HPV-associated cancers among people living with HIV: nationwide population-based retrospective cohort study 2004-21 in Estonia.

Cancers represent the primary cause of mortality among people living with HIV (PLWH). However, comprehensive nationwide data regarding cancer incidence remains limited. Our objective was to evaluate the incidence rates of cancers, particularly those associated with human papillomavirus (HPV), within a nationwide study cohort. Using data from the Estonian Health Insurance Fund and the National Cancer Registry from 2004 to 2021, we calculated standardized incidence ratios (SIRs) for various cancer types among PLWH to compare to the general population with special emphases on HPV-associated cancers. A total of 7011 individuals (65.7% men) diagnosed with HIV were identified. HPV-associated cancers accounted for 21.4% of all incident cancer cases among PLWH. SIRs for HPV-associated cancers were 3.7 [95% confidence interval (CI) 2.2-6.2] among men living with HIV (MLWH) and 5.7 (95% CI 4.0-7.9) among women living with HIV (WLWH). In MLWH, the highest SIRs were for penile 12.5 (95% CI 4.0-38.7), followed by oropharyngeal 3.6 (95% CI 1.7-7.6) and anal-rectal cancers 2.7 (95% CI 1.1-6.4) in comparison to the general population. In WLWH, an increased incidence of cervical (SIR = 5.8, 95% CI 3.9-8.5), oropharyngeal (SIR = 6.1, 95% CI 1.5-24.3), and anal-rectal (SIR = 3.6, 95% CI 1.2-11.2) cancers was observed. A significantly increased risk of AIDS-defining and non-AIDS-defining cancers is reported. We demonstrate a substantially heightened risk of HPV-associated cancers among PLWH compared to the general population, underscoring the imperative for intensified screening and scaled-up vaccination along with improvement in adherence to antiretroviral therapy.

Traffic noise in the bedroom in association with markers of obesity: a cross-sectional study and mediation analysis of the respiratory health in Northern Europe cohort.

BACKGROUND: Previous research suggests an association between road traffic noise and obesity, but current evidence is inconclusive. The aim of this study was to assess the association between nocturnal noise exposure and markers of obesity and to assess whether sleep disturbance might be a mediator in this association. METHODS: We applied data from the Respiratory Health in Northern Europe (RHINE) cohort. We used self-measured waist circumference (WC) and body mass index (BMI) as outcome values. Noise exposure was assessed as perceived traffic noise in the bedroom and/or the bedroom window's location towards the street. We applied adjusted linear, and logistic regression models, evaluated effect modifications and conducted mediation analysis. RESULTS: Based on fully adjusted models we found that women, who reported very high traffic noise levels in bedroom, had 1.30 (95% CI 0.24-2.37) kg/m2 higher BMI and 3.30 (95% CI 0.39-6.20) cm higher WC compared to women, who reported no traffic noise in the bedroom. Women who reported higher exposure to road traffic noise had statistically significant higher odds of being overweight and have abdominal obesity with OR varying from 1.15 to 1.26 compared to women, who reported no traffic noise in the bedroom. For men, the associations were rather opposite, although mostly statistically insignificant. Furthermore, men, who reported much or very much traffic noise in the bedroom, had a statistically significantly lower risk of abdominal obesity. Sleep disturbance fully or partially mediated the association between noise in bedroom and obesity markers among women. CONCLUSION: Our results suggest that self-reported traffic noise in the bedroom may be associated to being overweight or obese trough sleep disturbance among women, but associations were inconclusive among men.

Norovirus strains among children aged 0-18 years hospitalized with acute gastroenteritis in Estonia 2015-2016.

