Increased breadth and neutralization of antibodies against SARS-CoV-2 variants after infection and vaccination: A serosurveillance study in pediatric patients of Southern Switzerland.

Little information is available about the nature of the immune response in children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. The aim of this study is to define the seroprevalence and the features of the antibody response in children of Southern Switzerland during the different waves of Coronavirus Disease 2019 (COVID-19) pandemic. By analyzing 756 sera collected from children aged 0 to 16 years admitted to the Institute of Pediatrics of Southern Switzerland during the prepandemic period (before March 2020) and the first four pandemic waves (between March 2020 and June 2022), we investigated binding titers, cross-reactivity, and neutralizing properties of the serum antibodies against SARS-CoV-2 variants. Seroprevalence varied from 6% during the first wave to 14% and 17% during the second and third waves, respectively, peaking at 39% during the fourth wave. The 96 seropositive cases were mostly asymptomatic (42.7%) or showed mild (20.8%) to moderate (32.3%) symptoms. Moderate symptoms and close contact with COVID-19-positive individuals were associated with a higher infection risk (P < 0.001). The antibody response was mainly driven by IgG directed to the receptor-binding domain (RBD) of Wuhan-1 SARS-CoV-2 Spike (S). Children infected in the first three waves produced antibodies with up to 11-fold and 5.5-fold reduction in binding and neutralizing titers, respectively, against different SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, BA.2, and BA.5. Such reductions were less pronounced in children infected during the fourth wave, who showed the highest frequency and titers of neutralizing antibodies against the same variants. Compared to infection, vaccination with a Wuhan-1-based messenger RNA (mRNA) vaccine induced higher and heterogenous levels of antibodies cross-reacting to the different SARS-CoV-2 variants analyzed.   Conclusions: Despite the high burden of COVID-19 in Southern Switzerland, we observed an initial low seroprevalence of SARS-CoV-2 in children, which increased in the later waves. The antibody response was poor in the first three waves and improved in the fourth wave, when children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants. What is Known: • Children were marginally affected by the initial SARS-CoV-2 variants. • The number of infected and hospitalized children increased after the appearance of the Omicron variants. What is New: • Seroprevalence of SARS-CoV-2 in children of Southern Switzerland increased overtime. • Children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants in the fourth wave compared to children infected in the first three waves.

Transient secondary pseudo-hypoaldosteronism in infants with urinary tract infections: systematic literature review.

Infants with a congenital anomaly of the kidney and urinary tract sometimes present with hyponatremia, hyperkalemia, and metabolic acidosis due to under-responsiveness to aldosterone, hereafter referred to as secondary pseudo-hypoaldosteronism. The purpose of this report is to investigate pseudo-hypoaldosteronism in infant urinary tract infection. A systematic review was conducted following PRISMA guidelines after PROSPERO (CRD42022364210) registration. The National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar without limitations were used. Inclusion criteria involved pediatric cases with documented overt pseudo-hypoaldosteronism linked to urinary tract infection. Data extraction included demographics, clinical features, laboratory parameters, management, and course. Fifty-seven reports were selected, detailing 124 cases: 95 boys and 29 girls, 10 months or less of age (80% of cases were 4 months or less of age). The cases exhibited hyponatremia, hyperkalemia, acidosis, and activated renin-angiotensin II-aldosterone system. An impaired kidney function was found in approximately every third case. Management included antibiotics, fluids, and, occasionally, emergency treatment of hyperkalemia, hyponatremia, or acidosis. The recovery time averaged 1 week for electrolyte, acid-base imbalance, and kidney function. Notably, anomalies of the kidney and urinary tract were identified in 105 (85%) cases. CONCLUSIONS: This review expands the understanding of overt transient pseudo-hypoaldosteronism complicating urinary tract infection. Management involves antimicrobials, fluid replacement, and consideration of electrolyte imbalances. Raising awareness of this condition within pediatric hospitalists is desirable. WHAT IS KNOWN: • Infants affected by a congenital anomaly of the kidney and urinary tract may present with clinical and laboratory features resembling primary pseudo-hypoaldosteronism. • Identical features occasionally occur in infant urinary tract infection. WHAT IS NEW: • Most cases of secondary pseudo-hypoaldosteronism associated with a urinary tract infection are concurrently affected by a congenital anomaly of the kidney and urinary tract. • Treatment with antibiotics and parenteral fluids typically results in the normalization of sodium, potassium, bicarbonate, and creatinine within approximately 1 week.

