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RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively).ConclusionsThe results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

Mycobacterial infections, both tuberculosis and nontuberculous, are more common in patients with haematological malignancies and haematopoietic stem cell transplant recipients than in the general population-although these infections remain rare. Mycobacterial infections pose both diagnostic and therapeutic challenges. The management of mycobacterial infections is particularly complicated for patients in haematology because of the many drug-drug interactions between antimycobacterial drugs and haematological and immunosuppressive treatments. The management of mycobacterial infections must also consider the effect of delaying haematological management. We surveyed the management practices for latent tuberculosis infection (LTBI) in haematology centres in Europe. We then conducted a meticulous review of the literature on the epidemiology, diagnosis, and management of LTBI, tuberculosis, and nontuberculous mycobacterial infections among patients in haematology, and we formulated clinical guidelines according to standardised European Conference on Infections in Leukaemia (ECIL) methods. In this Review, we summarise the available literature and the recommendations of ECIL 8 for managing mycobacterial infections in patients with haematological malignancies.

Zusammenfassung Hintergrund Mit etwa 190.000 Asylanträgen im Jahr 2021 ist Deutschland das wichtigste Aufnahmeland von Asylsuchenden in Europa. Die vorliegenden Handlungsempfehlungen sollen eine Grundlage für eine evidenzbasierte und zielgerichtete infektiologische Versorgung minderjähriger Flüchtlinge schaffen. Ziele Die Handlungsempfehlungen sollen medizinisches Personal in der Versorgung minderjähriger Flüchtlinge unterstützen, um 1. einen unvollständigen Impfschutz frühzeitig zu erkennen und zu vervollständigen; 2. übliche Infektionskrankheiten zu diagnostizieren und zu behandeln; 3. in Deutschland seltene Infektionskrankheiten frühzeitig zu erkennen und zu therapieren. Material und Methoden Die Handlungsempfehlungen wurden als AWMF-Leitlinie Stufe 1 verfasst. Entsprechend wurden die Empfehlungen durch eine repräsentativ zusammengesetzte Expertengruppe der beteiligten Fachgesellschaften im informellen Konsens erarbeitet und final von den Vorständen der Fachgesellschaften offiziell verabschiedet. Ergebnisse Es werden Empfehlungen ausgesprochen, für den Umfang der Anamnese und der körperlichen Untersuchung minderjähriger Flüchtlinge. Für alle minderjährigen Flüchtlinge werden die Bestimmung eines Differenzialblutbildes sowie Untersuchungen auf Tuberkulose und Hepatitis B empfohlen. Je nach Herkunft und Alter werden weitere gezielte Untersuchungen z. B. auf Hepatitis C, HIV oder Schistosomiasis empfohlen. Zur raschen Vervollständigung des Impfstatus wird eine alters- und indikationsbezogene Priorisierung einzelner Impfungen vorgenommen. Diskussion Angesichts anhaltend hoher Flüchtlingszahlen ist eine weitere Professionalisierung der medizinischen Versorgung minderjähriger Flüchtlinge notwendig. Hierzu sollten die notwendigen strukturellen und personellen Rahmenbedingungen geschaffen werden.

Aerococcus urinae (A. urinae) is primarily recognized as a common pathogen in the geriatric population, causing urinary tract infection (UTI), sepsis, and endocarditis, predominantly in female patients. In the paediatric population, only a few case reports exist suggesting A. urinae causes malodorous urine in otherwise healthy boys. In this study, we investigated the spectrum of clinical and laboratory presentations of A. urinae detection in children. A retrospective, single-centre, case series including all patients with the detection of A. urinae during a 7-year study period. Patients with detection of A. urinae only in non-urogenital skin swabs were excluded. A total of 40 samples from 33 patients were identified of which 20 patients were included in the final analysis. The median (IQR) age was 6.8 (2.9–9.5) years; 18 (90%) patients were boys. Four patients were diagnosed with a UTI, six had malodorous urine without UTI, three were diagnosed with balanitis and seven showed A. urinae colonization in the urine culture. Urogenital disorders were present in 12 patients. Additional pathogens were detected in 13 patients. Recurrence of detection during our study period was observed in four (20%) patients. Conclusion: Beyond malodorous urine, A. urinae detection is associated with more severe presentations including UTI in the paediatric population. Pre-existing urogenital disorders were frequent, and therefore, a nephro-urological investigation should be considered in all cases of A. urinae detection in the paediatric population. What is Known:• Aerococcus urinae (A. urinae) is known to be a common pathogen in the geriatric population, causing urinary tract infection (UTI), sepsis, and endocarditis, predominantly in female patients.• In the paediatric population, A. urinae is mainly described as a low-grade pathogen. Some case reports describe A. urinae as the cause of extraordinary malodorous urine in otherwise healthy boys. What is New:• Beyond malodorous urine, A. urinae detection is associated with more severe presentations including UTI in the paediatric population.• A. urinae was mainly detected in boys with pre-existing urogenital disorders; therefore, a nephro-urological investigation should be considered in cases of A. urinae detection in the paediatric population.

