From evidence to practice: A systematic review-based diagnostic algorithm for paediatric eosinophilia across socioeconomic context.

AIM: Paediatric eosinophilia is a common clinical dilemma, often leading to resource- and time-consuming assessments. We aim to evaluate the main aetiologies of eosinophilia in children from different socioeconomic settings and propose a diagnostic algorithm. METHODS: A systematic literature review was conducted through PubMed, Embase and the Cochrane Library. Studies published from January 2012 to June 2023 reporting the incidence and aetiology of peripheral eosinophilia in children were included. Evidence from studies on children originating from low- or high-income countries was compared. RESULTS: A total of 15 observational studies, encompassing 3409 children, were included. The causes of eosinophilia varied based on the children's origin and the eosinophilia severity. In children from high-income countries, allergic diseases were the leading cause, with a prevalence of 7.7%-78.2%, while parasitosis ranged from 1.0% to 9.1%. In children from low-income countries, parasitosis was predominant, ranging from 17.7% to 88.3%, although allergic diseases were found in 2.5%-4.8% of cases. Concerning severity, allergic diseases were the leading cause of mild-to-moderate eosinophilia; parasitosis was associated with moderate-to-severe eosinophilia, while immunological disorders were mostly found in severe cases. CONCLUSION: We developed a step-up diagnostic algorithm that considers the child's origin and eosinophilia severity and could optimise resource allocation.

Severe A(H1N1)pdm09 influenza acute encephalopathy outbreak in children in Tuscany, Italy, December 2023 to January 2024.

A severe outbreak of influenza A(H1N1pdm09) infection in seven children (median age: 52 months) occurred between December 2023 and January 2024 in Tuscany, Italy. Clinical presentation ranged from milder encephalopathy to acute necrotizing encephalopathy (ANE) with coma and multiorgan failure; one child died. This report raises awareness for clinicians to identify and treat early acute encephalopathy caused by H1N1 influenza and serves as a reminder of severe presentations of influenza in young children and the importance of vaccination.

Use of Remdesivir in children with COVID-19: report of an Italian multicenter study.

BACKGROUND: COVID-19 is generally milder in children than in adults, however severe infection has been described in some patients. Few data are available on use of Remdesivir (RDV) in children, as most clinical trials focused on adult patients. We report a multicenter study conducted in 10 Italian Hospitals to investigate the safety of RDV in children affected by COVID-19. METHODS: We collected the clinical data of children with COVID-19 treated with RDV between March 2020 and February 2022 in 10 Italian hospitals. Clinical data were compared according to a duration of RDV therapy more or less than 5 days. Linear regression model was used to determine the association of significant variables from the bivariate analysis to the duration of RDV therapy. RESULTS: A total of 50 patients were included, with a median age of 12.8 years. Many patients had at least one comorbidity (78%), mostly obesity. Symptoms were fever (88%), cough (74%) and dyspnea (68%). Most patients were diagnosed with pneumonia of either viral and/or bacterial etiology. Blood test showed leukopenia in 66% and increased C-reactive protein (CRP) levels in 63% of cases. Thirty-six patients received RDV for 5 days, nine patients up to 10 days. Most children who received RDV longer were admitted to the PICU (67%). Treatment with RDV was well tolerated with rare side effects: bradycardia was recorded in 6% of cases, solved in less than 24 h after discontinuation. A mild elevation of transaminases was observed in 26% of cases, however for the 8%, it was still detected before the RDV administration. Therefore, in these cases, we could not establish if it was caused by COVID-19, RDV o both. Patients who received RDV for more than 5 days waited longer for its administration after pneumonia diagnosis. The presence of comorbidities and the duration of O2 administration significantly correlated with the duration of RDV therapy at the linear regression analysis. CONCLUSION: Our experience indicates that RDV against SARS-CoV-2 is safe and well-tolerated in pediatric populations at high risk of developing severe COVID-19. Our data suggest that delaying RDV therapy after diagnosis of pneumonia may be associated with a longer duration of antiviral therapy, especially in patients with comorbidities.

Remdesivir for COVID-19 in Hospitalized Children: A Phase 2/3 Study.

OBJECTIVES: Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children. METHODS: This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction-confirmed SARS-CoV-2 infection. Participants received for ≤10 days once-daily intravenous remdesivir doses defined using physiologically based pharmacokinetic modeling (for ≥40 kg, 200 mg day 1, then 100 mg/day; for age ≥28 days and ≥3 to <40 kg, 5 mg/kg day 1, then 2.5 mg/kg/day). Sparse pharmacokinetic samples were analyzed using population-pharmacokinetic approaches for remdesivir and metabolites GS-704277 and GS-441524. RESULTS: Among 53 participants, at enrollment the median (Q1, Q3) number of days of COVID-19 symptoms was 5 (3, 7) and hospitalization was 1 (1, 3). Underlying conditions included obesity in 19 (37%), asthma in 11 (21%), and cardiac disorders in 11 (21%). Median duration of remdesivir treatment was 5 days (range, 1-10). Remdesivir treatment had no new apparent safety trends. Two participants discontinued treatment because of adverse events including elevated transaminases; both had elevated transaminases at baseline. Three deaths occurred during treatment (and 1 after). When compared with phase 3 adult data, estimated mean pediatric parameters (area under the concentration-time curve over 1 dosing interval, AUCτ, Cmax, and Cτ) were largely overlapping but modestly increased (remdesivir, 33%-129%; GS-704277, 37%-124%; GS-441524, 0%-60%). Recovery occurred for 62% of participants on day 10 and 83% at last assessment. CONCLUSIONS: In infants and children with COVID-19, the doses of remdesivir evaluated provided drug exposure similar to adult dosing. In this study with a small sample size, no new safety concerns were observed.

Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy.

Paediatric tuberculosis (TB) is a substantial threat among infectious diseases, particularly considering the high risk of extrapulmonary tuberculosis (EPTB), severe forms of the disease, and the spreading of drug-resistant strains. Describing the characteristics of children with EPTB and those with drug-resistant tuberculosis (DR-TB) and analysing the role of second-line drugs could facilitate the management of these cases. This retrospective study was conducted on 271 children diagnosed with active TB disease (44 EPTB cases, 9 DR-TB cases), originating from diverse geographic areas, who were referred to the infectious disease unit at Meyer Children's Hospital, Florence, Italy, from 2006 to 2022. In most patients, the management of therapies was complicated by the impossibility to obtain drug susceptibility testing (DST) results, which improved over the years: 17/154 (11.04%) children had DST results between 2006 and 2013, and 50/117 (42.73%, p < 0.001) between 2014 and 2022. Second-line drugs were not exclusively administered to DR-TB cases, but also to EPTB cases (20/44, 45.45%). Drugs were generally well tolerated; adverse events occurred in 13 children (13/271, 4.80%) and were generally mild and reversable. Therapies were successful in 267 children (98.52%) considered cured, while 4 (1.48%) presented sequelae. Both univariate and multivariate logistic regression analyses were conducted to investigate factors associated with EPTB, DR-TB, and second-line drugs administration. Originating from Asia emerged as a risk factor associated with both EPTB and DR-TB (p = 0.013 and p = 0.045, respectively). The introduction of GeneXpert tests has significantly improved TB diagnosis and the obtaining of DST results. The administration of second-line therapies should be limited primarily to DR-TB cases, but it is possible that these drugs may also be beneficial in selected EPTB cases.

Fixed-dose antiretroviral combinations in children living with human immunodeficiency virus type 1 (HIV-1): a systematic review.

Fixed-Dose antiretroviral Combinations (FDCs) are the most used drug regimes in adult patients with human-immunodeficiency virus 1 infection, since they increase adherence to antiretroviral therapy and enable good quality of life. The European AIDS Clinical Society guidelines recommend the use of FDCs in paediatrics. However, the use of FDCs in paediatric population is restricted since studies in children and adolescents are mostly conducted in small sample sizes and are heterogeneous in settings and design. This systematic review aims to summarize the current knowledge about the use of FDCs in paediatric population, highlighting the relevant outcomes regarding efficacy and effectiveness, adherence, safety, and adverse events of these regimens.