Norovirus (NoV) is the leading cause of acute gastroenteritis (AGE) in many countries that have introduced universal rotavirus mass vaccination. This is the first study to report data on NoV strains in Estonia. We recruited 2249 children aged 0-18 years hospitalized for AGE in Estonian hospitals from February 1, 2015 to August 31, 2016. Norovirus gastroenteritis (NoVGE) was diagnosed in 14.5% (n = 325) cases. Stool sample for RNA extraction and genotyping was available in 86% (n = 280) of NoVGE cases (2015, n = 91; 2016, n = 189). Dominant capsid types detected in 75% (n = 210) samples were, GII.4 (63.8%, n = 134), GII.3 (15.2%, n = 32), GII.17 (6.7%, n = 14), and GII.6 (5.2%, n = 11). Prevailing RNA polymerase types found in 77% (n = 215) samples were GII.P31 (51.1%, n = 110), GII.P21 (17.7%, n = 38), GII.P4 (11.2%, n = 24), and GII.P7 (6.5%, n = 14). Both regions were typeable for 67% (n = 189) of samples. Most prevalent strains were GII.4Sydney_2012[P31] (48.7%, n = 92), GII.3[P21] (15.3%, n = 29), GII.4Sydney_2012[P4] (5.8%, n = 11) and GII.17[P17] (5.8%, n = 11). Simpson's diversity index showed a significant difference between the age groups 1-4 and 5-9 years: D 0.64 (95% confidence interval [CI]: 0.55-0.73) versus 0.83 (95% CI: 0.81-0.86), respectively (p = 0.03). An accurate understanding of NoV strain diversity is important for control and preventive measures, especially in the postrotavirus vaccine era.

Systematic review and meta-analysis of head-to-head trials comparing sulfonylureas and low hypoglycaemic risk antidiabetic drugs.

BACKGROUND: Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes. METHODS: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs. STUDY SELECTION: Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. OUTCOMES: The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia. SYNTHESIS OF RESULTS: Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780). RESULTS: Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules. CONCLUSION: Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.

Dynamics of hepatitis C epidemic among people living with HIV in Estonia based on Estonian HIV cohort study.

BACKGROUND: Estonia has a typical Eastern European HIV epidemic where the most frequent co-infection is chronic hepatitis C (HCV). We aimed to describe the changes in HCV prevalence, the distribution of HCV genotypes (GT), and HCV treatment in Estonian people living with HIV over 15 years. METHODS: We used data of subjects included to the Estonian HIV Cohort Study (E-HIV) before 31st of December 2015. We compared two time periods-first, 1st of January 2000 to 31st of December 2008 when the HIV epidemic was mostly spreading among people who inject drugs (PWID) and second, 1st of January 2009 to 31st of December 2015 when HIV started to emerge to the general population. RESULTS: Of 4422 HIV positives 3708 (84%) had information about their HCV serostatus; 2706 (61%) were HCV seropositive, of latter 1625 (60%) were HCV RNA positive, 239 (9%) had their HCV GT determined, and 141 (5%) received treatment for HCV. The dominating subtypes were 1b (42%) and 3a (37%) followed by 1a (16%), and the few cases of 2 (1.5%). HCV prevalence was 1.5 times (95% CI 1.4-1.6) higher in subjects diagnosed with HIV in first as compared to those diagnosed in second period (84% vs 56%, respectively). There were more men and the median age at HIV diagnosis was lower in HIV/HCV co-infected than in HIV mono-infected patients (70% vs 47% and 24 years vs. 30 years, respectively; both p < 0.001). CONCLUSION: There is a decrease in HCV prevalence but it remains high among HIV positive PWID, suggesting that there is need for improvement of harm reduction programs among PWID.

Association of IFNλ4 rs12979860 polymorphism with the acquisition of HCV and HIV infections among people who inject drugs.

We investigated the presence of a single-nucleotide polymorphism designated rs12979860 in the interferon λ4 (IFNλ4) gene among 345 people who inject drugs (PWID) and 495 blood donors to evaluate associations between the rs12979860 genotypes and human immunodeficiency virus/hepatitis C virus (HIV/HCV). The rs12979860 TT genotype was over-represented among HIV+ PWID than HIV- PWID and blood donors (16% vs 8% and 10%, P = 0.03, respectively). PWID with TT genotype had approximately twice the probability of being HIV+ (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.11 to 4.33) than PWID without TT. Every additional year of intravenous drug use (IVDU) decreased the OR 1.16 times (OR, 0.86; 95% CI, 0.75 to 0.98). This suggests that rs12979860 TT increases susceptibility to HIV and this impact decreases with increasing duration of IVDU.