Coronavirus disease 2019 (COVID-19) is usually less severe in children compared to adults. This study describes detailed clinical characteristics, treatment and outcomes of children with COVID-19 in a non-hospitalised and hospitalised setting and quantifies factors associated with admission to hospital and intensive care unit in children with SARS-CoV-2 infection on a nationwide level. Data were collected through the Swiss Paediatric Surveillance Unit from children p-value p-value p-value p-value Conclusion: This study confirms that COVID-19 is mostly a mild disease in children. Fever, rash and comorbidities are associated with higher admission rates. Continuous observation is necessary to further understand paediatric COVID-19, guide therapy and evaluate the necessity for vaccination in children.What is Known:• Clinical manifestations of SARS-CoV-2 infection in children vary from asymptomatic to critical disease requiring intensive care unit admission.• Most studies are based on hospitalised children only; currently, there is limited data on non-hospitalised children.What is New:• The clinical spectrum and severity of COVID-19 is influenced by age: in children less than 2 years, fever, cough and rhinorrhoea are the most common symptoms and in adolescents, fever, cough and headache are more common.• Hospitalised children more often presented with fever and rash, while anosmia/dysgeusia is more prevalent in non-hospitalised children.• Children with pre-existing comorbidities are more frequently hospitalised but do not require ICU admission more often.

Human saliva is a complex fluid containing proteins such as salivary cytokines, which can be used for diagnostic purposes, particularly among the pediatric population. This study aimed to assess the concentrations of salivary cytokines in healthy children and adolescents and determine their associations with age, sex, and oral and dental findings. Healthy children and adolescents aged 4–18 years were enrolled in this cross-sectional study. The concentrations of the following salivary cytokines were measured by Luminex technology: IFN-γ, IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IP-10, TNF-α, and VEGF-A. Additionally, oral and dental parameters were recorded using a standardized protocol. A total of 128 participants (mean age, 10.7 years; males, 50.8%) were enrolled. The levels of 1β, IL-6, IL-8, and IL-10 were significantly higher in those with gingivitis. Increased salivary flow rates were negatively correlated with IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, and VEGF-A concentrations. The findings of this study showed that the concentrations of most of the salivary cytokines were positively correlated with age and the presence of oral pathologies (such as gingivitis and caries) and negatively correlated with salivary flow rate.

BackgroundSubclinical tuberculosis (TB) is well recognized and defined as a disease state with absent or nonrecognized symptoms. The study identifies factors associated with subclinical TB and diagnostic strategies in a low-burden, high-resource country.MethodsData were collected between December 2013 and November 2019 through the Swiss Pediatric Surveillance Unit (SPSU). Children with culture/molecular confirmed TB, or who were treated with ≥3 antimycobacterial drugs, were included.ResultsA total of 138 (80%) children with TB disease were included in the final analysis, of which 43 (31%) were subclinical. The median age of children with subclinical compared to symptomatic TB was 3.7 (interquartile range [IQR] 2.2–7) and 9.7 (IQR 2.7–14.3) years, respectively (P = .003). The cause of investigation for TB was recorded in 31/43 (72.1%) of children with subclinical TB and included contact exposure in 25 (80.6%) of children. In children with subclinical TB, diagnosis was made by a combination of the following abnormal/confirming results: culture/molecular + immunodiagnostic + chest radiography in 12 (27.9%) cases, immunodiagnostic + chest radiography in 19 (44.2%) cases, culture/molecular + chest radiography in 2 (4.7%) cases, culture + immunodiagnostic in 1 (2.3%) case, chest radiography only in 8 (18.6%) cases, and immunodiagnostic only in 1 (2.3%) case.ConclusionsA notable proportion of children with TB had subclinical disease. This highlights the importance of non-symptom-based TB case finding in exposed children and refugees from high-TB-prevalence settings. TB screening in these asymptomatic children should therefore include a combination of immunodiagnostic testing and imaging followed by culture and molecular testing.

Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can be more severe in infants than in older children. To date, only a few case series have reported data on neonates with COVID-19, including mostly asymptomatic neonates who were tested because of exposure to maternal SARS-CoV-2 infection. This study summarises nationwide epidemiological data, clinical characteristics, treatment and outcomes of neonates presenting with symptomatic SARS-CoV-2 infection. METHODS: Data were prospectively collected through the Swiss Paediatric Surveillance Unit from hospitalised neonates with laboratory-confirmed SARS-CoV-2 infection (positive polymerase chain reaction on a respiratory sample) from 1 March 2020 to 31 September 2021. All 29 paediatric hospitals in Switzerland reported cases. RESULTS: In total, 73 neonates were included; 7 (10%) were preterm. The median age at presentation was 17 days (interquartile range [IQR] 11–23); 40 (55%) were female. The majority of neonates (64, 88%) were admitted from home. Nine (12%) had a pre-existing medical condition. Overall, the most common symptom recorded was fever in 52 (71%), followed by rhinorrhoea or nasal congestion in 32 (44%) and respiratory distress in 19 (26%). Twenty (27%) neonates presented with fever without a source. Seven (10%) neonates were admitted to an intensive care unit (5 for respiratory failure and 2 for monitoring). One (1%) neonate required inotropic support. The median length of hospital stay in term neonates was 4 days (IQR 3–5). Two (3%) were treated with corticosteroids and 1 (1%) with remdesivir. In total, 60 (82%) neonates had contact with a known or suspected SARS-CoV-2 index case. All of the 71 neonates for whom data were available were discharged to their homes without symptoms. CONCLUSION: In neonates, COVID-19 mainly presents with fever, and symptoms of upper and lower respiratory tract infection. The clinical course is mostly mild, requiring a short period of hospitalisation. COVID-19 needs to be added as a differential diagnosis in neonates who present with fever without a source. However, the presence of SARS-CoV-2 should not deter from the search for a serious bacterial infection. Further data from surveillance studies are needed to better understand COVID-19 in neonates, guide therapy and to evaluate whether the clinical spectrum is changing with new SARS-CoV-2 variants.

Background Bacillus Calmette–Guerin (BCG) vaccine provides partial protection against Buruli ulcer caused by Mycobacterium ulcerans in epidemiological studies. This study aimed to quantify M. ulcerans-specific immune responses induced by BCG immunisation. Methods Intracellular cytokine analysis of in-vitro experiments done 10 weeks after BCG immunisation in 130 Australian infants randomised to one of three BCG vaccine strains given either at birth (BCG-Denmark, BCG-Japan, or BCG-Russia) or at two months of age (BCG-Denmark). Results Proportions of polyfunctional CD4+ T-cells were higher in M. ulcerans-stimulated compared to unstimulated control samples. These proportions were not influenced by the vaccine strain or timing of the immunisation. The M. ulcerans-specific immune responses showed similar patterns to those observed in M. tuberculosis-stimulated samples, although they were of lower magnitude. Conclusions Our data show that BCG immunisation induces M. ulcerans-specific immune responses in infants, likely explaining the cross-protective effect observed in epidemiological studies. (ACTRN12608000227392)

Based on 190,000 applications for asylum, Germany remains a top destination for refugees and asylum seekers in Europe. The updated recommendations are considered evidence-based and targeted guidelines for the diagnosis and prevention of infectious diseases in underage refugees and asylum seekers.The objective of these recommendations is to guide medical staff in the care of minor refugees, in particular to:1. assure early recognition and completion of incomplete vaccination status,2. diagnose and treat common infectious diseases,3. recognize and treat imported infectious diseases that are considered uncommon to the German healthcare system.The recommendations have been formally written to be published as AWMF S1 guidelines.This includes a representative expert panel appointed by several professional societies, and formal adoption of the recommendations by the board of directors of all societies concerned.Recommendations are given for the medical evaluation of minor refugees, including medical history and physical examination. A blood count as well as screening for tuberculosis and hepatitis B should be offered to all minor refugees. In addition, screening for other infectious diseases like hepatitis C, HIV or schistosomiasis should be considered depending on age and country of origin. Vaccinations are recommended based on both age and country of origin.As thousands of minor refugees continue to seek shelter in Germany every year, professional health care with adequate financial support needs to be established to ensure an appropriate medical treatment of this particularly vulnerable population.

The risk of tuberculosis (TB) disease is increased in children with chronic kidney disease (CKD), even higher in stage 5 CKD/kidney failure and especially high after kidney transplantation due to immunosuppression. TB disease may follow recent primary infection, or result from reactivation of latent infection. Reactivation is more common in adults, while progression following primary infection makes up a greater proportion of disease in children. Recommendations for preventing TB disease in some low TB incidence countries have previously included offering Bacillus Calmette-Guérin (BCG) vaccine to all children listed for kidney transplant if they had not received this as part of previous national immunisation programmes. Based on the available evidence, we recommend modifying this practice, focusing instead on awareness of risk factors for TB exposure, infection and disease and the use of appropriate testing strategies to identify and treat TB infection and disease. Supplementary Information The online version contains supplementary material available at 10.1007/s00467-020-04844-5.

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG’s effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.

The aim of this study was to assess the characteristics of asylum-seeking children with medical complexity visiting a tertiary care hospital in Switzerland, detailing their underlying medical conditions and management. Asylum-seeking patients with frequent visits between January 2016 and December 2017 were identified using administrative and electronic health records. Of 462 patients, 19 (4%) fulfilled the inclusion criteria with 811 (45%) visits. The age of the 19 patients ranged from 0 to 16.7 years (median of 7 years) with two main age groups identified: 12 years. Nine (47%) patients originated from Syria. A total of 34/811(4%) visits were hospital admissions, 66/811 (8%) emergency department visits and 320/811(39%) outpatient department visits. In children

The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis.What is Known:•Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age.•Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture.What is New:•Vesicoureteric reflux (VUR) remains a risk factor for UTI butper seis neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended.•A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.

