Challenges in assessing the immunization status of adults in Germany-lessons from a population-based VACCELERATE survey on polio vaccination.

PURPOSE: Considering the re-emergence of poliomyelitis (PM) in non-endemic regions, it becomes apparent that vaccine preventable diseases can rapidly develop epi- or even pandemic potential. Evaluation of the current vaccination status is required to inform patients, health care providers and policy makers about vaccination gaps. METHODS: Between October 28 2022 and November 23 2022, 5,989 adults from the VACCELEREATE Volunteer Registry completed an electronic case report form on their previous PM vaccine doses including number, types/-valencies and the time of administration based on their vaccination records. A uni-/multivariable regression analysis was performed to assess associations in participant characteristics and immunization status. RESULTS: Among German volunteers (n = 5,449), complete PM immunization schedule was found in 1,981 (36%) participants. Uncertain immunization, due to unknown previous PM vaccination (n = 313, 6%), number of doses (n = 497, 9%), types/-valencies (n = 1,233, 23%) or incoherent immunization schedule (n = 149, 3%) was found in 40% (n = 2,192). Out of 1,276 (23%) participants who reported an incomplete immunization schedule, 62 (1%) never received any PM vaccine. A total of 5,074 (93%) volunteers reported having been vaccinated at least once and 2,087 (38%) indicated that they received vaccination within the last ten years. Female sex, younger age, as well as availability of first vaccination record were characteristics significantly associated with complete immunization (p < 0.001). CONCLUSION: Full PM immunization schedule was low and status frequently classified as uncertain due to lack of details on administered doses. There is an obviousneed for improved recording to enable long-term access to detailed vaccination history in the absence of a centralized immunization register.

Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis.

BACKGROUND: Although global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design. METHODS: We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants and examined the impact of key study characteristics on these estimates. RESULTS: We reviewed 3328 articles through 14 August 2020 and identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants <1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate of 19.4 (95% confidence interval [CI], 17.9-20.9). Study type influenced RSV-associated hospitalization rates (P = .003), with active surveillance studies having pooled rates (11.0; 95% CI, 9.8-12.2) that were half that of studies based on administrative claims (21.4; 19.5-23.3) or modeling approaches (23.2; 20.2-26.2). CONCLUSIONS: Applying our pooled rates to the 2020 US birth cohort suggests that 79 850 (95% CI, 73 680-86 020) RSV-associated infant hospitalizations occur each year. The full range of RSV-associated hospitalization rates identified in our review can better inform future evaluations of RSV prevention strategies. More research is needed to better understand differences in estimated RSV burden across study design.

County-level Predictors of Coronavirus Disease 2019 (COVID-19) Cases and Deaths in the United States: What Happened, and Where Do We Go from Here?

BACKGROUND: The United States has been heavily impacted by the coronavirus disease 2019 (COVID-19) pandemic. Understanding microlevel patterns in US rates of COVID-19 can inform specific prevention strategies. METHODS: Using a negative binomial mixed-effects regression model, we evaluated the associations between a broad set of US county-level sociodemographic, economic, and health status-related characteristics and cumulative rates of laboratory-confirmed COVID-19 cases and deaths between 22 January 2020 and 31 August 2020. RESULTS: Rates of COVID-19 cases and deaths were higher in US counties that were more urban or densely populated or that had more crowded housing, air pollution, women, persons aged 20-49 years, racial/ethnic minorities, residential housing segregation, income inequality, uninsured persons, diabetics, or mobility outside the home during the pandemic. CONCLUSIONS: To our knowledge, this study provides results from the most comprehensive multivariable analysis of county-level predictors of rates of COVID-19 cases and deaths conducted to date. Our findings make clear that ensuring that COVID-19 preventive measures, including vaccines when available, reach vulnerable and minority communities and are distributed in a manner that meaningfully disrupts transmission (in addition to protecting those at highest risk of severe disease) will likely be critical to stem the pandemic.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Invasive Disease Caused by Serotype 3 in Children: A Systematic Review and Meta-analysis of Observational Studies.

