SARS-CoV-2 variants and the risk of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 among children in Germany.

PURPOSE: To investigate the relationship between the risk of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children and the predominance of different SARS-CoV-2 variants of concern (VOC) over time. METHODS: In relation to the Alpha, Delta, and Omicron VOC phases of the pandemic, the risk of developing PIMS-TS was calculated by analyzing data for rtPCR-confirmed SARS-CoV-2 infections reported to the German statutory notification system, along with data captured by a separate, national PIMS-TS registry. Both overall infection rates and age group-specific ratios of PIMS-TS during the different pandemic phases were calculated using the Alpha period as the baseline. RESULTS: The PIMS-TS rate changed significantly over time. When the Alpha VOC was dominant [calendar week (CW) 11 in March-CW 31 in August 2021], the PIMS-TS rate was 6.19 [95% confidence intervals (95% CI) 5.17, 7.20]. When Delta prevailed (CW 32 in August 2021-CW 4 in January 2022), the rate decreased to 1.68 (95% CI 1.49, 1.87). During the Omicron phase (CW 5 in January-CW 16 in April 2022), the rate fell further to 0.89 (95% CI 0.79, 1.00). These changes correspond to a decreased PIMS-TS rate of 73% (rate ratio 0.271, 95% CI 0.222; 0.332) and 86% (rate ratio 0.048, 95% CI 0.037; 0.062), respectively, in comparison to the Alpha period. Rate ratios were nearly identical for all age groups. CONCLUSION: The data strongly suggest an association between the risk for PIMS-TS and the prevailing VOC, with highest risk related to Alpha and the lowest to Omicron. Given the uniformity of the decreased risk across age groups, vaccination against SARS-CoV-2 does not appear to have a significant impact on the risk of children developing PIMS-TS.

[Care of infectious diseases in underage refugees exemplified by Ukraine]. / Infektiologische Versorgung minderjähriger Flüchtlinge am Beispiel der Ukraine: Vorgehen in Deutschland gemäß der S1-Leitlinine (AWMF-Register Nr. 048-017).

Background: By early June 2022, around 300,000 children and adolescents from Ukraine were registered in the German central registry for foreigners.The updated recommendations for action should provide the foundations for an evidence-based and targeted care for the diagnosis and prevention of infectious diseases in underage refugees and asylum seekers, exemplified by Ukraine. Objective: The recommendations for action are intended to support medical personnel in the care of minor refugees in order to1) ensure early recognition and completion of an incomplete vaccination status,2) diagnose and treat common infectious diseases,3) ensure early recognition and treatment of infectious diseases that are rare in the German healthcare system. Material and methods: The recommendations for action were drafted as level 1 (S1) guidelines coordinated by the Association of the Scientific Medical Societies in Germany (AWMF) and were adapted to the situation of refugees from Ukraine.The recommendations were compiled by a representative expert panel appointed by the participating professional societies in an informal consensus and finally officially adopted by the board of directors of all societies concerned. Results: Recommendations are given for the extent of the medical evaluation of minor refugees, including the medical history and physical examination, adapted to the situation of refugees from Ukraine. A blood count and screening for tuberculosis, hepatitis B and C as well as human immunodeficiency virus (HIV) infections are recommended for all minor refugees.For a rapid completion of the vaccination status, an age-related and indications-related prioritization of individual vaccinations will be undertaken. Conclusion: In view of the continuing high numbers of refugees not only from Ukraine, a further professionalization of medical health care is necessary. For this purpose, the necessary structural and personnel framework conditions need to be accomplished.

[Travelling with children and adolescents with rheumatic diseases]. / Reisen mit Kindern und Jugendlichen mit rheumatischen Erkrankungen.