Background Malaria is a leading cause of morbidity and mortality in refugee children in high-transmission parts of Africa. Characterizing the clinical features of malaria in refugees can inform approaches to reduce its burden. Methods The study was conducted in a high-transmission region of northern Zambia hosting Congolese refugees. We analyzed surveillance data and hospital records of children with severe malaria from refugee and local sites using multivariable regression models and geospatial visualization. Results Malaria prevalence in the refugee settlement was similar to the highest burden areas in the district, consistent with the local ecology and leading to frequent rapid diagnostic test stockouts. We identified 2197 children hospitalized for severe malaria during the refugee crisis in 2017 and 2018. Refugee children referred from a refugee transit center (n = 63) experienced similar in-hospital mortality to local children and presented with less advanced infection. However, refugee children from a permanent refugee settlement (n = 110) had more than double the mortality of local children (P < .001), had lower referral rates, and presented more frequently with advanced infection and malnutrition. Distance from the hospital was an important mediator of the association between refugee status and mortality but did not account for all of the increased risk. Conclusions Malaria outcomes were more favorable in refugee children referred from a highly outfitted refugee transit center than those referred later from a permanent refugee settlement. Refugee children experienced higher in-hospital malaria mortality due in part to delayed presentation and higher rates of malnutrition. Interventions tailored to the refugee context are required to ensure capacity for rapid diagnosis and referral to reduce malaria mortality.

Background Transmission chains within small urban areas (accommodating∼30% of the European population) greatly contribute to case burden and economic impact during the ongoing COVID-19 pandemic, and should be a focus for preventive measures to achieve containment. Here, at very high spatio-temporal resolution, we analysed determinants of SARS-CoV-2 transmission in a European urban area, Basel-City (Switzerland). Methodology. We combined detailed epidemiological, intra-city mobility, and socioeconomic data-sets with whole-genome-sequencing during the first SARS-CoV-2 wave. For this, we succeeded in sequencing 44% of all reported cases from Basel-City and performed phylogenetic clustering and compartmental modelling based on the dominating viral variant (B.1-C15324T; 60% of cases) to identify drivers and patterns of transmission. Based on these results we simulated vaccination scenarios and corresponding healthcare-system burden (intensive-care-unit occupancy). Principal Findings. Transmissions were driven by socioeconomically weaker and highly mobile population groups with mostly cryptic transmissions, whereas amongst more senior population transmission was clustered. Simulated vaccination scenarios assuming 60-90% transmission reduction, and 70-90% reduction of severe cases showed that prioritizing mobile, socioeconomically weaker populations for vaccination would effectively reduce case numbers. However, long-term intensive-care-unit occupation would also be effectively reduced if senior population groups were prioritized, provided there were no changes in testing and prevention strategies. Conclusions. Reducing SARS-CoV-2 transmission through vaccination strongly depends on the efficacy of the deployed vaccine. A combined strategy of protecting risk groups by extensive testing coupled with vaccination of the drivers of transmission (i.e. highly mobile groups) would be most effective at reducing the spread of SARS-CoV-2 within an urban area., medRxiv

In childhood tuberculosis (TB), with an estimated 69% of missed cases in children under 5 years of age, the case detection gap is larger than in other age groups, mainly due to its paucibacillary nature and children’s difficulties in delivering sputum specimens. Accurate and accessible point-of-care tests (POCTs) are needed to detect TB disease in children and, in turn, reduce TB-related morbidity and mortality in this vulnerable population. In recent years, several POCTs for TB have been developed. These include new tools to improve the detection of TB in respiratory and gastric samples, such as molecular detection of Mycobacterium tuberculosis using loop-mediated isothermal amplification (LAMP) and portable polymerase chain reaction (PCR)-based GeneXpert. In addition, the urine-based detection of lipoarabinomannan (LAM), as well as imaging modalities through point-of-care ultrasonography (POCUS), are currently the POCTs in use. Further to this, artificial intelligence-based interpretation of ultrasound imaging and radiography is now integrated into computer-aided detection products. In the future, portable radiography may become more widely available, and robotics-supported ultrasound imaging is currently being trialed. Finally, novel blood-based tests evaluating the immune response using “omic-“techniques are underway. This approach, including transcriptomics, metabolomic, proteomics, lipidomics and genomics, is still distant from being translated into POCT formats, but the digital development may rapidly enhance innovation in this field. Despite these significant advances, TB-POCT development and implementation remains challenged by the lack of standard ways to access non-sputum-based samples, the need to differentiate TB infection from disease and to gain acceptance for novel testing strategies specific to the conditions and settings of use., Pathogens, 11 (3), ISSN:2076-0817

