BackgroundIn Estonia, during the first wave of COVID-19 total number of cases confirmed by PCR wa... more BackgroundIn 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.AimWe 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.MethodsParticipants were selected using stratified (formed by age decades) random sampling and recruited by general practitioners. IgG were determined from sera by four assays. Symptoms of acute respiratory illness associated with seropositivity were analyzed by multiple correspondence analysis, antibody concentrations by multiple linear regression.ResultsTotal 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...
Background: Estonia implemented the rotavirus (RV) vaccine into its national immunization program... more 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...
The clinical features of SARS-CoV-2 infection range from asymptomatic to severe disease with life... more 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 correlat...
Background: In a country-wide seroprevalence study of COVID-19 in Estonia, we aimed to determine ... more 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 increasedecrease 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 ¼ 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.
Background: Children with cancer and infection may develop glomerular hyperfiltration. With the a... more Background: Children with cancer and infection may develop glomerular hyperfiltration. With the aim to determine the prevalence of glomerular hyperfiltration in children and young adults with haemato‐oncological disease and infection, we developed population pharmacokinetic model of iohexol. We further aimed to assess the accuracy of estimated glomerular filtration rate (eGFR) equations and single‐ or two‐point measured GFR (mGFR) formulas compared with GFR based on iohexol clearance from our population pharmacokinetic model (iGFR).Procedure: Hospitalised patients (0.5–25 years) with haemato‐oncological disease and infection were included if their eGFR was ≥80 ml/min/1.73 m2at the screening visit. Iohexol plasma concentrations were described by population pharmacokinetic model. Bias, precision and accuracy of 23 eGFR equations and 18 mGFR formulas were calculated.Results: Total of 32 iohexol administrations were performed in 28 patients. Median (range) eGFR was 136 ml/min/1.73 m2 (7...
PurposeIn a country-wide seroprevalence study of COVID-19 in Estonia we aimed to determine the se... more PurposeIn 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.MethodsLeftover blood samples were selected between February 8 to March 25, 2021, by SYNLAB Estonia from all counties and age groups (0-9, 10-19, 20-59, 60-69, 70-79, 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 nonlinear model.ResultsA total of 2517 samples were tested. Overall seroprevalence (95% CI) was 20.1% (18.5-21.7%), similar in all age groups. If all individuals vaccinated with the first dose at least 14 days before antibody measurement were assumed to be seronegative, the overall seroprevalence was 15.8% (14.4-17.3%), 4-fold larger than the proportion of confirm...
Background and aim: The knowledge of dynamics of pertussis toxin (PT)-IgG after pertussis and the... more Background and aim: The knowledge of dynamics of pertussis toxin (PT)-IgG after pertussis and the appropriate diagnostic cutoff 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.
Läkaköha täpne ja õigeaegne diagnoosimine on ka praegu väljakutse igale arstile, sest läkaköhavas... more Läkaköha täpne ja õigeaegne diagnoosimine on ka praegu väljakutse igale arstile, sest läkaköhavastane vaktsineerimine on oluliselt muutnud läkaköha epidemioloogiat ja sümptomatoloogiat. Seetõttu võib läkaköha teismelistel, täiskasvanutel ja vaktsineeritud lastel kulgeda ebatüüpiliselt vaid 1-2 nädalat kestva köhana. Seega peaks läkaköha diagnoos põhinema alati laboratoorsetel uuringutel. Bordetella pertussis'e isoleerimine ninaneelu materjali külvil ja/või PCRil (polümeraasahelreaktsioon) on väga tundlikud meetodid haiguse varases staadiumis. Seroloogilised meetodid sobivad enam läkaköha hiliseks diagnoosimiseks.
A unified surveillance mechanism for hand hygiene and hospital-acquired infections for pediatric ... more A unified surveillance mechanism for hand hygiene and hospital-acquired infections for pediatric wards is lacking in Europe. We managed to setup such a mechanism in 9 pediatric intensive care units in 7 European countries, using World Health Organization’s definitions and common methodology which allows for benchmarking among units and countries. Median hand hygiene compliance was found high 82.3% (interquartile range 71.6–94.5%), but gaps in practices were identified.