Pertussis and parapertussis in children and adults with a persistent cough: an observational study.

PURPOSE: We aimed to determine the prevalence, symptoms and course of pertussis and parapertussis among patients at any age with a cough of unknown aetiology that had lasted for ≥ 7 days and to assess the diagnostic value of the symptoms included in the World Health Organisations' (WHO) clinical case definition of pertussis. METHODS: Patients were enrolled between the 23 April 2012 and 31 December 2014 at 25 general practitioner (GP) centres and three paediatric hospitals. Pertussis was confirmed by culture and/or polymerase chain reaction (PCR) and/or quantitative serology. Parapertussis was confirmed by culture and/or PCR. RESULTS: Altogether, 549 patients were recruited. Of them, 22 (4.0%; 95% CI 2.5-6.0) had pertussis (predominately diagnosed by positive serology 17/22) and 7 (1.3%; 95% CI 0.5-2.6) had parapertussis. Patients with pertussis were more likely to have inspiratory whooping and posttussive emesis than those with a cough of another/unknown aetiology. However, the presence or absence of these two symptoms did not definitively confirm or exclude pertussis. The sensitivity and specificity of the WHO's clinical definition was 0.77 and 0.38, respectively. CONCLUSIONS: The prevalence of pertussis and parapertussis among patients with a persistent cough of unknown aetiology in Estonia is low. As clinical symptoms alone cannot be used to distinguish pertussis, we recommend that laboratory testing for pertussis is performed in all patients with a persistent cough regardless of age.

Hysterectomy types in Estonia are still different from the Nordic countries.

OBJECTIVE: To describe hysterectomy rates in different age groups, indications and proportion of surgery types over time. DESIGN: Nationwide register-based study. SETTING: Estonia. POPULATION: Women who had hysterectomies for benign indications from 2004 to 2011. METHODS: For each case, diagnosis according to ICD-10, type of surgery according to Nordic Medico-Statistical Committee, age, and time of operation were retrieved from the Estonian Health Insurance Fund database. Mid-year female population statistics were obtained from Statistics Estonia. MAIN OUTCOME MEASURES: Rate of hysterectomies per 100 000 women, proportions of different operation types, and main indications for hysterectomies. RESULTS: The total number of hysterectomies was 12 336, with a yearly mean of 1542. The rate of hysterectomies per 100 000 women/year decreased between 2004 and 2011 from 239.1 to 204.9. The proportion of abdominal hysterectomies decreased from 86.0 to 56.1% and the proportion of laparoscopic hysterectomies increased from 6.3 to 34.7%, while the proportion of vaginal hysterectomies remained more or less stable (7.8-9.1%). Most hysterectomies (74.4%) occurred in the age group 35-54 years. The main indications for hysterectomies were leiomyoma (61.5%), female genital prolapse (9.0%) and endometriosis (8.8%). CONCLUSIONS: Population rates and indications for hysterectomies in Estonia were similar to those in most Nordic countries, but the proportion of abdominal hysterectomies was higher and that of vaginal hysterectomy lower. The rates of laparoscopic and vaginal hysterectomies should be increased.

Comparison of two alternative study designs in assessment of medicines utilisation in neonates.