Due to the underlying disease and immunosuppressive treatment, pediatric patients with rheumatic diseases are at increased risk for (long distance) travel-related health problems. A pretravel comprehensive consultation is therefore strongly recommended. Whether a child with rheumatic disease is sufficiently fit for travel essentially depends on the disease activity, the age of the child and the intended travel destination. Depending on the level of immunosuppression, the risks for this patient group include (travel-related) infections and the possibility of disease activity flares. Of particular importance is adequate exposure prevention: standard vaccinations should be updated and indications for travel vaccinations evaluated in advance of travelling. In this context, potential contraindications, especially for live vaccines, in the case of specific immunosuppressive treatment should be considered. In the event of travel to malaria endemic areas, the necessity for chemoprophylaxis or stand-by medication must be evaluated but caution is needed regarding potential drug interactions. Detailed education about careful hand, food and contact hygiene is critical. Because photosensitivity may be increased in some rheumatic diseases and/or medications, UV protection is crucial. Barriers (clothes and mosquito nets) and age-appropriate chemical insect repellents should be used to prevent insect-borne diseases. Before start of travel, possibilities for on-site medical help in the event of disease deterioration and/or infection should be evaluated. This should be included in the assessment of the patient's ability to travel. Travelers with rheumatic disease should carry a first aid kit that includes both a sufficient supply of regular antirheumatic medication and supplemental medication in case of a disease flare. Storage conditions must be taken ínto account for some medications. Ultimately, the success of a journey depends on the planning from the perspective of the child with its specific needs.

Diagnosis and treatment of Guillain-Barré Syndrome in childhood and adolescence: An evidence- and consensus-based guideline.

This evidence- and consensus-based practical guideline for the diagnosis and treatment of Guillain-Barré Syndrome (GBS) in childhood and adolescence has been developed by a group of delegates from relevant specialist societies and organisations; it is the result of an initiative by the German-Speaking Society of Neuropediatrics (GNP), and is supported by the Association of Scientific Medical Societies (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften). A systematic analysis of the literature revealed that only a few adequately-controlled studies exist for this particular age group, while none carries a low risk of bias. For this reason, the diagnostic and therapeutic recommendations largely rely on findings in adult patients with GBS, for which there are a higher number of suitable studies available. Consensus was established using a written, multi-step Delphi process. A high level of consensus could be reached for the crucial steps in diagnosis and treatment. We recommend basing the diagnostic approach on the clinical criteria of GBS and deriving support from CSF and electrophysiological findings. Repetition of invasive procedures that yield ambiguous results is only recommended if the diagnosis cannot be ascertained from the other criteria. For severe or persistently-progressive GBS treatment with intravenous immunoglobulin (IVIG) is recommended, whereas in cases of IVIG intolerance or inefficacy we recommended treatment with plasmapheresis. Corticosteroids are ineffective for GBS but can be considered when acute onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is suspected due to a prolonged disease course. The full German version of the Guideline is available on the AWMF website (https://www.awmf.org/leitlinien/detail/ll/022-008.html).

Breastfeeding and vitamin D supplementation reduce the risk of Kawasaki disease in a German population-based case-control study.

BACKGROUND: In Kawasaki disease (KD), a vasculitis of unknown etiology, the most serious complication is the development of coronary artery aneurysm (CAA). To date, the exact pathomechanism of KD is unknown. Both environmental and genetic factors seem to be associated with the development of the disease. METHODS: Data on KD patients recruited from the population-based German Pediatric Surveillance Study during 2012-2014 were used to evaluate the impact of various factors from the perinatal and infancy period on the development of KD. The study design was a matched case-control study with respect to age, sex and place of residence (n = 308 KD cases, n = 326 controls). All KD patients were individually re-evaluated; all fulfilled the international diagnostic KD criteria. A standardized questionnaire was used to review breastfeeding practices, vitamin D supplementation and birth characteristics. Logistic regression analyses were performed to obtain odds ratios (OR) for various risk factors among the case-control pairs. Simple measures of association were used to assess the impact of these factors on the clinical course. RESULTS: There was no difference in lengths of gestation, birth weight or parturition between KD patients and controls, but independently from each other vitamin D supplementation and breastfeeding were negatively associated with KD, even when adjusted for age, place of residence and sex. The duration of vitamin D was significantly shorter among children with KD than among children without KD (p = 0.039, OR = 0.964, 95% CI: 0.931-0.998), as was the duration of breastfeeding (p = 0.013, OR = 0.471, 95% CI: 0.260-0.853). Comparing KD patients with and without breastfeeding and/or vitamin D supplementation, there were no differences regarding developing CAA, being refractory to intravenous immunoglobulin treatment, age at onset of the disease and levels of inflammatory laboratory values. CONCLUSION: Our findings indicate breastfeeding and vitamin D supplementation to have protective effects in association with KD in our study population; however, these seem not to influence the natural course of the disease. Although the overall effects were relatively small, they nevertheless underline the overall benefit of both interventions. TRIAL REGISTRATION: Clinical Trial Registration: German clinical trial registration, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00010071 . Date of registration was 26. February 2016. The trial was registered retrospectively.

