Katharina Schönberger

Epidemiology of Subacute Sclerosing Panencephalitis (SSPE) in Germany from 2003 to 2009: A Risk Estimation

Subacute sclerosing panencephalitis (SSPE) is a fatal long-term complication of measles infection. We performed an estimation of the total number of SSPE cases in Germany for the period 2003 to 2009 and calculated the risk of SSPE after an acute measles infection. SSPE cases were collected from the Surveillance Unit for Rare Paediatric Diseases in Germany and the Institute of Virology and Immunobiology at the University of Würzburg. The total number of SSPE cases was estimated by capture-recapture analysis. For the period 2003 to 2009, 31 children with SSPE who were treated at German hospitals were identified. The capture-recapture estimate was 39 cases (95% confidence interval: 29.2–48.0). The risk of developing SSPE for children contracting measles infection below 5 years of age was calculated as 1∶1700 to 1∶3300. This risk is in the same order of magnitude as the risk of a fatal acute measles infection.

Parental smoking and childhood obesity: higher effect estimates for maternal smoking in pregnancy compared with paternal smoking—a meta-analysis

BACKGROUND Some studies reported similar effect estimates for the impact of maternal smoking in pregnancy and paternal smoking on childhood obesity, whereas others suggested higher effects for maternal smoking. We performed a meta-analysis to compare the effect of in utero exposure to maternal smoking and that of paternal or household smoking exposure in utero or after birth with mutual adjustment. METHODS Meta-analysis of observational studies identified in MEDLINE, EMBASE and Web of Knowledge published in 1900-2013. Study inclusion criterion was assessment of the association of maternal smoking during pregnancy and paternal or household smoking (anyone living in the household who smokes) at any time with childhood overweight and obesity. The analyses were based on all studies with mutually adjusted effect estimates for maternal and paternal/household smoking applying a random-effects model. RESULTS Data for 109,838 mother/child pairs were reported in 12 studies. The pooled odds ratios (ORs) for overweight 1.33 [95% confidence interval (CI) 1.23;1.44] (n=6, I2=0.00%) and obesity 1.60 (95% CI 1.37;1.88) (n=4, I2=32.47%) for maternal smoking during pregnancy were higher than for paternal smoking: 1.07 (95% CI 1.00;1.16) (n=6, I2=41.34%) and 1.23 (95% CI 1.10;1.38) (n=4, I2=14.61%), respectively. Similar estimates with widely overlapping confidence limits were found for maternal smoking during pregnancy and childhood overweight and obesity: 1.35 (95% CI 1.20;1.51) (n=3, I2=0.00%) and 1.28 (95% CI 1.07;1.54) (n=3, I2=0.00%) compared with household smoking 1.22 (95% CI 1.06;1.39) (n=3, I2=72.14%) and 1.31 (95% CI 1.15;1.50)] (n=3, I2=0.00%). CONCLUSIONS Higher effect estimates for maternal smoking in pregnancy compared with paternal smoking in mutually adjusted models may suggest a direct intrauterine effect.

Determinants of Long-term protection after hepatitis B vaccination in infancy: a meta-analysis.

Background: The duration of protection after hepatitis B vaccination in early infancy is unclear and may be related to vaccination schedule, dosage, vaccine type and population characteristics. Factors potentially influencing waning immunity were assessed. Methods: A systematic review was performed. The main outcomes were prevalence of anti-hepatits B antibodies ≥ 10 mIU/mL after primary or booster vaccination. Factors potentially influencing protection were assessed in an adjusted random-effects meta-analysis model by age for both outcomes. Results of both meta-analyses were combined in a prognostic model. Results: Forty-six studies reporting on the anti-hepatits B antibodies ≥ 10 mIU/mL 5 to 20 years after primary immunization and 29 on booster response were identified. The adjusted meta-analyses identified maternal carrier status (odds ratio [OR]: 2.37 [1.11; 5.08]), lower vaccine dosage than presently recommended (OR: 0.14 [0.06; 0.30]) and gap time between last and preceding dose of the primary vaccine series (OR: 0.44 [0.22; 0.86]) as determinants for persistence of anti-hepatits B antibodies ≥ 10. A lower vaccine dosage was also associated with failure to respond to booster (OR: 0.20 [0.10; 0.38]). The prognostic model predicted long-term protection of 90% [77%; 100%] at the age of 17 years for offspring of noncarrier mothers vaccinated with a presently recommended dose and vaccination schedule. Conclusions: Based on meta-analyses, predictors of waning immunity after hepatitis B vaccination in infancy could be identified. A prognostic model for long-term protection after hepatitis B vaccination in infancy was developed.