Vaccines against human papillomavirus (HPV), the primary causative agent in cervical cancer, are ... more Vaccines against human papillomavirus (HPV), the primary causative agent in cervical cancer, are licensed. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on the introduction of HPV vaccines in central Europe. Eight countries currently have medical representatives on CEVAG: the Czech Republic, Estonia, Hungary, Lithuania, Poland, Romania, Slovakia and Turkey. By raising awareness and disseminating information, CEVAG aims to promote the efficient and safe use of vaccines to prevent, control and if possible eliminate infectious diseases. In January 2008, the European Centre for Disease Prevention and Control published a report entitled Guidance for the Introduction of HPV Vaccines in EU Countries. Members of CEVAG have taken the information relevant to their countries from this report and, with consideration of local issues, produced these guidance recommendations for the introduction of HPV vaccines in the CEVAG region, which may be adapted for use in individual countries.
PURPOSE Estimated glomerular filtration rate (eGFR) equations reflect kidney function imprecisely... more PURPOSE Estimated glomerular filtration rate (eGFR) equations reflect kidney function imprecisely. We aimed to describe whether iohexol-based GFR or eGFRs predict clearance of cefepime, piperacillin, and tazobactam in pharmacokinetic (PK) models in this population and its clinical significance. METHODS Hospitalized patients (0.5-25 years) with haemato-oncological disease and infection receiving cefepime or piperacillin/tazobactam were included. PK samples were collected at a steady state concomitantly with samples for iohexol-based GFR. PK models were developed in NONMEM. Weight, postmenstrual age, iohexol-based GFR, different eGFR equations (Schwartz updated, Lund-Malmö revised, CKD-EPI, Bouvet, Schwartz cystatin C-based) were tested as covariates. Probabilities of neurotoxic/therapeutic concentrations were assessed by simulations. RESULTS Fifteen patients receiving cefepime and 17 piperacillin/tazobactam were included (median (range) age 16.2 (1.9-26.0) and 10.5 (0.8-25.6) years, iohexol-based GFR 102 (68-140) and 116 (74-137) mL/min/1.73 m2, respectively). Two-compartment model provided the best fit for all drugs. Weight was covariate for central and peripheral compartment, clearance and intercompartmental clearance (only tazobactam), and postmenstrual age for clearance (excluding cefepime). Iohexol-based GFR was the best predictor of clearance. The model of cefepime without vs with iohexol-based GFR underestimated the probability of neurotoxic concentrations (28.3-28.6% vs 52.1-69.3%) and overestimated the probability of therapeutic concentrations (> 90% vs 81.9-87.1%) in the case of iohexol-based GFR 70-80 and 130-140 mL/min/1.73 m2, respectively. CONCLUSION Iohexol-based GFR can predict better than eGFRs the clearance of cefepime, piperacillin, and tazobactam in children and young adults with haemato-oncological disease and infection, warranting further investigation as an indicator of renal function to improve targeting of therapeutic window. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION EudraCT 2015-000,631-32, EudraCT 2016-003,374-40 (24.10.2016).
Estonia had the highest rate of newly diagnosed human immunodeficiency virus (HIV) cases in the E... more Estonia had the highest rate of newly diagnosed human immunodeficiency virus (HIV) cases in the European Union (24.6/100,000) and an estimated adult HIV prevalence of 1.3% in 2013. HIV medical care, including antiretroviral therapy (ART), is free of charge for people living with HIV (PLHIV). To maximise the health benefits of HIV treatment, universal access should be achieved. Using data from surveillance and administrative databases and the treatment cascade model, we assessed the number of people infected with HIV, diagnosed with HIV, linked to HIV care, retained in HIV care, on ART, and with suppressed viral load (HIV-RNA: < 200 copies/mL). We identified that about one quarter of the 8,628 HIV-positive people estimated to live in Estonia in 2013 had not been diagnosed with HIV, and another quarter, although aware of their HIV-positive serostatus, had not accessed HIV medical care. Although altogether only 12–15% of all PLHIV in Estonia had achieved viral suppression, the main ...