The changing clinical presentation of COVID-19 in children during the course of the pandemic.

AIM: To investigate the evolution of clinical symptoms of COVID-19 in children throughout the pandemic. METHODS: In this national prospective surveillance study, symptoms in children hospitalised with COVID-19 were collected from all paediatric hospitals in Switzerland between March 2020 and March 2023. Data was analysed across four time periods, according to the predominantly circulating SARS-CoV-2 variant: T1 (wild-type), T2 (Alpha), T3 (Delta) and T4 (Omicron), as well as by age group. RESULTS: The study included 1323 children. The proportion of children admitted to an intensive care unit remained stable throughout the pandemic. However, the pattern and frequency of clinical manifestations changed over time. Respiratory symptoms were less prevalent during T1 (wild-type), fever during T2 (Alpha) and rash during T4 (Omicron). In contrast, fever and neurological symptoms were more prevalent during T4 (Omicron). Newly described symptoms during T4 (Omicron) included conjunctivitis, laryngotracheitis and seizures. Fever was more prevalent among neonates and infants whereas respiratory symptoms were more common among infants. Gastrointestinal symptoms were more frequent among toddlers, while both toddlers and school-aged children presented with neurological symptoms more often than other age groups. CONCLUSION: Continuous surveillance is required to detect changes in manifestations and there by be prepared for the optimal management of complications in children with COVID-19.

Epstein-Barr virus as promoter of Lemierre syndrome: systematic literature review.

PURPOSE: To investigate a possible link between acute Epstein-Barr virus infection and Lemierre syndrome, a rare yet life-threatening infection. METHODS: A systematic review was conducted adhering to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Diagnosis criteria for Lemierre syndrome were established, and data extraction encompassed demographic data, clinical, and laboratory information. RESULTS: Out of 985 initially identified papers, 132 articles were selected for the final analysis. They reported on 151 cases of Lemierre syndrome (76 female and 75 male patients with a median of 18 years) alongside interpretable results for Epstein-Barr virus serology. Among these, 38 cases (25%) tested positive for acute Epstein-Barr virus serology. There were no differences in terms of age, sex, or Fusobacterium presence between the serologically positive and negative groups. Conversely, instances of cervical thrombophlebitis and pulmonary complications were significantly higher (P = 0.0001) among those testing negative. The disease course was lethal in one case for each of the two groups. CONCLUSIONS: This analysis provides evidence of an association between acute Epstein-Barr virus infection and Lemierre syndrome. Raising awareness of this link within the medical community is desirable.

Bilateral upper eyelid swelling (Hoagland sign) in Epstein-Barr infectious mononucleosis: prospective experience.

BACKGROUND: The typical presentation of Epstein-Barr virus infectious mononucleosis includes fever, pharyngitis, measles-like rash, jaundice, and enlarged lymph nodes, liver, or spleen. A painless bilateral swelling of the upper eyelid, sometimes with drooping of the lateral aspect, may also occur. This sign, referred to as Hoagland sign, is not or only marginally mentioned in reviews and textbooks. METHODS: Between 2019 and 2021, two of us evaluated all subjects with a positive acute Epstein-Barr virus serology for the typical signs of mononucleosis and for the possible existence of the Hoagland sign. RESULTS: During the mentioned period, the diagnosis of mononucleosis was made in 26 (14 females and 12 males) subjects aged from 9.0 to 33 years. The initial presentation included fever in 24, enlarged cervical lymph nodes in 23, pharyngitis in 21, a palpable liver in 7, a palpable spleen in 7, jaundice in 2, and a measles-like rash in 2 cases. The Hoagland sign was noted in 14 cases. Patients with and without Hoagland sign did not significantly differ with respect to age and sex. CONCLUSIONS: The Hoagland sign is an easily identifiable clinical sign that is common and likely helpful early in the course of Epstein-Barr virus infectious mononucleosis. There is a need to expand awareness of this sign among physicians.

Mucosal Respiratory Syndrome: A Systematic Literature Review.

