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Abstract Background Invasive meningococcal disease is a serious global health threat in the world; in 2016, the European Centre for Disease Control and Prevention reported 3280 confirmed cases (including 304 deaths) of Invasive Meningococcal Diseases in Europe. In Italy, in 2017 were reported 200 cases 41% of which due to menB serogroup. From January 2013 the European Medicines Agency (EMA) has authorized the marketing of the meningococcal B vaccine 4CMenB. Methods The study aimed to evaluate and complement the safety profile of 4CMenB in high risk children accessing the vaccine service of the Bambino Gesù Children’s Hospital. All individuals aged six weeks or more receiving the meningococcal 4CMenB (Bexsero®) vaccine that approached the vaccine Centre at the Bambino Gesù Children’s Hospital in Rome, were asked to participate. All parents or caregivers of vaccinated individuals in the study period, were recruited and requested to answer to a questionnaire on adverse events following immunization (AEFI) observed after 7 days, starting from the date of vaccination. Results During the study period (October 2016–October 2017), we collected 157 completed questionnaires (out of 200 distributed). Of those 132 were first doses and 25 were booster administered doses. The median age of the study population was 4.5 years (range 0.29 to 26.8 years), the majority of subjects were high-risk individuals (64%) with chronic health conditions. Overall, 311 adverse events were reported in the 7 days after vaccine administration. In particular 147 events (47%) after administration of first dose and 58 (19%) after the booster doses. A large majority of those events, were of little clinical importance and concentrated in the 24 h after vaccine administration. No hospitalizations or Emergency Department access were reported. Conclusions Results of our study demonstrated that the Bexsero® vaccine is almost well tolerated, with a low incidence of severe AEFIs. Our results also shown that the occurrence of AEFIs is similar within healthy and high risk children.

Objectives: This survey was conducted to describe current European postnatal prophylaxis (PNP) and infant feeding policies with the aim of informing future harmonized guidelines., Methods: A total of 32 senior clinicians with relevant expertise, working in 20 countries within the European Region, were invited to complete a REDCap questionnaire between July and September 2023., Results: Twenty-three of the 32 invited paediatricians responded, representing 16/20 countries. There were multiple respondents from the same country for Italy (n = 5), the UK (n = 2), Germany (n = 2) and France (n = 2). All countries use risk stratification to guide PNP regimen selection. Nine out of 16 countries reported three risk categories, six out of 16 reported two, and one country reported differences in categorization. Criteria used to stratify risk varied between and within countries. For the lowest risk category, the PNP regimen reported ranged from no PNP to up to four weeks of one drug; the drug of choice reported was zidovudine, apart from one country which reported nevirapine. For the highest risk category, the most common regimen was zidovudine/lamivudine/nevirapine (20/23 respondents); regimen duration varied from two to six weeks with variation in recommended dosing. Guidelines support breastfeeding for infants born to people living with HIV in eight out of 16 countries; in the other eight, guidelines do not support/specify., Conclusions: Guidelines and practice for PNP and infant feeding vary substantially across Europe and within some countries, reflecting the lack of robust evidence. Effort is needed to align policies and practice to reflect up-to-date knowledge to ensure the vertical transmission risk is minimized and unnecessary infant HIV testing and PNP avoided, while simultaneously supporting families to make informed decisions on infant feeding choice., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Community-acquired pneumonia (CAP) is an acute infection of the lung parenchyma acquired outside the hospital or other healthcare settings, typically affecting previously healthy individuals. This intersociety consensus aims to provide evidence-based recommendations for the antibiotic treatment of mild to moderate CAP in previously healthy children in Italy.A systematic review was conducted to identify the most recent and relevant evidence. Embase, Scopus, PubMed, and Cochrane databases were systematically screened, with a date restriction from 2012 to April 2024, but without language limitations. The review included studies conducted in high-income countries on antibiotic therapy in children over 3 months of age diagnosed with mild-moderate CAP. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods. The final recommendations were obtained through a Delphi consensus of an expert panel.Amoxicillin is the first-line treatment if the child is at least immunized against Haemophilus influenzae type b (low/very low quality of evidence, strong recommendations), while amoxicillin-clavulanate or second- or third-generation cephalosporins should be prescribed for those unimmunized or with incomplete immunization coverage for both H. influenzae type b and Streptococcus pneumoniae (low/very low quality of evidence, strong recommendations). Macrolides should be considered in addition to amoxicillin in children over 5 years old, if symptoms persist and the clinical condition remains good after 48 h of therapy (low/very low quality of evidence, strong recommendations). The dosage of amoxicillin is 90 mg/kg/day divided in three doses, although two doses could be considered to improve compliance (moderate quality of evidence, weak recommendations). A five-day duration of therapy is recommended, with clinical monitoring and re-assessment approximately 72 h after the start of antibiotic treatment to evaluate symptom resolution (moderate quality of evidence, strong recommendations).To improve the management of CAP in pediatric patients, we have developed this consensus based on a thorough review of the best available evidence and extensive discussions with an expert panel. However, further efforts are needed. Future research should focus on enhancing diagnostic accuracy, optimizing antibiotic utilization, comparing the efficacy of different antibiotic regimens, and determining the optimal dosage and duration of treatment in different setting., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Sotrovimab is a monoclonal antibody approved in adult and adolescents at high risk for COVID-19. Thirty-three children evaluated in five Italian paediatric centres received Sotrovimab infusion and were retrospectively enrolled from December 2021 to April 2022. In more than half of cases (19/33, 57.6%) Sotrovimab was prescribed off-label. Overall, the infusion was well tolerated with no significative differences in those receiving an off-label prescription. All children had a complete recovery. Data on the safety of Sotrovimab should be investigated in a larger paediatric cohort, considering the continuous selection of new SARS CoV-2 variants which may be more or less susceptible to the effects of the Sotrovimab.

