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International audience; Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4 + and CD8 + memory T cells and CD4 + T REG s. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV + smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4 + T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.

We investigated severe acute respiratory syndrome coronavirus 2 infections in primary schools, kindergartens, and nurseries in Germany. Of 3,169 oropharyngeal swab specimens, only 2 were positive by real-time reverse transcription PCR. Asymptomatic children attending these institutions do not appear to be driving the pandemic when appropriate infection control measures are used.

Exclusive breastfeeding is recommended for women living with HIV (WLWH) in low-income-but not in high-income-countries, where milk substitutes are preferred. Some guidelines for high-income countries opted for a shared decision-making process regarding breastfeeding in optimal scenarios with adherence to antiretroviral therapy (cART), suppressed maternal viral load (mVL), and clinical monitoring. Although vertical transmission (VT) risk under cART is estimated below 1% in low-income settings, data from high-income countries are rare.We retrospectively analyzed all 181 live births from WLWH at the LMU Munich university hospital perinatal center in Germany between January 2016 and December 2020. We focused on VT, suppressed mVL and optimal scenario rates, breastfeeding frequency, cART regimens, and infant prophylaxis. All women were counseled according to current guidelines, foremost recommending avoidance of breastfeeding.In the 5-year cohort, no VT was observed. One hundred fifty-one WLWH (83.4%) decided not to breastfeed, even in optimal scenarios. Thrity infants (16.6%) were nursed, of which 25 were within an optimal scenario, whereas in 5 cases, breastfeeding was performed with a detectable VL in pregnancy or the postpartum period. All WLWH were treated with cART at delivery, and 91.7% sustained suppressed mVL. Zidovudine infant prophylaxis was given between 2 and 8 weeks but not necessarily over the whole breastfeeding duration and was declined from 5 breastfeeding WLWH.Although the cohort is too small to assess VT risk through breastfeeding with cART-suppressed mVL, breastfeeding might be an alternative even in high-income countries, but further studies are needed.

Children have been disproportionately affected during the COVID-19 pandemic. We aimed to assess a saliva-based algorithm for SARS-CoV-2 testing to be used in schools and childcare institutions under pandemic conditions. A weekly SARS-CoV-2 sentinel study in primary schools, kindergartens, and childcare facilities was conducted over a 12-week-period. In a sub-study covering 7 weeks, 1895 paired oropharyngeal and saliva samples were processed for SARS-CoV-2 rRT-PCR testing in both asymptomatic children (n = 1243) and staff (n = 652). Forty-nine additional concurrent swab and saliva samples were collected from SARS-CoV-2 infected patients (patient cohort). The Salivette® system was used for saliva collection and assessed for feasibility and diagnostic performance. For children, a mean of 1.18 mL saliva could be obtained. Based on results from both cohorts, the Salivette® testing algorithm demonstrated the specificity of 100% (95% CI 99.7–100) and sensitivity of 94.9% (95% CI 81.4–99.1) with oropharyngeal swabs as reference. Agreement between sampling systems was 100% for moderate to high viral load situations (defined as Ct-values &lt, 33 from oropharyngeal swabs). Comparative analysis of Ct-values derived from saliva vs. oropharyngeal swabs demonstrated a significant difference (mean 4.23, 95% CI 2.48–6.00). In conclusion, the Salivette® system proved to be an easy-to-use, safe and feasible saliva collection method and a more pleasant alternative to oropharyngeal swabs for SARS-CoV-2 testing in children aged 3 years and above.

Children have been disproportionately affected during the COVID-19 pandemic. We aimed to assess a saliva-based algorithm for SARS-CoV-2 testing to be used in schools and childcare institutions under pandemic conditions. A weekly SARS-CoV-2 sentinel study in primary schools, kindergartens, and childcare facilities was conducted over a 12-week-period. In a sub-study covering 7 weeks, 1895 paired oropharyngeal and saliva samples were processed for SARS-CoV-2 rRT-PCR testing in both asymptomatic children (n = 1243) and staff (n = 652). Forty-nine additional concurrent swab and saliva samples were collected from SARS-CoV-2 infected patients (patient cohort). The Salivette® system was used for saliva collection and assessed for feasibility and diagnostic performance. For children, a mean of 1.18 mL saliva could be obtained. Based on results from both cohorts, the Salivette® testing algorithm demonstrated the specificity of 100% (95% CI 99.7–100) and sensitivity of 94.9% (95% CI 81.4–99.1) with oropharyngeal swabs as reference. Agreement between sampling systems was 100% for moderate to high viral load situations (defined as Ct-values ® system proved to be an easy-to-use, safe and feasible saliva collection method and a more pleasant alternative to oropharyngeal swabs for SARS-CoV-2 testing in children aged 3 years and above.

