Andrea Streng

The impact of Rotavirus mass vaccination on hospitalization rates, nosocomial Rotavirus gastroenteritis and secondary blood stream infections.

BackgroundThe aim of the study was to evaluate the effects of universal mass vaccination (UMV) against rotavirus (RV) on the hospitalization rates, nosocomial RV infections and RV-gastroenteritis (GE)-associated secondary blood stream infections (BSI).MethodsThe retrospective evaluation (2002–2009) by chart analysis included all clinically diagnosed and microbiologically confirmed RV-GE cases in a large tertiary care hospital in Austria. The pre-vaccination period (2002–2005) was compared with the recommended and early funded (2006–2007) and the funded (2008–2009) vaccination periods. Primary outcomes were RV-GE-associated hospitalizations, secondary outcomes nosocomial RV disease, secondary BSI and direct hospitalization costs for children and their accompanying persons.ResultsIn 1,532 children with RV-GE, a significant reduction by 73.9% of hospitalized RV-GE cases per year could be observed between the pre-vaccination and the funded vaccination period, which was most pronounced in the age groups 0–11xa0months (by 87.8%), 6–10xa0years (by 84.2%) and 11–18xa0years (88.9%). In the funded vaccination period, a reduction by 71.9% of nosocomial RV-GE cases per year was found compared to the pre-vaccination period. Fatalities due to nosocomial RV-GE were only observed in the pre-vaccination period (3 cases). Direct costs of hospitalized, community-acquired RV-GE cases per year were reduced by 72.7% in the funded vaccination period. The reduction of direct costs for patients (by 86.9%) and accompanying persons (86.2%) was most pronounced in the age group 0–11xa0months.ConclusionsUMV may have contributed to the significant decrease of RV-GE-associated hospitalizations, to a reduction in nosocomial RV infections and RV-associated morbidity due to secondary BSI and reduced direct hospitalization costs. The reduction in nosocomial cases is an important aspect considering severe disease courses in hospitalized patients with co-morbidities and death due to nosocomial RV-GE.

Varicella routine vaccination and the effects on varicella epidemiology - results from the Bavarian Varicella Surveillance Project (BaVariPro), 2006-2011

BackgroundIn 2004, routine varicella vaccination was recommended in Germany for children 11-14 months of age with one dose, and since 2009, with a second dose at 15-23 months of age. The effects on varicella epidemiology were investigated.MethodsData on varicella vaccinations, cases and complications were collected from annual parent surveys (2006-2011), monthly paediatric practice surveillance (Oct 2006 - Sep 2011; five varicella seasons) and paediatric hospital databases (2005-2009) in the area of Munich (about 238,000 paediatric inhabitants); annual incidences of cases and hospitalisations were estimated.ResultsVaricella vaccination coverage (1st dose) in children 18-36 months of age increased in two steps (38%, 51%, 53%, 53%, 66% and 68%); second-dose coverage reached 59% in the 2011 survey. A monthly mean of 82 (62%) practices participated; they applied a total of 50,059 first-dose and 40,541 second-dose varicella vaccinations, with preferential use of combined MMR-varicella vaccine after recommendation of two doses, and reported a total of 16,054 varicella cases <17 years of age. The mean number of cases decreased by 67% in two steps, from 6.6 (95%CI 6.1-7.0) per 1,000 patient contacts in season 2006/07 to 4.2 (95%CI 3.9-4.6) in 2007/08 and 4.0 (95%CI 3.6-4.3) in 2008/09, and further to 2.3 (95%CI 2.0-2.6) in 2009/10 and 2.2 (95%CI 1.9-2.5) in 2010/11. The decrease occurred in all paediatric age groups, indicating herd protection effects. Incidence of varicella was estimated as 78/1,000 children <17 years of age in 2006/07, and 19/1,000 in 2010/11. Vaccinated cases increased from 0.3 (95%0.2-0.3) per 1,000 patient contacts in 2006/07 to 0.4 (95%CI 0.3-0.5) until 2008/09 and decreased to 0.2 (95%CI 0.2-0.3) until 2010/11. The practices treated a total of 134 complicated cases, mainly with skin complications. The paediatric hospitals recorded a total of 178 varicella patients, including 40 (22.5%) with neurological complications and one (0.6%) fatality due to varicella pneumonia. Incidence of hospitalisations decreased from 7.6 per 100,000 children <17 years of age in 2005 to 4.3 in 2009, and from 21.0 to 4.7 in children <5 years of age.ConclusionsOverall, the results show increasing acceptance and a strong impact of the varicella vaccination program, even with still suboptimal vaccination coverage.

