Tick-borne encephalitis epidemic in Hungary 1951-2021: The story and lessons learned.

The authors analysed epidemiological data of the Hungarian tick-borne encephalitis epidemic from the past seven decades. A total of 911 meningitis serosa cases were described from 1930-1950 s by local hospital physicians, indicating that the virus had been present in the country decades before its official identification in 1952. The virus spread freely in the 1950s-1960s, occupying almost all habitats where ticks occurred in large numbers. The increasing number of cases drove authorities to classify this illness as a notifiable disease in 1977 and to organize the first measures to stop the epidemic. Statistical analysis revealed that the large-scale vaccination launched from the 1990s was responsible for the sharp decrease in the number of human cases from 1997. A significant negative correlation was found between the number of vaccine doses sold and human cases 6 years later. The TBEV endemic area covers 16.57% of the territory and 16.65% of the population of the country. In the last 10 years, 186,000 vaccine doses/year in average were enough to keep the incidence of human TBEV infections between 0.45 and 0.06/100,000 persons. A 20-year-long study found evidence for easing clinical signs in TBEV-infected hospitalized patients. Statistics found a sharp decrease in the number of samples sent for TBEV diagnosis after 1989. Male dominance of patients was characteristic of the epidemics since the 1940s, but now analysis of detailed data from the 1981-2021 period (60.5%-87.5%) proved the statistical significance of this dominance. Obviously, the voluntary vaccination programme was the tool which broke the spread of the epidemic. Widespread public awareness of the disease and the tick vector, probable evolutionary spread of less pathogenic virus strains supplemented with the vaccination campaign led to a negligible level of human TBE cases in Hungary in the last years.

Multiple SARS-CoV-2 Introductions Shaped the Early Outbreak in Central Eastern Europe: Comparing Hungarian Data to a Worldwide Sequence Data-Matrix.

Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019, the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of 21 April 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here, we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.

Nursing homes and the elderly regarding the COVID-19 pandemic: situation report from Hungary.

The global impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is significant in terms of public health effects and its long-term socio-economic implications. Among all social groups, the elderly is by far the most affected age group regarding morbidity and mortality. In multiple countries spanning several continents, there are an increasing number of reports referencing the novel coronavirus disease-2019 (COVID-19) spread among nursing homes. These areas are now recognized as potent hotspots regarding the pandemic, which one considers with special regard. Herein, we present currently available data of fatal COVID-19 cases throughout Hungary, along with the analysis of the co-morbidity network. We also report on viral genomic data originating from a nursing home resident. The genomic data was used for viral haplotype network analysis. We emphasize the urgent need for public health authorities to focus on nursing homes and residential service units worldwide, especially in the care of the elderly and infirmed. Our results further emphasize the recent statement released by the World Health Organization (WHO) regarding the vulnerability among seniors and especially the high risk of COVID-19 emergence throughout nursing and social homes.

Destination specific risks of acquisition of notifiable food- and waterborne infections or sexually transmitted infections among Finnish international travellers, 1995-2015.

BACKGROUND: Overnight international travels made by Finns more than doubled during 1995-2015. To estimate risks and observe trends of travel-related notifiable sexually transmitted and food- and water-borne infections (STIs and FWIs) among travellers, we analysed national reports of gonorrhoea, syphilis, hepatitis A, shigellosis, campylobacteriosis and salmonellosis cases and related them to travel statistics. METHOD: Cases notified as travel-related to the Finnish infectious diseases register were used as numerators and overnight stays of Statistics Finland surveys as denominator. We calculated overall risks (per 100,000 travellers) and assessed trends (using regression model) in various geographic regions. RESULTS: Of all travel-related cases during 1995-2015, 2304 were STIs and 70,929 FWIs. During 2012-2015, Asia-Oceania showed highest risk estimates for gonorrhoea (11.0; 95%CI, 9.5-13), syphilis (1.4; 0.93-2.1), salmonellosis (157; 151-164), and campylobacteriosis (135; 129-141), and Africa for hepatitis A (4.5; 2.5-7.9), and shigellosis (35; 28-43). When evaluating at country level, the highest risks of infections was found in Thailand, except for hepatitis A ranking Hungary the first. During 2000-2011, significantly decreasing trends occurred for most FWIs particularly in the European regions and for STIs in Russia-Baltics. CONCLUSIONS: Our findings can be used in targeting pre-travel advice, which should also cover those visiting Thailand or European hepatitis A risk areas.

Knowledge, attitudes, and practices regarding ticks and tick-borne diseases, Finland.