BACKGROUND: Estimates of prevalence are known to be affected by the design of cross-sectional studies. A pan-European study provided an opportunity to compare the effect of two cross-sectional study designs on estimates of medicines use. METHODS: A Service evaluation survey (SES) and a web-based point-prevalence study (PPS) were conducted as part of a European study of neonatal exposure to excipients. Neonatal units from all European Union countries plus Iceland, Norway, Switzerland and Serbia were invited to participate. All medicines prescribed to neonates were recorded during three-day and one-day study periods in the SES and PPS, respectively. In the PPS individual demographic and prescription data were also collected.To compare the probabilities that a particular medicine would be reported by each study multilevel mixed effects logistic regression models with crossed random effects were applied. The relationship between medicines exposure at the unit and individual levels in the PPS data was assessed using polynomial regression with square root transformation. RESULTS: Of 31 invited countries 20 and 21 with 115 and 89 units joined the SES and PPS, respectively. Out of 5,572,859 live births in invited countries in 2010 a higher proportion was covered by units participating in the SES compared to the PPS (11% vs 6%, respectively; OR 1.89; 95% CI 1.87-1.89). A greater number of active pharmaceutical ingredients (API), manufacturers and trade names were registered in the SES compared to the PPS. High correlation between the two studies in frequency of use for each specified API was seen (R2 = 0.86). The average probability of a department to use a given API was greater in the SES compared to the PPS (OR 2.36; 95% CI 2.05-2.73) with higher frequency of use and longer average duration of prescription further increasing the difference. The polynomial regression model described the correlation between APIs exposure on unit and individual level well (R2 = 0.93). CONCLUSION: The simple data structure and longer study period of the SES resulted in improved recruitment and higher likelihood of capture for a given API. The frequency of use at the unit level appears a good surrogate of individual exposure rates.

The COVID-19 pandemic and the use of benzodiazepines and benzodiazepine-related drugs in Estonia: an interrupted time-series analysis.

BACKGROUND: The COVID-19 pandemic has posed challenges that worsened people's mental health. We explored the impact of the COVID-19 pandemic on the mental well-being of the population, as indicated by the prevalence rates of benzodiazepine and benzodiazepine-related drug (BDZ) use. METHODS: This population-based, time-series analysis included all prescriptions of BDZs dispensed in Estonia between 2012 and 2021. The monthly prevalence rates of BDZ use were calculated. Autoregressive integrated moving average models with pulse and slope intervention functions tested for temporary and long-term changes in monthly prevalence rates after the onset of the COVID-19 pandemic. RESULTS: Throughout the 10-year study period, a total of 5,528,911 BDZ prescriptions were dispensed to 397,436 individuals. A significant temporary increase in the overall prevalence rate of BDZ use in March 2020 (2.698 users per 1000, 95% CI 1.408-3.988) was observed, but there was no statistically significant long-term change. This temporary increase affected all the examined subgroups, except for new users, individuals aged 15-29 years, and prescribing specialists other than general practitioners and psychiatrists. The long-term increase in BDZ use was confined to females aged 15-29 years (0.056 users per 1000 per month, 95% CI 0.033-0.079), while no significant change was observed among males of the same age (0.009 users per 1000 per month, 95% CI - 0.017 to 0.035). Among females aged 15-29 years, a significant long-term increase in BDZ use was observed for anxiety disorders (0.017 users per 1000 per month, 95% CI 0.010-0.023), depressive disorders (0.021 users per 1000 per month, 95% CI 0.012-0.030), and other mental and behavioral disorders (0.020 users per 1000 per month, 95% CI 0.010-0.030), but not for sleep disorders (- 0.008 users per 1000 per month, 95% CI - 0.018-0.002). CONCLUSION: The COVID-19 pandemic led to a short-term increase in BDZ use immediately after the pandemic was declared. In the long term, young females experienced a sustained increase in BDZ use. The prolonged effect on girls and young women suggests their greater vulnerability. These results underscore the need to effectively address the long-term effects of the pandemic among youth.

Planned improvement actions based on patient safety incident reports in Estonian hospitals: a document analysis.

AIM: Aim of this study was to describe and analyse associations of incidents and their improvement actions in hospital setting. METHODS: It was a retrospective document analysis of incident reporting systems' reports registered during 2018-2019 in two Estonian regional hospitals. Data were extracted, organised, quantified and analysed by statistical methods. RESULTS: In total, 1973 incident reports were analysed. The most commonly reported incidents were related to patient violent or self-harming behaviour (n=587), followed by patient accidents (n=379), and 40% of all incidents were non-harm incidents (n=782). Improvement actions were documented in 83% (n=1643) of all the reports and they were focused on (1) direct patient care, (2) staff-related actions; (3) equipment and general protocols and (4) environment and organisational issues. Improvement actions were mostly associated with medication and transfusion treatment and targeted to staff. The second often associated improvement actions were related to patient accidents and were mostly focused on that particular patient's further care. Improvement actions were mostly planned for incidents with moderate and mild harm, and for incidents involving children and adolescents. CONCLUSION: Patient safety incidents-related improvement actions need to be considered as a strategy for long-term development in patient safety in organisations. It is vital for patient safety that the planned changes related to the reporting will be documented and implemented more visibly. As a result, it will boost the confidence in managers' work and strengthens all staff's commitment to patient safety initiatives in an organisation.

Age-specific and genotype-specific carcinogenic human papillomavirus prevalence in a country with a high cervical cancer burden: results of a cross-sectional study in Estonia.

OBJECTIVES: To describe age-specific and type-specific carcinogenic human papillomavirus (HPV) prevalence prior to large-scale effect of HPV vaccines in Estonia and to analyse the risk factors associated with carcinogenic HPV. DESIGN: Cross-sectional study using self-administered questionnaire and self-collected vaginal swabs for detection of HPV infection. SETTING: Estonian Biobank database. PARTICIPANTS: Stratified random sample of women aged 30-33, 57-60 and 67-70 years living in one of the three largest counties in Estonia. Of 3065 women approached, 1347 (43.9%) returned questionnaires and specimens for HPV DNA detection. OUTCOME MEASURES: HPV prevalence and fully adjusted ORs with 95% CIs for risk factors. RESULTS: HPV prevalence was highest among women aged 30-33 years (18.7%; 95% CI 15.8 to 21.9) followed by those aged 67-70 years (16.7%; 95% CI 12.4 to 22.0) and 57-60 years (10.2%; 95% CI 7.8 to 13.3). HPV16 and HPV56 were the most common among women aged 30-33 years (both 4.0%; 95% CI 2.7 to 5.9), and HPV68 was the most common among women aged 57-60 years (2.8%; 95% CI 1.5 to 4.7) and 67-70 years (6.4%; 95% CI 3.6 to 10.4). Vaccination with nonavalent vaccine would have halved the carcinogenic HPV prevalence among women aged 30-33 years. The odds of infection with carcinogenic HPV were higher among women with six or more sexual partners among younger (OR 2.99; 95% CI 1.54 to 5.81) and older (OR 3.80; 95% CI 1.25 to 11.55) women and lower (OR 0.35; 95% CI 0.17 to 0.72) among younger married women. CONCLUSIONS: This study demonstrated U-shaped age-specific genotype profile of carcinogenic HPV prevalence, indicating that public health providers should focus on developing exit strategies for the cervical cancer screening programme in Estonia with a possible extension of HPV testing beyond the current screening age of 65 years. Generalisability of the findings of this study may be affected by the low response rate.

Cluster randomised, controlled, triple-blind trial assessing the efficacy of intranasally administered virus-neutralising bovine colostrum supplement in preventing SARS-CoV-2 infection in household contacts of SARS-CoV-2-positive individuals: a study protocol.

The SARS-CoV-2 enters into the human body mainly through the nasal epithelial cells. Prevention of SARS-CoV-2 infection at the point of nasal entry is a novel strategy that has the potential to help contain the ongoing pandemic. BioBlock is a nasal spray of anti-SARS-CoV-2 preparation based on virus-neutralising antibodies prepared from colostrum from cows immunised with SARS-CoV-2 spike protein. This triple-blind placebo-controlled cluster randomised parallel trial seeks to evaluate the efficacy of a BioBlock spray in the prevention and treatment of SARS-CoV-2 infection. Laboratory-confirmed COVID-19 cases and their household members will be randomly allocated to each of either the intervention (BioBlock nasal spray) or the placebo (nasal spray) arms. The intervention is a 14-day course of nasal spray used by index case and household contacts. In most countries, those with confirmed or suspected infections are requisitioned to isolate at home, putting other members of their household at risk of infection. Therefore, in parallel to the need of household transmission prevention measures, households also present as a good model for infection transmission studies, allowing for the testing of several close contact transmission prevention study hypotheses. Our hope is that if the trial results are encouraging, this will provide new and additional COVID-19 prevention strategies. TRIAL REGISTRATION: ISRCTN48554326 Registered on June 14, 2021.