Novel Respiratory Syncytial Virus A Genotype, Germany, 2011–2012

To the Editor: Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and elderly persons. RSV strains have been divided into 2 major antigenic groups (A and B), which are further divided into several genotypes. The main genetic and antigenic differences between genotypes are found within the 2 hypervariable regions of the attachment (G) glycoprotein. In 1999, a novel RSV B genotype, which contained a 60-nt duplication in the second hypervariable region of the G protein, was discovered in Buenos Aires, Argentina, and named BA (1). Since then, genotype BA has almost completely replaced other RSV B strains worldwide and has diversified into several subgenotypes (2). n nIn February 2012, as part of routine RSV surveillance, we identified a novel RSV A genotype with a 72-nt duplication in the second hypervariable region of G, thus representing the first RSV A genotype with nucleotide duplications in the G gene. Shortly thereafter, circulation of this genotype was reported in Ontario, Canada, in 2010–11 and 2011–12, and the genotype was named ON1 (3). To investigate the frequency of genotype ON1 in Germany, we extended the molecular analysis of RSV strains from the previous 2 RSV seasons. The study was approved by the ethics committee of the medical faculty at the University of Wurzburg, Germany. n nFrom July 2010 through June 2011 and from July 2011 through June 2012, we identified 271 and 181 RSV-positive patients, respectively. Patients were identified from respiratory specimens sent by hospitals in Bavaria, Germany, for routine testing of respiratory viruses at the Institute of Virology and Immunobiology at the University of Wurzburg. The mean age of all patients was 1.2 years (median 8.2 years; range 0.03–81.4 years), and 259 were male. Of the RSV-positive samples, 183 (67.5%) from season 2010–11 and 171 (94.5%) from season 2011–12 were analyzed by sequencing a fragment of ≈500 nt that encompassed the complete second hypervariable region of the G gene (4). Alignment with reference sequences and phylogenetic analyses were conducted by using MEGA 5.0 (5). n nMolecular analysis of RSV-positive samples revealed that RSV A and B cocirculated during both seasons (98 A and 85 B during 2010–11; 99 A and 73 B during 2011–12). In accordance with previous reports (2), all RSV B strains from both seasons were identified as genotype BA. The novel RSV A genotype ON1 was not detected during 2010–11. However, 10 (10.1%) of 99 RSV A strains were assigned to genotype ON1 during 2011–12. All other RSV A strains of both seasons belonged to genotype GA2. An amino acid alignment of ON1 sequences is shown in the Figure. The duplication regions of 2 of the 10 ON1 strains contained 2-aa and 3-aa exchanges compared with the ON1 reference sequence (which has no exchanges) (3). Of note, an ON1 sequence from Japan with similar, partially even identical mutations was retrieved from GenBank (Figure). All mutations observed so far did not affect potential O-glycosylation sites. n n n nFigure n nAmino acid sequence alignment of the second hypervariable region of the respiratory syncytial virus (RSV) G gene. RSV ON1 sequences and RSV A reference sequences in the upper part of the alignment are designated by GenBank numbers. ON1 sequences in the ... n n n nOf the 99 patients with RSV A infection diagnosed during 2011–12, a total of 91 were hospitalized children. Genotype ON1 was identified in 7 (25.0%) of 28 children in intensive care units (ICUs) and in 2 (3.2%) of 63 children in other wards (p = 0.003, Fisher exact test). Children admitted to an ICU were younger (median 0.2 years) than those not in an ICU (median age 1.2 years; p<0.001, Mann-Whitney U test). An exploratory logistic regression analysis on ICU admittance, adjusted for age, confirmed a strong association between RSV genotype ON1 and ICU admittance (adjusted odds ratio 8.4; 95% CI 1.5%–46.6%; p = 0.015). However, this significant difference should be interpreted with caution for 2 reasons: 1) samples from patients in wards other than an ICU originated mainly in the Wurzburg area, whereas samples from patients in ICUs were received from pediatric hospitals in various regions of Bavaria; 2) clinical information on patients not in ICUs was not available for assessment of whether the difference persisted when taking into account other risk factors for severe RSV disease. n nIn summary, the novel RSV A genotype ON1 containing a 72-nt duplication in the G gene was not found during 2010–11, but it constituted already 10.1% of all RSV A strains in a patient cohort from Bavaria, Germany, in the next season, 2011–12. In the context of the primary report of ON1 in Ontario, Canada (3), and the GenBank entry from Japan, our data suggest worldwide emergence of ON1. The almost complete worldwide replacement of circulating RSV B genotypes with the BA strain containing a comparable 60-nt duplication, which began in 1999, suggests that these duplications provide a selective advantage (2). Thus, molecular analysis of circulating RSV strains should be continued to determine whether ON1 has the potential to replace other RSV A strains in the years to come as did RSV B genotype BA during the past decade.

The effectiveness of varicella vaccination in children in Germany: a case-control study.

Background: Effectiveness of 1 dose of varicella vaccination was estimated to be 85–88% against clinical varicella of any severity in case-control studies in non-European countries, but lower effectiveness has been demonstrated in outbreaks. Methods: A prospective, age- and practice-matched case-control study was conducted in Germany to assess the effectiveness of 1 dose of OKA/GSK varicella vaccine (derived from the OKA strain, a Japanese clinical isolate) and of any varicella vaccine (including OKA/GSK, OKA/Merck and MMR-OKA/GSK) against polymerase chain reaction (PCR)-confirmed varicella under conditions of routine use. Results: The cohort included 432 PCR-confirmed cases and 432 matched controls (1–7 years old). Varicella vaccination was reported for 13.2% (57/432) of cases and 45.1% (195/432) of controls. Median time since vaccination was 28 and 25 months, respectively. Vaccinated cases experienced milder disease (P < 0.0001) and shorter duration of disease (P = 0.004) compared with unvaccinated cases. After adjusting for gender and school/day-care attendance, vaccine effectiveness of 1 dose of OKA/GSK against PCR-confirmed varicella of any severity was 71.5% (95% confidence interval [CI]: 49.1–84.0) and 94.7% (95% CI: 77.8–98.7) against PCR-confirmed moderate or severe varicella. Adjusted effectiveness for any varicella vaccine was 86.4% (95% CI: 77.3–91.8) against any severity and 97.7% (95% CI: 90.5–99.4) against moderate or severe varicella. Conclusions: One dose of varicella vaccine provided high protection against moderate and severe varicella disease for a period of up to 5 years after vaccination. However, further effectiveness data are needed to assess long-term protection.

Post-Pandemic Seroprevalence of Pandemic Influenza A (H1N1) 2009 Infection (Swine Flu) among Children <18 Years in Germany

Background We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. Methodology/Principal Findings Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1st to July 31st 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1–4 and 5–17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5–31.3) and 53.5% (95% CI: 50.9–56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3–30.5) in children aged 1–4 years and 48.0% (95% CI: 42.6–52.0) in 5–17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5–28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0–96.6) of the 5–17 year old but only 47.8% (95%-CI: 33.5–66.5) of the 1–4 year old children exhibited HI titers against influenza A virus (H1N1) 2009. Conclusion Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5–17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03B-adjuvanted split virion vaccine need further scrutiny.

Post-Pandemic Seroprevalence of Pandemic Influenza A (H1N1) 2009 Infection (Swine Flu) among Children

Background We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. Methodology/Principal Findings Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1st to July 31st 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1–4 and 5–17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5–31.3) and 53.5% (95% CI: 50.9–56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3–30.5) in children aged 1–4 years and 48.0% (95% CI: 42.6–52.0) in 5–17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5–28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0–96.6) of the 5–17 year old but only 47.8% (95%-CI: 33.5–66.5) of the 1–4 year old children exhibited HI titers against influenza A virus (H1N1) 2009. Conclusion Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5–17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03B-adjuvanted split virion vaccine need further scrutiny.

Prevalence of hepatitis E virus antibodies in children in Germany.

Background: Since asymptomatic hepatitis E virus (HEV) infections particularly affect children, there is a need for studies to determine the HEV seroprevalence among infants, children and adolescents. Methods: The prevalence of anti-HEV IgG antibodies was determined in sera taken in 2008–2010 from 1646 children aged 0–17 years living in Germany. Antibody testing was carried out using the enzyme-linked immunosorbent assay recomWell HEV IgG as well as the recomLine HEV IgG/IgM distributed by Mikrogen. Furthermore, the performance of MP Biomedicals enzyme-linked immunosorbent assay HEV and the HEV-Ab enzyme-linked immunosorbent assay from Axiom was analyzed in comparison with the recomWell/recomLine test system using a defined subset of sera. Results: In children, the overall prevalence of antibodies was 1.0%. Starting with the 5- to 6-year olds, there was a significant increase of HEV seroprevalence to 1.5% in the group of the 15- to 17-year olds. There was no statistically significant difference between seroprevalences of boys (1.2%) and girls (0.7%). Passively transmitted maternal antibodies persisted for about 3 months. The strength of agreement between the recomWell/recomLine system and the ELISAs from MP Biomedicals or Axiom varied between 0.229 and 0.542 and was calculated at 0.111 when the assays from MP Biomedicals and Axiom were compared. Conclusions: In Germany, only a very small number of HEV infections occur in children. Many infections occur in adults with increasing age. Because of considerable variations in assay accordance, there is an urgent need for standardization of HEV serology.

