Search

Rotavirus (RV) vaccination was included in the Finnish National immunization Program (NIP) in 2009. RotaTeq (RV5) has been used exclusively with a national average vaccination coverage rate (VCR) of 90%. While previous studies have demonstrated that inpatient rotavirus gastroenteritis (RVGE) admissions declined by as much as 96% in Finnish children ≤ 5 years old following RV vaccination introduction, no study has evaluated long-term protection after vaccination in Finland. In this study, we analyze incidence of hospital outpatient visits and inpatient admissions of gastroenteritis in children up to 7 years of age.We first describe the incidence of RVGE, viral gastroenteritis (VGE), and acute gastroenteritis (AGE) for all Finnish children born during 2008-2011. Children were stratified by the year of birth into not-eligible, partially eligible and rotavirus vaccine-eligible (born in 2008, 2009, 2010 and 2011, respectively). Hospital inpatient and outpatient data was collected from the National Care Register for all children from birth until December 31st, 2018. We also studied RVGE incidence during 2014-2017 for children3 years of age in municipalities with VCRs of 90% and above and municipalities with VCRs below 90%.RVGE incidence decreased significantly soon after implementation of RV vaccination in the NIP. In vaccine-eligible cohorts, no clear peak incidence in the youngest age groups could be observed, and no RVGE cases were observed beyond 6 years after vaccination, in contrast to vaccine ineligible and partially eligible cohorts. Despite an overall high VCR in Finland, regions with high VCR had lower incidence of RVGE than regions with lower VCR.Incidence of RVGE has remained low in all age groups during the 10 years following introduction of RV vaccine in the Finnish NIP. Differences in RVGE incidence were observed in regions with high as compared with lower VCR, highlighting the importance of maintaining high vaccination coverage.

Background: Older adults are at risk of pneumococcal disease and associated morbidity and mortality. This phase 3 study (V114-020) assessed lot-to-lot consistency across safety and immunogenicity outcomes for V114, a 15-valent pneumococcal conjugate vaccine (PCV), in healthy adults aged ≥ 50 years. Methods: Adults were randomized in a 3:3:3:1 ratio to receive a single dose of one of three lots of V114 or 13-valent PCV (PCV13), stratified by age (50–64 years, 65–74 years, and ≥ 75 years). Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were evaluated at baseline (Day 1) and 30 days post-vaccination. Non-serious and serious adverse events (AEs) were evaluated post-vaccination through 14 days and Month 6, respectively. Results: Of 2340 participants enrolled, 2282 (97.5%) completed the study. Proportions of participants experiencing ≥ 1 AE were 81.0%, 77.4%, and 78.0% for V114 lots 1, 2, and 3, respectively. Comparison of V114 combined lots with PCV13 showed that proportions of participants experiencing AEs, solicited AEs, and serious AEs were comparable for both vaccines, with the exception of injection-site pain (more frequently reported with V114). OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) at 30 days post-vaccination were comparable across V114 lots, and all lots met predefined equivalence criteria for all 15 vaccine serotypes (lower and upper limits of the 95% confidence intervals of serotype-specific OPA GMT ratios for all possible pairwise comparisons across the three lots were within the equivalence margin of 0.5–2.0). Serotype-specific OPA GMTs and IgG GMCs were comparable in the V114 combined lots and PCV13 groups for the 13 shared serotypes and higher in the V114 group for serotypes unique to V114 (22F and 33F). Conclusions: V114 is well tolerated with a consistent safety profile and immune response across manufacturing lots. Clinical trials registration: NCT03950856 (www.clinicaltrials.gov); 2018-004266-33 (EudraCT).

