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Purpose: To evaluate the microbiology of acute otitis media (AOM) with otorrhea due to spontaneous tympanic membrane perforation (STMP) in children living in Milan, Italy. Methods: We evaluated middle ear fluid (MEF) specimens taken from children affected by AOM associated with STMP and otorrhea between January 2001 and December 2011. The fluid was collected by means of direct swab sampling, sent for culture, and processed within 4 h. Results: A total of 705 specimens were obtained from 458 children (233 boys; mean age ± SD 28.3 ± 19.9 months), and were positive for bacteria in 487 cases (69.1 %). The most frequently cultured infectious agent in single-pathogen cultures was Haemophilus. influenzae (51.0 %), followed by Streptococcus pneumoniae (19.4 %), Streptococcus pyogenes (17.4 %), and Staphylococcus aureus (10.7 %). After adjusting for the sub-period of data collection, age, gender, and previous full heptavalent pneumococcal conjugate vaccine (PCV-7) schedule, it was found that the prevalence of H. influenzae slightly increased in 2008-2010, and the prevalence of S. pneumoniae significantly decreased over time ( p = 0.02). Conclusions: AOM with STMP is a particular form of AOM in which S. pyogenes plays a significant causative role although, as in uncomplicated cases, H. influenzae and S. pneumoniae retain their etiological importance. The frequency of the detection of S. aureus in MEF deserves further study because this pathogen can give rise to severe clinical problems. Finally, although the use of PCV-7 was relatively efficacious, the benefit of pneumococcal vaccination would be increased by vaccines including a larger number of serotypes. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to determine how specialists in paediatric infectious diseases (PIDs) manage children with suspected Lyme disease (LD) by comparing their approaches in Italian endemic and non-endemic areas. A cross-sectional survey of the PID specialists participating in the Italian Society for Pediatric Infectious Disease (SITIP) Registry of LD was carried out between 1 January and 30 April 2012. A total of 160 children (80 living in endemic areas and 80 living in non-endemic areas) were diagnosed as having LD between 1 January 2005 and 31 December 2011. The clinical manifestations were erythema migrans in 130 cases (81.3 %), arthritis in 24 (15.0 %) and neuroborreliosis in six (3.8 %). Significant differences from the recommendations concerning serology and the tests to undertake were mainly observed in the children with erythema migrans, especially those living in non-endemic areas ( p < 0.05). The children with erythema migrans who lived in non-endemic areas were treated with antibiotics significantly less frequently than those living in endemic areas ( p < 0.05), and significantly fewer children with erythema migrans or arthritis living in non-endemic areas were treated with amoxicillin in comparison with those living in endemic regions ( p < 0.05). The duration of antimicrobial therapy was significantly shorter than recommended in the children with erythema migrans or arthritis, especially those living in non-endemic areas ( p < 0.05). Paediatric LD is also present in areas of Italy in which it is not considered endemic, but knowledge concerning its management is generally poor among PID specialists and characterised by enormous gaps in non-endemic areas. [ABSTRACT FROM AUTHOR]

In this multicentre study we evaluated the prevalence and risk factors of otitis media with effusion (OME) in Italian school-children and the effectiveness of medical treatment of chronic OME with a new cephalosporin, ceftibuten. During two winter periods, 3413 children, aged 5 to 7 years, were examined for the presence of OME by means of pneumotoscopy and a portable, hand-held tympanometer. The prevalence of asymptomatic OME was 14.2%, with no difference as regards sex, age, month of examination or geographic area. Younger children had significantly more bilateral than unilateral effusion. A recent episode of acute otitis media and previous tonsillectomy or adenoidectomy were associated with an increased risk of OME in multivariate logistic regression models. The presence of OME was unrelated to such factors as birthweight, prematurity, sibling or parental history of allergy, duration of daycare attendance, family history of ear infections. After 12 weeks, 26.6% of children with OME still had middle-ear fluid: 52 were randomized to ceftibuten (9 mg/kg q.d. for 14 days) and 59 to no treatment (nasal saline drops allowed). Children treated with ceftibuten had a significantly better resolution of middle-ear effusion after 4 and 8 weeks. As mass screening programmes for OME in the year of school entry are questioned, a focus only on children with known risk factors seems advisable. Ceftibuten can be useful in reducing the duration of middle-ear effusion. [ABSTRACT FROM AUTHOR]