Transmission chains within small urban areas (accommodating ∼30 per cent of the European population) greatly contribute to case burden and economic impact during the ongoing coronavirus pandemic and should be a focus for preventive measures to achieve containment. Here, at very high spatio-temporal resolution, we analysed determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in a European urban area, Basel-City (Switzerland). We combined detailed epidemiological, intra-city mobility and socio-economic data sets with whole-genome sequencing during the first SARS-CoV-2 wave. For this, we succeeded in sequencing 44 per cent of all reported cases from Basel-City and performed phylogenetic clustering and compartmental modelling based on the dominating viral variant (B.1-C15324T; 60 per cent of cases) to identify drivers and patterns of transmission. Based on these results we simulated vaccination scenarios and corresponding healthcare system burden (intensive care unit (ICU) occupancy). Transmissions were driven by socio-economically weaker and highly mobile population groups with mostly cryptic transmissions which lacked genetic and identifiable epidemiological links. Amongst more senior population transmission was clustered. Simulated vaccination scenarios assuming 60-90 per cent transmission reduction and 70-90 per cent reduction of severe cases showed that prioritising mobile, socio-economically weaker populations for vaccination would effectively reduce case numbers. However, long-term ICU occupation would also be effectively reduced if senior population groups were prioritised, provided there were no changes in testing and prevention strategies. Reducing SARS-CoV-2 transmission through vaccination strongly depends on the efficacy of the deployed vaccine. A combined strategy of protecting risk groups by extensive testing coupled with vaccination of the drivers of transmission (i.e. highly mobile groups) would be most effective at reducing the spread of SARS-CoV-2 within an urban area., Virus Evolution, 8 (1), ISSN:2057-1577

The Bacillus cereus-group (B. cereus sensu lato) includes common, usually avirulent species, often considered contaminants of patient samples in routine microbiological diagnostics, as well as the highly virulent B. anthracis. Here we describe 16 isolates from 15 patients, identified as B. cereus-group using a MALDI-TOF MS standard database. Whole genome sequencing (WGS) analysis identified five of the isolates as B. anthracis species not carrying the typical virulence plasmids pXO1 and pXO2, four isolates as B. paranthracis, three as B. cereus sensu stricto, two as B. thuringiensis, one as B. mobilis, and one isolate represents a previously undefined species of Bacillus (B. basilensis sp. nov.). More detailed analysis using alternative MALDI-TOF MS databases, biochemical phenotyping, and diagnostic PCRs, gave further conflicting species results. These cases highlight the difficulties in identifying avirulent B. anthracis within the B. cereus-group using standard methods. WGS and alternative MALDI-TOF MS databases offer more accurate species identification, but so far are not routinely applied. We discuss the diagnostic resolution and discrepancies of various identification methods.

In low tuberculosis-burden countries, children and adolescents with the highest incidence of tuberculosis (TB) infection or disease are usually those who have immigrated from high-burden countries. It is, therefore, essential that low-burden countries provide healthcare services to immigrant and refugee families, to assure that their children can receive proper testing, evaluation, and treatment for TB. Active case-finding through contact tracing is a critical element of TB prevention in children and in finding TB disease at an early, easily treated stage. Passive case-finding by evaluating an ill child is often delayed, as other, more common infections and conditions are suspected initially. While high-quality laboratory services to detect Mycobacterium tuberculosis are generally available, they are often underutilized in the diagnosis of childhood TB, further delaying diagnosis in some cases. Performing research on TB disease is difficult because of the low number of cases that are spread over many locales, but critical research on the evaluation and treatment of TB infection has been an important legacy of low-burden countries. The continued education of medical providers and the involvement of educational, professional, and non-governmental organizations is a key element of maintaining awareness of the presence of TB. This article provides the perspective from North America and Western Europe but is relevant to many low-endemic settings. TB in children and adolescents will persist in low-burden countries as long as it persists throughout the rest of the world, and these wealthy countries must increase their financial commitment to end TB everywhere.

The

Background: In individuals living with HIV infection the development of tuberculosis (TB) is associated with rapid progression from asymptomatic TB infection to active TB disease. Sputum-based diagnostic tests for TB have low sensitivity in minimal and subclinical TB precluding early diagnosis. The immune response to novel Mycobacterium tuberculosis in-vivo expressed and latency associated antigens may help to measure the early stages of infection and disease progression and thereby improve early diagnosis of active TB disease.Methods: Serial prospectively sampled cryopreserved lymphocytes from patients of the Swiss HIV Cohort Study developing TB disease (“cases”) and matched patients with no TB disease (“controls”) were stimulated with 10 novel Mycobacterium tuberculosis antigens. Cytokine concentrations were measured in cases and controls at four time points prior to diagnosis of TB: T1-T4 with T4 being the closest time point to diagnosis.Results: 50 samples from nine cases and nine controls were included. Median CD4 cell count at T4 was 289/ul for the TB-group and 456/ul for the control group. Viral loads were suppressed in both groups. At T4 Rv2431c-induced and Rv3614/15c-induced interferon gamma-induced protein (IP)-10 responses and Rv2031c-induced and Rv2346/Rv2347c-induced tumor necrosis factor (TNF)-α responses were significantly higher in cases compared to controls (p < 0.004). At T3 - being up to 2 years prior to TB diagnosis - Rv2031c-induced TNF-α was significantly higher in cases compared to controls (p < 0.004). Area under the receiver operating characteristics (AUROC) curves resulted in an AUC > 0.92 for all four antigen-cytokine pairs.Conclusion: The in vitro Mycobacterium tuberculosis-specific immune response in HIV-infected individuals that progress toward developing TB disease is different from those in HIV-infected individuals that do not progress to developing TB. These differences precede the clinical diagnosis of active TB up to 2 years, paving the way for the development of immune based diagnostics to predict TB disease at an early stage.