Background: US Food and Drug Administration has issued Emergency Use Authorizations for hundreds of serological assays to support Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) diagnosis. The aim of this study is to evaluate, for the first time in children, the performance of three widely utilized SARS-CoV-2 serology commercial assays, Diesse Diagnostics (IgG, IgA, IgM) and Roche Diagnostics, both Roche Nucleocapsid (N) IgG and Roche Spike (S) IgG assays., Methods: Sensitivity and 95% confidence intervals (CIs) were estimated for each of the three different serological tests and mixed and direct comparison were performed. Univariate and multivariate Poisson regression models were fitted to calculate incidence rate ratios and 95% CIs as estimate of the effects of age, gender, time on the serology title. A p-value < 0.05 indicated statistical significance., Results: Overall, 149 children were enrolled in the study. A low sensitivity was found for Diesse IgA, IgM and IgG. Compare to Diesse, Roche S had a higher sensitivity at 15-28 days from infection (0.94, 95%CI: 0.73-1.0) and Roche N at 28-84 days (0.78, 95%CI: 0.58-0.91). When a direct comparison of IgG tests sensitivity was feasible for patients with pairwise information, Roche S and Roche N showed a statistically significant higher sensitivity compared to Diesse in all the study periods, whereas there was no difference between the two Roche tests., Conclusion: Roche S and Roche N serology tests seem to better perform in children. Large prospective studies are needed to better define the characteristics of those tests., (© 2022. The Author(s).)

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale’s severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