BACKGROUND: Mycoplasma pneumoniae atypical pneumonia is frequently associated with erythema multiforme. Occasionally, a mycoplasma infection does not trigger any cutaneous but exclusively mucosal lesions. The term mucosal respiratory syndrome is employed to denote the latter condition. Available reviews do not address the possible association of mucosal respiratory syndrome with further atypical bacterial pathogens such as Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, or Legionella species. We therefore performed a systematic review of the literature addressing this issue in the National Library of Medicine, Excerpta Medica, and Web of Science databases. SUMMARY: We found 63 patients (≤18 years, n = 36; >18 years, n = 27; 54 males and 9 females) affected by a mucosal respiratory syndrome. Fifty-three cases were temporally associated with a M. pneumoniae and 5 with a C. pneumoniae infection. No cases temporally associated with C. psittaci, C. burnetii, F. tularensis, or Legionella species infection were found. Two cases were temporally associated with Epstein-Barr virus or influenzavirus B, respectively.

Factors associated with hospital and intensive care admission in paediatric SARS-CoV-2 infection: a prospective nationwide observational cohort study.

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 < 18 years with confirmed SARS-CoV-2 infection. All 33 paediatric hospitals in Switzerland reported non-hospitalised and hospitalised cases from March 1 to October 31, 2020 during both pandemic peaks. In total, 678 children were included. The median age was 12.2 years (IQR 5.0-14.6), 316 (46.6%) were female and 106 (15.6%) had comorbidities. Overall, 126 (18.6%) children were hospitalised of whom 16 (12.7%) required ICU admission. Comorbidities were the only factor associated with hospital admission in a multivariable regression analysis (odds ratio 3.23, 95%CI 1.89 to 5.50; p-value < 0.01). Children with preexisting comorbidities did not require ICU admission more often. Hospitalised children more often presented with fever (96 [76.2%] vs 209 [38.1%], p-value < 0.01) and rash (16 [12.8%] vs 6 [1.1%], p-value < 0.01). Anosmia/dysgeusia was more prevalent in non-hospitalised children (73 [13.3%] vs 3 [2.4%], p-value < 0.01). In hospitalised children, oxygen treatment was required in 34 (27.0%), inotropes in nine (7.3%) and mechanical ventilation in eight (6.3%) cases. Complications were reported in 28 (4.1%) children with cardiovascular complications being most frequent (12 [1.8%]). Three deaths were recorded.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.

Atypical primary varicella rash: Systematic literature review.

AIM: In previously healthy subjects, primary varicella presents with a distinctive vesicular rash that is more intense on the trunk and head than on the extremities. However, an atypical presentation may occasionally develop. We aimed at systematically assessing the characteristics of cases affected by atypical primary varicella rash. METHODS: The United States National Library of Medicine, Excerpta Medica and Web of Science databases were reviewed, without date or language restrictions. Articles were eligible if reporting previously healthy and immunocompetent subjects with a primary varicella rash (i.e., a photo-localised primary varicella or skin inflammation-associated primary varicella). RESULTS: Thirty-eight reports providing information on 59 cases of atypical primary varicella were identified. Twenty-four cases (median 8.5 years of age, 19 females) were photo-localised and 35 (median 4.8 years of age, 15 females) were associated with pre-existing skin inflammation (including cast occlusion, diaper irritation, operative sites, burns, insect bites, vaccinations or pre-existing skin disease). The skin rash was monomorphic and without a "starry sky" appearance. CONCLUSION: Primary varicella may have a modified presentation in areas of irritation such as sun exposure or pre-existing inflammation. There is a need for a wider awareness of these modulators of varicella rash.

Skin and Mucous Membrane Eruptions Associated with Chlamydophila Pneumoniae Respiratory Infections: Literature Review.

BACKGROUND: Mycoplasma pneumoniae pneumonia is sometimes associated with skin or mucous membrane eruptions. Available reviews do not address the association of Chlamydophila pneumoniae pneumonia with skin eruptions. We therefore conducted a systematic review of the literature addressing this issue. The National Library of Medicine, Excerpta Medica, and Web of Science databases were employed. SUMMARY: In two reports, skin lesions and especially urticaria were more common (p < 0.05) in atypical pneumonia caused by C. pneumoniae as compared with M. pneumoniae. We found 47 patients (<18 years, n = 16; ≥18 years, n = 31) affected by a C. pneumoniae atypical pneumonia, which was associated with erythema nodosum, erythema multiforme minus, erythema multiforme majus, isolated mucositis, or cutaneous vasculitis. We also found the case of a boy with C. pneumoniae pneumonia and acute generalized exanthematous pustulosis. We did not find any case of C. pneumoniae respiratory infection associated with either Gianotti-Crosti syndrome, pityriasis lichenoides et varioliformis acuta Mucha-Habermann, or varicella-like skin eruptions.