Vorgeschichte: Eine 11-jährige Patientin stellte sich auf der Notfallstation aufgrund einer seit einem Tag progredienten Zungenschwellung vor. Es bestanden keine bekannten Vorerkrankungen und eine unauffällige Familienanamnese. Anamnestisch habe sie seit 3 Monaten rezidivierende, teils juckende[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2021, 49. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 35. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

In anticipation of an interseasonal respiratory syncytial virus (RSV) epidemic, a clinician-led reporting system was rapidly established to capture RSV infections in Swiss hospitals, starting in January 2021. Here, we present details of the reporting system and first results to June 2021. An unusual epidemiology was observed with an interseasonal surge of RSV infections associated with COVID-19-related non-pharmacological interventions. These data allowed real-time adjustment of RSV prophylaxis guidelines and consequently underscore the need for and continuation of systematic nationwide RSV surveillance.

Introduction: Immunisation during pregnancy to protect infants against tetanus, pertussis and influenza is recommended in many countries. However, maternal antibodies can interfere with infant vaccine responses. We investigated the effect of antenatal diphtheria-tetanus-acellular pertussis (dTpa) and trivalent inactivated influenza (TIV) immunisation on specific and heterologous antibody responses to routine immunisations given in the first year of life. Methods: In total, 471 healthy infants were included. At 7 and 13 months of age, antibodies to the primary course of routine vaccines given at 6 weeks, 4 and 6 months of age (pertussis (pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN)), polio (type 1, 2, 3), Haemophilus influenzae type b (Hib), pneumococcus (serotype 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F)) were measured, and at 13 months of age, antibodies to the 12-month routine vaccines (Hib, meningococcus C, measles, mumps and rubella). The seroprotection rates for each vaccine and the geometric mean concentrations (GMC) of antibodies were compared between infants whose mothers did or did not receive dTpa or TIV immunisation during pregnancy. Results: A total of 369 infants were included in the final analysis. Maternal dTpa immunisation was associated with reduced antibody responses to both specific (diphtheria and pertussis) and heterologous (polio and pneumococcus) vaccine antigens. This effect was stronger for persistence of antibodies at 13 months of age than it was at 7 months of age. At 7 months of age, adjusted average antibody concentrations were significantly lower for diphtheria, pertussis (PT, FHA, PRN) and polio type 2, and at 13 months of age, for diphtheria, pertussis (PT, FHA, PRN), polio type 1–3 and pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 18C and 23F. Additionally, at 13 months of age, seroprotection rates for diphtheria, PT, pneumococcal serotype 1, 6A and 6B were significantly lower in infants after maternal dTpa immunisation. In contrast, for Hib, in infants with maternal dTpa immunisation, the adjusted average antibody concentration and the seroprotection rate were higher, particularly at 7 months of age. Maternal TIV immunisation had minimal effect on infant vaccine responses. Conclusion: Whilst maternal immunisation protects infants in the first few months of life, it might interfere with both specific and heterologous (unrelated) vaccines responses in infants. Research in context: Evidence before this study: Maternal immunisation during pregnancy helps to protect infants during the period before they complete their primary immunisations. It has been proven to be safe and beneficial. However, pre-existing maternal antibodies can influence antibody responses following infant immunisation, an effect called ‘blunting’. Previous studies have investigated the influence of dTpa but not influenza immunisation during pregnancy on infant vaccine responses. The majority of studies investigated antibody concentrations only to the specific vaccine antigens included in the maternal immunisation, and there is scarce data available on heterologous vaccine responses, particularly pneumococcal responses.Added value of this study: In this study, we have shown that maternal dTpa immunisation during pregnancy is associated with reduced antibody responses to both specific (diphtheria and pertussis) and heterologous (polio and pneumococcus) vaccine antigens. This effect is stronger for persistence of antibodies at 13 months of age than after primary immunisation at 7 months of age. In contrast, for Hib, in infants with maternal dTpa immunisation, antibody concentrations are higher, particularly at 7 months of age. Maternal TIV immunisation has minimal effect on infant vaccine responses.Implications of all the available evidence: Whilst maternal immunisation protects infants in the first few months of life, it might interfere with both specific and heterologous (unrelated) vaccines responses in infants. As most vaccines induce very high antibody responses, small differences in antibody concentrations may not be of clinical significance. However, since maternal immunisation during pregnancy also influences seroprotection rates, strategies, such as additional booster doses in the second year of life, particularly for pertussis and pneumococcus, might need to be considered to address this. Keywords: Adacel, Boostrix, dTpa, Flu, Influenza, Vaccination, Antibodies, Humoral, Immunoglobulin, Immunisation, Titre, Heterologous, Non-specific