BACKGROUND Estonia implemented rotavirus universal mass vaccination (RV UMV) in July 2014. We aim... more BACKGROUND Estonia implemented rotavirus universal mass vaccination (RV UMV) in July 2014. We aimed to describe changes in acute gastroenteritis (AGE) hospitalization during RV seasons before (2007-2013) and after (2015-2018) RV UMV and compare patient profile of hospitalized AGE patients aged 0-18 years during first two consecutive RV seasons 2015 vs 2016. METHODS We described AGE hospitalization patterns pre-and post-vaccine era using Estonian Health Insurance Fund (HIF) database. During a two-year observational multicenter study in seven Estonian hospitals from 01st of February 2015 to 30th August 2016 we assessed patient profile of all patients who met pre-determined AGE criteria. RESULTS In post-vaccine era AGE hospitalization rate decreased from 10 to 8 per 1000 population (RR 0.81, 95% CI 0.79-0.83) compared to pre-vaccine era. Decreased RV seasonal activity, 81% (95% CI 77-84) and 55% (95% CI 52-58) reduction of rotavirus gastroenteritis (RVGE) hospitalization among age groups <1 and 1-4, respectively and upsurge of norovirus gastroenteritis (NoVGE) hospitalizations (RR = 1.8; 95% CI 1.6-1.9) was seen. In the multicenter observational study, among 2249 AGE patients hospitalized median age of RVGE patients increased from 2 to 3 years (p < 0.01) and duration of hospital stay decreased among RVGE, NoVGE and other GE patients during two consecutive RV seasons. According to Vesikari Clinical Severity Scoring System statistically significant change of severity score distribution in two RV seasons was seen (p < 0.001) with trend towards less severe AGE hospitalizations; 82.5% vs 70.5% severe cases in 2015 vs 2016, respectively. CONCLUSION RV UMV lead to immediate and sustainable reduction of hospitalizations due to RVGE in children aged <4 years and reduction of overall AGE accompanied with the decrease in the severity of hospitalized children.
Background Estonia has a typical Eastern European HIV epidemic where the most frequent co-infecti... more 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 31 st of December 2015. We compared two time periods-first, 1 st of January 2000-31 st of December 2008 when HIV epidemic was mostly spreading among people who inject drugs (PWID) and second, 1 st of January 2009 to 31 st of December 2015 when HIV started to emerge to 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. 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 coinfected 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. Considering the absence of detail description and dynamic data of HIV/HCV co-infection in an Eastern European HIV epidemic, we aimed to describe the change in HCV prevalence along with the distribution of HCV GTs, and HCV treatment in Estonian people living with HIV (PLWH) over the years to evaluate the HCV epidemic in Estonian HIV infected subjects representing Eastern European PLWH. Methods Study design This was a cross-sectional study. The data was collected using Estonian HIV Cohort Study (E-HIV)
ABSTRACTBackgroundHospitalized neonates receive the highest number of drugs compared to all other... more ABSTRACTBackgroundHospitalized neonates receive the highest number of drugs compared to all other age groups, but consumption rates vary between studies depending on patient characteristics and local practices. There are no large scale international studies on drug use in neonatal units. We aimed to describe drug use in European neonatal units and characterize its associations with geographic region and gestational age (GA).MethodsA one-day point prevalence study (PPS) was performed as part of the European Study of Neonatal Exposure to Excipients (ESNEE) from January to June 2012. All neonatal prescriptions and demographic data were registered in a web-based database. The impact of GA and region on prescription rate were analyzed with logistic regression.ResultsIn total, 21 European countries with 89 neonatal units participated. Altogether 2173 prescriptions given to 726 neonates were registered. The 10 drugs with the highest prescription rate were multivitamins, vitamin D, caffeine...