Sore throat represents one of the main causes of antibiotic overprescription in children. Its management is still a matter of debate, with countries considering streptococcal pharyngotonsillitis a benign and self-limiting condition and others advocating for its antibiotic treatment to prevent suppurative complications and acute rheumatic fever. Italian paediatricians frequently prescribe antibiotics on a clinical basis regardless of microbiological results. Moreover, broad-spectrum antibiotics are inappropriately prescribed for this condition. In this regard, an intersociety consensus conference was issued to promote the judicious use of antibiotic therapy in paediatric outpatient settings. A systematic review of the literature was performed, and updated recommendations were developed according to the GRADE methodology. Antibiotic treatment with amoxicillin (50 mg/kg/day) for 10 days is recommended in all children with proven streptococcal pharyngitis. Benzathine-penicillin could be prescribed in children with impaired intestinal absorption or inability to tolerate enteral intake and in those at high risk of suppurative complications with low compliance to oral therapy. In children with suspected amoxicillin allergy, third-generation cefalosporins for five days are recommended in low-risk patients, and macrolides are recommended in high-risk ones. Candidates for tonsillectomy due to recurrent pharyngitis could be treated with amoxicillin-clavulanic acid, clindamycin, or combined therapy with amoxicillin plus rifampicin for four days, in an attempt to avoid surgery., (© 2024. The Author(s).)

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: Despite efforts to increase coverage by two doses of measles vaccine in Italy, measles continues to circulate, with over 13 000 cases of disease since 2013. This study aimed to evaluate immunity to measles in Italian children and adolescents., Methods: A total of 378 serum samples from subjects aged 9 months-18 years were collected in Northern, Central and Southern regions of Italy between 2012 and 2016. Specific IgG antibodies against measles were measured by a commercial ELISA kit., Results: The frequency of IgG-positive samples ranged from 10.5% in infants under 1 year to 98.3% in children aged 6-7 years. The frequency of IgG was 72.2% in subjects aged 1-2 years, 85.6% in those aged 3-5 years and 88.3 and 86.8% in those aged 8-10 and 11-18 years, respectively. In Northern Italy, IgG prevalence was consistent with data on vaccination coverage, whereas some differences were observed in samples from subjects aged more than 8 years in Central and Southern Italy., Conclusions: Our findings confirm that a large proportion of children and adolescents in Italy are still susceptible to measles. While data on first- and second-dose measles vaccination are essential, they are not sufficient to identify susceptible population cohorts to be targeted by vaccination., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Women with aesthetic prostheses must be included in the target population of mammography screening programmes. Breast implants are radiopaque and partially obscure the breast tissue. This can be avoided with the use of the Eklund technique, which causes an increased radiation exposure. In this study, augmented women undergoing a dedicated protocol within a population-based screening programme were compared according to selected indicators with the standard screening population. Essential dosimetric parameters and their time trend were also assessed., Materials and Methods: The study was conducted in a screening centre in Milan in the years 2009-2016. The screening protocol for women with breast implants included a double-read mammography with the Eklund views, ultrasound and clinical breast examination., Results: A total of 28,794 women were enrolled, including 588 (2%) women with breast implants and 28,206 (98%) undergoing the standard screening protocol. The invasive assessment rate was 9.0‰ for women with breast implants vs. 15‰ in the standard cohort. The surgical referral rate was 2.2% vs. 0.9%. The detection rate was similar in the two groups (4.0 and 4.5‰, respectively). There were significant differences in the average glandular dose according to the mammography equipment. The use of the Eklund views increased over time., Conclusions: Screening of augmented women according to a specific protocol in the contexts of population-based programmes is feasible. Observed differences in screening indicators relative to the standard screening population require further research. The increasing use of Eklund views probably results from quality assurance measures associated with screening programmes.

Background: communicating breast cancer screening (BCS) limits and overdiagnosis implies providing complete and balanced information to allow informed decision-making., Objectives: to describe women's perceptions, preconceptions, and information preferences regarding the breast cancer screening (BCS) programme paper and web information materials of the Agency for Health Protection of the Metropolitan Area of Milan (Lombardy Region, Northern Italy)., Design: qualitative, descriptive study., Setting and Participants: participants' voluntary recruitment took place in the registration departments of three hospitals. Participants were purposively recruited based on sociodemographic characteristics of the target population of the programme (44 women aged 40-74 years, living in the Metropolitan Area of Milan). In each material type subgroup, different health literacy levels and age classes were included, until thematic saturation was reached., Main Outcome Measures: thematic analysis of qualitative data collected during think-aloud interviews., Results: the thematic analysis identified 5 main themes: 1. validation of the information reported in the materials, according to the interviewees' personal experiences;2. information preferences of particular subgroups of women, which led to a tailored approach for the web materials;3. negative emotions elicited while receiving information regarding BCS limits, which guided the rewriting of certain definitions; 4. disproportioned risk perception, with greater weight attributed to the risk of false negative results than the risk of overdiagnosis; 5. organizational preferences regarding the type and frequency of the provided tests and the age limits of the programme., Conclusions: in the present sample of women living in the Metropolitan Area of Milan, knowledge and comprehension of overdiagnosis are scarce. The main reasons for distrust in the BCS programme rely on the preexisting beliefs regarding the most appropriate tests and age limits. These beliefs were established from previously received information, inconsistent with that officially provided by the programme.