Immunogenicity of pneumococcal conjugate vaccines in infants after two or three primary vaccinations: a systematic review and meta-analysis.

Pneumococcal conjugate vaccines have been successfully used in infant vaccination programs. While most countries have used vaccination schedules with three primary immunisations and one booster dose, some countries have implemented schedules with only two primary immunisations and a booster dose. This systematic review aims to summarize evidence on immunogenicity of pneumococcal conjugate vaccines in infants comparing two and three primary immunisations before a booster dose is given. We systematically reviewed papers published between 1999 and 2011. Results from individual studies were pooled in a meta-analysis with the difference in proportion of children achieving serotype-specific ELISA antibody levels of ≥0.35 μg/ml. We estimated that about 10% less children achieve ELISA antibody levels of ≥0.35 μg/ml after two primary immunisations compared to three primary immunisations for most of serotypes included in one of the licensed pneumococcal conjugate vaccines. This difference in proportion was higher for serotypes 6B and 23F, where -49.4% (-66.0; -32.9%) and -26.9% (-37.2%; -16.6%) less children achieved protective antibody levels. These results support the notion that the majority of children are protected by two primary immunisations with pneumococcal conjugate vaccines in the first year of life. However, for serotypes 6B and 23F protection may be reduced.

Effectiveness of 2 + 1 PCV7 vaccination schedules in children under 2 years: A meta-analysis of impact studies

Although a case control study suggested high effectiveness of the 2+1 PCV-7 vaccination, schedule against invasive pneumococcal disease (IPD) in children the results of impact studies in, different countries yield considerable differences in the magnitude of the effects. A systematic, literature review was conducted to identify all relevant studies on IPD incidence reduction after onset, of PCV7 vaccination programmes in children younger than 2 years of age given in the 2+1 schedule. The incidence rate ratio between IPI incidences for vaccine serotypes before and after beginning of the, vaccination programme was calculated for each study. Heterogeneity was assessed and attempts to, identify causes for heterogeneity were made. In the literature search 4 studies which fulfilled inclusion, criteria were identified. The summary estimates yielded an IRR 0.10 [0.04; 0.30] suggesting a 90%, incidence reduction. Heterogeneity was high with I(2)=93%. Heterogeneity might be explained by, differences in vaccination rates, the way vaccination rates were assessed, matching of the periods of, vaccination and case ascertainment, time between onset of the vaccination programme and onset of, case ascertainment during the vaccination period and the length of the observation period after onset, of the vaccination programme. A study which started 3 years after onset of the vaccination programme, with vaccination rates ≥80% throughout the ascertainment period of the incidence rates reported a, 98% reduction in the incidence rates. A meta-analysis on IRR studies on reductions of the IPD, incidence in children <2 years of age suggested high effectiveness of the 2+1 vaccination schedule for PCV 7.

Impact of maternal carrier status on immunologic markers for protection after hepatitis B vaccination in infancy: a meta-analysis.