BACKGROUND: Sapovirus, norovirus and rotavirus are major causes of childhood acute gastroenteritis (AGE) globally. Asymptomatic infections of these viruses have not been extensively studied. AIM: To examine the prevalence and the genetic variations of sapovirus, norovirus and rotavirus in children with and without symptoms of AGE. METHODS: We collected 999 stool samples from children under 16 years old from September 2009 to August 2011 at Tampere University Hospital, Finland. In total 442 children (44%) had symptoms of AGE and 557 patients (56%) had acute respiratory tract infection (ARTI) only. Samples were examined for sapovirus, norovirus and rotavirus using reverse transcription-polymerase chain reaction and the positive amplicons were sequenced. RESULTS: Totally 54% and 14% of the patients in AGE and ARTI groups, respectively, tested positive. All viruses were more frequently detected in AGE patients than in ARTI patients (norovirus, 25% vs. 7.2%, respectively; rotavirus, 24% vs. 6.1%; sapovirus, 5.2% vs. 1.4%). In ARTI patients, the cases were seen most frequently during the first two years of life. Norovirus was the most detected pathogen in both groups with genogroup GII covering ≥97% of norovirus strains. Sapovirus was mostly detected in children under 18 months old without predominating genotype. Rotavirus was often detected after recent rotavirus vaccination and 18% and 88% of the strains were rotavirus vaccine-derived in AGE and ARTI groups, respectively. CONCLUSIONS: We showed that the most common viruses causing gastroenteritis in children may be found in the stools of an asymptomatic carrier which may function as a potential reservoir for AGE. publishedVersion

Background Live oral pentavalent bovine-human reassortant rotavirus (RV) vaccine, RotaTeq®, contains bovine rotaviruses reassorted with human G-types G1, G2, G3 and G4, and P-type P[8]. Shedding of RotaTeq® vaccine, as studied by RT-PCR, has been shown to be more common than initially reported, and may include formation of vaccine-derived double-reassortant G1P[8] RVs. We studied the extent and duration of RotaTeq® vaccine virus shedding, genotypes shed, and clinical symptoms associated with shedding. Material and methods We enrolled a total of 301 infants who received RotaTeq® vaccine according to Finnish schedule at 2, 3 and 5 months of age. Stool samples were collected 5–10 days after the first and 0–7 days before the third dose of the vaccine. Additional stool samples 6 and 12 weeks later were collected if the second stool sample was positive. All stools were studied with RT-PCR for RV VP7, VP4 and VP6. Parents filled a symptom diary for a week after each vaccine dose. Results We found that 93% of the vaccinees shed vaccine related viral particles in one sample taken 5–10 days after the first dose, indicating that stool shedding is very common and may be regarded as a marker of successful vaccination. Genotype G1 was the predominant genotype in shedding, often in association with P[8], and the only genotype found in long-term shedding. Also G4 was commonly detected whereas other vaccine G-types and bovine-type P[5] were not. Conclusions Shedding of RotaTeq® vaccine-derived viruses is a sign for successful vaccination. Intense shedding of G1 with or without P[8]reflects effective multiplication and may be an important factor in the induction of protective immunity. Shedding of G1 containing vaccine viruses may be prolonged up to 8 months of age. These results suggest that the pentavalent vaccine functions largely like a monovalent G1 vaccine. Eudra-CT: 2014-004252-60.

Aim This study examined the prevalence and clinical significance of the sapovirus infection in children with acute gastroenteritis before and after the introduction of the rotavirus vaccination in Finland in 2009. Methods We collected 1437 stool samples from children under 16 years during three prospective hospital-based surveillance studies of acute gastroenteritis at Tampere University Hospital, Finland. The children were seen in the emergency department (47%) or admitted to the ward (53%). Sapovirus findings from 2006 to 2008 (n = 759), before national immunisation, were compared to 2009-2011 (n = 330) and 2012-2014 (n = 348), after the national programme was launched. Results The overall incidence of the sapovirus was 3.3%. It was present in 1.4% of acute gastroenteritis cases in 2006-2008 and 5.5% in the post-vaccination years, but the absolute number did not increase. Sapoviruses mainly occurred in the winter and spring, but did not follow the prevalence of the norovirus or rotavirus. Sapovirus GI.1 and GII.1 were the most common genotypes, but the predominant strain was different each season. Many sapovirus lineages appeared during multiple seasons and reappeared later. Conclusion The sapovirus was uncommonly and sporadically detected in children seen in the hospital for acute gastroenteritis, and its relative role increased after national immunisation was introduced.