The 13-valent pneumococcal conjugate vaccine (PCV13) is the only licensed PCV with serotype 3 polysaccharide in its formulation. Postlicensure PCV13 effectiveness studies against serotype 3 invasive pneumococcal disease (IPD) in children have shown inconsistent results.  We performed a systematic review and meta-analysis of observational studies to assess PCV13 vaccine effectiveness (VE) for serotype 3 IPD in children. We systematically searched PubMed, Embase, and the Cochrane library for studies published before 14 August 2017. We identified 4 published studies and 2 conference posters that provided PCV13 VE estimates stratified by serotype. The pooled PCV13 VE against serotype 3 IPD from the random-effects meta-analysis was 63.5% (95% confidence interval [CI], 37.3%-89.7%). A sensitivity analysis including conference posters gave a pooled VE estimate of 72.4% (95% CI, 56.7%-88.0%). The pooled data from case-control studies with similar methodologies and high quality support direct PCV13 protection against serotype 3 IPD in children.

Pertussis: Microbiology, Disease, Treatment, and Prevention.

Pertussis is a severe respiratory infection caused by Bordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. Sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution of B. pertussis strains. During the past 20 years, the scientific community has recognized pertussis among adults as well as infants and children. Increased recognition that older children and adolescents are at risk for disease and may transmit B. pertussis to younger siblings has underscored the need to better understand the role of innate, humoral, and cell-mediated immunity, including the role of waning immunity. Although recognition of adult pertussis has increased in tandem with a better understanding of B. pertussis pathogenesis, pertussis in neonates and adults can manifest with atypical clinical presentations. Such disease patterns make pertussis recognition difficult and lead to delays in treatment. Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology. Together, these advances provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines.

Pneumococcal serotype evolution in Western Europe.

BACKGROUND: Pneumococcal diseases remain a leading cause of vaccine-preventable death worldwide in children <5 years of age. The seven-valent pneumococcal conjugate vaccine (PCV7) was approved in 2001 in Europe and was introduced into the national immunization programmes of many European countries from 2006-2008. In 2009, higher-valent PCVs (PCV10 and PCV13) became available, replacing PCV7 from 2009-2011. This article describes the evolution of vaccine and non-vaccine serotypes causing invasive pneumococcal disease (IPD) following the introduction of PCVs in Western Europe, based on data from publicly-available medical publications and national surveillance systems from January 2010 to May 2015. DISCUSSION: In countries with high vaccine uptake, 5-7 years after PCV7 introduction IPD caused by vaccine serotypes has almost disappeared in children. Non-PCV7 serotypes have emerged, particularly serotypes 19A, 7 F, 3 and 1. A rapid and significant reduction of the additional serotypes included in higher-valent vaccines has been observed consistently following the introduction of these vaccines. A significant and rapid decline of serotypes 19A, 7 F, 1 and 6A in both vaccine-eligible and older age groups has been observed in countries using PCV13 while serotype 19A and 3 has increased in countries using PCV10. Serotype 3 has become one of the most prevalent serotypes in adults, with some reduction only in the UK and France. Serotype diversity increased and varied by age group, the type of vaccine in use, and the time since the introduction of higher-valent PCVs. Serotypes that are currently more frequent include 24 F, 22 F, 8 and 15A in countries that use PCV13, and serotypes 19A and 3 in countries that use PCV10. Compared with the time before the introduction of higher valent PCVs, to date, there is no single '19A-like' serotype emerging across countries and most of the newly emerging non-PCV13 vaccine types are less invasive with a low case-carrier ratio. CONCLUSIONS: It is important to closely monitor not only evolving serotypes but also the magnitude of the effect in order to evaluate the overall impact of pneumococcal vaccination programmes and to initiate the appropriate vaccination strategy. Emerging serotypes may also need to be considered for the future development of new vaccines.

Oil-in-water emulsion adjuvant with influenza vaccine in young children.