[Recommendations for the diagnosis and prevention of infectious diseases in pediatric and adolescent refugees in Germany : Statement of the German Society of Pediatric Infectious Diseases, the Society of Tropical Pediatrics and International Child Health, and the Professional Association of Pediatricians]. / Empfehlungen zur infektiologischen Versorgung von Flüchtlingen im Kindes- und Jugendalter in Deutschland : Stellungnahme der Deutschen Gesellschaft für Pädiatrische Infektiologie, der Gesellschaft für Tropenpädiatrie und Internationale Kindergesundheit und des Berufsverbandes der Kinder- und Jugendärzte.

Child and adolescent refugees in Germany represent a particularly vulnerable social group and treating infectious diseases forms a crucial part of providing their medical care. From an infectious diseases perspective, refugees themselves, as a result of their difficult personal circumstances, are the ones at highest risk. Even in crisis situations, medical practitioners are medically and ethically obliged to provide a high standard of care. The guidelines presented here propose recommendations for diagnosing and preventing infectious diseases among refugees under 18 in Germany. The guidelines are intended to assist in optimizing vaccine protection and treatment of diseases while taking into consideration factors such as refugees' challenging living conditions, cultural differences and potential language barriers.Upon refugees' arrival at the first housing sites, it is recommended that a basic clinical screening (and not just a brief visual inspection) be provided in order to identify and initiate treatment for acute medical problems and potentially contagious diseases (including tuberculosis), as well as to close gaps in vaccination coverage. Documentation of the clinical findings is critical, both to avoid redundant investigations and to optimize individual medical care. For this, an effective communication system must be established.Once refugees have been transferred into their destination community, outpatient and inpatient care providers should collaborate to bring refugees up-to-date with all vaccines recommended by STIKO (German Standing Committee on Vaccination). The same high standard of medical care should be delivered to refugees as would be to the general population. Due to the high prevalence of multi-resistant organisms (MRO) in the refugees' countries of origin, MRO screening is recommended for most patients receiving inpatient care.

Cardiac thrombus with risk of fulminant pulmonary embolism in paediatric antiphospholipid syndrome.

Antiphospholipid Syndrome (APS) describes a systemic disease caused by autoantibodies to membrane components. Involving coagulation pathways, complement factors and immune cells, it results in thrombosis in any blood vessel. Its clinical presentation varies considerably depending upon the organ affected. Paediatric data on APS remain sparse. Most case reports focus on catastrophic APS with multiple small-vessel occlusions and a life-threatening course. Here, we report on a 15-year-old patient with deep vein thrombosis and a right ventricular tumour posing the risk of a fulminant pulmonary embolism. The tumour was surgically removed. Histology revealed it to be a thrombus. The patient fully recovered and is currently treated with long term anticoagulation.

Primary cutaneous cryptococcosis in an eight-year-old immunocompetent child: how to treat?

Here we report on a case of primary cryptococcal skin infection in an immunocompetent 8-year-old boy. The infection first manifested itself as a subcutaneous abscess around the proximal joint of his right thumb after a minor injury from contact with a thorny shrub. After surgical incision and drainage was performed, Cryptococcus neoformans var. neoformans was the only pathogen cultured from the lesion. An agglutination test for the capsular antigen in serum displayed negative results and the immunological work-up revealed no underlying immunodeficiency. A "watch and wait" strategy - one without systemic antifungal treatment - was adopted and this resulted in uneventful healing. In summary, primary cryptococcal skin infections in immunocompetent hosts may be managed successfully by surgical treatment in combination with careful clinical follow-up. This approach may help avoid unnecessary antimicrobial treatments.

Detection of opsonic antibodies against Enterococcus faecalis cell wall carbohydrates in immune globulin preparations.