Swiss consensus recommendations on urinary tract infections 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 but per se is 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.

Lipschütz's acute vulvar ulcer: a systematic review.

In previously healthy subjects, vulvar ulcers are mostly caused by sexually transmitted microorganisms. Lipschütz's acute vulvar ulceration, first reported in 1912, is a non-sexually acquired condition characterized by sudden onset of a few genital ulcers. We systematically review presentation, underlying causes, and disease duration of Lipschütz's ulceration. A comprehensive source of Excerpta Medica, National Library of Medicine, and Web of Science databases was performed. Reports including cases of apparently previously healthy females affected by Lipschütz's ulceration were selected. A predefined database was used to extract data on demographics, history, clinical and microbiological findings, and treatment.The search disclosed 158 cases. Almost 90% of cases were ≤ 20 years of age and sexually inactive. Lesions were usually one to about three, painful, ≥ 10 mm large, well-delimited, with a fibrinous and necrotic center and a symmetric distribution. Voiding disorders and enlarged inguinal lymph nodes were observed in a large subset of cases. Canker sores were noted in 10% of patients. Lipschütz's vulvar ulceration occurred concomitantly with an infectious disease in 139 cases. Infectious mononucleosis syndrome (N = 40) was the most frequently detected well-defined infection, followed by mycoplasma species infections (N = 11). The disease resolved after ≤ 3 weeks.Conclusions: Lipschütz's ulceration mainly affects both sexually inactive and, less frequently, sexually active subjects ≤ 20 years of age, presents with ≤ 3 vulvar ulcers, resolves without recurrences within 3 weeks and is temporarily associated with an infection, most frequently a flu-like illness or an infectious mononucleosis syndrome. What is Known: • Lipschütz's acute vulvar ulceration is a non-sexually acquired condition, which is characterized by a sudden onset of a few necrotic and painful genital ulcers. • The condition tends to resolve spontaneously and is usually triggered by an infection. What is New: • The condition mainly affects subjects ≤ 20 years of age, tends to resolve within 3 weeks, and is usually temporarily associated with a flu-like illness or an infectious mononucleosis syndrome. • Systemic corticosteroids do not reduce disease duration.

Nontyphoidal Salmonella Outbreaks Associated With Chocolate Consumption: A Systematic Review.

BACKGROUND: A large, cross-border outbreak of nontyphoidal salmonellosis connected to chocolate product consumption was recently reported. This occurrence motivated us to conduct a comprehensive review of existing literature concerning outbreaks of nontyphoidal salmonellosis associated with chocolate consumption. METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022369023) in 3 databases: U.S. National Library of Medicine, Web of Science and Excerpta Medica. Google Scholar and the bibliography of each identified report were also screened. Eligible were articles published after 1970, describing outbreaks of more than 10 patients with a nontyphoidal salmonellosis associated with chocolate consumption. RESULTS: Twenty-three articles were included, which described 12 outbreaks involving a total of 3266 patients. All outbreaks occurred in high-income countries: 1 was limited to 1 city, 6 involved 1 country and the remaining 5 involved 2 or more countries. Six outbreaks peaked in winter, 3 in autumn, 2 in spring and 1 in summer. Children were mainly affected. No predominant serotype was identified. CONCLUSIONS: Our data documents that chocolate is an optimal medium for the transmission of nontyphoidal salmonellosis. A connected worldwide reporting system including high-income, middle-income and low-income countries is crucial to detect infectious diseases outbreaks in an early phase and avoid their spread.

Clinical and Laboratory Biomarkers as Predictors of Severity in Pediatric Inflammatory Multisystem Syndrome-temporally Associated With SARS-CoV-2: Data From a Prospective Nationwide Surveillance Study in Switzerland.