Tick-borne encephalitis (TBE) and Lyme borreliosis (LB) are endemic in Finland, with tens and thousands of cases, respectively, reported annually. We performed a field survey to investigate people's knowledge, attitudes and practices (KAP) regarding ticks, tick-borne diseases, and prevention strategies. The KAP were assessed using a pre-validated anonymous questionnaire consisting of 39 questions and statements. On two consecutive days in July 2016, convenience sampling was used in the cities of Parainen and Kotka, located in high-risk areas of tick-borne diseases, particularly of TBE. In attitudes and practices sections, each question was scored and analysed with ordered logistic regression model. In total, 101 individuals responded. The TBE vaccination rate among respondents was 40%. The best known preventive measures were having vaccination against TBE (88%), and wearing long sleeves and pants against ticks (81%). Two-thirds incorrectly identified the ring-like rash as a symptom of TBE. Of all respondents, 78% could not exclude that TBE can be treated with antibiotics; 55% that vaccine protects against LB; and 46% that it protects against ticks. The minority (14%) believed tick repellents to be effective. Among preventive behaviour, the quick removal of an attached tick was most frequently applied (97%). Repellents were used by 21% when visiting tick-infested areas. Significant associations were found between the vaccination status and having a correct belief that the vaccine protects against TBE (P<0.001) but not against ticks (P<0.05), or LB (P<0.001). KAP is a quick and easy tool to get a rough estimation on people's awareness regarding ticks and tick-borne diseases. We identified gaps in knowledge and misbeliefs. Our results can be used in public health communication tools on tick-borne diseases, especially those on intervention strategies.

Decreased incidence of pertussis in young adults after the introduction of booster vaccine in military conscripts: Epidemiological analyses of pertussis in Finland, 1995-2015.

INTRODUCTION: In 2005, in Finland, the whole-cell pertussis vaccine was replaced by acellular given at 3-5-12months, and boosters at 4 and 11-15years of age. From July 2012, military conscripts have been offered a pertussis booster dose. Conscription is mandatory for Finnish men, and >95% were 19-21years old when enrolled during 2012-2015. We describe the epidemiology of pertussis in Finland during 1995-2015, and show the indirect effect of the booster in conscripts on pertussis incidence in the Finnish population. MATERIALS AND METHODS: We extracted data on laboratory confirmed notified pertussis cases from the National Infectious Diseases Register. We calculated annual incidence using as denominator population data and incidence rate ratios (IRR) using Poisson regression. RESULTS: The overall pertussis incidence peaked in 2004 (31/100,000) and was lowest in 2015 (3.0/100,000), with 66 reported cases in <3months infants in 2004 versus 6 in 2015. The majority of the cases were female (59%) with a male-to-female case ratio of 1:1.5. Cases were spread throughout the year with highest incidence during August-February. Among the 19- to 21-year-olds in the general population, incidence decreased from 49/100,000 in 2011 to 0.51/100,000 in 2015 (IRR=0.01; 95%CI, 0.00-0.16). Among the same age group, comparing the 3.5-year period before and after July 2012, incidence decreased from 33/100,000 to 5.3/100,000 (IRR=0.16; 95%CI, 0.06-0.40) in males and from 16/100,000 to 5.0/100,000 (IRR=0.31; 95%CI, 0.11-0.84) in females. CONCLUSIONS: Implementation of the pertussis booster dose in Finnish military conscripts was followed by a significant decrease in pertussis incidence both among the 19- to 21-year-old males and females, possibly reflecting herd immunity effect. Together with booster doses in adolescents this has resulted in low incidence in the whole population including infants. Our results support the implementation of the booster dose for conscripts. We recommend continuing monitoring pertussis epidemiology to optimize pertussis vaccination strategies in Finland.

A cluster of measles linked to an imported case, Finland, 2017.

One imported and five secondary cases of measles were detected in Finland between June and August 2017. The measles sequences available for five laboratory-confirmed cases were identical and belonged to serotype D8. The large number of potentially exposed Finnish and foreign individuals called for close cooperation of national and international public health authorities and other stakeholders. Raising awareness among healthcare providers and ensuring universally high vaccination coverage is crucial to prevent future clusters and outbreaks.

Bank voles show high seropositivity rates in a natural TBEV focus in Hungary.

Rodents captured in a known tick-borne encephalitis virus (TBEV) focus were serologically surveyed for 4 years, with 28 visits. The collected sera were analysed by virus neutralization test. Bank vole (Myodes glareolus) had a significantly higher incidence rate of antibodies to TBEV (20.5%) than Apodemus flavicollis (3.7%) and Apodemus agrarius (4.6%). In all species, rates were higher in adults (6.8%) than in juveniles (1.7%). A higher incidence rate was observed in female A. flavicollis individuals (6.7%) than in males (1.5%). Smaller bank vole population coincided with lower (1.2-4.8%) seropositivity in all small rodents, while more abundant bank vole population meant higher (17.9%) total seropositivity. The TBEV focus originally had only Apodemus mice, bank voles appeared later, reached 20.5% positivity and raised the positivity in small rodents from 4% to 10.2% in 3 years. The results highlight the role of M. glareolus and of adult rodents in maintaining the TBEV in nature.

A 4-year study of a natural tick-borne encephalitis virus focus in Hungary, 2010-2013.