Between 2015 and 2017, an estimated 200,000 to 400,000 children were seeking asylum each year in EU/EEA countries. As access to high-quality health care is important, we collected and compared current recommendations across Europe for a consensus recommendation on medical care for migrant (asylum-seeking and refugee) children. Existing recommendations were collected from published literature and identified through national representatives from paediatric societies of 31 EU/EEA countries through the European Academy of Paediatrics (EAP). Recommendations were systematically extracted and collected in a database. Those mentioned in at least one recommendation were evaluated for inclusion, and evidence on recommendations was specifically identified in literature searches focused on recent evidence from Europe. For eight EU/EEA countries, a national recommendation was identified. Growth and development, vision and hearing impairment, skin and dental problems, immunisations, anaemia, micronutrient deficiency, helminths, hepatitis B and C, human immunodeficiency virus, malaria, schistosomiasis, syphilis, tuberculosis, mental health disorder and sexual health were most frequently mentioned and therefore selected for inclusion in the recommendation. Conclusion: The current document includes general recommendations on ethical standards, use of interpreters and specific recommendations for prevention or early detection of communicable and non-communicable diseases. It may serve as a tool to ensure the fundamental right that migrant children in Europe receive a comprehensive, patient-centred health care.

Background Migrants and refugees have important health needs and face inequalities in their health status. Health care delivery to this patient group has become a challenging public health focus in high income countries. This paper summarizes current knowledge on health care delivery to migrants and refugees in high-income countries from multiple perspectives. Methods We performed a systematic literature review including primary source qualitative and quantitative studies between 2000 and 2017. Articles were excluded if the study setting was in low- or middle-income countries or focused on skilled migration. Quality assessment was done for qualitative and quantitative studies separately. Predefined variables were extracted in a standardized form. Authors were approached to provide missing information. Results Of 185 identified articles, 35 were included in the final analysis. We identified three main topics of challenges in health care delivery: communication, continuity of care and confidence. All but one study included at least one of the three main topics and in 21/35 (60%) all three topics were mentioned. We further developed the 3C model and elaborated the interrelatedness of the three topics. Additional topics identified showed that the specific regional context with legal, financial, geographical and cultural aspects is important and further influences the 3C model. Conclusions The 3C model gives a simple and comprehensive, patient-centered summary of key challenges in health care delivery for refugees and migrants. This concept is relevant to support clinicians in their day to day practice and in guiding stakeholders in priority setting for refugee and migrant health policies. Electronic supplementary material The online version of this article (10.1186/s12889-019-7049-x) contains supplementary material, which is available to authorized users.

Background Childhood tuberculosis (TB) is acquired after exposure to an infectious TB case, often within the household. We prospectively screened children 6-59 months of age, exposed and unexposed to an infectious TB case within the same household, for latent tuberculosis infection (LTBI), in Dar es Salaam, Tanzania. Methods We collected medical data and clinical specimens (to evaluate for helminths, TB and HIV coinfections) and performed physical examinations at enrollment and at 3-month and 6-month follow-up surveys. LTBI was assessed using QuantiFERON-TB Gold (QFT) at enrollment and at 3 months. Results In total, 301 children had complete data records (186 with TB exposure and 115 without known TB exposure). The median age of children was 26 months (range: 6-58); 52% were females, and 4 were HIV positive. Eight children (3%) developed TB during the 6-month follow-up. We found equal proportions of children with LTBI among those with and without exposure: 20% (38/186) versus 20% (23/115) QFT-positive, and 2% (4/186) versus 4% (5/115) indeterminate QFT. QFT conversion rate was 7% (22 children) and reversion 8% (25 children). Of the TB-exposed children, 72% initiated isoniazid preventive therapy, but 61% of parents/caregivers of children with unknown TB exposure and positive QFT refused isoniazid preventive therapy. Conclusions In this high burden TB setting, TB exposure from sources other than the household was equally important as household exposure. Nearly one third of eligible children did not receive isoniazid preventive therapy. Evaluation for LTBI in children remains an important strategy for controlling TB but should not be limited to children with documented TB exposure.

