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Background In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe. Methods Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000–2020. Results A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P =.013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P <.001; odds ratio [95% confidence interval], 2.073 [1.37–3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P <.001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P <.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P =.083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P =.004). Conclusions Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies. [ABSTRACT FROM AUTHOR]

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children. [ABSTRACT FROM AUTHOR]

Background: Pancreatic Stone Protein (PSP) is one of the most promising diagnostic and prognostic markers. The aim of the study was to assess the accuracy of PSP, compared to C-Reactive Protein (CRP), and Procalcitonin (PCT) for sepsis diagnosis in pediatric patients. Furthermore, we explored the correlation of PSP levels with sepsis severity and organ failure measured with PELOD-2 score. Methods: Forty pediatric patients were enrolled following admission to pediatric intensive care, high dependency care or pediatric ward. PSP blood levels were measured in Emergency Department (nanofluidic point-of-care immunoassay; abioSCOPE, Abionic SA, Switzerland) on day 1, 2, 3, 5 and 7 from the onset of the clinical signs and symptoms of sepsis or SIRS. Inclusion criteria were: 1) patient age (1 month to 18 years old), 2) signs and symptoms of SIRS, irrespective of association with organ dysfunction. Exclusion criteria were: 1) hemato-oncological diseases and/or immunodeficiencies, 2) pancreatic diseases. Results: Septic patients showed higher PSP levels than those with non-infectious systemic inflammation. The optimal cut-off in diagnosis of sepsis for PSP at day 1 was 167 ng/ml resulted in a sensitivity of 59% (95% IC 36%—79%) and a specificity of 83% (95% IC 58%-96%) with an AUC of 0.636 for PSP in comparison to AUC of 0.722 for PCT and 0.503 for C-RP. ROC analysis for outcome (survival versus no survival) has showed AUC 0.814 for PSP; AUC 0.814 for PCT; AUC of 0.657 for C-RP. Conclusions: PSP could distinguish sepsis from non-infectious systemic inflammation; however, our results need to be confirmed in larger pediatric population. [ABSTRACT FROM AUTHOR]

Infections due to carbapenem-resistant Enterobacterales (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes, especially in critically ill patients. Novel beta lactam antibiotics, including ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol, have been released in recent years to face the emerging challenge of multidrug-resistant (MDR) Gram-negative bacteria. Nonetheless, several novel agents lack pediatric indications approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA), leading to uncertain pediatric-specific treatment strategies and uncertain dosing regimens in the pediatric population. In this narrative review we have summarized the available clinical and pharmacological data, current limitations and future prospects of novel beta lactam antibiotics in the pediatric population. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are currently two major causes of death among infectious diseases. Active tuberculosis and a history of tuberculosis appear to be associated with an increased risk of COVID-19. This coinfection, named COVID-TB, was never described in previously healthy children. We report three cases of pediatric COVID-TB. We describe three girls affected by tuberculosis, who tested positive for SARS-CoV-2. The first patient is a 5-year-old girl who was hospitalized for recurrent TB lymphadenopathy. As she never had any complications related to the concomitant infection with SARS-CoV-2, she received TB treatment. The second case is a 13-year-old patient with a history of pulmonary and splenic tuberculosis. She was admitted to the hospital due to deteriorating respiratory dynamics. She was already undergoing treatment for TB, but in the absence of improvement, she also required treatment for COVID-19. Slowly, the general condition improved until discharge. The last patient, a 10-year-old girl, was hospitalized for supraclavicular swelling. The investigations showed disseminated TB characterized by lung and bone involvement without COVID-19-related complications. She was treated with antitubercular and supportive therapy. Based on the data obtained from the adult population and our small experience, a pediatric patient with COVID-TB infection should be considered potentially at risk of worse clinical outcomes; for this reason, we suggest close observation, careful clinical management, and consideration of targeted anti-SARS-CoV-2 therapies. [ABSTRACT FROM AUTHOR]

Background: Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed. Main findings: Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type. Conclusions: Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue. [ABSTRACT FROM AUTHOR]

Monoclonal antibody therapies for COVID-19 have been frequently used in adults, whereas there are little data regarding the safety or efficacy of monoclonal antibody treatments in pediatric patients affected by COVID-19. We report our experience in the administration of mAb as a treatment for SARS-CoV-2 infection in children aged from 24 days to 18 years old. [ABSTRACT FROM AUTHOR]