BACKGROUND: PIMS-TS (pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2) is a rare but serious condition in children following SARS-CoV-2 infection, characterized by a range of clinical symptoms with varying severity. Understanding risk factors for severe PIMS-TS is crucial for appropriate and timely intervention. OBJECTIVE: To identify factors associated with increased PIMS-TS severity in children. METHODS: In this nationwide prospective observational study, epidemiological and clinical data was collected from children <18 years of age with suspected or confirmed PIMS-TS from all 29 pediatric hospitals in Switzerland. Children were categorized into 3 groups according to admission to intensive care unit (ICU): non-ICU, ICU-moderate and ICU-severe, defined as requirement of invasive ventilation and/or inotropic support. RESULTS: A total of 204 children were included; 99 (49%) were categorized as non-ICU, 50 (25%) as ICU-moderate and 55 (27%) as ICU-severe. In ICU-severe cases, respiratory and neurological symptoms were more frequent compared with non-ICU cases: 72% versus 47%, P < 0.001 and 66% versus 41%, P = 0.001, respectively. Compared with the non-ICU group, children in the ICU-severe group had lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower platelet counts, as well as higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin T and creatinine levels at admission. Lymphopenia and elevated troponin T levels at admission were associated with an increased risk of being in the ICU-severe group. CONCLUSION: The severity of PIMS-TS may be predicted using clinical symptoms and laboratory biomarkers, which help clinicians in decision-making and management of patients.

Clinical Characteristics and Management of Children and Adolescents Hospitalized With Pyomyositis.

BACKGROUND: Pyomyositis, a bacterial muscle infection, is an important differential diagnosis in children and adolescents with musculoskeletal pain. In contrast to tropical regions, it is rarely recognized in temperate countries, but incidence is increasing and major studies are missing. METHODS: This retrospective multicenter study included patients <18 years of age hospitalized with pyomyositis in 11 Swiss children's hospitals between January 2010 and December 2022. Cases were identified by ICD-10 code (Myositis; M60-M60.9), and data was extracted from electronic hospital records. RESULTS: Of 331 patients identified, 102 fulfilled the case definition. Patient age at presentation ranged from 2 weeks to 17 years (median 8 years). The majority had no underlying illness and all presented with fever and localized pain. At the respective site of pyomyositis, 100 (98%) had impaired movement and 39 (38%) presented with local swelling. Pelvic (57%) and leg (28%) muscles were mostly affected. Blood or tissue cultures were obtained in 94 (92%) and 59 (57%) patients, respectively. Of those, 55 (58%) blood and 52 (88%) tissue cultures were positive, mainly for Staphylococcus aureus (35 and 19, respectively) and Streptococcus pyogene s (12 and 15, respectively). All patients received antibiotic treatment during hospitalization for a median of 10 days (interquartile range: 7-17), followed by outpatient treatment for a further median of 16 days (interquartile range: 11-22) in 95 (93%) patients. Fifty-nine (57%) patients required surgery. CONCLUSIONS: Pyomyositis is a challenging diagnosis that requires a high level of awareness. Blood and/or tissue cultures revealed S. aureus and S. pyogenes as the predominant causative agents.

Cohort profile: the Swiss Mother and Child HIV Cohort Study (MoCHiV).

PURPOSE: Prospective, multicentric observational cohort study in Switzerland investigating measures to prevent mother-to-child transmission in pregnant women with HIV (WWH) and assessing health and development of their exposed children as well as of children with HIV (CWH) in general. PARTICIPANTS: Between January 1986 and December 2022, a total of 1446 mother-child pairs were enrolled. During the same period, the study also registered 187 CWH and 521 HIV-exposed but uninfected children (HEU), for whom detailed maternal information was not available. Consequently, the cohort comprises a total of 2154 children. FINDINGS TO DATE: During these 37 years, research by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and its international collaborators has strongly influenced the prevention of vertical transmission of HIV (eg, introduction and discontinuation of elective caesarean section, neonatal postexposure prophylaxis and breastfeeding). Contributions have also been made to the management of diagnostics (eg, p24 antigen assay) and the effects of antiretroviral treatment (eg, prematurity, growth) in HEU and CWH. FUTURE PLANS: Most children present within the cohort are now HEU, highlighting the need to investigate other vertically transmitted pathogens such as hepatitis B and C viruses, cytomegalovirus or Treponema pallidum. In addition, analyses are planned on the longitudinal health status of CWH (eg, resistance and prolonged exposure to antiretroviral therapy), on social aspects including stigma in CWH and HEU, and on interventions to further optimise antenatal and postpartum care in WWH.

