenetic analysis has shown that enteroviruses ECHO30 of both subtypes were closely related to the strains detected in different provinces of China in 2010-2013. Probably enteroviruses ECHO30 of the genotype H which largely circulated in Russia in 2013 and practically had not been detected in the country earlier had been imported on the territory of Russia from South-East Asia. Enteroviruses ECHO30 isolated in Arkhangelsk and Novgorod regions in 2008-2009 belonged to another genotype Ec2. Enteroviruses of this genotype had circulated at that time in the European countries.

Abstract. The analysis of epidemic process and definition of the etiology of the seasonal increase of serosal meningitis incidence in the Novgorod oblast in September-November, 2008 has been carried out. It was shown that in the specified period 73 persons had enteroviral meningitis. The proportion of children under 17 years old in the group of patients was 89.9%. The etiological agents of disease (enteroviruses ECHO 6 и ECHO 30) were detected by the virological and molecular-biological methods. It was established that two genetic variants of ECHO 6 and one variant of ECHO 30 co-circulated in the Novgorod oblast. The last virus variant was closely related to the strain isolated from enteroviral meningitis patients in Nizhniy Novgorod in 2007. The obtained data support the idea about necessity of systematic epidemiological and virological surveillance on enteroviral infection to get new information about circulation of non-poliomyelitis enteroviruses in the population and to define peculiarities of epidemic process development.

Abstract. Enteroviruses are widely distributed human infectious pathogens. In spite of infection a disease does not manifest in majority number of cases. However, in some infected persons the different kind of symptoms can be observed; from common cold signs up to aseptic (serous) meningitis and myocarditis. Severe enteroviral cases with lethal outcomes are rarely reported. Ability of enteroviruses to cause large outbreaks and even epidemic distribution is very significant for health care systems. Taking in account a high genetic diversity of enteroviruses it is possible appearance of new highly pathogenic strains in the future. In some countries including the Russian Federation the permanent surveillance for enteroviral infections is provided besides of WHO polio elimination program. The laboratory diagnostics of enterovirus infections is complicated by numerous of pathogen serotypes. Thus, classical virological methods should be supported by molecular-biological tools to sequence pathogen genome and to define phylogenetic relations between different enterovirus strains.

Abstract. The etiology of seasonal increasing of enteroviral infection incidence in Arkhangelsk oblast in 2008–2011 has been studied. The ECHO 6, ECHO 9 and ECHO 30 viruses were isolated and identified from patients with enteroviral infection in this period. The highest enteroviral infection incidence rate in Arkhangelsk oblast which was 5,1 times higher in compare with average country index was registered in 2008. It was proved by the virological and molecular biological methods that the main etiological agent caused enteroviral meningitis cases in the seasonal outbreak in 2008 was ECHO 30 virus which was very similar to the ECHO 30 strain identified in the Veliky Novgorod in 2008. In 2009 from patients in enteroviral meningitis epidemic focus the ECHO 9 viruses were isolated. These viruses were similar to the ECHO 9 strains circulated in Russia in 2009. It was established that in the period of seasonal increasing of enteroviral infection in Arkhangelsk oblast in 2010–2011 in general circulated ECHO 6 viruses which clustered in 3 separate phylogenetic groups. Viruses ECHO 6 detected in Arkhangelsk oblast in 2011 were different from viruses identified in 2010. Results of the study confirm that monitoring of viruses in case of enteroviral infection remains the one of the important types of additional measures in the frame of Global Program of poliomyelitis eradication. This monitoring is absolutely necessary to define characteristics of epidemic process of enteroviral infection.