Three different commercially available polyvalent immune globulins (IG) were investigated for the existence of antibodies against cell wall carbohydrates of four different E. faecalis serotypes (using a cell wall carbohydrate-enzyme-linked immunosorbent assay), and whether these antibodies mediated opsonic killing (using an opsonic-killing assay). All three IG preparations contained antibodies against all four serotypes (CPS-A to CPS-D). However, only one of the three IG preparations showed opsonic killing against all four serotypes. Average killing was higher against serotypes A and B (72 and 79 %, respectively) than against serotypes C and D (30 and 37 %, respectively). Such IG preparations could play a role as an adjuvant therapeutic option in life-threatening infections with E. faecalis, particularly when resistant strains are involved.

Antibiotic susceptibility profiles of neonatal invasive isolates of Escherichia coli from a 2-year nationwide surveillance study in Germany, 2009-2010.

A nationwide 2-year surveillance study on invasive neonatal Escherichia coli infections in Germany was conducted. A total of 158 isolates were tested for antibiotic susceptibility. The empirical treatment regimen of ampicillin plus gentamicin for neonatal sepsis appears to remain effective, but emerging resistance needs to be closely monitored.

Impact of technical training on rapid antigen detection tests (RADT) in group A streptococcal tonsillopharyngitis.

Rapid antigen detection tests (RADT) are widely used for the rapid diagnosis of group A streptococcal (GAS) tonsillopharyngitis. In a prospective 3-year study, the reliability of two different RADT methods was compared, as performed by lab technicians versus physicians. Sensitivity and specificity, as well as positive and negative predictive values, were calculated. When performed by physicians, the results (44.4 %, 8.3 %, 26.7 % and 16.7 %) of a latex agglutination test (LAT) were unacceptably low. However, after switching to a lateral-flow immunoassay (LFIT) and implementing additional hands-on training, the performance improved dramatically (100 %, 92.6 %, 84.6 % and 100 %). In conclusion, technical errors, along with a lack of experience and expertise, negatively impact RADT accuracy.

[The pain situation for residents of nursing homes. Results of a study in Münster]. / Die Schmerzsituation von Bewohnern in der stationären Altenhilfe. Ergebnisse einer Studie in Münster.

BACKGROUND: Little is known about the phenomenon of pain in German nursing homes. In particular, it is unknown to what extent and severity pain occurs among residents and how their pain can be described. MATERIAL AND METHODS: A total of 13 nursing homes located in the city of Münster, Germany, were included as part of the health services research project "Action Alliance Pain-free City Münster." Data were collected from 436 residents over 65 years old via self-report or the observational pain tool pain assessment in advanced dementia, german version (PAINAD-G), according to the cognitive status of the residents. RESULTS: At the time of the interview, the majority of the residents questioned reported suffering from pain at rest and/or during movement. Approximately one quarter of residents complained about moderate to intolerable pain at rest and nearly 45% during movement. Residents encountered pain most often when standing up, sitting, resting in bed and walking and three quarters of residents had suffered from pain for more than 1 year. Many residents experienced pain in several body regions. Among residents assessed solely by the observational pain scale PAINAD-G, signs indicating pain existed in 21% (≥ 6) or 69% (≥ 2), respectively, depending on the cut-off value chosen on the PAINAD-G scale. CONCLUSION: Pain in nursing homes is a challenge that needs more attention as it has considerable negative consequences for the persons concerned. The extent of pain in the studied facilities indicates an urgent need for action on the part of all professionals caring for residents in nursing homes.

Prevention of group B streptococcal neonatal disease revisited. The DEVANI European project.

The purpose of this paper was to present the current knowledge on the prevention of group B streptococcus (GBS) neonatal infections and the status of prevention policies in European countries and to present the DEVANI pan-European program, launched in 2008. The aim of this program was to assess the GBS neonatal infection burden in Europe, to design a new vaccine to immunize neonates against GBS infections, to improve the laboratory performance for the diagnosis of GBS colonization and infection, and to improve the methods for the typing of GBS strains. The current guidelines for GBS prevention in different countries were ascertained and a picture of the burden before and after the instauration of prevention policies has been drawn. After the issue of the Centers for Disease Control and Prevention (CDC) guidelines, many European countries have adopted universal screening for the GBS colonization of pregnant women and intrapartum prophylaxis to colonized mothers. Nevertheless, some European countries continue advocating the risk factor approach to GBS prevention. Most European countries have implemented policies to prevent GBS neonatal infections and the burden of the disease has decreased during the last several years. Nevertheless, further steps are necessary in order to develop new strategies of prevention, to improve microbiological techniques to detect GBS colonization and infection, and to coordinate the prevention policies in the EU.