Too eesmargiks oli vorrelda ampitsilliini-gentamutsiini vs penitsilliinigentamutsiini kombinatsio... more Too eesmargiks oli vorrelda ampitsilliini-gentamutsiini vs penitsilliinigentamutsiini kombinatsioonide kliinilist efektiivsust vastsundinute varase sepsise (VVS) ravis. Kahekeskuseline prospektiivne klastriga juhuslikustatud uuring holmas koik VVS-kahtlusega alla 72 tunni vanused vastsundinud. Esimesel uuringuperioodil kasutati uhes keskuses ampitsilliini ja teises penitsilliini kombinatsioonis gentamutsiiniga. Beetalaktaamantibiootikumid vahetati, kui pooled haiged olid uuringusse lulitatud. Primaarne tulem oli ravi ebaonnestumine (vajadus antibakteriaalse ravi muutmiseks 72 tunni jooksul) ja/voi surm 7 paeva jooksul. Soole kolonisatsiooni hinnati perineumi kaape alusel. Toestatud VVSi sagedus oli 4,9%. Ampitsilliini ja penitsilliini skeemide vahel ei olnud erinevust 72 tunni jooksul antibakteriaalse ravi vahetuse, 7 paeva suremuse ega ravi ebaonnestumise osas. Ampitsilliin ja penitsilliin kombinatsioonis gentamutsiiniga on vordselt tohusad vastsundinu varase sepsise empiirilises r...
<p>On the basis of the linkage disequilibrium patterns between the polymorphisms in the cod... more <p>On the basis of the linkage disequilibrium patterns between the polymorphisms in the coding (Δ32) and noncoding (promoter) region of <i>CCR5</i> and the coding polymorphism (V64I) in <i>CCR2</i>, we previously used an evolutionary-based strategy to generate the <i>CCR5</i> human haplogroups (HH) shown below the CCR5 gene structure. These <i>CCR5</i> HH are designated as HHA to HHG*2, with HHF*2 and HHG*2 denoting the haplotypes that bear the CCR2–64I and CCR5-Δ32 polymorphisms, respectively. Because of its similarity to the chimpanzee <i>CCR5</i> sequence, the human <i>CCR5</i> HHA haplotype is classified as the ancestral CCR5 haplotype <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070561#pone.0070561-Mummidi1" target="_blank">[28]</a>. Nucleotide variations relative to the ancestral sequence are shown. The <i>CCR5</i> numbering systems used in the literature are shown. Top numbering is based on GenBank accession numbers AF031236 and AF031237; middle numbering is based on GenBank accession number U95626; bottom numbering is the numbering system in which the first nucleotide of the <i>CCR5</i> translational start site is designated as+1 and the nucleotide immediately upstream as -1 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070561#pone.0070561-Mummidi1" target="_blank">[28]</a>. ORF, open-reading frame; Wt, wild-type; Δ32, 32-basepair deletion.</p
The mortality of central nervous system (CNS) aspergillosis approaches 100%, re-quiring improved ... more The mortality of central nervous system (CNS) aspergillosis approaches 100%, re-quiring improved therapies. Voriconazole gives superior efficacy and survival in invasive aspergillosis, compared with am-photericin B. Also, in contrast to other antifungal drugs, voriconazole penetrates well into the CNS. We evaluated, retro-spectively, the outcome and survival of 81 patients who were treated with voricon-azole for definite (n 48) or probable (n 33) CNS aspergillosis. Complete and partial responses were recorded in 35% of patients and varied by the underlying disease group: hematologic malignancies (54%), other underlying conditions (50%), chronic immunosuppression (45%), solid organ transplantation (36%), and hemato-poietic stem cell transplantation (16%). Thirty-one percent of patients survived CNS aspergillosis for a median observa-tion time of 390 days. There were 31 patients who underwent neurosurgical procedures, including craniotomy/ab-scess resection (n 14), abscess drain-age (...