Seit 2016 grassieren die Masern wieder in Europa. Auch Deutschland ist hiervon betroffen. Deshalb ist es wichtig, die Erkrankung schnell zu erkennen und die Ausbreitung zu verhindern. Besonders hohe Bedeutung haben die Infektionsschutzmasnahmen in Gemeinschaftseinrichtungen sowie die Impfpravention.

ObjectivesChildren have been disproportionately affected during the COVID-19 pandemic. Novel test strategies are urgently needed to ensure safe operation of schools and childcare institutions and to avoid prolonged closures. MethodsA weekly SARS-CoV-2 sentinel study in primary schools, kindergartens and childcare facilities over a 12-week-period was conducted. In total, 3123 concurrent oropharyngeal and saliva samples were processed for SARS-CoV-2 rRT-PCR testing in both children (n=2104) and staff (n=1019). Saliva sampling was optimised, and a novel sampling system was introduced and assessed for feasibility, the Salivette(R) system. ResultsFor children across all age groups a mean of 1,18 ml saliva could be obtained with this easy-to-handle system. Using 1293 concurrent oropharyngeal swabs from children, staff and participants of a positive control cohort as reference, the Salivette testing method could be assigned an overall specificity of 99.8% and sensititity of 95.1%. Of note, clinical sensitivity, defined as detection of positive cases with an oropharyngeal-swab derived Ct-value < 33, was 100%. Comparative analysis of Ct-values derived from saliva vs. oropharyngeal swabs demonstrated a significant difference (mean difference 4.23 (95% CI 2.48-6.00). ConclusionsThe Salivette system is an easy-to-use, safe and feasible collection method for saliva sampling and subsequent SARS-CoV-2 testing in children aged 3 years and above. In view of the excellent sensitivity and specificity documented in our study, this novel testing approach is a very reliable and much more pleasant alternative to oropharyngeal swab based testing, particularly in children and for self-testing in the home setting.

A 12-week sentinel programme monitored SARS-CoV-2 in primary schools, kindergartens and nurseries. Out of 3169 oropharyngeal swabs, only two tested positive on rRT-PCR while general incidence rates were surging. Thus, children attending respective institutions are not significantly contributing to the pandemic spread when appropriate infection control measures are in place.

Complete signal transducer and activator of transcription 1 (STAT1) deficiency causes a rare primary immunodeficiency that is characterized by defective IFN-dependent gene expression leading to life-threatening viral and mycobacterial infections early in life.To characterize a novel STAT1 loss-of-function variant leading to pathological infection susceptibility and hyperinflammation.Clinical, immunologic, and genetic characterization of a patient with severe infections and hemophagocytic lymphohistiocytosis-like hyperinflammation was investigated.We reported a child of consanguineous parents who presented with multiple severe viral infections that ultimately triggered hemophagocytic lymphohistiocytosis and liver failure. Despite intensified therapy with antivirals and cytomegalovirus-specific donor cells, the child died after hematopoietic stem cell transplantation because of cytomegalovirus reactivation with acute respiratory distress syndrome. Exome sequencing revealed a homozygous STAT1 variant (p.Val339ProfsTer18), leading to loss of STAT1 protein expression. Upon type I and type II IFN stimulation, immune and nonimmune cells showed defective upregulation of IFN-stimulated genes and increased susceptibility to viral infection in vitro. Increased viral infection rates were paralleled by hyperinflammatory ex vivo cytokine responses with increased production of TNF, IL-6, and IL-18.Complete STAT1 deficiency is a devastating disorder characterized by severe viral infections and ensuing hyperinflammatory responses. Early diagnosis can be made by exome sequencing and variant validation by functional testing of STAT1-dependent programmed cell death 1 ligand 1 surface expression on monocytes. Furthermore, high awareness for hyperinflammatory complications and potential targeted treatment strategies such as IL-18 binding protein could be considered. Hematopoietic stem cell transplantation is the only definitive treatment strategy but remains challenging.