BACKGROUND: The efficacy of inactivated influenza vaccines is known to be poor in infants and young children. METHODS: We studied the effect of the adjuvant MF59, an oil-in-water emulsion, on the efficacy of trivalent inactivated influenza vaccine (TIV) in 4707 healthy children 6 to less than 72 months of age who had not previously been vaccinated against influenza. The children were randomly assigned to three study groups, each of which received the assigned vaccines in two doses, 28 days apart, during two consecutive influenza seasons. Two of the groups were given age-appropriate doses of TIV either with or without the MF59 adjuvant, and the third group was given control (noninfluenza) vaccines to assess their absolute and relative efficacy against influenza-like illness, as confirmed by means of polymerase-chain-reaction (PCR) assay. RESULTS: Attack rates of influenza-like illness across both influenza seasons were 0.7%, 2.8%, and 4.7% in the adjuvant, nonadjuvant, and control vaccine groups, respectively. The absolute vaccine efficacy rates against all influenza strains (94 of 110 cases were due to vaccine-matched H3N2 viruses) were 86% (95% confidence interval [CI], 74 to 93) for the MF59-adjuvant vaccine (ATIV) and 43% (95% CI, 15 to 61) for the vaccine without the adjuvant (TIV); the relative vaccine efficacy rate for ATIV versus TIV was 75% (95% CI, 55 to 87). The efficacy rates for ATIV were 79% (95% CI, 55 to 90) in children 6 to less than 36 months of age and 92% (95% CI, 77 to 97) in those 36 to less than 72 months of age, as compared with 40% (95% CI, -6 to 66) and 45% (95% CI, 6 to 68), respectively, for TIV. Antibody responses were higher with ATIV and remained so through day 181. The rates of systemic and local reactions to the influenza vaccines with and without the adjuvant were similar in the younger age group (relative risk, 1.04; 95% CI, 0.98 to 1.09), but systemic events in the older age group were more frequent after administration of ATIV (63%) than after administration of TIV (44%) or the control vaccine (50%). Serious adverse events were distributed evenly across the three vaccine groups. CONCLUSIONS: Influenza vaccine with the MF59 adjuvant is efficacious against PCR-confirmed influenza in infants and young children. (Funded by Novartis Vaccines and Diagnostics; ClinicalTrials.gov number, NCT00644059.).

Vaccine uptake in 20 countries in Europe 2020: Focus on tick-borne encephalitis (TBE).

Vaccination as a highly effective measure to protect against tick-borne encephalitis (TBE) comes into new focus as known risk areas are expanding across Europe and Asia. Here we present an online household survey conducted in 20 European countries spanning endemic and non-endemic regions of TBE in 2020. With a comprehensive and standardized list of questions, this survey provided a unique opportunity to compare TBE/TBE vaccine awareness, TBE severity perception, vaccine uptake, vaccination completeness/compliance and motivators/barriers for vaccination across Europe. Among the 51,478 participants, tetanus- (72-92%), influenza- (83-98%), and measles-awareness (79-96%) were highest, but awareness was low for Lyme borreliosis, bacterial meningitis and pneumococcal pneumonia. Awareness towards TBE and a TBE vaccine was 74% and 56% in endemic countries, respectively, compared to 30% and 12% in non-endemic countries. Vaccine uptake defined as at least one TBE vaccination was found to be highly heterogenous across both endemic (range 7-81%) and non-endemic countries (range 1-8%). Compliance with the recommended vaccination schedule was 21% for the primary vaccination series and dropped to 7% for the first booster vaccination in endemic countries. The percentage of participants protected against TBE by vaccination at the time of the survey ranged from 21% in Slovakia to 69% in Lithuania. The perception of personal risk or lack thereof was found to be the most influencing factor for and against TBE vaccination. Overall, these data indicate highly heterogenous responses in different European countries regarding not only awareness towards a TBE vaccine, but also regarding TBE vaccine uptake and compliance. Regionally focused strategies to increase diagnostic completeness as well as TBE vaccination are needed across Europe.

Effectiveness of TBE vaccination in southern Germany and Latvia.