BackgroundIn Estonia, during the first wave of COVID-19 total number of cases confirmed by PCR wa... more BackgroundIn 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.AimWe 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.MethodsParticipants were selected using stratified (formed by age decades) random sampling and recruited by general practitioners. IgG were determined from sera by four assays. Symptoms of acute respiratory illness associated with seropositivity were analyzed by multiple correspondence analysis, antibody concentrations by multiple linear regression.ResultsTotal 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...
Background: Estonia implemented the rotavirus (RV) vaccine into its national immunization program... more 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...
The clinical features of SARS-CoV-2 infection range from asymptomatic to severe disease with life... more 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 correlat...
Background: In a country-wide seroprevalence study of COVID-19 in Estonia, we aimed to determine ... more 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 increasedecrease 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 ¼ 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.
Background: Children with cancer and infection may develop glomerular hyperfiltration. With the a... more Background: Children with cancer and infection may develop glomerular hyperfiltration. With the aim to determine the prevalence of glomerular hyperfiltration in children and young adults with haemato‐oncological disease and infection, we developed population pharmacokinetic model of iohexol. We further aimed to assess the accuracy of estimated glomerular filtration rate (eGFR) equations and single‐ or two‐point measured GFR (mGFR) formulas compared with GFR based on iohexol clearance from our population pharmacokinetic model (iGFR).Procedure: Hospitalised patients (0.5–25 years) with haemato‐oncological disease and infection were included if their eGFR was ≥80 ml/min/1.73 m2at the screening visit. Iohexol plasma concentrations were described by population pharmacokinetic model. Bias, precision and accuracy of 23 eGFR equations and 18 mGFR formulas were calculated.Results: Total of 32 iohexol administrations were performed in 28 patients. Median (range) eGFR was 136 ml/min/1.73 m2 (7...
PurposeIn a country-wide seroprevalence study of COVID-19 in Estonia we aimed to determine the se... more PurposeIn 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.MethodsLeftover blood samples were selected between February 8 to March 25, 2021, by SYNLAB Estonia from all counties and age groups (0-9, 10-19, 20-59, 60-69, 70-79, 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 nonlinear model.ResultsA total of 2517 samples were tested. Overall seroprevalence (95% CI) was 20.1% (18.5-21.7%), similar in all age groups. If all individuals vaccinated with the first dose at least 14 days before antibody measurement were assumed to be seronegative, the overall seroprevalence was 15.8% (14.4-17.3%), 4-fold larger than the proportion of confirm...
Background and aim: The knowledge of dynamics of pertussis toxin (PT)-IgG after pertussis and the... more Background and aim: The knowledge of dynamics of pertussis toxin (PT)-IgG after pertussis and the appropriate diagnostic cutoff 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.
Läkaköha täpne ja õigeaegne diagnoosimine on ka praegu väljakutse igale arstile, sest läkaköhavas... more Läkaköha täpne ja õigeaegne diagnoosimine on ka praegu väljakutse igale arstile, sest läkaköhavastane vaktsineerimine on oluliselt muutnud läkaköha epidemioloogiat ja sümptomatoloogiat. Seetõttu võib läkaköha teismelistel, täiskasvanutel ja vaktsineeritud lastel kulgeda ebatüüpiliselt vaid 1-2 nädalat kestva köhana. Seega peaks läkaköha diagnoos põhinema alati laboratoorsetel uuringutel. Bordetella pertussis'e isoleerimine ninaneelu materjali külvil ja/või PCRil (polümeraasahelreaktsioon) on väga tundlikud meetodid haiguse varases staadiumis. Seroloogilised meetodid sobivad enam läkaköha hiliseks diagnoosimiseks.
A unified surveillance mechanism for hand hygiene and hospital-acquired infections for pediatric ... more A unified surveillance mechanism for hand hygiene and hospital-acquired infections for pediatric wards is lacking in Europe. We managed to setup such a mechanism in 9 pediatric intensive care units in 7 European countries, using World Health Organization’s definitions and common methodology which allows for benchmarking among units and countries. Median hand hygiene compliance was found high 82.3% (interquartile range 71.6–94.5%), but gaps in practices were identified.