The Sofia fluorescent immunoassay showed excellent sensitivity and specificity compared to conventional fluorescent immunoassay for Influenza A (Influenza B was not detected during the study period) and RSV in patients with suspected ILI (influenza-like illness). Thus the fast and easy-to-handle Sofia FIA leads to rapid and reliable diagnosis, which can be used by clinicians to avoid unnecessary antibiotic treatment and rapidly identify patients who need to be isolated upon hospital admission.

STAT3 hyper-IgE syndrome (STAT3-HIES) patients presented with significantly lower Staphylococcus aureus-specific serum IgG compared to cystic fibrosis patients despite recurrent S. aureus infections. Immunoglobulin replacement therapy increased S. aureus-specific IgG in STAT3-HIES patients and attenuated the clinical course of disease suggesting a role of humoral immunity in S. aureus clearance.

Universal varicella vaccination for 1-year-old children was introduced in Germany in 2004. We investigated changes in the incidence and type of varicella-associated neurologic complications in children during the first 7 years after universal vaccination recommendation.A surveillance study was conducted based on patients17 years of age with an International Classification of Diseases (10th Revision) discharge diagnosis of varicella, annually reported by 22-29 pediatric hospitals in Bavaria, Germany, 2005 to 2011. Annual incidences were estimated and linear trend across years was assessed by Poisson regression models.Of a total of 1263 varicella-associated pediatric hospitalizations, 228 children (18.1%) had neurologic complications (median age 4 years, interquartile range 2-7; 56% male). The most frequent neurologic complications were febrile convulsion (32.0% of 228 children, median age 3.0 years), varicella encephalitis or meningitis (28.9%; median age 4.5 years), syncope (13.2%; median age 7.0 years) and cerebral convulsion (11.0%; median age 4.0 years). Other complications included ataxia (3.1%), facial nerve palsy (2.6%) and cerebral vasculitis/infarction (1.8%). Neurologic complications showed a continuous decrease between 2005 and 2011, from an incidence of 2.8 (95% confidence interval: 2.1-3.6) per 100,000 children17 years of age to 1.2 (95% confidence interval: 0.7-2.1; P0.001). In particular, a marked decline was observed among children up to 7 years of age, mainly because of a decrease in the number of febrile convulsions and encephalitis or meningitis.The incidence of varicella-associated neurologic complications in children decreased approximately by 60% during the first 7 years following the recommendation for universal vaccination.

Kleinkinder mit Fieber stellen manchmal eine differenzialdiagnostische Herausforderung dar. Handelt es sich um eine unkomplizierte Erkrankung oder ist eine rasche, erweiterte Diagnostik erforderlich? Damit Sie die richtige Entscheidung treffen, sollten Sie auch seltene Ursachen kennen und die Alarmzeichen, die zu sofortigem Handeln zwingen.

Ist ein Kind infektionsanfallig, kann dies auf einen primaren Immundefekt hinweisen. Welche Basisdiagnostik hilft bei der Abklarung? Wann sollten Sie das Kind zu einem Spezialisten uberweisen bzw. ein Immundefektzentrum kontaktieren?

Leidet ein Kind haufig unter Infektionen, kann dies auf einen primaren Immundefekt hinweisen. Welche Basisdiagnostik hilft bei der Abklarung? Wann sollten Sie das Kind zu einem Spezialisten uber weisen beziehungsweise ein Immundefektzentrum kontaktieren?