Rotavirus (RV) infection has been proposed to trigger type 1 diabetes mellitus (DM1) and celiac disease (CD) by molecular mimicry in genetically susceptible children. If so, a live attenuated oral RV vaccine could also trigger these autoimmune diseases, or else, prevent the effect of wild-type RV infection.In Rotavirus Efficacy and Safety Trial, conducted between 2001 and 2003, the participant children received RotaTeq (Kenilworth, NJ) vaccine or placebo in 1:1 ratio. The surveillance was extended as Finnish Extension Study. A questionnaire was sent in 2015 to the parents of 19,133 Finnish Extension Study participants and 5764 (30%) returned the questionnaire. Diagnosis of DM1, biopsy-proven CD and other autoimmune disease over the 11-14 year period were inquired.At the time of questionnaire, the prevalence of DM1 was similar in both groups, 0.97% (25 of 2580 children) in the placebo group and 1.04% (33 of 3184 children) in the vaccine group (P = 0.810). The prevalence of CD was significantly higher in placebo recipients (1.11%; confidence interval: 0.78%-1.6%) than in vaccine recipients (0.60%; confidence interval: 0.38%-0.93%) (P = 0.027).RV vaccination using RotaTeq did not alter the occurrence of DM1 but decreased the prevalence of CD in childhood and adolescence. We propose that wild-type RV may trigger CD and the triggering effect can be prevented or reduced by RV vaccination.

Objectives To determine occurrence of residual rotavirus (RV) disease in different age groups in Finland after five to nine years of high coverage (≥90 %) mass-vaccination with RotaTeq® vaccine, and to examine the vaccine effect on circulating genotypes. Methods Since 2013 all clinical laboratories in the country were obliged to send RV positive stool samples for typing. RVs were genotyped by RT-PCR for VP7 and VP4 proteins, sequenced and compared to reference strains. Results RV continued to circulate throughout the study period at low level with a small increase in 2017-2018. There were three age-related clusters: young children representing primary or secondary vaccine failures, school-age children who may not have been vaccinated, and the elderly. Genotype distribution differed from the pre-vaccination period with a steady decline of G1P[8], emergence of G9P[8] and especially more recently G12P[8]. In the elderly, G2P[4] was predominant but was also replaced by G12P[8] in 2017-18. Conclusions RV vaccination with a high coverage keeps RV disease at low level but does not prevent RV circulation. New RV genotypes have emerged replacing largely the previously predominant G1P[8]. Increase of overall RV activity with emergence of G12P[8] in the latest follow-up season 2017-18 might be a potential alarm sign.

Background Antigenemia and viremia are common in rotavirus infection but only few studies have shown norovirus (NoV) RNA in the blood circulation. Objectives To detect NoV RNA from serum of NoV-infected children and study if NoV RNAemia correlates with clinical severity of acute gastroenteritis. Study design Serum specimens were collected from 176 Finnish children with acute NoV gastroenteritis. Semi-nested PCR was optimized to detect NoV capsid RNA from sera. NoV positive samples were further analyzed by sequencing. Results NoV RNA was found in 11/176 (6.3%) of serum specimens. NoV GII.4 was found in 8 cases and GII.3, GII.6 and GII.7 in one case each. The genotypes detected in serum were identical to findings in stools in all cases. Most of the NoV RNA detections in serum were in young children less than 18 months of age. The clinical features of NoV serum-positive cases were not different from NoV serum-negative cases. Conclusion NoV RNA in serum is an uncommon finding limited to young children.

Rotavirus (RV) vaccination using RotaTeq364 RV positive stool samples collected from clinical laboratories over a 2-year period were G- and P-typed using RT-PCR, and the results were confirmed by sequencing. In addition, the genome segment encoding for VP6 was sequenced to distinguish between wild-type and vaccine origin (bovine) RVs.RV winter epidemic seasons 2013-2014 and 2014-2015 lasted until July each. The age distribution of RV cases showed two unusual clusters: one in children 6-16 years of age, too old to have been vaccinated in NIP, and the other in elderly over 70 years of age. In children, diverse genotypes were observed without any obvious predominance. The most common ones were G1P[8] (30.0%), G2P[4] (22.4%), G9P[8] (15.8%), G3P[8] (12.2%) and G4P[8] (11.2%). The genotype distribution was not different among vaccinated and unvaccinated children. Most cases in the elderly were associated with G2P[4].Even at high vaccine coverage and high effectiveness of RV vaccine, RV activity continues to persist, particularly in unvaccinated older children. RV genotypes show greater diversity than before RV vaccinations. We conclude that RV disease can be controlled but not eliminated by vaccinations. Herd-protection in long-term follow-up may be less than at the start of RV vaccinations.