Vaccines against human papillomavirus (HPV), the primary causative agent in cervical cancer, are ... more Vaccines against human papillomavirus (HPV), the primary causative agent in cervical cancer, are licensed. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on the introduction of HPV vaccines in central Europe. Eight countries currently have medical representatives on CEVAG: the Czech Republic, Estonia, Hungary, Lithuania, Poland, Romania, Slovakia and Turkey. By raising awareness and disseminating information, CEVAG aims to promote the efficient and safe use of vaccines to prevent, control and if possible eliminate infectious diseases. In January 2008, the European Centre for Disease Prevention and Control published a report entitled Guidance for the Introduction of HPV Vaccines in EU Countries. Members of CEVAG have taken the information relevant to their countries from this report and, with consideration of local issues, produced these guidance recommendations for the introduction of HPV vaccines in the CEVAG region, which may be adapted for use in individual countries.
PURPOSE Estimated glomerular filtration rate (eGFR) equations reflect kidney function imprecisely... more PURPOSE Estimated glomerular filtration rate (eGFR) equations reflect kidney function imprecisely. We aimed to describe whether iohexol-based GFR or eGFRs predict clearance of cefepime, piperacillin, and tazobactam in pharmacokinetic (PK) models in this population and its clinical significance. METHODS Hospitalized patients (0.5-25 years) with haemato-oncological disease and infection receiving cefepime or piperacillin/tazobactam were included. PK samples were collected at a steady state concomitantly with samples for iohexol-based GFR. PK models were developed in NONMEM. Weight, postmenstrual age, iohexol-based GFR, different eGFR equations (Schwartz updated, Lund-Malmö revised, CKD-EPI, Bouvet, Schwartz cystatin C-based) were tested as covariates. Probabilities of neurotoxic/therapeutic concentrations were assessed by simulations. RESULTS Fifteen patients receiving cefepime and 17 piperacillin/tazobactam were included (median (range) age 16.2 (1.9-26.0) and 10.5 (0.8-25.6) years, iohexol-based GFR 102 (68-140) and 116 (74-137) mL/min/1.73 m2, respectively). Two-compartment model provided the best fit for all drugs. Weight was covariate for central and peripheral compartment, clearance and intercompartmental clearance (only tazobactam), and postmenstrual age for clearance (excluding cefepime). Iohexol-based GFR was the best predictor of clearance. The model of cefepime without vs with iohexol-based GFR underestimated the probability of neurotoxic concentrations (28.3-28.6% vs 52.1-69.3%) and overestimated the probability of therapeutic concentrations (> 90% vs 81.9-87.1%) in the case of iohexol-based GFR 70-80 and 130-140 mL/min/1.73 m2, respectively. CONCLUSION Iohexol-based GFR can predict better than eGFRs the clearance of cefepime, piperacillin, and tazobactam in children and young adults with haemato-oncological disease and infection, warranting further investigation as an indicator of renal function to improve targeting of therapeutic window. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION EudraCT 2015-000,631-32, EudraCT 2016-003,374-40 (24.10.2016).
Estonia had the highest rate of newly diagnosed human immunodeficiency virus (HIV) cases in the E... more Estonia had the highest rate of newly diagnosed human immunodeficiency virus (HIV) cases in the European Union (24.6/100,000) and an estimated adult HIV prevalence of 1.3% in 2013. HIV medical care, including antiretroviral therapy (ART), is free of charge for people living with HIV (PLHIV). To maximise the health benefits of HIV treatment, universal access should be achieved. Using data from surveillance and administrative databases and the treatment cascade model, we assessed the number of people infected with HIV, diagnosed with HIV, linked to HIV care, retained in HIV care, on ART, and with suppressed viral load (HIV-RNA: < 200 copies/mL). We identified that about one quarter of the 8,628 HIV-positive people estimated to live in Estonia in 2013 had not been diagnosed with HIV, and another quarter, although aware of their HIV-positive serostatus, had not accessed HIV medical care. Although altogether only 12–15% of all PLHIV in Estonia had achieved viral suppression, the main ...