Surgical site infections (SSIs), which are a potential complications in surgical procedures, are associated with prolonged hospital stays and increased postoperative mortality rates, and they also have a significant economic impact on health systems. Data in literature regarding risk factors for SSIs in pediatric age are scarce, with consequent difficulties in the management of SSI prophylaxis and with antibiotic prescribing attitudes in the various surgical procedures that often tend to follow individual opinions. The lack of pediatric studies is even more evident when we consider surgeries performed in subjects with underlying conditions that may pose an increased risk of complications. In order to respond to this shortcoming, we developed a consensus document to define optimal surgical antimicrobial prophylaxis (SAP) in neonates and children with specific high-risk conditions. These included the following: (1) colonization by methicillin-resistant Staphylococcus aureus (MRSA) and by multidrug resistant (MDR) bacteria other than MRSA; (2) allergy to first-line antibiotics; (3) immunosuppression; (4) splenectomy; (5) comorbidity; (6) ongoing antibiotic therapy or prophylaxis; (7) coexisting infection at another site; (8) previous surgery in the last month; and (9) presurgery hospitalization lasting more than 2 weeks. This work, made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, represents, in our opinion, the most up-to-date and comprehensive collection of recommendations relating to behaviors to be undertaken in a perioperative site in the presence of specific categories of patients at high-risk of complications during surgery. The application of uniform and shared protocols in these high-risk categories will improve surgical practice with a reduction in SSIs and consequent rationalization of resources and costs, as well as being able to limit the phenomenon of antimicrobial resistance.

The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options.The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors.Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron).These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children.AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories.Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts' agreement.This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients., (© 2022. The Author(s).)

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission ( p < 0.01) and linearly to length of stay ( p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications ( p < 0.001). Viral coinfections, underlying clinical conditions, age 5-9 years and lymphopenia were statistically related to ICU admission ( p < 0.05). Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Garazzino, Lo Vecchio, Pierantoni, Calò Carducci, Marchetti, Meini, Castagnola, Vergine, Donà, Bosis, Dodi, Venturini, Felici, Giacchero, Denina, Pierri, Nicolini, Montagnani, Krzysztofiak, Bianchini, Marabotto, Tovo, Pruccoli, Lanari, Villani, Castelli Gattinara and the Italian SITIP-SIP Pediatric Infection Study Group.)

Background: Although eHealth technology makes it possible to improve the management of complex health care systems and follow up on chronic patients, it is not without challenges, thus requiring the development of efficient programs and graphic user interface (GUI) features. Similar information technology tools are crucial, as health care populations are going to have to endure social distancing measures in the forthcoming months and years., Objective: This study aims to provide adequate and personalized support to complex health care populations by developing a specific web-based mobile app. The app is designed around the patient and adapted to specific groups, for example, people with complex or rare diseases, autism, or disabilities (especially among children) as well as Alzheimer or senile dementia. The app's core features include the collection, labeling, analysis, and sorting of clinical data. Furthermore, it authorizes a network of people around the patient to securely access the data contained in his or her electronic health record., Methods: The application was designed according to the paradigms of patient-centered care and user-centered design (UCD). It considers the patient as the main empowered and motivating factor in the management of his or her well-being. Implementation was informed through a family needs and technology perception assessment. We used 3 interdisciplinary focus groups and 2 assessment surveys to study the contexts of app use, subpopulation management, and preferred functions. Finally, we developed an observational study involving 116 enrolled patients and 253 system users, followed by 2 feedback surveys to evaluate the performance and impact of the app., Results: In the validated general GUI, we developed 10 user profiles with different privacy settings. We tested 81 functions and studied a modular structure based on disease or medical area. This allowed us to identify replicable methods to be applied to module design. The observational study not only showed good family and community engagement but also revealed some limitations that need to be addressed. In total, 42 of 51 (82%) patients described themselves as satisfied or very satisfied. Health care providers reported facilitated communication with colleagues and the need to support data quality., Conclusions: The experimented solution addressed some of the health system challenges mentioned by the World Health Organization: usability appears to be significantly improved when the GUI is designed according to patients' UCD mental models and when new media and medical literacy are promoted. This makes it possible to maximize the impact of eHealth products, thereby overcoming some crucial gaps reported in the literature. Two main features seemed to have potential benefit compared with other eHealth products: the modeling, within the app, of both the formal and informal health care support networks and the modular structure allowing for comorbidity management, both of which require further implementation., (©Francesca Ferrucci, Manuele Jorio, Stefano Marci, Antonia Bezenchek, Giulia Diella, Cinzia Nulli, Ferdinando Miranda, Guido Castelli-Gattinara. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 13.01.2021.)

A statement of consensus was formulated after reviewing available literature on pediatric treatment strategies for COVID-19 by the Steering and Scientific Committee of the Italian Society of Infectious Pediatric Diseases in connection with the Italian Society of Paediatrics.