Key points The effectiveness of pentavalent rotavirus vaccine against rotavirus-associated hospitalization was more than 90% 4 years after introduction into the national immunization program in Finland. A major impact on hospitalization for all-cause gastroenteritis was observed also. Background Rotavirus vaccination with exclusive use of RotaTeq was added to the National Immunization Programme (NIP) of Finland in September 2009. The objective of our study was to estimate the effectiveness and impact of RotaTeq after 4 years of follow-up. Methods Between 2009 and 2013, we conducted a prospective surveillance study of children aged 95%) has led to a major reduction in RV-AGE and AC-AGE hospitalizations without a resurgence of rotavirus activity. However, rotavirus continues to circulate in older unvaccinated children.

Rotavirus (RV) antigenemia and RNAemia are common findings in rotavirus-infected children. Sporadic associations between RV antigenemia and extraintestinal manifestations of RV infection have been observed. We examined the clinical severity of RV gastroenteritis in patients with and without RV antigenemia or RNAemia.Stool, serum and whole blood samples were collected from children seen with acute gastroenteritis in Tampere University Hospital and studied for RV using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Only exclusively RV-positive specimens were included into this study. The patients were divided into groups according to RV findings from stool, serum and blood specimens. Clinical manifestations were graded according to 20-point Vesikari scoring system.Of 374 children, 155 (41%) had RV in their stools. Of these 155 children, 105 (67%) were found to have RV RNA in the serum; of those, 94 (90%) had also RV enzyme-linked immunosorbent assay antigen. Thus antigenemia occurred in 61% (94 cases) of RV-infected children all of whom had concomitant RNAemia. Neither antigenemia nor RNAemia were detected in 85 patients with non-RV gastroenteritis. Patients who had RV RNA and RV antigen in both serum and stools were more likely to have a higher level of fever and more severe vomiting than patients who had RV only in stools. G1 genogroup RV was more often associated with RNAemia and antigenemia than other genogroups combined.Rotavirus antigenemia and viremia are commonly detected in children hospitalized for RV gastroenteritis and may be associated with increased severity of fever and vomiting.

We conducted a survey on the presence of RotaTeq vaccine viruses in infants hospitalized with respiratory infection, and detected shedding in 17% of children (

Two live-attenuated oral vaccines (Rotarix™ and Rotateq®) against rotavirus gastroenteritis were licensed in 2006 and have been introduced into National Immunization Programs (NIPs) of several countries. Large scale use of rotavirus vaccines might cause antigenic pressure on circulating rotavirus types or lead to selection of new rotaviruses thus decreasing vaccine efficacy. We examined the nucleotide and amino acid sequences of the surface proteins VP7 and VP4 (cleaved to VP8∗ and VP5∗) of a total of 108 G1P[8] rotavirus strains collected over a 20-year period from 1992, including the years 2006–2009 when rotavirus vaccine (mainly Rotarix™) was available, and the years 2009–2012 after implementation of RotaTeq® vaccine into the NIP of Finland. In G1 VP7 no changes at amino acid level were observed. In VP8∗ periodical fluctuation of the sublineage over the study period was found with multiple changes both at nucleotide and amino acid levels. Most amino acid changes were in the dominant antigenic epitopes of VP8∗. A change in VP8∗ sublineage occurred between 2008 and 2009, with a temporal correlation to the use of Rotarix™ up to 30% coverage in the period. In contrast, no antigenic changes in the VP8∗ protein appeared to be correlated to the exclusive use of RotaTeq® vaccine after 2009. Nevertheless, long-term surveillance of antigenic changes in VP4 and also VP7 proteins in wild-type rotavirus strains is warranted in countries with large scale use of the currently licensed live oral rotavirus vaccines.