Primary erythromelalgia in a 12-year-old boy: positive response to sodium channel blockers despite negative SCN9A mutations.

Erythromelalgia is a rare disorder characterized by recurrent pain attacks, swelling and redness in the distal extremities. The primary forms of the disorder are caused by mutations in voltage-gated sodium channels. Treatment is difficult and controlled therapeutic studies offer little to no guidance. We report on a 12-year-old boy and his first occurrence of primary erythromelalgia. Genetic findings for mutations in the SCN9A gene, which encodes for the α-subunit of sodium channel NaV1.7, were negative. Although initial treatment with sodium nitroprusside was ineffective, subsequent medication with lidocaine and mexiletine, in combination with gabapentin, was successful. Despite negative findings for mutations in the sodium channels, the use of sodium channel blockers should be considered in these patients.

Significant decline in the erythromycin resistance of group A streptococcus isolates at a German paediatric tertiary care centre.

Group A streptococcus (GAS) is considered to be a major pathogen of bacterial tonsillopharyngitis in children. Although GAS is generally susceptible to penicillin, macrolides are often used as the second-line treatment. Over the last several decades, the rising macrolide resistance of GAS has been detected in several countries. With the current study, we aimed to determine the development of macrolide resistance at our paediatric centre. From March 2006 to May 2009, 350 GAS isolates were tested for susceptibility to erythromycin, azithromycin, clindamycin, penicillin and cefotaxime. Macrolide-resistant isolates were screened for the presence of genes related to macrolide resistance (mefA, ermB, ermTR, prtF1). In comparison to a prior study at our hospital, the erythromycin resistance rate decreased significantly from 13.6 to 2.6%. This effect may be attributable to a more restrictive use of macrolides in children in our region.

[Hemorrhagic skin lesions associated with infections]. / Infektionsassoziierte Hautblutungen.

A broad spectrum of bacterial, viral, and parasitic infections is associated with hemorrhagic skin lesions, typically petechiae. The most prominent underlying entity is fulminant bacterial sepsis, which requires urgent and intensive treatment. In most cases, however, a self-limiting viral disease is the underlying cause. Thus, the pediatrician frequently encounters a diagnostic dilemma between timely diagnosis of sepsis and unnecessary invasive diagnostics. This article reviews the broad differential diagnosis and pathophysiology of infection-associated hemorrhagic skin lesions and proposes a diagnostic algorithm for the combination of fever and petechiae.

[Japanese encephalitis: risk for endemic populations and for travellers]. / Encéphalite japonaise: risque pour les populations vivant en zones d'endémie et pour les voyageurs.

The importance of Japanese encephalitis (JE) in endemic populations and in travellers requires a balanced assessment. This disease represents an important public health problem in some endemic areas, which contrasts with the minimal risk for travellers to endemic areas. This is reflected by high numbers of infections mainly among children in endemic countries and by few case reports among tourists and even expatriates. The total number of case reports between 1978 and 2008 amounts to a risk of one to two cases per year. Nevertheless, some travelling groups may be at higher risk when visiting or working in high risk areas. A new vaccine against Japanese encephalitis will soon be registered in Switzerland. This paper contributes to the scarce data available for decision making whether or not to recommend the vaccination to tourists and expatriates.

[Differential diagnosis of neurodegenerative disorders in young adults]. / Differenzialdiagnosen zu neurodegenerativen Erkrankungen im jungen Erwachsenenalter.

Neurodegenerative diseases are relatively common and usually occur in older patients. In young adulthood, neurodegeneration is less common and more frequent due to underlying inborn errors of metabolism (IEMs) that typically have a wide range of clinical presentations. In the following overview, we present a case of SSPE and NBIA. The main differential diagnoses, cardinal symptoms, diagnosis and treatment options of neurodegenerative-like disesase in young adults are presented.

[Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome]. / Multiorganversagen bei Early-onset-B-Streptokokkensepsis: Erfolgreicher Einsatz einer kontinuierlichen venovenösen Hämofiltration (CVVH) beim Neugeborenen.

BACKGROUND: Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. CASE REPORT: After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. CONCLUSION: Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.