Background: Measles is a highly communicable infection with potentially severe complications. It is rarely reported in high-income countries and the limited awareness and experience of pediatricians may result in misdiagnosis. The present study aimed at investigating physician's ability and timing to reach diagnosis during a recent outbreak in Italy., Methods: The Italian Society for Pediatric Infectious Diseases conducted a retrospective, multicenter study in children hospitalized for measles between 1 January 2016 and 30 August 2017 in secondary and tertiary care hospitals. The appropriateness of diagnosis at admission, the time to reach clinical diagnosis, and serological confirmation of measles were recorded., Results: At hospital admission, measles was misdiagnosed in 101 (40.5%) of the 249 children (median age, 14.5 months) enrolled. The appropriate diagnosis increased from 30% to 72.5% during the period of observation (P < .001). A greater chance of receiving an appropriate diagnosis was demonstrated in children who reported a contact with measles (odds ratio [OR], 5.2; 95% confidence interval [CI], 3.0-9.2) or in those seen in institutions that managed more cases (OR, 7.39; 95% CI, 3.22-16.9; P = .0001). In contrast, children with underlying chronic conditions had a higher risk of misdiagnosis (appropriate diagnosis OR, 0.19; 95% CI, 0.10-0.33). The mean time from the onset of symptoms to clinical diagnosis was 4.55 ± 2.2 days and to serological confirmation was 7.0 ± 3.4 days., Conclusions: Measles is frequently misdiagnosed in low-prevalence settings. Specific measures to increase pediatricians' awareness about vaccine-preventable infections need to be implemented., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Background: In recent years, new information has been acquired regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society, therefore, decided to issue an update to the Italian Pediatric Society guidelines published in 2010., Methods: The search was conducted on Pubmed, and only those studies regarding the pediatric age alone, in English or Italian, published between January 1, 2010 and December 31, 2018, were included. Each study included in the review was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The quality of the systematic reviews was evaluated using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts., Results: The importance of eliminating risk factors (passive smoking, environmental pollution, use of pacifier, obesity, limitation of day-care center attendance) and the promotion of breastfeeding and hygiene practices (nasal lavages) was confirmed. The importance of pneumococcal vaccination in the prevention of AOM was reiterated with regard to the prevention of both the first episode of AOM and recurrences. Grommets can be inserted in selected cases of recurrent AOM that did not respond to all other prevention strategies. Antibiotic prophylaxis is not recommended for the prevention of recurrent AOM, except in certain carefully selected cases. The use of complementary therapies, probiotics, xylitol and vitamin D is not recommended., Conclusions: The prevention of episodes of AOM requires the elimination of risk factors and pneumococcal and influenza vaccination. The use of other products such as probiotics and vitamin D is not supported by adequate evidence.

Background: Seasonal influenza in Health-Care Workers (HCWs) is a topic of growing interest in public health for its organizational implications. The study aims at measuring absenteeism due to influenza in HCWs of an Italian pediatric hospital., Research Design and Methods: A retrospective observational study on absenteeism for influenza and influenza-like illness was carried out on all hospital HCWs. Sickness absences up to 5 days and vaccination status of HCWs were recorded during the last two years (2016/2017, 2017 /2018). Average sickness absenteeism rate in vaccinated and unvaccinated HCWs and total working days lost were estimated. Daily mean cost for HCW was calculated in order to define the non-vaccination costs., Results: In this study, the authors analyzed the overlapping between the trend of weekly sickness absenteeism and the morbidity rate associated with influenza epidemics in adults living in the Lazio region, Italy. An excess of 0.38 (p = 0.03) and 0.46 (p = 0.01) of average days lost was recorded in unvaccinated HCWs in the 2016/2017 and 2017/2018 epidemic seasons. The total amount of days lost in unvaccinated HCWs is 1.485,4 with a total cost of € 252.060,54., Conclusions: Seasonal influenza vaccination confirms its key role in preventing outbreaks of influenza and promoting HCWs health.

