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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 ® 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?

International audience; The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). We also provide descriptive data on several previously unreported PID patients with iVDRV-induced cutaneous granulomas including cartilage hair hypoplasia (n = 1), warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (n = 1), MHC class II deficiency (n = 1), Coronin-1A deficiency (n = 1), X-linked severe combined immunodeficiency (X-SCID) (n = 1), and combined immunodeficiency without a molecular diagnosis (n = 1). At the time of this report, the median age of the patients with skin granulomas and DNA repair disorders was 9 years (range 3-18). Cutaneous granulomas have been documented in all, while visceral granulomas were observed in six cases (40%). All patients had received rubella virus vaccine. The median duration of time elapsed from vaccination to the development of cutaneous granulomas was 48 months (range 2-152). Hematopoietic cell transplantation was reported to result in scarring resolution of cutaneous granulomas in two patients with NBS, one patient with AT, one patient with Artemis deficiency, one patient with DNA Ligase 4 deficiency, one patient with MHC class II deficiency, and one patient with combined immunodeficiency without a known molecular etiology. Of the previously reported and unreported cases, the majority share the diagnosis of a DNA repair disorder. Analysis of additional patients with this complication may clarify determinants of rubella pathogenesis, identify specific immune defects resulting in chronic infection, and may lead to defect-specific therapies.

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.

Die haufigste Fieberursache im Kleinkindalter sind virale Infektionen, bei denen meist keine therapeutischen Interventionen notwendig sind. Doch auch andere Ursachen wie bakterielle Infektionen, Neoplasien und inflammatorische Erkrankungen konnen dahinter stecken und mussen abgeklart werden. Dieser CME-Beitrag soll Ihnen den Umgang mit den kleinen Patienten erleichtern.

Varicella is an acute febrile, highly infectious disease. We describe the incidence and types of neurologic complications in children up to 16 years old. Hospitalized varicella cases were prospectively captured by active nationwide surveillance through the German Pediatric Surveillance Unit for Rare Diseases from January 2003 to December 2004. Neurologic complications occurred in 232 (25.4%) of 918 hospitalized children with varicella, and were the most frequent reason for hospitalization. The median age was 4.2 years (interquartile range 2.5-5.9). The median duration of hospital stay was 6 days (interquartile range 3-11). Neurologic complications were more frequent (P=0.054) in immunocompetent (32%) than immunocompromised (4%) children. The most frequent diagnoses comprised acute cerebellar ataxia in 72 (31.0%), febrile convulsion in 69 (29.7%), meningoencephalitis in 52 (22.4%), cerebral convulsions in 21 (9.1%), syncope in 9 (3.9%), and cerebral vasculitis/infarction in 6 (2.6%) of all children with neurologic complications. Twenty-eight (12%) demonstrated sequelae (18 with ataxia, four with epilepsy, two with hemiparesis, three with cerebral nerve palsy, and one with dysesthesia). Three patients died. The yearly incidence of neurologic varicella-associated hospitalizations was estimated at 2.4 neurologic complications per 100,000 children, corresponding to about one neurologic complication in 2000 varicella cases.

ZusammenfassungHereditäre Störungen der Granulozyten betreffen das angeborene Immunsystem („innate immunity“). Sie lassen sich in Erkrankungen mit quantitativer Reduktion und funktionellen Störungen der Granulozyten/Phagozyten einteilen. Sie können ferner isoliert oder als Begleitsymptom weiterer Störungen auftreten. Pathogenetisch sind Mutationen in so unterschiedlichen Molekülen wie Enzymen, Transkriptionsfaktoren, Adhäsionsproteinen und Strukturproteinen ursächlich beteiligt. Der folgende Übersichtsartikel stellt die Krankheitsbilder schwere kongenitale Neutropenie, zyklische Neutropenie, Shwachman-Diamond-Syndrom, Glykogenose Ib, Chediak-Higashi-Syndrom, Dyskeratosis congenita, Knorpel-Haar-Hypoplasie, Leukozytenadhäsionsdefekte I-III, ß-Actin-Defizienz, RAC-2-Defizienz, spezifischer Granula-Defekt, Glukose-6-Phosphat-Dehydrogenase sowie chronische Granulomatose vor.

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.

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.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.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 (P0.0001) 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.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.

Background Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)–HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. Objective To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. Methods The clinical phenotype (suggested by a National Institutes of Health [NIH] score of ≥40 points), STAT3 genotype, and T H 17 cell counts were compared in a cohort of 78 patients suspected of having HIES. Results Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score ≥40 points. Patients with STAT3 mutations with HIES showed significantly lower T H 17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score ≥40 points and abnormal T H 17 cell counts (≤0.2% of CD4 + cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3 . Conclusion We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T H 17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES.

Background Hyper-IgE syndrome (HIES) is a rare, autosomal-dominant immunodeficiency characterized by eczema, Staphylococcus aureus skin abscesses, pneumonia with pneumatocele formation, Candida infections, and skeletal/connective tissue abnormalities. Recently it was shown that heterozygous signal transducer and activator of transcription 3 (STAT3) mutations cause autosomal-dominant HIES. Objective To determine the spectrum and functional consequences of heterozygous STAT3 mutations in a cohort of patients with HIES. Methods We sequenced the STAT3 gene in 38 patients with HIES (National Institutes of Health score >40 points) from 35 families, quantified T H 17 cells in peripheral blood, and evaluated tyrosine phosphorylation of STAT3. Results Most STAT3 mutations in our cohort were in the DNA-binding domain (DBD; 22/35 families) or Src homology 2 (SH2) domain (10/35) and were missense mutations. We identified 2 intronic mutations resulting in exon skipping and in-frame deletions within the DBD. In addition, we identified 2 mutations located in the transactivation domain downstream of the SH2 domain: a 10–amino acid deletion and an amino acid substitution. In 1 patient, we were unable to identify a STAT3 mutation. T H 17 cells were absent or low in the peripheral blood of all patients who were evaluated (n = 17). IL-6–induced STAT3-phosphorylation was consistently reduced in patients with SH2 domain mutations but comparable to normal controls in patients with mutations in the DBD. Conclusion Heterozygous STAT3 mutations were identified in 34 of 35 unrelated HIES families. Patients had impaired T H 17 cell development, and those with SH2 domain mutations had reduced STAT3 phosphorylation.