Seroprevalence and levels of IgG antibodies after COVID-19 infection or vaccination.

BACKGROUND: In a country-wide seroprevalence study of COVID-19 in Estonia, we aimed to determine the seroprevalence and the dynamics of IgG against SARS-CoV-2 after vaccination or positive PCR-test. METHODS: Leftover blood samples were selected between 8 February and 25 March 2021, by SYNLAB Estonia from all counties and age groups (0-9, 10-19, 20-59, 60-69, 70-79 and 80-100 years) proportionally to the whole Estonian population and tested for IgG against SARS-CoV-2 spike protein receptor-binding domain (anti-S-RBD IgG) using Abbott SARS-CoV-2 IgG II Quant assay. Antibody levels after positive PCR-test or vaccination were described by exponential increase-decrease models. RESULTS: According to total of 2517 samples, overall seroprevalence (95% confidence interval [CI]) was 20.1% (18.5-21.7%), similar in all age groups, but varied between counties. If individuals vaccinated with the first dose at least 14 d before antibody measurement were assumed to be seronegative, the overall seroprevalence was 15.8% (14.4-17.3%), 4.0-fold larger than the proportion of PCR-confirmed COVID-19 cases. Of seropositive individuals (n = 506) 194 (38.3%; 33.8-43.1%) had not had positive PCR-test or been vaccinated. According to exponential increase-decrease model, the peak of anti-S-RBD IgG in a 52-year-old (median age of PCR-positive and/or vaccinated individuals) was significantly higher after vaccination compared with positive PCR-test (22,082 (12,897-26,875) vs. 6732 (2321-8243) AU/mL), but half-life was similar (26.5 (6.9-46.1) vs. 38.3 (8.2-68.5) d). CONCLUSIONS: One year after the start of COVID-19 pandemic the actual prevalence of infection is still underestimated compared with PCR-confirmed COVID-19 cases. Older compared with younger individuals have lower anti-S-RBD IgG level after vaccination, but similar decline rate.

12-month prevalence of atopic dermatitis in resource-rich countries: a systematic review and meta-analysis.

There is a lack of robust prevalence estimates of atopic dermatitis (AD) globally and trends over time due to wide variation of populations and age groups studied, different study methodologies and case definitions used. We sought to characterize 12-month AD prevalence across the life span and change over time in resource-rich countries focusing on population-based studies and using a standardized AD case definition. This systematic review was conducted according to PRISMA guidelines. Medline (Ovid), Embase, WOS core collection, Cinahl, and Popline were searched for studies published since inception through August 15, 2016. Studies were synthesized using random effects meta-analysis. Sources of heterogeneity were investigated using subgroup analyses and meta-regression. From 12,530 records identified, 45 studies met the inclusion criteria. Meta-analysis with random effects revealed the 12-month period prevalence of 9.2% (95% confidence interval 8.4-10.1%). The prevalence was significantly higher among 0-5-year-old children (16.2%; 95% confidence interval 14.2-18.7%) than in older age groups. Studies using a random sampling strategy yielded lower prevalence estimates than studies relying on other sampling methods. There was no clear time trend in AD prevalence over the period of 1992-2013.

Rotavirus Strain Surveillance in Estonia After Introduction of Rotavirus Universal Mass Vaccination.