Despite relevant recommendations and evidences on the efficacy of influenza vaccination in health care workers (HCWs), vaccination coverage rates in Europe and Italy currently do not exceed 25%. Aim of the study is to measure the variations in vaccination coverage rates in an Italian pediatric hospital after a promotion campaign performed in the period October⁻December 2017. The design is a pre-post intervention study. The intervention is based on a wide communication campaign and an expanded offer of easy vaccination on site. The study was carried out at Bambino Ges&ugrave; Children&rsquo;s hospital in Rome, Italy, on the whole population of HCWs. Univariate and multivariate statistical analyses were performed. Vaccination coverage rate increased in 2017/18 campaign compared with the 2016/17 one (+95 HCWs vaccinated; +4.4%). The highest increases were detected in males (+45.7%), youngest employees (+142.9%), mean age of employment (+175%), other HCWs (+209.1%), Emergency Area (+151.6%) and Imaging Diagnostic Department (+200.0%). At multivariate logistic regression, working in some departments and being nurses represents a higher risk of being unvaccinated. Although the vaccination coverage rate remained low, a continuous increase of the coverage rate and development of a different consciousness in HCWs was highlighted. The study significantly identified the target for future campaigns.

Brain abscess is uncommon in paediatric population, but of clinical importance because of significant long-term morbidity and mortality. In this multicentre study, promoted by the Italian Society for Paediatric Infectious Diseases, we retrospectively collected patients aged 0-18 years, with a diagnosis of 'brain abscess'. Seventy-nine children were included; the median age was 8·75 years. As predisposing factor, 44 children had preceding infections. The Gram-positive cocci were mostly isolated (27 cases). Sixty (76%) children underwent a surgical intervention. Intravenous antibiotic therapy was administered in all patients, then switched to oral treatment. Clinical sequelae were recorded in 31 (39·2%) children. Twenty-one of them had a single sequela, of which, the most represented, was epilepsy in nine of them. This study focus the attention on the need to have standardized national guidelines or adequate recommendations on type and duration of antibiotic treatment.

Background: Invasive diseases (ID) caused by Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis are a major public health problem worldwide. Comprehensive data on the burden of bacteremia and ID in Italy, including data based on molecular techniques, are needed., Methods: We conducted a prospective, multi-centre, hospital-based study (GSK study identifier: 111334) to assess the burden of bacteremia and ID among children less than five years old with a fever of 39 °C or greater. Study participation involved a single medical examination, collection of blood for polymerase chain reaction (PCR) and blood culture, and collection of an oropharyngeal swab for colonization analysis by PCR., Results: Between May 2008 and June 2009, 4536 patients were screened, 944 were selected and 920 were enrolled in the study. There were 225 clinical diagnoses of ID, 9.8 % (22) of which were bacteremic. A diagnosis of sepsis was made for 38 cases, 5.3 % (2) of which were bacteremic. Among the 629 non-ID diagnoses, 1.6 % (10) were bacteremic. Among the 34 bacteremic cases, the most common diagnoses were community-acquired pneumonia (15/34), pleural effusion (4/34) and meningitis (4/34). S. pneumoniae was the most frequently detected bacteria among bacteremic cases (29/34) followed by H. influenzae (3/34). Ninety percent (27/30) of bacteremic patients with oropharyngeal swab results were colonized with the studied bacterial pathogens compared to 46.1 % (402/872) of non-bacteremic cases (p < 0.001). PCV7 (7-valent pneumococcal conjugate vaccine) vaccination was reported for 55.9 % (19/34) of bacteremic cases. S. pneumoniae serotypes were non-vaccine serotypes in children who had been vaccinated. Mean duration of hospitalization was longer for bacteremic cases versus non-bacteremic cases (13.6 versus 5.8 days)., Conclusions: These results confirm that S. pneumoniae is one of the pathogens frequently responsible for invasive disease.

Viral and host factors can influence HIV-1 progression, among them human leucocyte antigen (HLA) has shown the strongest effect. However, studies on the functional contribution of HLA in controlling HIV progression toward AIDS are limited by multiple issues, including the viral strain variability within the study subjects. In this study, in a cohort of children infected with a monophyletic strain (CRF02&#95;AG) during an outbreak, we evaluated the HIV-1 Gag, Vif, Vpr, Tat and hepatitis C virus E1/E2 (as control) proteins circulating in a cohort for the capability to be presented by the HLA molecules in the same population. A total of 70 Non-progressors and 37 Progressors to AIDS were evaluated. In the presence of a constant capability of HIV-1 to mutate in the region containing epitopes of Gag protein, the number of epitopes recognized in silico by the combination of the HLA alleles along the Gag consensus sequence is significantly higher in the Non-progressors compared with Progressors (HLA-A: Non-progressors = 1.532 ± 1.211, Progressors = 0.7714 ± 1.031, P = 0.0016; HLA-B: Non-progressors = 1.556 ± 1.298, Progressors = 1.000 ± 0.817, P = 0.0319; HLA-DR: Non-progressors = 13.30 ± 9.488, Progressors = 7.294 ± 6.952, P = 0.0006). Similar results were obtained for the other HIV-1 proteins Vif and Vpr, whereas no differences were obtained in the number of epitopes for the hepatitis C virus E1/E2 protein sequence or for the scrambled HIV-1 sequence. Finally, the results were confirmed also in a subgroup of subjects where both HLA typing and Gag sequence were available. In conclusion, in the absence of bias due to viral strain diversity, it is the overall fitting of the HLA molecules that are capable of better binding HIV-1 proteins in determining the major role in the control of HIV-1 replication and progression to AIDS., (© 2014 John Wiley & Sons Ltd.)

Active pulmonary tuberculosis was diagnosed in a 4-month-old infant 16 days after hospitalization; 186 exposed individuals were traced and one conversion detected. Although the risk of tuberculosis transmission in paediatric hospitals is low, paediatricians in low-incidence countries should maintain a high level of alert for timely identification of cases.

HIV-1 infection causes a severe T-cell impairment with alteration of immune response. However, in children the natural decline of lymphocytes and CD4 cells in early life makes it more difficult to monitor immunocompetence and progression of HIV-infection. Aim of this study was to characterize the CD8 response in non-vertically HIV-infected children exposed persistently to viremia and in HIV-infected children controlling efficiently viremia by ART, by analysing the effect of persistent viremia on CD4 and CD8 T-cells count, HIV-specific immune-response and naive/memory pattern of CD8 T-cell. Whereas, no differences of CD4 count between viremic patients and viral controllers were observed (1046.9 +/- 472.1 cells/microl vs 1101.3 +/- 415.4 cells/microl; p > 0.05), CD8 count was higher in the viremic patients (1080.6 +/- 652.1 cells/microl vs 747.5 +/- 389.9 cells/microl, p < 0.05). In viremic patients, HIV-specific CD8 T-cells correlated with viral load. However, in this group a loss of HIV-specific CD8 response was associated with a 7 fold decrease of naïve and increase of pre-effector CD8 T-cells (62.8% +/- 10.21% vs 10.37% +/- 7.91%, p < 0.03). Persistent exposure to viremia alters HIV-specific CD8 response possibly through a persistent immune activation process leading to exhaustion of naive CD8 T-cells and skewed maturation of memory subset. Therefore, memory CD8 T-cells might lose the ability to respond correctly and efficiently to HIV-antigen exposure.

The objective of this document is to identify and reinforce current recommendations concerning the management of HIV infection in infants and children in the context of good resource availability. All recommendations were graded according to the strength and quality of the evidence and were voted on by the 57 participants attending the first Italian Consensus on Paediatric HIV, held in Siracusa in 2008. Paediatricians and HIV/AIDS care specialists were requested to agree on different statements summarizing key issues in the management of paediatric HIV. The comprehensive approach on preventing mother-to-child transmission (PMTCT) has clearly reduced the number of children acquiring the infection in Italy. Although further reduction of MTCT should be attempted, efforts to personalize intervention to specific cases are now required in order to optimise the treatment and care of HIV-infected children. The prompt initiation of treatment and careful selection of first-line regimen, taking into consideration potency and tolerance, remain central. In addition, opportunistic infection prevention, adherence to treatment, and long-term psychosocial consequences are becoming increasingly relevant in the era of effective antiretroviral combination therapies (ART). The increasing proportion of infected children achieving adulthood highlights the need for multidisciplinary strategies to facilitate transition to adult care and maintain strategies specific to perinatally acquired HIV infection.