Background The clinical course of Campylobacter infection varies in symptoms and severity depending on host factors, virulence of the pathogen and initiated therapy. The type VI secretion system (T6SS) has been identified as a novel virulence factor, which mediates contact-dependent injection of enzymes and toxins into competing bacteria or host cells and facilitates the colonisation of a host organism. We aimed to compare the clinical course of Campylobacter infection caused by strains with and without the T6SS and identify possible associations between this putative virulence factor and the clinical manifestations of disease. Methods From April 2015 to January 2017, patients with detection of Campylobacter spp. were identified at the University Hospital of Basel and the University Children’s Hospital of Basel and included in this case-control study. Presence of the T6SS gene cluster was assayed by PCR targeting the hcp gene, confirmed with whole genome sequencing. Pertinent clinical data was collected by medical record review. Differences in disease- and host-characteristics between T6SS-positive (case) and –negative (control) were compared in a uni- and multi-variable analysis. Hospital admission, antibiotic therapy, admission to intensive care unit, development of bacteraemia and in-hospital mortality were considered as clinical endpoints. Results We identified 138 cases of Campylobacter jejuni infections and 18 cases of Campylobacter coli infections from a paediatric and adult population. Analyses were focused on adult patients with C. jejuni (n = 119) of which 16.8% were T6SS-positive. Comparisons between T6SS-positive and -negative C. jejuni isolates did not reveal significant differences regarding clinical manifestations or course of disease. All clinical endpoints showed a similar distribution in both groups. A higher score in the Charlson Comorbidity Index was associated with T6SS-positive C. jejuni isolates (p

One and seven months after the 6-month vaccinations and one month after the 12-month vaccinations, antibody concentrations to diphtheria, tetanus, pertussis, polio (serotypes 1-3), Haemophilus influenzae type b (Hib), pneumococcus (13 serotypes), meningococcus C, measles, mumps and rubella were measured using fluorescent bead-based multiplex immune-assays. For the correlation of antibody responses, Spearman's rank correlation coefficients (ρ) with 95% confidence intervals (CI) were calculated between responses to each vaccine antigen.

The administration of drugs for the treatment of tuberculosis (TB) in children can be time-consuming and challenging, and non-adherence is a major cause of treatment failure [1]. Several factors may contribute to non-adherence, including lack of paediatric formulations, pill burden, fasting requirements, palatability, length of therapy or toxicity. Recently, the World Health Organization (WHO) has pushed for the development of child-friendly TB medicines that meet the dosage guidelines set in 2009 [2]. These should include child-friendly fixed-dose combinations (pFDC) of first-line oral TB drugs, which are dispersible, palatable, simple to administer and affordable [3]. Some of these pFDC have been developed and produced by Macleods (India) and Micro Labs (India), are WHO-prequalified (WHO Prequalification of Medicines Programme, PQP) and were included in the 6th edition of the WHO Essential Medicines List for Children in 2017 [4]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Graham has nothing to disclose. Conflict of interest: Antoni NOGUERA-JULIAN was supported by “Subvencions per a la Intensificacio de Facultatius Especialistes” (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016-2020) [SLT008/18/00193]. Conflict of interest: Dr. Danilo Buonsenso has nothing to disclose. Conflict of interest: Dr. Lindsay Mckenna has nothing to disclose. Conflict of interest: James A. SEDDON is supported by a Clinician Scientist Fellowship jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement (MR/R007942/1). Conflict of interest: Dr. Nicole Ritz has nothing to disclose.

IntroductionThe humoral response to vaccinations varies widely between individuals. There is no data available on the correlation between responses to different vaccines. In this study, we investigated the correlation of antibody responses between routine vaccine antigens in infants.MethodsOne and seven months after the 6-month vaccinations and one month after the 12-month vaccinations, antibody concentrations to diphtheria, tetanus, pertussis, polio (serotypes 1-3), Haemophilus influenzae type b (Hib), pneumococcus (13 serotypes), meningococcus C, measles, mumps and rubella were measured using fluorescent bead-based multiplex immune-assays. For the correlation of antibody responses, Spearman’s rank correlation coefficients (ρ) with 95% confidence intervals (CI) were calculated between responses to each vaccine antigen.ResultsThe correlation between concentrations of antibodies to the vaccinations ending at 6 months of age was higher one month compared to seven months after vaccination. The strongest correlations at both time points were observed between antibody responses to different polio serotypes, certain pneumococcal serotypes and between responses to diphtheria and pneumococcal (conjugated to a diphtheria toxoid) vaccine antigens. Correlation between responses to tetanus, Hib, pertussis, polio and other vaccine antigens were weak. The correlation between antibody responses to the 12-month vaccine antigens was weaker than to the 6-month vaccine antigens and there was a negative correlation between responses to measles, mumps, rubella vaccine and non-live vaccine antigens (meningococcus C, tetanus and Hib). There was only weak correlation between antibody responses to vaccines of the same type (e.g. conjugated polysaccharide or toxoid vaccines).ConclusionCorrelation between antibody responses to similar antigens in the same vaccine (such as different serotypes of a bacteria or virus), as well as responses to antigens conjugated to similar carrier proteins, are strong. In contrast, correlation between responses to other vaccines are weak. Measuring antibody responses to one or a few vaccine antigens therefore does not offer a reliable surrogate marker of responses to unrelated vaccines.

The article “Swiss consensus recommendations on urinary tract infections in children”

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce.Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing.Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance.Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation.Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged.