Проведен ретроспективный анализ проявлений эпидемического процесса энтеровирусной инфекции в Хабаровском крае в предшествующий наводнению семилетний период. Показано наличие предпосылок возможного осложнения эпидемиологической обстановки в период чрезвычайной гидрологической ситуации 2013 г. В крае из года в год сохраняется стабильно неблагополучная ситуация по заболеваемости энтеровирусными инфекциями, наблюдаемая при благоприятных климатических условиях -высоких температурах воздуха и воды поверхностных водоемов, высокой влажности воздуха. Поддержанию эпидемического процесса в течение всего года способствуют «здоровое» вирусоносительство и обширное распространение энтеровирусов в водных объектах внешней среды. Отмечена широкая циркуляция различных генотипов энтеровирусов, в том числе имеющих высокую степень генетического сходства со штаммами, зарегистрированными на сопредельной территории Китайской Народной Республики.Ключевые слова: энтеровирусная инфекция, Хабаровский край, эпидемический процесс, заболеваемость, штаммы энтеровирусов.Carried out has been retrospective analysis of epidemiological process manifestations as regards enteroviral infection in the Khabarovsk Region over the period of 7 years, prior to rainfall floods in 2013. Revealed is the possibility of aggravation of epidemiological situation during hydrological emergency situation. The premises are as follows: persistent due to specific climate conditions prevalent in the Khabarovsk Territory (high air and surface water temperatures, and high humidity rates) unfavorable epidemiological situation on enteroviral infections, virus-carriage in "healthy" people and extensive dissemination of enteroviruses in the water bodies of ambient environment. Moreover, widespread circulation of different enterovirus genotypes, including the isolates with high genetic similarity to the strains identified earlier in the adjoining People's Republic of China, takes place.

Type of enterovirus was detected in 2753 cases when examining 4122 patients with various clinical forms of enterovirus infection (EVI) during the 2017-2018 period. We identified viruses of 42 types belonging to Enterovirus A-B-С species. The ratio of EV-A: EV-B: EV-C species was 51.29 percent: 47.06 percent: 1.65 percent. In 413 environment samples 29 non-polio enteroviruses were identified, three of which, CA14, EVA76 and ECHO25, were not detected in the period in patients with EVI. The Coxsackie A6 virus, which caused a drastic increase in the morbidity of exanthema forms was the dominant agent in the etiological structure of EVI in 2017 in most areas; the leading etiological agents of enteroviral meningitis (ECM) were the ECHO30, ECHO9, ECHO18 viruses. There was a decrease in the morbidity of both all forms of EVI and computers due to a decrease in the activity of the circulation of epidemic variants of the Coxsackie A6 and ECHO30 viruses as a whole in Russia in 2018. The computer epidemic process in 2018 was supported by the become active or remained active viruses of ECHO6, Coxsacke B5, ECHO9, ECHO18 and other viruses of the Enterovirus B species. The remaining relatively high morbidity of exanthema forms of EVI in addition to the Koksaki A6 virus was supported by the activated viruses Koksaki A16, Koksaki A5 and other viruses of the Enterovirus A species. The results of phylogenetic analysis of genome sequences that dominated etiological agents of EVI indicate that in 2018 there was a multiple importation of enterovirus epidemic variants into the territory of the Russian Federation, which supported the EVI / computer epidemiological process in the Russian Federation as a whole and caused a complication of the epidemiological situation in a number of subjects. It is possible that these events contributed to the arrival of a large number of fans at the 2018 FIFA World Cup and visa-free entry into the territory of the Russian Federation for this category of tourists until the end of the year.

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

Abstract.Enteroviruses are small RNA viruses, which are ubiquitous and commonly cause outbreaks with various clinical manifestations. In 2006, the Program on enterovirus surveillance was approved in the Russian Federation. Over the last years, molecular-biological and bioinformatics methods for enterovirus epidemiology studies have been developed both in Russia and worldwide. Currently, identification of enteroviruses is carried out by analyzing nucleotide sequence of the full-length VP1 genome region (ca. 900 nt). Routinely, it is sufficient to obtain a partial VP1 genome region sequence (ca. 300 bp) for enteroviruse verification in most cases; however, a more stringent type criterion of 80% sequence identity should be used compared to the 75% sequence identity cut-off for the complete VP1 genome region. Further sequence analysis may be performed by using Bayesian phylogenetic methods, which allow using molecular clock to trace outbreak emergence. Enteroviruses accumulate about 0.5–1% nucleotide substitutions per year. Therefore, a short genome fragment may be used to analyze virus phylodynamics at the level of international transfers and circulating virus variants. On a shorter timescale, a full-length VP1 genome region or a complete genome sequence are preferred for investigating molecular epidemiology, because a short sequence allows to reliably distinguish not more than 1–2 transmission events per year. Thus, determining enterovirus sequences for full-length VP1 genome region or full-genome sequence is preferred for examining viral outbreaks. It is increasingly apparent that analyzing available enterovirus nucleotide sequences reveals limitations related to uneven surveillance efficacy in various countries and short length of genome fragment measured in routine control. As a result, a proper global-scale analysis of enterovirus molecular epidemiology remains problematic. Over the last 20 years, the number of available enterovirus nucleotide sequences increased by hundred times, but understanding emergence of enterovirus infection outbreaks remains limited. Further development of enterovirus surveillance would require new methods for sewage monitoring, affordable high-throughput sequencing and harmonization of global surveillance systems.

Noroviruses are the leading etiologic cause of outbreaks and sporadic cases of acute gastroenteritis worldwide. The objective of research was to study the genotypes of noroviruses, that caused outbreaks and sporadic incidence of norovirus infection in the Khabarovsk region in 2015-2018. The analysis of outbreaks due to norovirus infection in the Khabarovsk Region in 2015-2018 was performed. The molecular genetic study of samples from 60 patients from three norovirus outbreaks in the Khabarovsk Region and from 164 children with sporadic acute gastroenteritis in Khabarovsk region was performed. Genotype of noroviruses was determined by sequencing method, phylogenetic analysis of the obtained nucleotide sequences was carried out. The norovirus genotypes GII.17, GII.4 Sydney_2012 and GII.6 had caused the outbreaks of norovirus infection in the Khabarovsk region in 2015-2018. Sporadic cases of acute gastroenteritis in children in Khabarovsk in 2016 were due to GII.4 Sydney_2012, GII.3 and GII.6 norovirus genotypes. Detection of the GII.4 Sydney_2012 strain in both outbreaks and sporadic norovirus infection cases in the Khabarovsk region in 2016 evidenced of active circulation of this variant type during this period. The genotype GII.6 had been identified in Khabarovsk from 2016 to 2018.