Shared transmission routes of HCV and HIV mean parenteral HIV/HCV coinfection still occurs, often in resource-limited settings. The extent to which coinfection and treatment impact on morbidity and mortality in HIV/HCV coinfected children remains unknown thus optimal management and treatment is difficult to achieve. Using data from a unique, large, prospective cohort of parenterally HIV/HCV coinfected children in Libya we determine the immunological, virological and clinical profiles of HIV/HCV coinfected children documenting the natural and treated history of parenterally acquired coinfection for the first time in such a large group. 160 parenterally HIV/HCV coinfected children were analysed. Thirty-three (21%) received antiretroviral treatment (ART) for HIV disease during follow-up. In children receiving ART, HIV RNA viral load decreased in two-thirds 6-12 months after initiation. 85% (17/20) experienced a positive immunological response to ART with a median increase in CD4 cell count z-score of 131%. Half had progressed to moderate or severe immunosuppression and/or moderate or severe clinical symptoms three years after infection. In those who progressed during follow-up, 85% had done so within three years of infection. Children progressing to moderate or severe immunosuppression and/or clinical symptoms were significantly more likely to be receiving ART. This novel investigation of the natural and treated history of parenterally HIV/HCV coinfected children in a large prospectively followed group demonstrates minimal clinical symptoms and immunosuppression to date, despite low prevalence of treatment, and a response to ART similar to vertically HIV-only infected children.

Background: Obesity in Prader-Willi Syndrome (PWS) is progressive, severe, and resistant to dietary, pharmacological, and behavioral treatment. A body weight reduction is mandatory to reduce the risk of cardio-respiratory and metabolic complications. The aim of the study was to assess risks and benefits of BioEnterics Intragastric Balloon (BIB) for treatment of morbid obesity in PWS patients., Methods: Twenty-one BIB were positioned in 12 PWS patients (4 M, 8 F), aged from 8.1 to 30.1 years, and removed after 8 +/- 1.4 months (range: 5-10 months). Auxological, clinical, and nutritional evaluations were performed every 2 months. Variations in body composition were analysed by dual energy X-ray absorbiometry (DXA)., Results: One patient (28.5 years, BMI: 59.3 kg/m(2)) died 22 days after BIB positioning because of gastric perforation. In another case (26.2 years, BMI: 57.6 kg/m(2)), BIB was surgically removed after 25 days because of symptoms suggesting gastric perforation (not confirmed). The remaining ten patients showed a significant decrease of BMI (p = 0.005) and of fat tissue as measured by DXA (p = 0.012). No significant modifications in bone mineral density (BMD) occurred, but a slight loss in lean body mass (p = 0.036) was documented. In five patients, BIB treatment was repeated more than once., Conclusion: This study shows that when noninvasive pharmacological therapies fail, BIB may be effective to control body weight in PWS patients with morbid obesity, particularly when treatment is started in early childhood. However, careful clinical follow-up and close collaboration with parents are crucial to avoid severe complications, which can be caused by persisting unrestrained food intake.

Antiviral T-cell immune responses appear to be crucial to control HIV replication. Infants treated before the third month of life with highly active antiretroviral treatment (HAART) did not develop a persistent HIV-specific immune response. We evaluated how delayed initiation of HAART after 3 months of age influences the development of HIV-1-specific T-cell responses during long-term follow-up in 9 HIV-1 vertically infected infants. These data suggest that a longer antigenic stimulation, due to a larger window for therapeutic intervention with HAART, is associated with the establishment of a persistent specific HIV immune response resulting in a long-term viral control of vertically infected infants.