Better protection against hepatitis B infection in offspring of carrier mothers has been postulated because of a booster effect by close maternal contact. Empirical evidence, however, is inconclusive. Immunologic markers for protection against hepatitis B are anti-HBs ≥ 10 mIU/ml or response to booster in case anti-HBs had fallen below 10 mIU/ml. The objective of this paper was to asses whether immunologic markers suggest a higher protection after hepatitis B vaccination in offspring of carrier mothers. A systematic review was performed in order to identify all studies in offspring of carrier and non-carrier mothers reporting the proportions of individuals with anti-HBs ≥ 10 mIU/ml after infant hepatitis B vaccination with a presently recommended dose in children aged 5 years or older or response to a booster dose in case anti-HBs was below 10 mIU/ml. Associations between carrier status and the proportions of anti-HBs ≥ 10 mIU/ml or booster response were analysed by random effects models with adjustment for age and potential confounders. We identified 19 studies providing proportions of anti-HBs ≥ 10 mIU/ml with explicit information regarding the maternal carrier status. These studies reported 3245 children of carrier mothers aged up to 20 years and 4602 children of non-carrier mothers aged up to 14 years. Antibody titres ≥ 10 mIU/ml were detected in 75.8% of children of carrier and 63.6% of non-carrier mothers. A random effects model with adjustment for confounding yielded an odds ratio of 2.43 (95% CI 1.24-4.75) suggesting a markedly higher probability of anti-HBs ≥ 10 mIU/ml in offspring of carrier compared to non-carrier mothers. The distribution of proportions of individuals with post booster increase of anti-HBs titres ≥ 10 mIU/ml stratified by age at booster (≤ 10 years and >10 years) showed no differences between offspring of carrier and non carrier mothers up to the age of 10 years and only marginal differences thereafter. In conclusion the proportions of anti-HBs ≥ 10 mIU/ml were clearly higher in offspring of carrier mothers years after infant vaccination but there appeared to be no clinically relevant difference in response to booster. It is unclear to which extent higher proportions of breakthrough infections contribute to the higher proportions of protective antibody titres in offspring of carrier mothers.

Epidemiologische Nachbefragung eines Gastroenteritis Ausbruchs in den Allgäuer Alpen

Hintergrund: Am 07.08.09 wurde dem Gesundheitsamt Oberallgau eine Haufung von Brechdurchfallerkrankungen vom Allgauer Hauptkamm gemeldet. Mehrere Tage vor dem Geschehen war ein Problem mit der UV-Wasserdesinfektionsanlage auf der Rappensee Hutte aufgetreten. Ziel der vorliegenden Befragung war die Prufung der Hypothese, ob ein Zusammenhang zwischen den Erkrankungen und der defekten Trinkwasseraufbereitungsanlage vorlag. Material und Methoden: Es wurde eine retrospektive Befragung der Besucher von drei betroffenen Hutten (Rappensee Hutte, Kemptener Hutte und Prinz-Luitpold-Haus) durchgefuhrt. Als Falle wurden alle Personen betrachtet, die sich im relevanten Zeitraum (zwischen 29.07.09 (Defekt der UV Wasserdesinfektionsanlage) und dem 11.08.09 (maximaler Inkubationszeitraum)) auf einer der drei Hutten aufgehalten hatten und mit gastroenteritischen Beschwerden erkrankten. Ergebnisse: 350 Personen nahmen an der Befragung teil (Rucklauf: 87,5%). Hiervon waren 60,3% Manner und 37,1% Frauen. In der bivariaten Analyse zeigte sich ein signifikanter Zusammenhang (OR=13,5) zwischen einem Besuch auf der Rappensee Hutte und dem Krankheitsstatus. Bei der Berechnung einzelner Erkrankungsrisiken fur mogliche Einflussfaktoren zeigten sich besonders „etwas auf der Hutte getrunken zu haben“ (OR=15,6) und „die Toilette benutzt zu haben“ (OR=13,5) signifikant. In der logistische Regression zeigt sich, dass Personen, die etwas auf der Hutte getrunken hatten, ein 5-fach, Personen, die Wasser von der Hutte mitnahmen ein knapp 6-fach erhohtes Erkrankungsrisiko hatten. Diskussion/Schlussfolgerungen: Es konnten signifikante Risikoerhohungen fur den Aufenthalt auf der Rappensee Hutte, sowie fur „Etwas auf der Hutte getrunken zu haben“ und „Wasser von der Rappensee Hutte mitgenommen zu haben“ gezeigt werden. Bei der Interpretation muss berucksichtigt werden, dass fast alle Personen, die die Rappensee Hutte besuchten, dort auch etwas tranken oder Wasser mitnahmen. Da unvermeidlicher Weise jeder Huttenbesucher Kontakt zu anderen Personen hatte, ist das Ausbruchsgeschehen grundsatzlich mit einer Norovirusinfektion vereinbar. Da das Kontaktverhalten bei der Befragung nicht erfasst wurde, lasst sich das diesbezugliche Risiko einer Ubertragung durch Mensch-zu-Mensch-Kontakt nicht bestimmen.