Background: Acute cerebellitis (AC) and acute cerebellar ataxia (ACA) are the principal causes of acute cerebellar dysfunction in childhood. Nevertheless. there is no accepted consensus regarding the best management of children with AC/ACA: the aim of the study is both to assess clinical, neuroimaging and electrophysiologic features of children with AC/ACA and to evaluate the correlation between clinical parameters, therapy and outcome. Methods: A multicentric retrospective study was conducted on children ≤ 18 years old admitted to 12 Italian paediatric hospitals for AC/ACA from 01/01/2003 to 31/12/2013. A score based on both cerebellar and extracerebellar signs/symptoms was computed for each patient. One point was given for each sign/symptom reported. Severity was divided in three classes: low, moderate, severe. Results: A total of 124 children were included in the study. Of these, 118 children received a final diagnosis of ACA and 6 of AC. The most characteristic finding of AC/ACA was a broad-based gait disturbance. Other common symptoms included balance disturbances, slurred speech, vomiting, headache and fever. Neurological sequelae were reported in 6 cases (5%) There was no correlation among symptoms, cerebrospinal fluid findings, clinical outcome. There was no correlation between clinical manifestations and clinical score on admission and length of hospital stay, sex, age and EEG findings with sequelae (P > 0.05). Children with pathological magnetic resonance imaging (MRI) or computed tomography (CT) had a higher probability of having clinical sequelae. Treatment was decided independently case by case. Patients with a higher clinical score on admission had a higher probability of receiving intravenous steroids. Conclusions: We confirmed the literature data about the benign course of AC/ACA in most cases but we also highlighted a considerable rate of patients with neurological sequelae (5%). Pathological MRI or CT findings at admission correlate to neurological sequelae. These findings suggest the indication to perform an instrumental evaluation in all patients with AC/ACA at admission to identify those at higher risk of neurological outcome. These patients may benefit from a more aggressive therapeutic strategy and should have a closer follow-up. Randomized controlled trials are needed to confirm these observations. The ultimate goal of these studies could be to develop a standardized protocol on AC/ACA. The MRI/CT data, associated with the clinical manifestations, may allow us to define the class risk of patients for a neurological outcome. [ABSTRACT FROM AUTHOR]

Background: Varicella pneumonia has been studied extensively in adults; it may also affect children and may require hospitalization. Methods: We examined pneumonia complications in children hospitalized for varicella, over a 13 year period. Results: Pneumonia occurred in 8.2% of children hospitalized for varicella. The median length of hospitalization was 6 days. No statistically significant difference in length of stay was detected between immunodepressed children and previously healthy children. The hospitalization was on average shorter in patients who started antiviral therapy within 24 h of varicella onset. None of the included patients had been previously immunized for varicella. Conclusions: Our results support the need for increased awareness of current varicella prevention recommendations among both immunocompetent and immunodepressed individuals. In children affected by varicella, prompt antiviral therapy may be indicated to reduce the number of days of hospitalization. [ABSTRACT FROM AUTHOR]

Background: Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis. We review the clinical and molecular aspects of LMM and discuss on clinical and diagnostic implications.Case Presentation: A 27-month-old girl with a 1-week history of vomiting with mild intermittent strabismus underwent Magnetic Resonance Imaging, showing diffuse brainstem and spinal leptomeningeal enhancement. Cerebrospinal fluid analysis was unremarkable. Antitubercular treatment was started without any improvement. A spinal intradural biopsy was suggestive for primary leptomeningeal melanomatosis. Chemotherapy was started, but general clinical conditions progressively worsened and patient died 11 months after diagnosis. Molecular investigations were performed post-mortem on tumor tissue and revealed absence of BRAF(V600E), GNAQ(Q209) and GNA11(Q209) mutations but the presence of a NRAS(Q61K) mutation.Conclusions: Our case adds some information to the limited experience of the literature, confirming the presence of the NRAS(Q61K) mutation in children with melanomatosis. To our knowledge, this is the first case of leptomeningeal melanocytic neoplasms (LMN) without associated skin lesions to harbor this mutation. Isolated LMN presentation might be insidious, mimicking tuberculous meningitis, and should be suspected if no definite diagnosis is possible or if antitubercular treatment does not result in dramatic clinical improvement. Leptomeningeal biopsy should be considered, not only to confirm diagnosis of LMN but also to study molecular profile. Further molecular profiling and preclinical models will be pivotal in testing combination of target therapy to treat this challenging disease. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is still one of the most difficult infectious diseases to treat, and the second most frequent cause of death due to infectious disease throughout the world. The number of cases of multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB), which are characterised by high mortality rates, is increasing. The therapeutic management of children with MDR- and XDR-TB is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life. Furthermore, most of the available drugs are burdened by major adverse events that need to be taken into account, particularly in the case of prolonged therapy. This document describes the recommendations of a group of scientific societies on the therapeutic approach to pediatric MDR- and XDR-TB. On the basis of a systematic literature review and their personal clinical experience, the experts recommend that children with active TB caused by a drug-resistant strain of Mycobacterium tuberculosis should always be referred to a specialised centre because of the complexity of patient management, the paucity of pediatric data, and the high incidence of adverse events due to second-line anti-TB treatment. [ABSTRACT FROM AUTHOR]

Abstract: We explored complications and risk factors for severe disease in 78 children with swine influenza admitted to Bambino Gesù Children Hospital. The majority of our children experienced respiratory complications (55%). Previously healthy children developed a chest consolidation more frequently than chronic diseases affected patients (p =0.04). Apparently, the incidence of respiratory complications was slightly higher in the neutropenic group than in those with a normal value of neutrophilis (respectively 94.1% and 80%). [Copyright &y& Elsevier]

Abstract: A child referred to Infectious Disease Unit for varicella complicated by pneumonia with pleural effusion. Due to not improvement, laboratory search was extended to uncommon pathogens, revealing Nocardia transvalensis infection. It is likely that varicella induced immunodepression, facilitating opportunistic infection in an otherwise healthy and immunocompetent child. To our knowledge, our report is the first case of Nocardia infection in varicella. [Copyright &y& Elsevier]