Susceptibility of Common Family Anatidae Bird Species to Clade 2.3.4.4e H5N6 High Pathogenicity Avian Influenza Virus: An Experimental Infection Study

Background: There were large outbreaks of high pathogenicity avian influenza (HPAI) caused by clade 2.3.4.4e H5N6 viruses in the winter of 2016–2017 in Japan, which caused large numbers of deaths among several endangered bird species including cranes, raptors, and birds in Family Anatidae. In this study, susceptibility of common Anatidae to a clade 2.3.4.4e H5N6 HPAI virus was assessed to evaluate their potential to be a source of infection for other birds. Eurasian wigeons (Mareca penelope), mallards (Anas platyrhynchos), and Northern pintails (Anas acuta) were intranasally inoculated with 106, 104, or 102 50% egg infectious dose (EID50) of clade 2.3.4.4e A/teal/Tottori/1/2016 (H5N6). Results: All birds survived for 10 days without showing any clinical signs of infection. Most ducks inoculated with ≥104 EID50 of virus seroconverted within 10 days post-inoculation (dpi). Virus was mainly shed via the oral route for a maximum of 10 days, followed by cloacal route in late phase of infection. Virus remained in the pancreas of some ducks at 10 dpi. Viremia was observed in some ducks euthanized at 3 dpi, and ≤106.3 EID50 of virus was recovered from systemic tissues and swab samples including eyeballs and conjunctival swabs. Conclusions: These results indicate that the subject duck species have a potential to be a source of infection of clade 2.3.4.4e HPAI virus to the environment and other birds sharing their habitats. Captive ducks should be reared under isolated or separated circumstances during the HPAI epidemic season to prevent infection and further viral dissemination.

Socio-economic substantiation of expediency of seasonal influenza vaccine prophylaxis among medical workers

The purpose of this study is to determine the socio-economic effectiveness of seasonal influenza vaccine prophylaxis among health professionals based on the analysis of the morbidity with temporal disability (MTD) and the financial benefits of this preventive measure. The study included the collection and analysis of information on MTD and direct and indirect costs of influenza treatment compared to vaccine prophylaxis in “Dnipropetrovsk Regional Perinatal Center with Hospital” Dnipropetrovsk Regional Council” (ME “DRPC with Hospital” DRC”) during 2017-2020 (3 epidemic seasons). To assess the consequences of vaccine prophylaxis, the analysis of MTD indicators was performed, and the index and coefficient of anti-epidemic effectiveness were used. The economic effect was determined on the basis of the cost-benefit method using the analysis algorithm in the form of a “decision tree”. The information base for the analysis was the accounting and reporting and financial and economic documentation of the health care institution (HCI). The analysis of influenza MTD during the observation period revealed that all studied morbidity rates (number of cases per 100 employees; number of days per 100 employees; average case duration) were statistically significantly lower in vaccinated compared to unvaccinated (p<0.001). Precautionary number of cases of MTD for influenza in the last year of observation (2019-2020) was 11.07 (95% CI 6.68-15.46) per 100 employees; days – 96.23 (95% CI 81.86-110.60) per 100 employees. The index of anti-epidemic efficiency during the study increased by 2.37 (95% CI 1.95-2.79), the coefficient of anti-epidemic effectiveness – by 15.16% (95% CI 11.17-18.01). The economic efficiency of vaccination of 69.44% of employees for one epidemic season (2019-2020) amounted to a total of UAH 248,976 or UAH 494 (56%) benefits per employee. The study proved the high medical, social and economic effectiveness of vaccine prophylaxis in HCI. Medical efficiency consists in a significant reduction in the morbidity with temporary disability, high levels and a tendency to increase the indicators of anti-epidemic efficiency. The economic effect is defined as the available monetary benefit from the vaccine prophylaxis. The resulting savings are the basis for optimizing the use of resources of the medical institution, including labor.

West Nile fever in Volgograd Oblast: features of the epidemic process’s manifestations at the present stage

Objective: To study the regional features of the West Nile fever (WNF) epidemic process manifestations using the example of the territory with stable and long-term pathogen circulation (Volgograd Oblast).Materials and Methods: We used the data of the Reference Center for monitoring the WNF pathogen based on the Volgograd Research Anti-Plague Institute of Rospotrebnadzor over 1999–2021. The main method is a comprehensive epidemiological method.Results: The long-term changes in the WNF incidence in Volgograd Oblast is characterized by a cyclical nature with an interval of 1–8 years and a tendency to decrease. The maximum risk of infection occurs in August (58.8%), but there is an increase in the number of cases in September. The average duration of the epidemic season is 8.4 weeks. Case fatality rate is at the level of 4.3%; the prevalence of the number of deaths in the group of 70 years and older (75%), as well as among men (63.6%) has been established. The greatest contribution to the incidence rate is made by the age group of 60 years and older (37.7%). Features of the clinical presentation include the dominance of forms without damage to the central nervous system (91.1%) and moderate clinical course (72.3%). The prevalence of the urban population among the infected was noted (85.5%).Conclusion: A comparative analysis of the clinical and epidemiological WNF manifestations in Volgograd Oblast, territories with a stable circulation of the pathogen (Astrakhan and Rostov Oblasts) and, in overall, the Russian Federation, established differences in the duration of cyclical fluctuations in incidence, seasonality (Rostov Oblast), age structure of incidence (Astrakhan Oblast), distribution of cases by the severity of the clinical course, the site of the alleged infection and social status.

Rational selection of hemagglutinin variants of H3N2 influenza viruses in preparation of live influenza vaccine strains to optimize growth characteristics

BACKGROUND: Up to date Russian live attenuated influenza vaccines are produced in developing chicken embryos. During passaging in embryos, the virus isolated from the human respiratory tract undergoes adaptation to the receptors in embryos. The population of the virus, at any passage in chicken embryos, is heterogeneous and contains variants of viruses with one or another set of adaptive substitutions. Before preparing the vaccine strain, the population of the epidemic virus is cloned and the genetic sequence of the hemagglutinin and neuraminidase clones is analyzed. The growth characteristics of the vaccine strain and its antigenic properties depend on the correct choice of the variant of the virus. AIM: The aim of the study was to select the variant of the H3N2 subtype virus for the preparation of a vaccine reassortant based on data on the composition of the population and an assessment of its growth properties. MATERIALS AND METHODS: Viruses were cloned in developing chicken embryos, sequencing of the hemagglutinin and neuraminidase genes of the clones was performed. On the basis of the clones selected based on the results of the analysis of the population, strains of a live influenza vaccine were obtained by the reassortment in the chicken embryos. The growth characteristics of the strains, the phenotype in eggs, and the antigenic properties by hemagglutination inhibition test were evaluated. RESULTS: The influenza virus A/Kansas/14/2017 recommended by WHO for the epidemic season 2019-2020 acquired a pair of D190N + N246T substitutions dominating in the population at the 7th passage in eggs. From the population of A/Kansas/14/2017-like strain A/Brisbane/34/2018, from the third passage in the eggs, it was possible to obtain a variant of the virus with substitutions G186V + S219Y in hemagglutinin. The growth characteristics of the strain based on A/Kansas/14/2017 (passage E7) were significantly inferior to the characteristics of the strain based on A/Brisbane/34/2018 (passage E3), in the absence of differences in antigenic properties. CONCLUSIONS: The variant of egg adaptation of hemagglutinin G186V in strains of clade 3c.3a is preferable for the preparation of live influenza vaccine strains; variant N246T is not optimal. When preparing strains, it is necessary to analyze the composition of the virus population by cloning and choose the most optimal option for preparing strains. The persistence of egg-adaptive substitutions in passaged variants of the virus is not always optimal for strains of live influenza vaccine, and therefore it is preferable to use the population as close as possible to the initial variant to start work on the strain.

Influenza vaccination coverage and factors associated with severe laboratory-confirmed influenza-related illness in patients receiving care at a tertiary hospital in Catalonia (Spain) during the 2018–2019 epidemic season

Introduction Influenza vaccination rates in risk groups remain suboptimal. Evidence supporting a significant association between influenza vaccination and severe illness is limited. Methods We retrospectively analyzed the epidemiological characteristics of out- and inpatients with laboratory-confirmed influenza infection attended during the 2018–19 epidemic season. Influenza vaccination coverage by indication was analyzed. Logistic regression was used to compare the odds of vaccination between severe and non-severe influenza-positive patients. Severe cases were defined as presenting pneumonia, admission to critical care units and/or death. Results The overall vaccination coverage among influenza-positive patients was 30.4%. In subjects with ≥ 1 indication for vaccination, the vaccination coverage was 42.4%. By indication, coverage rates were: 52.5% in patients aged ≥ 59 years, 42.2% in obese patients, 29.2% in immunosuppressed subjects and 6.5% in pregnant women. In patients with underlying chronic diseases, a higher coverage was found in patients with cognitive impairment (77%), muscular dystrophy (63.6%) and renal disease (60.4%). The multivariate logistic regression model showed severe influenza-related illness was associated with a lack of influenza vaccination before seeking care during the 2018–2019 season [0.59 (95%CI 0.36–0.97); p = 0.038], older age [1.01 (95%CI 1.00–1.02); p = 0.009] and current or former smoking status [1.63 (95%CI 0.84–3.18) and 2.03 (95%CI 1.16–3.57); p = 0.031], adjusted by underlying disease. Conclusion Adjusting by age, smoking status and underlying disease, a moderate association between the influenza vaccine and severe laboratory-confirmed influenza-related illness was found in an epidemic season in which there was matching between the vaccine and circulating strains. Protection against complications, especially in older subjects and in those with underlying disease is postulated as one of the strengths of annual influenza vaccination. However, influenza vaccination is a pending issue in these groups, especially in pregnant women and obese people. To avoid suboptimal vaccination coverages, health professionals should recommend the seasonal influenza vaccination according to the annual instructions of the health authorities.

Impact of respiratory infectious epidemics on STEMI incidence and care

The effect of respiratory infectious diseases on STEMI incidence, but also STEMI care is not well understood. The Influenza 2017/2018 epidemic and the COVID-19 pandemic were chosen as observational periods to investigate the effect of respiratory virus diseases on these outcomes in a metropolitan area with an established STEMI network. We analyzed data on incidence and care during the COVID-19 pandemic, Influenza 2017/2018 epidemic and corresponding seasonal control periods. Three comparisons were performed: (1) COVID-19 pandemic group versus pandemic control group, (2) COVID-19 pandemic group versus Influenza 2017/2018 epidemic group and (3) Influenza 2017/2018 epidemic group versus epidemic control group. We used Student’s t-test, Fisher’s exact test and Chi square test for statistical analysis. 1455 patients were eligible. The daily STEMI incidence was 1.49 during the COVID-19 pandemic, 1.40 for the pandemic season control period, 1.22 during the Influenza 2017/2018 epidemic and 1.28 during the epidemic season control group. Median symptom-to-contact time was 180 min during the COVID-19 pandemic. In the pandemic season control group it was 90 min (p = 0.183), and in the Influenza 2017/2018 cohort it was 90 min, too (p = 0.216). Interval in the epidemic control group was 79 min (p = 0.733). The COVID-19 group had a door-to-balloon time of 49 min, corresponding intervals were 39 min for the pandemic season group (p = 0.038), 37 min for the Influenza 2017/2018 group (p = 0.421), and 38 min for the epidemic season control group (p = 0.429). In-hospital mortality was 6.1% for the COVID-19 group, 5.9% for the Influenza 2017/2018 group (p = 1.0), 11% and 11.2% for the season control groups. The respiratory virus diseases neither resulted in an overall treatment delay, nor did they cause an increase in STEMI mortality or incidence. The registry analysis demonstrated a prolonged door-to-balloon time during the COVID-19 pandemic.

2019–2020 herd immunity to seasonal influenza viruses prior to epidemic season and rate of severe disease cases

The aim was to analyze heard immunity against influenza viruses as well as severe course of influenza infection prior to the 2019–2020 epidemic season. Methods. Blood sera samples were collected prior to and after conducting population-wide influenza vaccination campaign at the sanitary and epidemiological centers in different regions of the Russian Federation as well as at the Siberian Federal District, respectively. Sera samples were tested by using hemagglutination inhibition (HI) assay with vaccine strains A/Brisbane/02/2018 (H1N1)pdm09, A/Kansas/14/2017 (H3N2), B/Colorado/06/2017 (Victoria lineage). Baseline clinical and autopsy materials in case of influenza infection in vaccinated patients or severe and fatal influenza cases were collected to be tested by RT-PCR at the sanitary and epidemiological centers, Rospotrebnadzor. All influenza-virus positive samples were further sent to the SRC VB “Vector”. Results. A total of 7,896 and 600 blood serum samples were collected from subjects at Siberian Federal District prior to and after the populationwide influenza vaccination campaign, respectively. Prior to the epidemic season, the proportion of individuals seropositive for the influenza A virus subtypes A/(H1N1)pdm09 and A/H3N2 exceeded 50% in most of the regions, whereas frequency of those seropositive for the influenza B virus was profoundly lower ranging from 12 to 46% in the Northwestern Federal District and Volga Federal District, respectively. After influenza vaccination, the percentage of seropositive subjects in the Siberian Federal District increased as follows: for influenza subtype A/(H1N1)pdm09 — from 66 up to 79%, influenza subtype A/H3N2 — from 68 up to 78%, and for influenza B/Victoria — from 32 up to 47%. In 2019–2020, influenza B virus more frequently caused severe infection that agrees with the herd immunity data prior to the epidemic season. However, the vast majority of the influenza cases with fatal outcome was associated with influenza virus A A/H1N1pdm09 subtype. Conclusion. Quality of influenza vaccine, especially that one intended to vaccinate risk group subjects remains a crucial issue for contemporary scientific community. The study was conducted within the framework of the State Assignments no. 1/16 and 2/18.

Infection with severe fever with thrombocytopenia virus in healthy population: a cohort study in a high endemic region, China

Background Severe fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region. Methods A cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates. Results Totally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334–4.461 compared to the group of < 50 years old, P = 0.004], recent contact with cats (adjusted OR = 2.195, 95% CI: 1.261–3.818, P = 0.005), and working in tea garden (adjusted OR = 1.698, 95% CI: 1.002–2.880, P = 0.049) by applying multivariate logistic regression model. The NAb based seropositivity was similarly related to the patients aged ≥ 70 years old (adjusted OR = 2.691, 95% CI: 1.271–5.695 compared to the group of < 50 years old, P = 0.010), and recent contact with cats (OR = 2.648, 95% CI: 1.419–4.941, P = 0.002). For a cohort of individuals continually sampled with 1-year apart, the anti-SFTSV IgG were maintained at a stable level, while the NAb level reduced. Conclusions Subclinical infection might not provide adequate immunity to protect reinfection of SFTSV, thus highlighting the ongoing threats of SFTS in endemic regions, which called for an imperative need for vaccine development. Identification of risk factors might help to target high-risk population for public health education and vaccination in the future. Graphical Abstract

Evaluation of the Preventive Effectiveness of Influenza Vaccines in the Epidemic Season 2019–2020 in St. Petersburg

Background. The vaccine is the best available instrument to prevent influenza and reduce the risks of major disease complications and mortality. The vaccine effectiveness during the influenza season depends on a number of factors: (1) a person vaccinated (their age and health status); (2) the vaccine formulation; (3) types and subtypes of the circulating viruses; (4) vaccination timeline, as the immune response fades over time. An influenza vaccine can yield different effectiveness in people who have been infected or vaccinated previously and in those who have not been yet exposed to the circulating viruses. At present, trivalent and quadrivalent influenza vaccines are registered and produced in Russia. It allows for vaccination of all social groups, including high-risk populations, and for increasing the number of vaccinated individuals yearly. Russian Federation constantly improves the production of influenza vaccines, introducing new variants of vaccine formulations into national clinical usage. It is thus essential to monitor and analyze the changes in the effectiveness of influenza vaccines every season.Aim of the study. To evaluate of the effectiveness of Russian domestic influenza vaccines during the epidemic season 2019–2020 in St. Petersburg compared to the season 2018–2019.Materials and Methods. 3315 female and male adult participants aged 18 years and older were monitored from October 2019 to March 2020. The group included university students and tutors, researchers, and production and office workers of industrial enterprises. Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri influenza vaccines were used for immunization.Results and Discussion. In the context of incomplete correspondence between the viruses circulating in Russia and the strains used in the vaccines, the vaccination of the St. Petersburg population during the epidemic season 2019-2020 with Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri influenza vaccines cumulatively reduced influenza and ARI incidences by half; the total vaccine effectiveness against influenza and ARI amounted to 50.0%. The strongest preventive effect was identified for Grippol Plus, Ultrix, and Ultrix Quadri which demonstrated the total vaccine effectiveness from 70.6% to 75.0%, and their effectiveness against influenza A and B viruses reached from 65.5% to 83.5%.Conclusion. In the context of incomplete correspondence between the viral strains used in the vaccines and the strains circulating in Russia and St. Petersburg during the epidemic season 2019- 2020 and considering the active circulation of non-influenza viruses such as rhinoviruses and adenoviruses, we found a moderate preventive effectiveness of the influenza vaccines during the seasonal epidemic increase in ARI cases. Russian domestic influenza vaccines were shown to have good acceptability, be safe, and non-reactogenic.