Universal rotavirus (RV) vaccination is expected to reduce hospitalizations for acute gastroenteritis (GE) of children by eliminating most of severe RVGE, but it does not have any effect on norovirus (NV), the second most common causative agent of GE in children. After the introduction of the RV vaccine into the National Immunization Programme (NIP) of Finland in 2009, we conducted a prospective 2-year survey of GE in children seen in Tampere University Hospital either as outpatients or inpatients and compared the results with a similar 2-year survey conducted prior to NIP in the years 2006–2008. Compared with the pre-NIP 2-year period, in 2009–2011, hospitalizations for RVGE were reduced by 76 % and outpatient clinic visits were reduced by 81 %. NVGE showed a slight decreasing trend and accounted for 34 % of all cases of GE seen in hospital in pursuance of RVGE having decreased to 26 % (down from 52 %). In cases admitted to the hospital ward, RV accounted for 28 % and NV accounted for 37 %.The impact of RV vaccination was reflected as a 57 % decrease in all hospital admissions and 62 % decrease in all outpatient clinic visits for GE of any cause. Conclusion: RV vaccination in NIP has led to a major reduction of hospital admissions and clinic visits due to RVGE, but has had no effect on NVGE. After 2 years of NIP, NV has become the leading cause of acute GE in children seen in hospital.

Universal rotavirus (RV) vaccination with RotaTeq was introduced into National Immunization Programme (NIP) of Finland in September 2009. We have previously reported the reduction of RV gastroenteritis (GE) cases in the first 2 years after RV vaccination in NIP in Finland.In Tampere University Hospital, a 2-year survey of acute GE (AGE) in children was conducted before NIP in the years 2006 to 2008. This was followed by a similar prospective survey in years 2009 to 2011 and now extended to years 2012 to 2014. Stool samples from children examined in the hospital for AGE were analyzed by real-time polymerase chain reaction assays for RV and norovirus, and positive samples were typed by sequencing.The proportion of RVGE of all AGE cases decreased from 52% (421 of 809 cases) in pre-NIP years to 26% (86 of 330 cases) in post-NIP years 2009 to 2011 falling to 12% (40 of 347 cases) in 2012 and 2014. The hospitalizations for RVGE were reduced by 90% and the outpatient clinic visits also by 90% in 2012 to 2014, compared with pre-NIP year; all AGE cases were reduced by 59%. Norovirus was a major causative agent of AGE in the post-NIP period, accounting for 34% of the cases in 2009 to 2011 and 29% in 2012 to 2014.RV vaccination in NIP has led to a major reduction of RVGE cases seen in hospital with no resurgence in 5 years after NIP. A high coverage of RV vaccination will maintain RV activity at a low level but not eliminate wild-type RV circulation.

We describe 3 cases of acute gastroenteritis in healthy infants after vaccination with RotaTeq, shedding a G1P[8] human-bovine double reassortant rotavirus in stools. Such a double reassortant virus appears stable in vitro and may explain diarrheal symptoms in a small percentage of RotaTeq recipients, and might also be transmitted to contacts in the environment.

Noroviruses (NoVs) are the major causative agents of acute gastroenteritis (AGE) in outbreaks and in sporadic AGE in young children. Since the mid-1990s, NoV genotype GII.4 has been predominant worldwide. New GII.4 variants appear every two to three years, and antigenic variation is focused on the highly variable protruding domain (P2) of the NoV capsid protein which contains the receptor-binding regions. We studied NoV GII.4 variants in cases of endemic AGE in Finnish children from 1998 to 2013. Fecal specimens were collected from cases of AGE followed prospectively in rotavirus vaccine trials from 1998 to 2007, and from children seen at Tampere University Hospital because of AGE from 2006 to 2013. Partial capsid sequences were identified with RT-PCR and sequenced allowing P2 domain alignment and phylogenetic comparison of different GII.4 strains, with virus-like particles (VLPs) developed as candidate vaccines. Of 1495 NoV positive specimens 829 (55%) were of the GII.4 genotype, and altogether twelve GII.4 variants were identified. Identical GII.4 variants were detected in outbreaks of NoVs worldwide. A phylogenetic tree of the amino acid changes in the P2 region showed nine variants that arose over time. Our data indicates that GII.4 continues to be the predominant NoV genotype circulating in the Finnish community, and the changes in the P2 domain over time result in the development of new variants that cause AGE in children. Future NoV vaccines should either induce type specific immunity for each variant or, alternatively, induce broadly reactive protective immunity covering multiple variants.