BACKGROUND: Tick-borne encephalitis (TBE) is a vaccine-preventable disease which may cause long-term sequelae and even death. The data on the long-term effectiveness of TBE vaccines are limited. Additionally, the vaccination schedule is complex which in part contributes towards sub-optimal uptake in TBE-endemic areas. The current ecological study measures vaccine effectiveness (VE) in two European countries. METHODS: TBE VE was measured from 2007 to 2018 in Latvia and Southern German states by age group, vaccination history, and schedule compliance. TBE cases and vaccination history were obtained from the public health agencies for Latvia and the southern German federal states of Bavaria and Baden-Wuerttemberg. Cases were "within schedule" if a TBE infection was diagnosed within the time interval preceding the next scheduled dose and "outside schedule" if the diagnosis occurred after the next scheduled dose. Vaccine uptake was estimated via representative nationwide surveys. RESULTS: VE after 2, 3, and ≥4 doses was high in both countries at 97.2%, 95.0%, and 95.4% for southern Germany, and 98.1%, 99.4%, and 98.8% for Latvia while within- schedule, and only showed marginal differences outside schedule at 90.6%, 89.9%, and 95.6% for southern Germany, and 97.4%, 98.4%, and 99.0% for Latvia regardless of age groups. CONCLUSIONS: In both countries, VE after two and three primary doses within-schedule was very high in all age groups. Once receiving booster doses, high VE continued to be observed even in persons with extended intervals since the last dose received, suggesting that longer and more flexible booster intervals may be considered for sustainable long-term protection.

Booster vaccination after neonatal priming with acellular pertussis vaccine.

After a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses.

[Prion safety of medicinal products using the example of an influenza vaccine produced in a cell line]. / Prionen-Sicherheit von Arzneimitteln am Beispiel eines Zellkultur-Impfstoffs.

Prions are pathogenic proteins and are the cause for spongiform encephalopathies. Pathogenic prions differ from physiologically common non-pathogenic prions only in their sterical structure. Upon infection by a pathogenic prion protein, a series of reactions is initiated in which common non-pathogenic prion proteins are transformed into pathogenic prions. Animals, mainly ruminants like cattle, sheep and goats are susceptible to prions, but also man. Prions are very robust and it is difficult to inactivate them. During the production processes of pharmaceuticals, the risk for contamination by infectious prions can be reduced by careful choice of animal material, the replacement of animal material and by appropriate production procedures. For instance biologicals like influenza vaccines can be produced by a permanent canine cell line, whose prion safety has been proven by useful methods (standard scrapy cell assay). Mandatory guidelines ensure that the risk for contamination by pathogenic prions has to be considered and excluded in the production of bio-pharmaceuticals.

[Safety of cell culture-based influenza vaccines]. / Sicherheit von Influenza-Impfstoffen auf Zellkulturbasis.

After more than 60 years, the conventional production of influenza vaccines employing fertilized chicken eggs has reached its limits - both in terms of temporal flexibility and vaccine production volume. This situation is compounded by the fact that the present pandemic-driven situation has roughly doubled the overall vaccine demand virtually "overnight". Modem cell culture technology has significant advantages over the conventional method of manufacturing influenza vaccines employing embryonated chicken eggs, and enables manufacturers to respond rapidly to the exploding worldwide seasonal and pandemic-driven need for influenza vaccines. Recent articles in the popular press claiming that cell culture-based influenza vaccines can cause tumours raised uncertainty among physicians and the general population, and also discredit officially accepted assessments and product licensing by the relevant authorities. The present article provides an overview on the cell culture technology and on the safety profile of the cells and of the vaccine product.

Are meteorological parameters associated with acute respiratory tract infections?

BACKGROUND: Information on the onset of epidemics of acute respiratory tract infections (ARIs) is useful in timing preventive strategies (eg, the passive immunization of high-risk infants against respiratory syncytial virus [RSV]). Aiming at better predictions of the seasonal activity of ARI pathogens, we investigated the influence of climate on hospitalizations for ARIs. METHODS: Samples obtained from 3044 children hospitalized with ARIs in Mainz, Germany, were tested for pathogens with a multiplex reverse-transcriptase polymerase chain reaction enzyme-linked immunosorbent assay from 2001 through 2006. Hospitalizations for ARIs were correlated with meteorological parameters recorded at the University of Mainz. The frequency of hospitalization for RSV infection was predicted on the basis of multiple time series analysis. RESULTS: Influenza A, RSV, and adenovirus were correlated with temperature and rhinovirus to relative humidity. In a time series model that included seasonal and climatic conditions, RSV-associated hospitalizations were predictable. CONCLUSIONS: Seasonality of certain ARI pathogens can be explained by meteorological influences. The model presented herein is a first step toward predicting annual RSV epidemics using weather forecast data.

