Incidence of SCID in Germany from 2014 to 2015 an ESPED* Survey on Behalf of the API*** Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) ** Arbeitsgemeinschaft Pädiatrische Immunologie.

PURPOSE: Severe combined immunodeficiencies (SCID) are a heterogeneous group of fatal genetic disorders, in which the immune response is severely impaired. SCID can be cured if diagnosed early. We aim to determine the incidence of clinically defined SCID cases, acquire data of reported cases and evaluate their possible prediction by newborn screening, before introduction of a general screening program in Germany. METHODS: The German Surveillance Unit for rare Paediatric Diseases (ESPED) prospectively queried the number of incident SCID cases in all German paediatric hospitals in 2014 and 2015. Inclusion criteria were (1) opportunistic or severe infections or clinical features associated with SCID (failure to thrive, lacking thymus or lymphatic tissue, dysregulation of the immune system, graft versus host reaction caused by maternal T cells), (2) dysfunctional T cell immunity or proof of maternal T cells and (3) exclusion of a secondary immunodeficiency such as human immunodeficiency virus (HIV) infection. In a capture-recapture analysis, cases were matched with cases reported to the European Society for Immunodeficiencies (ESID). RESULTS: Fifty-eight patients were initially reported to ESPED, 24 reports could be confirmed as SCID, 21 patients were less than 1 year old at time of diagnosis. One SCID case was reported to ESID only. The estimated incidence of SCID in Germany is 1.6/100,000 (1:62,500) per year in children less than 1 year of age. Most patients reported were symptomatic and mortality in regard to reported outcome was high (29% (6/22)). The majority of incident SCID cases were considered to be probably detectable by newborn screening. CONCLUSIONS: SCID is a rare disease with significant mortality. Newborn screening may give the opportunity to improve the prognosis in a significant number of children with SCID.

Rotavirus disease in Germany--a prospective survey of very severe cases.

OBJECTIVE: Rotavirus (RV) gastroenteritis is a notifiable disease in Germany. The reports to the authorities contain few data concerning the severity of disease. The aims of this study were to determine incidence and outcome of very severe cases of RV disease. METHODS: Cases of very severe RV disease were collected by the German Paediatric Surveillance Unit for rare diseases (Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland) using anonymous questionnaires based on hospitalized patients between April 2009 and March 2011. Inclusion criteria were detection of RV antigen in feces, patient aged 0-16 years and 1 or more of the following criteria: intensive care treatment, hypernatremia or hyponatremia (>155 mmol/L or <125 mmol/L), clinical signs of encephalopathy (somnolence, seizures, apnea) and RV-associated death. RESULTS: During 2 years, 130 cases of very severe RV disease were reported, 101 of 130 were verified. Seventeen patients had nosocomial infection, of whom 14 were neonates in intensive care. Among those, 12 infants had verified or suspected necrotizing enterocolitis. Eighty-four community-acquired cases were reported, median age was 10.5 months (0-108 months). The median hospital stay was 6 days, and 48 patients needed intensive care treatment. Among children less than 5 years of age, the yearly incidence of community-acquired very severe RV disease was 1.2 of 100,000 (95% confidence interval: 0.9-1.4/100,000). A total of 26 of 84 and 10 of 84 patients had severe hypernatremia or hyponatremia, respectively, and 58 of 84 patients had signs of encephalopathy. Three deaths were reported (1 nosocomial and 2 community acquired). CONCLUSIONS: RV infection in Germany can have a life-threatening course. A substantial number are nosocomial infections.

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 1(st) to July 31(st) 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 AS03(B)-adjuvanted split virion vaccine need further scrutiny.

On the design of a capillary flow phantom for the evaluation of ultrasound contrast agents at very low flow velocities.

Recently, a new imaging technology has become available that allows the evaluation of tissue perfusion using echo-contrast agents in real-time imaging: power pulse inversion imaging (PPI). Although numerous in vitro phantoms have been designed for different imaging modalities in ultrasound (US), there is a need for a phantom that mimics microcirculation and allows, in particular, the assessment of contrast replenishment kinetics following US-induced destruction of microbubbles using the new method. We, therefore, designed a new capillary flow phantom that takes the requirements of the new US imaging techniques and the physical properties of microbubbles into account and serves flow velocities in the range of microcirculation (1 to 10 mm/s). PPI studies were performed in the newly designed phantom. The contrast agent used was AF0150. We studied homogeneity of contrast distribution within the capillary phantom, constancy of contrast infusion, the dose-effect relationship and, finally, the feasibility of flow assessment using the method of contrast replenishment following US-induced microbubble destruction in a flow velocity range of 2.1 to 9.45 mm/s. Analysis of the replenishment kinetics was performed using the mathematical model f(t) = A(1 - e(-beta t)), with A representing the blood volume and beta the microbubble velocity. The new capillary phantom allowed homogeneous contrast opacification within the perfused capillaries independently of the flow. Constancy of signal intensity was achieved over a time period of almost 2 h, indicating constant contrast delivery. A strong linear correlation between the PPI signal and the contrast dose was found (r = 0.998). Analysis of the replenishment parameters revealed a strong linear relationship between parameter beta and flow (r = 0.994) as well as A * beta and flow (r = 0.984) in the observed flow range. The newly designed perfusion phantom for the evaluation of echo-contrast replenishment kinetics fulfills, at very low flow velocities, important prerequisites such as constancy of contrast delivery, homogeneity of contrast signals, linear dose-effect relation and minimal attenuation. Thus, the new phantom allows standardized analysis of contrast replenishment kinetics using real-time perfusion imaging techniques at flow velocities comparable to those of the microcirculation.