A randomized controlled non-inferiority trial of placebo versus macrolide antibiotics for Mycoplasma pneumoniae infection in children with community-acquired pneumonia: trial protocol for the MYTHIC Study.

BACKGROUND: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in school-aged children. Macrolides are the first-line treatment for this infection. However, it is unclear whether macrolides are effective in treating M. pneumoniae CAP, mainly due to limitations in microbiological diagnosis of previous studies. The extensive global use of macrolides has led to increasing antimicrobial resistance. The overall objective of this trial is to produce efficacy data for macrolide treatment in children with M. pneumoniae CAP. METHODS: The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3-17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and -7.5%. The "at least one" success criterion is used to handle multiplicity with the two co-primary endpoints. With a power of 80% to reject at least one null hypothesis at a one-sided significance level of 1.25%, 376 patients will be required. DISCUSSION: This trial will produce efficacy data for macrolide treatment in children with M. pneumoniae CAP that might help to reduce the prescription of antibiotics and therefore contribute to the global efforts toward reducing antimicrobial resistance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06325293. Registered on 24 April 2024.

Neonatal hemolytic uremic syndrome after mother-to-child transmission of a low-pathogenic stx2b harboring shiga toxin-producing Escherichia coli.

This case describes evidence for a Shiga toxin-producing Escherichia coli (STEC) O146:H28 infection leading to hemolytic uremic syndrome in a neonate. STEC O146:H28 was linked hitherto with asymptomatic carriage in humans. Based on strain characteristics and genotyping data, the mother is a healthy carrier who transmitted the STEC during delivery. STEC strains belonging to the low-pathogenic STEC group must also be considered in the workup of neonatal hemolytic uremic syndrome.

Cardiac involvement in children with paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): data from a prospective nationwide surveillance study.

BACKGROUND: Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) may occur 4 to 8 weeks after SARS-CoV-2 infection. The acute presentation of PIMS-TS has been well described, but data on longer-term outcomes, particularly cardiac, is scarce. METHODS: This prospective nationwide surveillance study included children and adolescents less than 18 years of age who were hospitalised with PIMS-TS in Switzerland between March 2020 and March 2022. Data was collected from all 29 paediatric hospitals through the Swiss Paediatric Surveillance Unit (SPSU) during hospitalisation and approximately six weeks after discharge. The data was analysed after categorising the participants into three groups based on their admission status to the intensive care unit (ICU) (non-ICU, ICU-moderate) and the requirement for invasive ventilatory and/or inotropic support (ICU-severe). RESULTS: Overall, 204 children were included of whom 194 (95.1%) had follow-up data recorded. Median age was 9.0 years (interquartile range [IQR] 6.0-11.5) and 142 (69.6%) were male. In total, 105/204 (51.5%) required ICU admission, of whom 55/105 (52.4%) received inotropic support and 14/105 (13.3%) mechanical ventilation (ICU-severe group). Echocardiography was performed in 201/204 (98.5%) children; 132 (64.7%) had a cardiac abnormality including left ventricular systolic dysfunction (73 [36.3%]), a coronary artery abnormality (45 [22.4%]), pericardial effusion (50 [24.9%]) and mitral valve regurgitation (60 [29.9%]). Left ventricular systolic dysfunction was present at admission in 62/201 (30.8%) children and appeared during hospitalisation in 11 (5.5%) children. A coronary artery abnormality was detected at admission in 29/201 (14.2%) children and developed during hospitalisation or at follow-up in 13 (6.5%) and 3 (1.5%) children, respectively. None of the children had left ventricular systolic dysfunction at follow-up, but a coronary abnormality and pericardial effusion were found in 12 (6.6%) and 3 (1.7%) children, respectively. School absenteeism at the time of follow-up was more frequent in children who had been admitted to the ICU (2.5% in the non-ICU group compared to 10.4% and 17.6% in the ICU-moderate and ICU-severe group, respectively) (p = 0.011). CONCLUSION: Cardiac complications in children presenting with PIMS-TS are common and may worsen during the hospitalisation. Irrespective of initial severity, resolution of left ventricular systolic dysfunction is observed, often occurring rapidly during the hospitalisation. Most of the coronary artery abnormalities regress; however, some are still present at follow-up, emphasising the need for prolonged cardiac evaluation after PIMS-TS.