Serotype evolution in Western Europe: perspectives on invasive pneumococcal diseases (IPD).

Introduction: Epidemiologic trends for IPD have evolved with the introduction of pneumococcal conjugate vaccines into childhood immunization programs. We document the ongoing impact of PCV programs in 15 Western European countries.Areas covered: Data were collected from relevant published observational studies and national surveillance websites from January 2010 through January 2018. In countries using PCV13, the proportion of IPD due to PCV13 serotypes declined significantly (from 60-78% to 8-26%) in children <5 years of age within 5-8 years following vaccine introduction. In countries using PCV10, a marked decrease in PCV10-serotype IPD was reported; however, the proportion of IPD due to PCV13 serotypes remained high at 58-64%, predominantly due to serotypes 19A and 3.Expert opinion: The prevalence of vaccine-type IPD in adults remained high; emerging non-vaccine serotypes such as 8, 12F, 22F, 33F, and 15B/C should be a focus of future vaccine development.

The impact of pneumococcal conjugate vaccines on serotype 19A nasopharyngeal carriage.

Introduction: By preventing nasopharyngeal carriage acquisition among vaccinated persons, and thus reducing transmission, pneumococcal conjugate vaccines (PCVs) provide protection against pneumococcal vaccine serotypes among unvaccinated individuals. This systematic review assessed PCVs containing serotype 19A or cross-reactive 19F for 19A carriage effects.Areas covered: Peer-reviewed literature was searched for manuscripts published between 1/1/2000 and 06/18/2018 assessing the impact of PCV on 19A carriage.Expert opinion: Fifty-five, 12, and 32 articles were identified for PCV7, PCV10, and PCV13, respectively. In two of four PCV7 randomized controlled trials (RCTs), 19A carriage was significantly higher in PCV7-vaccinated vs control subjects; in two of two PCV10 RCTs, there was no significant difference in 19A carriage and acquisition between PCV10-vaccinated (2 + 1 schedule) vs control subjects, apart from one timepoint (3 + 1 schedule); and one of one RCTs of PCV13 showed significant decreases in 19A carriage and acquisition in PCV13- vs PCV7-vaccinated (3 + 1 schedule) children. These findings were consistent with observational studies in which an increase or no change in 19A carriage was observed in 91% and 67% of PCV7 and PCV10 studies, respectively, whereas 87% of PCV13 studies documented a decrease. Countries in which serotype 19A transmission is substantial should consider the use of vaccines containing serotype 19A.

The impact of routine childhood immunization with higher-valent pneumococcal conjugate vaccines on antimicrobial-resistant pneumococcal diseases and carriage: a systematic literature review.

Introduction: The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in childhood immunization programs reduced antimicrobial-resistant pneumococcal infections by vaccine serotypes. However, emerging antimicrobial-resistant non-vaccine serotypes, particularly serotype 19A, attenuated the overall effect. In 2010, higher-valent PCVs became available containing serotypes that are prone to become antimicrobial-resistant, like serotype 7F in PCV10 and PCV13, and serotype 19A in PCV13.Areas covered: This review evaluated literature published between June 1, 2008 and June 1, 2017 reporting on the effect of PCV10 or PCV13 implementation in routine infant immunization schedules on antimicrobial-resistant invasive pneumococcal disease (IPD), otitis media (OM), and nasopharyngeal carriage (NPC) in children and adults.Expert opinion: In countries with relatively high prior pneumococcal antimicrobial resistance (AMR), PCV13 childhood vaccination programs have reduced antimicrobial-resistant IPD, OM, and NPC in children and IPD in adults. The effectiveness of PCV13 against serotype 19A is likely an important contributing factor. Only few studies have documented the impact of PCV10 on AMR. Multiple factors may influence observed decreases in pneumococcal AMR including antimicrobial stewardship, case definition, time since PCV10/13 introduction, and pre-PCV10/13 AMR levels. This review emphasizes the importance of including impact on AMR when evaluating the full public health of pneumococcal vaccination programs.

Self-reported tick-borne encephalitis (TBE) vaccination coverage in Europe: Results from a cross-sectional study.

Adequate vaccination is effective in preventing tick-borne encephalitis (TBE). A population survey conducted in 2015 in Czech Republic, Estonia, Finland, Germany, Hungary, Latvia, Lithuania, Poland, Slovakia, Slovenia, and Sweden obtained information on TBE vaccination. Respondents answered 10 questions for themselves and household members. Data were weighted according to age and fine-tuned for geographical spread. Across the 10 countries (excluding Poland), TBE awareness was 83%; of all respondents, 68% were aware of TBE vaccines and 25% had ≥1 injections. Vaccination rates were lowest in Finland and Slovakia (∼10%), highest in Austria (85%, results from a separate 2015 survey), and varied widely in Germany. Across the 11 countries (excluding Austria), compliance with vaccination schedule among TBE-vaccinated respondents was 61%; 27% and 15% of respondents received first and second booster injections; strongest motivators for vaccination were fear of TBE (38%) and residence/spending time in high-risk areas (31-35%); main reasons for not receiving vaccination were beliefs that vaccination was unnecessary (33%) and that there was no risk of contracting TBE (23%). TBE vaccine uptake and compliance could be improved with effective public health information to increase TBE awareness and trust in vaccination and by updating recommendations to include all subjects visiting TBE-risk areas.

Burden of pneumococcal community-acquired pneumonia in adults across Europe: A literature review.

BACKGROUND: The burden of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae (pneumococcus) among adults in Europe is poorly defined. METHODS: Structured searches of PubMed were conducted to identify the incidence of pneumococcal CAP among adults across Europe. RESULTS: The overall incidence rates for CAP was 68-7000 per 100,000 and the incidence in hospitalised CAP cases of all causes was 16-3581 per 100,000. In general the incidence of CAP increased consistently with age. Available data indicated higher burdens of pneumococcal CAP caused in groups with more comorbidities. Most cases of pneumococcal CAP (30%-78%) were caused by serotypes covered by PCV13 vaccine; the incidence of PCV13-related pneumonia decreased after the introduction of childhood vaccination. CONCLUSIONS: We observed a high burden adult pneumococcal CAP in Europe despite use of the 23-valent pneumococcal polysaccharide vaccine, particularly in elderly patients with comorbidities. CAP surveillance presented wide variations across Europe. Pneumococcal CAP has to be monitored very carefully due to the possible effect of current vaccination strategies.

Tick-borne encephalitis: A 43-year summary of epidemiological and clinical data from Latvia (1973 to 2016).

BACKGROUND: The incidence of tick-borne encephalitis (TBE) varies significantly over time. To better understand the annual incidence of all TBE cases in Latvia we investigated the disease burden in the country from 1973-2016 using several available sources and case definitions. METHODS: We identified cases of TBE from an electronic database (maintained by the Centre for Disease Prevention and Control of Latvia [CDPC]) by the use of ICD-10 diagnosis codes for TBE (A84; A84.0; A84.1; A84.8; A84.9). In addition, previously unreported TBE cases were found by review of TBE diagnoses according to ICD-10 codes in four hospital databases. RESULTS: From 1973 to 2016 a total of 15,193 TBE cases were reported to the CDPC, 2,819 of which were reported from January 2007 through December 2016, additionally for this time period, 104 cases were identified via hospital survey. From all 2,923 reported cases (2007-2016), 1,973 met TBE case definition criteria and were included in the TBE study analysis. The highest average 10 year incidence was observed from 1990-1999 (27.9 cases per 100,000; range 4.6-53.0), however, the average 10-year incidence from 2007-2016 using officially adopted TBE case definition was 9.6 cases per 100,000 (range 5.8-14.6). For this 10-year time period most cases were adults (95.1%) and male (52.2%). The most common clinical form of TBE was meningitis (90.6%). A tick bite prior to TBE onset was reported in 60.6% of TBE cases and 98.2% of cases were not vaccinated against TBE. CONCLUSION: The data demonstrate that the incidence of TBE varies by about one third based on the case definition used. TBE occurs almost entirely in the unvaccinated population. Regular TBE awareness campaigns could encourage the population in Latvia to use protective measures to further control TBE in the country, either via vaccination or tick avoidance.