BACKGROUND: Estonia implemented the rotavirus (RV) vaccine into its national immunization program in July 2014. We aimed to determine circulating RV genotypes and the clinical profile by genotypes from February 1, 2015, to August 30, 2016, among children 0-18 years hospitalized due to rotavirus gastroenteritis (RVGE). METHODS: During an observational study in 7 Estonian hospitals, we determined the RV genotypes in stool samples of RVGE patients who met predetermined criteria. Shannon's diversity index (H´) and Simpson's index (D) was used to evaluate genotype diversity by season and age and to compare prevaccine period data (2007-2008) for children 0-4 years of age (n = 77) to corresponding data from the postvaccine period (2015-2016, n = 346). The Vesikari Clinical Severity Scoring System was used for clinical profile evaluation. RESULTS: Stool samples of 479 RVGE patients were genotyped. Seventy-seven percent of RVGE infections were caused by G4P[8] (n = 150, 31%), G1P[8] (n = 100, 21%), G9P[8] (n = 79, 16%), G2P[4] (n = 23, 5%), G4P[4] (n = 17, 4%). The prevailing genotypes varied seasonally. Diversity increased during the postvaccine period among age groups 0-4: H´1.42 (95% CI: 1.2-1.7) in the prevaccine era versus 1.8 (95% CI: 1.7-2) in the postvaccine era (P = 0.008), and D 0.6 (95% CI: 0.5-0.7) versus 0.78 (0.75-0.80) (P = 0.01), respectively. The off-season period presented higher diversity compared with in-seasons. G2P[8], G1P[8], G4P[4], G9P[8], and G8P[8] presented with a different clinical profile compared with others. CONCLUSION: Since the introduction of universal mass vaccination in Estonia, the circulating RV genotypes have changed compared with those reported in the prevaccine era. Our study adds to knowledge about RV genotype distribution in Europe and expected dynamics after RV universal mass vaccination and provides insight on the clinical profile of prevailing genotypes.

Long-Term Elevated Inflammatory Protein Levels in Asymptomatic SARS-CoV-2 Infected Individuals.

The clinical features of SARS-CoV-2 infection range from asymptomatic to severe disease with life-threatening complications. Understanding the persistence of immune responses in asymptomatic individuals merit special attention because of their importance in controlling the spread of the infections. We here studied the antibody and T cell responses, and a wide range of inflammation markers, in 56 SARS-CoV-2 antibody-positive individuals, identified by a population screen after the first wave of SARS-CoV-2 infection. These, mostly asymptomatic individuals, were reanalyzed 7-8 months after their infection together with 115 age-matched seronegative controls. We found that 7-8 months after the infection their antibodies to SARS-CoV-2 Nucleocapsid (N) protein declined whereas we found no decrease in the antibodies to Spike receptor-binding domain (S-RBD) when compared to the findings at seropositivity identification. In contrast to antibodies to N protein, the antibodies to S-RBD correlated with the viral neutralization capacity and with CD4+ T cell responses as measured by antigen-specific upregulation of CD137 and CD69 markers. Unexpectedly we found the asymptomatic antibody-positive individuals to have increased serum levels of S100A12, TGF-alpha, IL18, and OSM, the markers of activated macrophages-monocytes, suggesting long-term persistent inflammatory effect associated with the viral infection in asymptomatic individuals. Our results support the evidence for the long-term persistence of the inflammation process and the need for post-infection clinical monitoring of SARS-CoV-2 infected asymptomatic individuals.

Prevalence of SARS-CoV-2 IgG antibodies and their association with clinical symptoms of COVID-19 in Estonia (KoroSero-EST-1 study).