BACKGROUND Estonia implemented rotavirus universal mass vaccination (RV UMV) in July 2014. We aim... more BACKGROUND Estonia implemented rotavirus universal mass vaccination (RV UMV) in July 2014. We aimed to describe changes in acute gastroenteritis (AGE) hospitalization during RV seasons before (2007-2013) and after (2015-2018) RV UMV and compare patient profile of hospitalized AGE patients aged 0-18 years during first two consecutive RV seasons 2015 vs 2016. METHODS We described AGE hospitalization patterns pre-and post-vaccine era using Estonian Health Insurance Fund (HIF) database. During a two-year observational multicenter study in seven Estonian hospitals from 01st of February 2015 to 30th August 2016 we assessed patient profile of all patients who met pre-determined AGE criteria. RESULTS In post-vaccine era AGE hospitalization rate decreased from 10 to 8 per 1000 population (RR 0.81, 95% CI 0.79-0.83) compared to pre-vaccine era. Decreased RV seasonal activity, 81% (95% CI 77-84) and 55% (95% CI 52-58) reduction of rotavirus gastroenteritis (RVGE) hospitalization among age groups <1 and 1-4, respectively and upsurge of norovirus gastroenteritis (NoVGE) hospitalizations (RR = 1.8; 95% CI 1.6-1.9) was seen. In the multicenter observational study, among 2249 AGE patients hospitalized median age of RVGE patients increased from 2 to 3 years (p < 0.01) and duration of hospital stay decreased among RVGE, NoVGE and other GE patients during two consecutive RV seasons. According to Vesikari Clinical Severity Scoring System statistically significant change of severity score distribution in two RV seasons was seen (p < 0.001) with trend towards less severe AGE hospitalizations; 82.5% vs 70.5% severe cases in 2015 vs 2016, respectively. CONCLUSION RV UMV lead to immediate and sustainable reduction of hospitalizations due to RVGE in children aged <4 years and reduction of overall AGE accompanied with the decrease in the severity of hospitalized children.
Background Estonia has a typical Eastern European HIV epidemic where the most frequent co-infecti... more 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 31 st of December 2015. We compared two time periods-first, 1 st of January 2000-31 st of December 2008 when HIV epidemic was mostly spreading among people who inject drugs (PWID) and second, 1 st of January 2009 to 31 st of December 2015 when HIV started to emerge to 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. 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 coinfected 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. Considering the absence of detail description and dynamic data of HIV/HCV co-infection in an Eastern European HIV epidemic, we aimed to describe the change in HCV prevalence along with the distribution of HCV GTs, and HCV treatment in Estonian people living with HIV (PLWH) over the years to evaluate the HCV epidemic in Estonian HIV infected subjects representing Eastern European PLWH. Methods Study design This was a cross-sectional study. The data was collected using Estonian HIV Cohort Study (E-HIV)
ABSTRACTBackgroundHospitalized neonates receive the highest number of drugs compared to all other... more ABSTRACTBackgroundHospitalized neonates receive the highest number of drugs compared to all other age groups, but consumption rates vary between studies depending on patient characteristics and local practices. There are no large scale international studies on drug use in neonatal units. We aimed to describe drug use in European neonatal units and characterize its associations with geographic region and gestational age (GA).MethodsA one-day point prevalence study (PPS) was performed as part of the European Study of Neonatal Exposure to Excipients (ESNEE) from January to June 2012. All neonatal prescriptions and demographic data were registered in a web-based database. The impact of GA and region on prescription rate were analyzed with logistic regression.ResultsIn total, 21 European countries with 89 neonatal units participated. Altogether 2173 prescriptions given to 726 neonates were registered. The 10 drugs with the highest prescription rate were multivitamins, vitamin D, caffeine...