Background Vaccination-impact studies of the live-attenuated pentavalent oral vaccine Rotateq® have demonstrated that the burden of rotavirus gastroenteritis has been reduced significantly after the introduction of RotaTeq® vaccination, but less is known about the benefit of this vaccination on hospital overcrowding. Methods As part of an observational surveillance conducted during the RV seasons 2000/2001 to 2011/2012, we analysed hospital discharge data collected retrospectively from two Finnish hospitals (Oulu and Tampere), concerning ICD 10 codes A00-09 (acute gastroenteritis, AGE) and A08.0 (rotaviral acute gastroenteritis RV AGE). We estimated the reduction in the number of beds occupied and analysed the bed occupancy rate, for RV AGE and all cause AGE, among 0–16 year-old children, before and after the implementation of the RV immunisation program. Results The rate of bed days occupied for RV AGE was reduced by 86% (95% CI 66%-94%) in Tampere and 79% (95% CI 47%-92%) in Oulu after RV vaccination implementation. For all cause AGE, reduction was 50% (95% CI 29% to 65%) in Tampere and 70% (95% CI 58% to 79%) in Oulu. Results were similar among 0–2 year-old children. This effect was also observed on overcrowding in both hospitals, with a bed occupancy rate for all cause AGE >25% in only 1% of the time in Tampere and 9% in Oulu after the implementation of the immunisation program, compared to 13% and 48% in the pre-vaccination period respectively. After extrapolation to the whole country, the annual number of prevented hospitalizations for all cause AGE in the post-vaccination period in Finland was estimated at 1,646 and 2,303 admissions for 0–2 and 0–16 year-old children respectively. Conclusions This study demonstrated that universal RV vaccination is associated with a clear decrease in the number of bed days and occupancy rates for RV AGE and all cause AGE. Positive consequences include increase in quality of care and a better healthcare management during winter epidemics. BioMed Central open access

Finland introduced universal rotavirus (RV) vaccination in September 2009, with exclusive use of the pentavalent human-bovine reassortant RV vaccine RotaTeq® and following a vaccination schedule at 2, 3 and 5 months of age. This study monitored the impact of RV vaccination on hospitalizations due to RV acute gastroenteritis (RVGE). The results following the first 3 RV seasons after implementation of universal RV vaccination are presented.Prospective hospital-based surveillance identified children with acute gastroenteritis admitted to 2 University Hospitals (Tampere and Oulu, Finland), from December 2009 to August 2012. The surveillance covered a population of approximately 173,000 children from the 2 hospitals' catchment areas. Stool samples were taken and analyzed centrally for RV by enzyme-linked immunosorbent assay, with genotyping by reverse transcription polymerase chain reaction. International Classification of Diseases discharge codes were collected retrospectively pre- and postvaccination.During the 3-year prospective surveillance, 127 RVGE episodes were identified. Of these, 117 were in unvaccinated children and 6 were in fully vaccinated children (RotaTeq, n = 3; Rotarix, n = 3). The vaccine effectiveness against hospitalized RVGE for fully vaccinated children was 92.1% [95% confidence interval (CI): 50.0-98.7] among children eligible for the National Immunization Program. When analyzing retrospectively the Tampere and Oulu hospital databases for all children aged16 years, hospitalizations for RVGE had decreased by 78% in the postvaccination period (2009-2012) compared with the prevaccination data (2001-2006).Severe RVGE requiring hospitalization was virtually eliminated in vaccine-eligible children in the 3 years following implementation of universal RotaTeq vaccination in Finland.