Der zunehmende Anteil multiresistenter Erreger ist eines der zentralen Probleme der modernen Medizin. Antibiotic-Stewardship-(ABS-)Programme sind wichtige Hilfsmittel, um den Antibiotikaverbrauch einzuschranken und damit der Resistenzentwicklung entgegenzuwirken. Eine zunehmende Anzahl von Kinderkliniken sind dabei, ABS-Programme zu etablieren, wobei international bisher nur wenige Daten bezuglich der Implementierung und Effektivitat dieser Programme im Bereich der Padiatrie vorliegen. Das Dr. von Haunersche Kinderspital ist eine Kinderklinik der Maximalversorgung mit allen notwendigen Fachabteilungen. Ein ABS-Programm wurde etabliert, wobei die Kernmasnahmen der Inneren Medizin ubernommen wurden. Die spezifischen antimikrobiellen Substanzen sowie die entsprechenden klinischen Endpunkte wurden an die Situation der Padiatrie angepasst. Kernmasnahmen waren 1. ein „pro­spektives Audit mit Feedback – nach Verordnung“ sowie 2. eine „Restriktion und Freigabe – vor Verordnung“. Das ABS-Team besteht aus einem padiatrischen Infektiologen, einer Assistentin in der Weiterbildung sowie einer Apothekerin mit infektiologischer Erfahrung. Durch die Implementierung eines padiatrischen ABS-Programms konnte der Verbrauch antimikrobieller Substanzen in unserer Klinik signifikant gesenkt werden. Die erwarteten Kosteneinsparungen werden ca. 330 000 € pro Jahr betragen; zudem konnte der Verbrauch von Breitspektrumantibiotika, Glykopeptiden und Antimykotika signifikant reduziert werden. Antibiotic-Stewardship-(ABS-)Programme konnen effektive Masnahmen sein, um den Antibiotikaverbrauch einzuschranken. Nationale Guidelines sollten fur die Padiatrie in Deutschland von den Fachgesellschaften erarbeitet werden.

We report 15 imported louse-borne relapsing fever (LBRF) cases in refugees in Bavaria, Germany. One patient died. Epidemiological findings confirmed that all were young males from the Horn of Africa (12 from Somalia), who had similar migration routes converging in Sudan continuing through Libya and Italy. The majority likely acquired their infection during migration. Healthcare workers should be aware of LBRF in refugees passing through north Africa to ensure correct treatment and preventive measures.

Ein 2-jahriges Madchen wird von seinen Eltern in der Notfallambulanz vorgestellt. Seit 4 Wochen besteht eine Schwellung unterhalb des linken Kieferwinkels. Im Verlauf war diese gerotet gewesen. Zuvor war das Kind an einer Atemwegsinfektion erkrankt. Die Schwellung wurde vom Kinderarzt als Lymphadenitis diagnostiziert und uber 7 Tage mit einem Cephalosporin behandelt, was allerdings keinen Effekt hatte. Das Kind wird aufgenommen und weiterer diagnostischer Masnahmen unterzogen.

The steady increase in antimicrobial resistance is of growing concern in healthcare. Antibiotic Stewardship [ABS] Strategies are important tools to control antibiotic use and -prevent antimicrobial resistance. An increasing number of institutions are developing ABS initiatives also in pediatrics. However, few data are available assessing the implementation and efficiency of these pediatric ABS programs.At the Dr. von Hauner Children's Hospital, Ludwig-Maximilian University, a tertiary care pediatric reference center, a pediatric ABS Team has been implemented. Key structural elements were the same as for adult patients, but antimicrobials agents selected for monitoring and appropriate clinical endpoints are different in pediatrics.Key features were: 1. prospective-audit with feedback and formulary restriction and 2. pre-authorization (also referred to as prior approval). The ABS team consisted of one pediatric infectious disease specialist, one clinical fellow in pediatric infectious diseases, and one clinical pharmacist with training in infectious diseases.With the implementation of a pediatric ABS strategy we could significantly influence antimicrobial consumption in our hospital. Cost-savings are estimated to be above 330 000 € per year, and concomitantly the use of broad-spectrum antibiotics and antifungal compounds was significantly reduced.Antibiotic Stewardship [ABS] Strategies may be an effective tool to control antibiotic use in the setting of a large tertiary pediatric teaching hospital. A national guideline for ABS initiatives may help to further improve rational use of antibiotics in the hospital setting.

Hintergrund: Der unbedachte und häufig unnötige Einsatz von antiinfektiven Substanzen hat schwerwiegende Folgen für den individuell behandelten Patienten und die gesamte Gesundheitsökonomie. Sowohl die hohen Kosten als auch das Auftreten multiresistenter Erreger und unerwünschte[for full text, please go to the a.m. URL], 21. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI)