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Strategies for prevention of HIV-1 mother-to-child transmission (PMTCT) have been continuously optimized. However, cases of vertical transmission continue to occur in high-income countries.To investigate changes in PMTCT strategies adopted by Italian clinicians over time and to evaluate risk factors for transmission.Data from mother-child pairs prospectively collected by the Italian Register, born in Italy in 1996-2016, were analyzed. Risk factors for MTCT were explored by logistic regression analyses.Six thousand five hundred three children (348 infections) were included. In our cohort, the proportion of children born to foreign mothers increased from 18.3% (563/3078) in 1996%-2003% to 66.2% (559/857) in 2011-2016 (P0.0001). Combination neonatal prophylaxis use significantly (P0.0001) increased over time, reaching 6.3% (56/857) after 2010, and it was largely (4.2%) adopted in early preterm infants. The proportion of vaginal deliveries in women with undetectable viral load (VL) increased over time and was 9.9% (85/857) in 2011-2016; no infection occurred among them. In children followed up since birth MTCT, rate was 3.5% (96/2783) in 1996-2003; 1.4% (36/2480) in 2004-2010; and 1.1% (9/835) in 2011-2016. At a multivariate analysis, factors associated with MTCT were vaginal delivery with detectable or missing VL or nonelective caesarean delivery, prematurity, breastfeeding, lack of maternal or neonatal antiretroviral therapy, detectable maternal VL, and age at first observation. Previously described increased risk of offspring of immigrant women was not confirmed.Risk of MTCT in Italy is ongoing, even in recent years, underling the need for implementation of the current screening program in pregnancy. Large combination neonatal prophylaxis use in preterm infants was observed, even if data on safety and efficacy in prematures are poor.

Acute/subacute haematogenous osteomyelitis (AHOM/SAHOM) are potentially devastating diseases. Updated information about the epidemiology, management and outcome of AHOM/SAHOM is needed to minimize the risk of complications and sequelae. METHODS: A multicenter study was performed to evaluate retrospectively the management and outcome of AHOM/SAHOM in Italy. Data from children aged >1 month, and hospitalized between 2010 and 2016, in 19 pediatric centers, were analyzed. RESULTS: 300 children with AHOM and 98 with SAHOM were included. Median age was 6.0 years (IQR: 2.0-11.0). No clinical difference was observed with the exception of fever at onset (63.0% vs. 42.9%; P < 0.0001), and a more common spinal involvement in SAHOM (6.7% vs 20.4%; P < 0.001). Fifty-Eight Staphylococcus aureus strains were isolated; 5 (8.6%) were MRSA. No Kingella kingae infection was documented. No different risk for complication/sequela was observed between AHOM and SAHOM (38.3% vs. 34.7%; OR:0.85; 95%CI: 0.53-1.38; P = 0.518). Duration and type of antibiotic therapy were not associated with risk of complication/sequelae. CONCLUSION: AHOM and SAHOM displayed some differences, however occurrence and risk factors for complications and sequelae are similar, and the same empiric treatment might be recommended.

The intestinal microbiota is an ecosystem formed by a variety of ecological niches, made of several bacterial species and a very large amount of strains. The microbiota is in close contact with the intestinal mucosa or epithelial interface which is, after the respiratory area, the largest surface of the body, occupying approximately 250-400 m(2). The physiological activities of the microbiota are manifold and are just being unraveled. Based on the observations of the multiple roles played by the microbiota in health and disease, the notion of modifying it with appropriate formulations, i.e. probiotics, is being tested in several settings. This review summarizes the current knowledge on probiotics and discusses both limitations and acquired evidence to support their use in preventive and therapeutic medicine.

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.

The Italian Society for Pediatric Infectious Diseases created a registry on children with infective endocarditis (IE) hospitalized in Italy.A cross-sectional survey was conducted on patients hospitalized due to IE in Italian paediatric wards between January 1, 2000, and June 30, 2015.Over the 15-year study period, 47 IE episodes were observed (19 males; age range, 2-17 years). Viridans Streptococci were the most common pathogens among patients with predisposing cardiac conditions and Staphylococcus aureus among those without (37.9% vs. 5.5%, p = 0.018, and 6.9% vs. 27.8%, p = 0.089, respectively). Six of the 7 (85.7%) S. aureus strains were methicillin-resistant. The majority of patients with and without predisposing cardiac conditions recovered without any complications.In Italy, paediatric IE develops without any previous predisposing factors in a number of children, methicillin-resistant S. aureus has emerged as a common causative agent and the therapeutic approach is extremely variable.

Introduction Multiple vaccination visits and administrations can be stressful for infants, parents and healthcare providers. Multivalent combination vaccines can deliver the required number of antigens in fewer injections and clinic visits, while vaccine co-administration can also reduce the number of visits. This non-inferiority study was undertaken to evaluate the feasibility of co-administering a combined measles-mumps-rubella-varicella (MMRV) vaccine with conjugated meningococcal C (MenC) vaccine in a large cohort of healthy Italian toddlers. Methods Healthy subjects aged 13–15 months were randomized (2:1:1) to receive single doses of either: co-administered MMRV + MenC at the same visit (MMRV + MenC group); or MMRV followed 42 days later by MenC (MMRV group); or MenC followed 42 days later by MMRV (MenC group). Blood samples were collected before and 43 days after vaccination. Antibody titers against MMRV were measured using ELISA. Functional-anti-meningococcal-serogroup activity (rSBAMenC) was assessed using a serum bactericidal test. Solicited local and general reactions were recorded for up to 4 and 42 days post-vaccination, respectively. Non-inferiority of MMRV + MenC to MMRV (post-dose-1 seroconversion rates) and MMRV + MenC to MenC (post-dose-1 seroprotection rates) was achieved if the lower limit (LL) of the 95% confidence interval (CI) for the group difference was ⩾−10% for each antigen. Results 716 subjects were enrolled in the study. At 42 days post-vaccination, the MMRV seroconversion rates were 99.3% (measles), 94.5% (mumps), 100% (rubella) and 99.7% (varicella) in the MMRV + MenC group, and 99.4%, 93.2%, 100% and 100%, respectively, in the MMRV group. The seroprotection rates against rSBA-MenC were 98.3% in the MMRV + MenC group and 99.3% in the MenC group. Non-inferiority was reached for all the vaccine antigens. The safety profiles were as expected for these vaccines. Conclusion The immune responses elicited by co-administered MMRV + MenC were non-inferior to those elicited by MMRV or MenC alone and support vaccination of children with both vaccines at a single visit. Clinical Trials registration: NCT01506193 .

To examine whether long-term consumption of fermented milk containing a specific Lactobacillus casei may improve the health status of preschool children suffering from allergic asthma and/or rhinitis a randomized, prospective, double blind, controlled trial was conducted in 187 children 2-5 y of age. The children received for 12 mo either fermented milk (100 mL) containing Lactobacillus casei (10(8) cfu/mL) or placebo. The time free from and the number of episodes of asthma/rhinitis after starting intervention were the outcome measures. The number of fever or diarrhea episodes and the change in serum immunoglobulin were further assessed. No statistical difference between intervention and control group occurred in asthmatic children. In children with rhinitis, the annual number of rhinitis episodes was lower in the intervention group, mean difference (95% CI), -1.6 (-3.15 to -0.05); the mean duration of an episode of diarrhea was lower in the intervention group, mean difference -0.81 (-1.52 to -0.10) days. While long-term consumption of fermented milk containing Lactobacillus casei may improve the health status of children with allergic rhinitis no effect was found in asthmatic children.

In order to evaluate the immunogenicity, safety and tolerability of influenza vaccination in children with inborn errors of metabolism (IEMs), we enrolled 20 patients with IEMs at risk of decompensation (14 males; mean age±SD, 8.5±3.9years) and 20 healthy age- and gender-matched controls. Four weeks after vaccination, seroconversion rates were 75-85% and seroprotection rates 85-95%, with high geometric mean titers (GMTs) of all three influenza antigen strains in both groups. Three months after vaccination, most of the subjects remained seroconverted with high seroprotection rates and high GMTs for all the three influenza strains. Safety and tolerability were also very good, with no differences between the groups.

Changes in gastrointestinal (GI) bacteria caused by diet, antibiotics or other factors could alter enteric and systemic immune functions; changing the gut microflora composition by diet supplementation with specific live microbiota (probiotics) may be beneficial. The ‘natural’ target of ingested probiotics is the intestine, its microflora and associated immune system. Most published data concern use of probiotics to prevent and treat GI infections. Evidence for possible beneficial effects on mucosal barrier dysfunctions, including food allergy, inflammatory bowel disease, and respiratory and urinary tract infections, is emerging. The role of prebiotics (non-digestible oligosaccharides that reduce the growth or virulence of pathogens and induce systemic effects) is being investigated. Preliminary studies indicate that prebiotics may be useful dietary adjuncts for managing GI infections. Prebiotic and probiotic use in infants is attempting to modify a complex microbial ecosystem. Better understanding of the long-term effects of these interventions on infant gut microflora is an important goal.

Children with human immunodeficiency virus are at higher risk of developing tumor than the general population, non-Hodgkin lymphoma and Kaposi sarcoma being the most frequent malignant tumor in these patients. The report describes the case of a human immunodeficiency virus-seropositive girl who developed an angiomatoid fibrous histiocytoma of the soft part of the right knee.

The frequency and severity of chronic herpes simplex virus (HSV-1) ulcerative infections were recorded in six HIV-infected children with severe immunodeficiency (mean CD4 + T lymphocytes/cmm = 39.4: range 8—66). The first episode of HSV infection consisted of vesicular-crusty lesions affecting the centro-facial cutis area. In five cases, relapses occurred 4 months later in the form of chronic ulcerative lesions that were always accompanied by a significant loss of tissue. Furthermore, three of the six children also showed perianal ulcerative lesions. Cytodiagnostic analysis revealed the typical cells in balloon degeneration; all of the children had HSV-1-positive vescicular fluid sample cultures. In our experience, chronic ulcerative HSV infection is relatively frequent in HIV-infected children (6.6%), and has unusual clinical manifestations with a good initial response to acyclovir treatment. Relapses are common and become increasingly worse and less responsive to treatment.

Background Streptococcus pneumoniae is a leading cause of invasive infection in young children causing morbidity and mortality. Active surveillance systems of invasive pneumococcal disease (IPD) are recommended worldwide. The aim of this study was to estimate the current incidence of IPD and to describe the serotype distribution and the antimocrobial susceptibility of S. pneumoniae isolates in children aged less than 5 years residing in North-West Lombardy, Italy. Methods A twelve-month prospective active surveillance system recruited all children aged less than 5 years admitted for suspicion of IPD at emergency room of ten hospitals located in the monitored area. Blood samples were taken in all participants for confirmation of IPD based on isolation of S. pneumoniae from blood. Pneumococcal meningitis and sepsis were additionally confirmed by cerebrospinal fluid analysis. Serotyping and antimicrobial susceptibility testing were performed on isolates from blood. Results A total of 15 confirmed cases of IPD were detected among 135 recruited children, including pneumonia (n = 8), bacteremia (n = 4), sepsis (n = 2) and meningitis (n = 1). The annual IPD incidence rate was 50.0/100,000 (95%CI, 30.5-82.5/100,000). Incidence was 58.3/100,000 (28.8-120.1/100,000) among children aged less than 2 years and 44.4/100,000 (22.9-87.5/100,000) among children aged 2–4 years. Thirteen isolates were typified. The most common serotype was 19A (23.1%) that together with serotypes 1, 7F and 19F accounted for 69.2% of typified isolates. Serotypes 14, 23F, 12B and 15C were also identified. The 7- and 13-valent pneumococcal conjugate vaccines covered respectively 30.8% and 84.6% of typified IPD cases. One isolate (serotype 15C) was penicillin-resistant and caused meningitis. Conclusions The inclusion of the 13-valent pneumococcal conjugate vaccine in immunization programs of young children might be considered to reduce incidence and morbidity of invasive pneumococcal disease in this surveilled population.

Background Growth impairment and bone toxicity due to tenofovir disoproxil fumarate (TDF) fetal exposure has been described mainly in animals. We evaluated growth pattern and bone health in TDF-exposed HIV-uninfected children born to HIV-infected mothers, defined as seroreverters (SR). Methods This was a multicentre observational cross-sectional cohort study enrolling 68 SR who were in utero exposed to an antiretroviral regimen including (TDF+) or not including (TDF-) tenofovir. Neonatal data and duration of antiretroviral exposure were recorded. At enrolment, anthropometric measures, tibial speed of sound (SOS) by quantitative ultrasound and several parameters of bone metabolism were assessed. Results Gestational age and median in utero antiretroviral exposure were similar in subjects exposed to TDF ( n=33) and those non-exposed ( n=35). Age at enrolment was comparable in the two groups (TDF-exposed range 11.8–76.2 months and TDF non-exposed range 11.8–77.9 months). The incidence of low weight and length measurements (Conclusions Exposure to TDF during pregnancy does not impair growth patterns, bone health and markers of bone metabolism in SR infants and young children born to HIV-infected women.

Anecdotal reports of restored immunoglobulin production in individuals with common variable immunodeficiency after acquiring HIV infection suggest that perturbation of the immune system occurring during HIV infection may force some underlying functional defects. These findings raise intriguing questions about the pathogenesis of common variable immunodeficiency. No study has investigated the possible influence of HIV infection on the development of selective IgA deficiency, a primary immunologic defect genetically related to common variable immunodeficiency. IgA serum levels were evaluated in a large cohort of children born to HIV-infected mothers from 1985 to 2006. To avoid differences possibly due to different follow-up durations we considered only infected and non-infected children aged over 4 years at last-follow-up. The study included 1,157 non-infected children and 964 infected children, aged ≥ 4 years at last-follow-up and with availability of two or more serum IgA determinations over six months of age. No child displayed immunoglobulin values compatible with diagnosis of common variable immunodeficiency. However, 0/964 infected children vs. 5/1157 non-infected children had selective IgA deficiency (P=0.048). It may be speculated that several immunological alterations, occurring simultaneously in perinatal HIV infection, surpass the functional defect exhibited in some children with selective IgA deficiency. Our data may shed light on the pathogenesis of selective IgA deficiency.

This study describes the clinical, immunologic, and virological characteristics of 30 vertically human immunodeficiency virus type 1 (HIV-1)-infected children older than 8 years of age (long-survivors) before the introduction of protease inhibitors therapy. All of them were followed from birth. At the age of 8 years, 7 children presented no HIV-1-associated signs or only mild ones and only 5 had severe clinical manifestations (acquired immune deficiency virus [AIDS]). The remaining 18 children presented moderate signs with some immunodeficiency. The follow-up from 8 years of age (3.5 years on the average) showed that 6 children remained asymptomatic and were therefore defined as long-survivors nonprogressors (average, 13 years) and only 4 children developed AIDS. Progressive encephalopathy was the most striking clinical manifestation at follow-up and occurred in 6 children (always after immunodeficiency) with a polymorphic picture combining eye movement alterations, pyramidal signs and symptoms and mental deterioration. The majority of our long-survivors carried a virus with nonsyncytia-inducing phenotype, thus confirming its association with long survival. A switch to syncytia-inducing phenotype was observed only in 2 cases during the follow-up, but their clinical status did not change at follow-up.

Seventeen children with vertically acquired hepatitis C virus (HCV) infection were followed from birth for a mean of 104 months. Alanine aminotransferase (ALT) levels were increased significantly at 3 and 6 months of age but were stable thereafter. HCV polymerase chain reaction was positive at 3 months in 16 patients and at 12 months in one patient. Viral load remained stable during follow-up at a mean value of 5.4 ± 0.4 log10. Mild chronic hepatitis was the most common histopathological feature on liver biopsy, occurring in six of the seven children biopsied at a mean age of 4.0 ± 2.4 years. Genotype did not seem to be related to the type of liver involvement. The results of this study suggest that vertically acquired HCV infection has a benign course in children, despite the presence of viraemia and persistent alterations in ALT levels.

Lactoferrin (LF) is a mammalian iron-binding glycoprotein with antiviral effects. This preliminary study evaluated 6 months' LF (3 g/day, orally) treatment in 22 human immunodeficiency virus type 1 (HIV-1) vertically infected children. Plasma viral load and CD4+ cell counts were assessed every 3 months; before, during and after LF administration. No significant changes were observed during the pre-treatment period. By 6 months, mean (± SD) plasma viral load (log10) declined from 4.54 (± 0.65) to 4.28 (± 0.60); median percentage CD4+ cell count increased from 21.5% to 24.5%. Two months after treatment discontinuation, mean plasma viral load did not differ significantly from baseline or month 6 levels, but the percentage CD4+ cell count remained significantly higher than the baseline value. LF plus antiretroviral (ARV) therapy was more effective at increasing CD4+ cell count than LF alone. None of the patients showed any new HIV-1-related symptoms at follow-up. LF might be a useful addition to ARV therapy, but further large-scale studies are required.

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day–17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.