Too eesmargiks oli vorrelda ampitsilliini-gentamutsiini vs penitsilliinigentamutsiini kombinatsio... more Too eesmargiks oli vorrelda ampitsilliini-gentamutsiini vs penitsilliinigentamutsiini kombinatsioonide kliinilist efektiivsust vastsundinute varase sepsise (VVS) ravis. Kahekeskuseline prospektiivne klastriga juhuslikustatud uuring holmas koik VVS-kahtlusega alla 72 tunni vanused vastsundinud. Esimesel uuringuperioodil kasutati uhes keskuses ampitsilliini ja teises penitsilliini kombinatsioonis gentamutsiiniga. Beetalaktaamantibiootikumid vahetati, kui pooled haiged olid uuringusse lulitatud. Primaarne tulem oli ravi ebaonnestumine (vajadus antibakteriaalse ravi muutmiseks 72 tunni jooksul) ja/voi surm 7 paeva jooksul. Soole kolonisatsiooni hinnati perineumi kaape alusel. Toestatud VVSi sagedus oli 4,9%. Ampitsilliini ja penitsilliini skeemide vahel ei olnud erinevust 72 tunni jooksul antibakteriaalse ravi vahetuse, 7 paeva suremuse ega ravi ebaonnestumise osas. Ampitsilliin ja penitsilliin kombinatsioonis gentamutsiiniga on vordselt tohusad vastsundinu varase sepsise empiirilises r...
<p>On the basis of the linkage disequilibrium patterns between the polymorphisms in the cod... more <p>On the basis of the linkage disequilibrium patterns between the polymorphisms in the coding (Δ32) and noncoding (promoter) region of <i>CCR5</i> and the coding polymorphism (V64I) in <i>CCR2</i>, we previously used an evolutionary-based strategy to generate the <i>CCR5</i> human haplogroups (HH) shown below the CCR5 gene structure. These <i>CCR5</i> HH are designated as HHA to HHG*2, with HHF*2 and HHG*2 denoting the haplotypes that bear the CCR2–64I and CCR5-Δ32 polymorphisms, respectively. Because of its similarity to the chimpanzee <i>CCR5</i> sequence, the human <i>CCR5</i> HHA haplotype is classified as the ancestral CCR5 haplotype <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070561#pone.0070561-Mummidi1" target="_blank">[28]</a>. Nucleotide variations relative to the ancestral sequence are shown. The <i>CCR5</i> numbering systems used in the literature are shown. Top numbering is based on GenBank accession numbers AF031236 and AF031237; middle numbering is based on GenBank accession number U95626; bottom numbering is the numbering system in which the first nucleotide of the <i>CCR5</i> translational start site is designated as+1 and the nucleotide immediately upstream as -1 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070561#pone.0070561-Mummidi1" target="_blank">[28]</a>. ORF, open-reading frame; Wt, wild-type; Δ32, 32-basepair deletion.</p
The mortality of central nervous system (CNS) aspergillosis approaches 100%, re-quiring improved ... more The mortality of central nervous system (CNS) aspergillosis approaches 100%, re-quiring improved therapies. Voriconazole gives superior efficacy and survival in invasive aspergillosis, compared with am-photericin B. Also, in contrast to other antifungal drugs, voriconazole penetrates well into the CNS. We evaluated, retro-spectively, the outcome and survival of 81 patients who were treated with voricon-azole for definite (n 48) or probable (n 33) CNS aspergillosis. Complete and partial responses were recorded in 35% of patients and varied by the underlying disease group: hematologic malignancies (54%), other underlying conditions (50%), chronic immunosuppression (45%), solid organ transplantation (36%), and hemato-poietic stem cell transplantation (16%). Thirty-one percent of patients survived CNS aspergillosis for a median observa-tion time of 390 days. There were 31 patients who underwent neurosurgical procedures, including craniotomy/ab-scess resection (n 14), abscess drain-age (...
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