Decline of varicella vaccination in German surveillance regions after recommendation of separate first-dose vaccination for varicella and measles-mumps-rubella.

BACKGROUNDnGermany introduced routine varicella (V) vaccination in 2004. Due to a slightly increased risk of febrile convulsions after first-dose application of combined measles-mumps-rubella-varicella (MMRV) vaccine separate first-dose vaccinations with MMR and monovalent V vaccine were recommended in September 2011.nnnMETHODSnWe compared V and MMR vaccinations in paediatric practices from two surveillance regions (Munich and Würzburg) one year before and after the change in the recommendation.nnnRESULTSnA total of 1405/326 monthly reports were provided by a monthly average of 79/14 practices participating in Munich/Würzburg. V first-dose vaccinations (monovalent V or MMRV vaccine) declined by 12% in Munich (from 10.1 to 8.9 vaccinations per month and practice; p<0.005) and by 4% in Würzburg (from 9.9 to 9.5; p=0.620), respectively. First-dose vaccinations for MMR (MMR or MMRV vaccine) did not change significantly in both regions.nnnCONCLUSIONnAcceptance of V vaccination depends in part on the use of combination vaccine.

Varicella vaccination coverage in Bavaria (Germany) after general vaccine recommendation in 2004.

Since 2004, general varicella vaccination has been recommended for all children 11-14 months of age in Germany. The objective of this study was to examine vaccination coverage in children and factors associated with parental acceptance during the first years after recommendation. In a regional surveillance area, cross-sectional parent surveys were conducted in 2006, 2007 and 2008 in random samples (n=600) of children aged 18-36 months; data were obtained for 372, 364 and 352 children, respectively. Parents were questioned on their childs varicella disease history, and on varicella vaccination status as recorded in the childs vaccination booklet. Overall coverage increased from 38% in 2006 to 51% in 2007 and stagnated at 53% in 2008; in susceptible children (without previous varicella disease until vaccination or time of survey) coverage was 42%, 61% and 59%, respectively. Recommendation by the paediatrician as reported by the parents increased from 48% (2006) to 57% (2007) and 60% (2008), and was the main independent factor associated with parental acceptance. In 32-35% of unvaccinated children parents had not yet decided whether to vaccinate against varicella. Additional programmes targeting paediatricians and parents acceptance of varicella vaccination are needed to achieve the WHO-defined goal of at least 85% coverage.

Universal Mass Vaccination Against Rotavirus: Indirect Effects on Rotavirus Infections in Neonates and Unvaccinated Young Infants Not Eligible for Vaccination

BACKGROUNDnRotavirus (RV)-associated infections account for high numbers of hospitalizations in neonates and young infants. Universal mass vaccination (UMV) has been shown to prevent the burden of disease in vaccinated children.nnnMETHODSnThe present study investigated the long-term effects of UMV on RV-associated hospitalizations in children with particular focus on neonates and young infants (≤42 days old) not eligible for vaccination. Ten years of Austrian surveillance data were compared, including 10 960 laboratory-confirmed RV cases before (prevaccination period [PreVP]) and after (postvaccination period [PostVP]) introduction of UMV.nnnRESULTSnA postvaccination decrease in hospitalized community-acquired RV infections by 89.3% was seen in all age groups, including unvaccinated neonates and young infants. Of the latter, 27.6% had a nosocomial RV infection in PreVP, and 19.3% in PostVP. Overall, the proportion of nosocomial RV infections increased from 5.5% in PreVP to 13.0% in PostVP. Breakthrough infections, usually after incomplete RV vaccination, could be identified in 6.2% of patients.nnnCONCLUSIONSnUnvaccinated neonates and infants ≤42 days old may indirectly benefit from UMV by reduction of RV infections. Breakthrough infections underline the importance of early and complete protection by the vaccine. In older patients, heightened awareness of nosocomial RV infections is warranted. Identification of RV reservoirs is also needed.