A tick-borne encephalitis virus focus was identified in a former goat pasture that had been associated with a milk-borne encephalitis outbreak in 2007. Ticks and rodents were sampled monthly from April 2010 to October 2013 on two separate 0.5 ha sampling sites. At site 1, three tick-borne encephalitis virus strains were isolated from a total of 7,247 sampled ticks; 28 of the 539 tested sera (5.19%) were seropositive. At site 2, from the 2,369 sampled ticks, virus was not isolated, tests of 284 rodent sera resulted in 14 positives (4.93%). For survival, the virus needs a territory with continuously dense rodent and tick population, although observed TBEV prevalence was low both in ticks and in rodents. Sampling points of positive ticks and rodents did not coincided exactly, at a certain time only some m(2) territory is dangerous, these hot spots change unpredictably as positive ticks die or move on with their hosts.

Subclinical Tick-Borne Encephalitis Virus in Experimentally Infected Apodemus agrarius.

OBJECTIVES: In this study, we investigated the dose dependence of tick-borne encephalitis virus (TBEV) infection in one of the reservoirs, i.e. Apodemus agrarius, a small rodent species. METHODS: The animals were challenged with TBEV per os and intramuscularly with infectious doses ranging from 1 to 1,500 plaque-forming units (pfu). Clinical signs were recorded and clinical and pathological features were evaluated by histological, immunohistochemical, and serological methods. RESULTS: High perorally administered infectious doses resulted in virus replication in the brain, which is the first sign of subclinical viral encephalitis in the Apodemus genus. The animals seroconverted at infectious doses greater than 100 pfu, and all animals remained asymptomatic. CONCLUSION: Our work shows the first evidence that subclinical TBEV encephalitis may occur in Apodemus species, depending on the virus load of the inoculum. The antiviral response of the local innate immune system may influence the resistance of Apodemus individuals to lower infectious doses. Per oral/nasal infection seems to be more dangerous for the host than other routes of infection.

Monitoring the diel activity of Ixodes ricinus ticks in Hungary over three seasons.

Ixodes ricinus is the most common tick species in Europe and vector of many diseases of humans. The risk of contracting such a disease is influenced by many factors, but one of the crucial points is questing activity of unfed ticks. In order to supplement the few literature data on patterns of diel activity of this tick species and to examine the correlations between data on diel activity of ticks and their small mammal hosts and some meteorological variables, a survey was performed. Diel activity of questing I. ricinus and small rodents was studied in a known natural tick-borne encephalitis virus focus over 7 months at one sampling day monthly. 1,063 I. ricinus ticks and 25 rodents were sampled. Air temperature and humidity data were also recorded in the 24 study plots at time of sampling. From April to October questing activity of nymphs increased in the 3-h-period after sunrise, comparing to activity of the 3 h before sunrise. Proportion of nymphs sampled 3 h after sunset compared to total sampled nymphs 3 h before and 3 h after sunset showed correlation to activity of rodents. In the period of April-July both nymphs and larvae showed stronger activity from sunrise to sunset, this turned to dominant nighttime activity in August-September, whereas activity changed to equal in day and night in October. Our results indicate that natural light and rodent population have positive effect on questing activity of I. ricinus.

Tick-borne encephalitis and Lyme disease in Hungary: the epidemiological situation between 1998 and 2008.

Diagnosed cases of tick-borne encephalitis (TBE) and Lyme disease (LD) have been reportable infectious diseases in Hungary since 1977 and 1998, respectively. Clinically diagnosed cases have been registered in the National Database of Epidemiological Surveillance System (NDESS). All reported TBE cases are confirmed by laboratory serological and, if necessary, PCR tests, whereas the registered cases of LD are mainly based on the appearance of erythema migrans concurring with possible exposure of tick bite. Our work is the first comparative epidemiological and geographical information analysis of these 2 diseases together. The following demographic data from each individual case (703 TBE and 13,606 LD) recorded in the NDESS were used: Sex, age, the starting date and place of the onset of disease, and a short report from the affected person. The descriptive epidemiological analysis of incidence was carried out using directly standardized rates, and smoothed indirectly standardized incidence ratios were calculated by hierarchical Bayesian methods at the municipality level using a Rapid Inquiry Facility (RIF). The average yearly incidence rate of TBE was 0.64 per 100,000 inhabitants (range, 0.46-0.84) and of LD was 12.37 per 100,000 inhabitants (range, 9.9-18.1), with the highest incidence rates in 1998 for TBE and 2008 for LD. The most affected age groups were men between 15 and 59 years of age for TBE, and women between 45 and 64 years of age for LD. Seasonality, based on the starting date of the illness, was also characterized. Extended areas of high risk were identified in western and northern Hungary, illustrated on high-resolution (municipality level) maps. On the basis of our analysis, it is possible to associate areas and periods of high-risk with characteristics (sex, age, residence) of groups most affected by tick-borne diseases in Hungary.