PURPOSE: In Estonia, during the first wave of COVID-19 total number of cases confirmed by PCR was 13.3/10,000, similar in most regions, including capital Tallinn, but in the hotspot of Estonian epidemic, an island Saaremaa, the cumulative incidence was 166.1/10,000. We aimed to determine the prevalence of SARS-CoV-2 IgG antibodies in these two regions, symptoms associated with infection and factors associated with antibody concentrations. METHODS: Participants were selected using stratified (formed by age decades) random sampling and recruited by general practitioners. IgG or neutralizing antibodies were determined from sera by four assays. Symptoms associated with seropositivity were analyzed by multiple correspondence analysis, antibody concentrations by multiple linear regression. RESULTS: Total of 3608 individual were invited and 1960 recruited from May 8 to July 31, 2020. Seroprevalence was 1.5% (95% confidence interval (CI) 0.9-2.5) and 6.3% (95% CI 5.0-7.9), infection fatality rate 0.1% (95% CI 0.0-0.2) and 1.3% (95% CI 0.4-2.1) in Tallinn and Saaremaa, respectively. Of seropositive subjects 19.2% (14/73) had acute respiratory illness. Fever, diarrhea and the absence of cough and runny nose were associated with seropositivity in individuals aged 50 or more years. IgG, but not neutralizing antibodies concentrations were higher if fever, difficulty breathing, shortness of breath, chest pain or diarrhea was present, or hospitalization required. CONCLUSION: Similarly to other European countries the seroprevalence of SARS-CoV-2 in Estonia was low even in the hotspot region Saaremaa suggesting that majority of population is susceptible to SARS-CoV-2. Focusing only on respiratory symptoms may delay accurate diagnosis of SARS-CoV-2 infection.

Characteristics of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Contact to Animals in Estonia.

We have attempted to define the prevalence and risk factors of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-Enterobacteriaceae) carriage, and to characterize antimicrobial susceptibility, beta-lactamase genes, and major types of isolated strains in volunteers, with a specific focus on humans in contact with animals. Samples were collected from 207 volunteers (veterinarians, pig farmers, dog owners, etc.) and cultured on selective agar. Clonal relationships of the isolated ESBL-Enterobacteriaceae were determined by whole genome sequencing and multi-locus sequence typing. Beta-lactamases were detected using a homology search. Subjects filled in questionnaires analyzed by univariate and multiple logistic regression. Colonization with ESBL-Enterobacteriaceae was found in fecal samples of 14 individuals (6.8%; 95%CI: 3.75-11.09%). In multiple regression analysis, working as a pig farmer was a significant risk factor for ESBL-Enterobacteriaceae carriage (OR 4.8; 95%CI 1.2-19.1). The only species isolated was Escherichia coli that distributed into 11 sequence types. All ESBL-Enterobacteriaceae isolates were of CTX-M genotype, with the blaCTX-M-1 being the most prevalent and more common in pig farmers than in other groups. Despite the generally low prevalence of ESBL-Enterobacteriaceae in Estonia, the pig farmers may still pose a threat to transfer resistant microorganisms. The clinical relevance of predominant blaCTX-M-1 carrying E. coli is still unclear and needs further studies.

Dynamics of pertussis toxin IgG after symptomatic pertussis in children and adults.

BACKGROUND AND AIM: The knowledge of dynamics of pertussis toxin (PT)-IgG after pertussis and the appropriate diagnostic cut-off value is limited. We aimed to describe the dynamics of PT-IgG in children and adults up to three years after symptomatic pertussis. METHODS: Patients with persistent cough of unknown aetiology were prospectively enrolled 2012-2014. Pertussis was confirmed by culture, PCR and/or serology. The follow-up samples were taken 4-6 weeks, 1, 2 and 3 years after enrolment. PT-IgG kinetics was described by biexponential model. RESULTS: Pertussis was diagnosed in 22 patients [median (IQR) age 17.7 (8.4-38.6) years]. Adults compared with children had higher peak of the PT-IgG 397 (IQR 374-518) vs 292 (200-363), p = 0.007, longer time to reach peak PT-IgG 16.4 (IQR 15.6-16.8) days vs 13.3 (13.2-13.4) days, p=<0.001 and shorter PT-IgG half-life 24 days (IQR 20-40) and 364 days (IQR 359-486) p < 0.001. CONCLUSION: After symptomatic pertussis, adults and children have different dynamics of PT-IgG. Clinical trial registry: Not applicable.