Background: Although the diagnosis of new coronavirus 2019 (COVID-19) is made through the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory secretions by means of molecular methods, a more accurate estimation of SARS-CoV-2 circulation can be obtained by seroprevalence studies. The main aim of this study was to evaluate the true epidemiology of SARS-CoV-2 infection among workers in the metal-mechanical sector who never stopped working during the pandemic period in an area with a high incidence of COVID-19 and to define whether and how they could continue the work without appreciable risks during a second wave. Methods: A total of 815 metal-mechanical workers who had never stopped working even during the pandemic period in three different factories in the Emilia-Romagna Region, Italy, and who had always used face masks during working hours, underwent a capillary blood rapid test for the determination of IgM and IgG against SARS-CoV-2 (COVID-19 IgG/IgM Rapid test, PrimaLab, Modena, Italy). In the event of a positive test, a nasopharyngeal was performed and tested for the presence of SARS-CoV-2. Results: The detection of serum IgG/IgM against SARS-CoV-2 was significantly more common among workers employed in Parma (21/345, 6.1%) than among those employed in Calerno (7/242, 2.9%) or in Spilamberto (3/228, 1.3%) ( p <0.001). The analysis of the role of the different variables as predictors of seropositivity for IgG/IgM against SARS-CoV-2 revealed that the presence of specific antibodies was strictly associated with a previous history of COVID-19-like symptoms (odds ratio [OR] 3.95, 95% confidence interval [CI] 1.9-8.2) and household members with COVID-19-like symptoms (OR 2.20, 95% CI 1.04-4.82). Conclusion: This study shows that seropositivity to SARS-CoV-2 is low even among employees who did not interrupt their work during the lockdown phase in a region with a high incidence of COVID-19. The use of face masks appears effective in the avoidance of the transmission of SARS-CoV-2 in factories even in the presence of asymptomatic or mildly symptomatic workers, suggesting that work activities can continue if adequate infection control measures are used during a second wave., 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 Esposito, Neglia, Affanni, Colucci, Argentiero, Veronesi, Messina, Deolmi, Principi and the Crown Study Group.)

Background: Controlling inappropriateness of care is an essential issue, especially in rehabilitation medicine. In fact, admitting a patient to a rehabilitation hospital or unit is a complex decision also due to the absence of shared and objective admission criteria., Aim: The aim was to define clinical admission criteria and rules in rehabilitation medicine., Design: Survey based on the application of the Delphi method on a sample of rehabilitation medicine experts., Setting: Administration of electronic online questionnaires concerning appropriateness of admission to intensive rehabilitation., Population: Volunteer sample of 53 experts with the following inclusion criteria: being members of the Italian Society of Physical and Rehabilitation Medicine, having practical experience in the research field, agreeing to the confidentiality of the information and being skilled in both rehabilitation and healthcare organization., Methods: A three-round Delphi survey was conducted according to international guidelines. The two initial rounds consisted of an electronic online questionnaire while in the third one a report of the results was provided to the participants. The experts had to score their agreement with each item in the questionnaires, based on either a Likert scale or a dichotomous statement. Consensus between the experts was assessed., Results: A total of 53 health professionals completed the Delphi survey. 19 out of 20 Italian regions were represented. The first round consisted of 8 multiple-choice questions. The second round was designed according to the suggestions provided by the panelists in the previous one and consisted of a twelve items questionnaire. At the end of the survey, seven criteria of appropriateness of admission to rehabilitation were identified and five rules defining an appropriate admission to a rehabilitation facility were elaborated., Conclusions: This study represents an attempt to create a worthwhile and reliable tool for a more conscious clinical practice in admission to rehabilitation, based on a set of shared criteria and rules., Clinical Rehabilitation Impact: To increase appropriateness of admission to rehabilitation. Improving appropriateness in healthcare delivery must be a primary goal in order to improve healthcare quality, save money and ensure system sustainability.

Background: Acute gastroenteritis (AGE) due to group A rotavirus (RVA) agent is one of the major causes of hospitalization in paediatric age. The G3P[8] RVA genotype has been usually considered as one of the major human genotypes, largely circulating in Asia, but showing low detection rates in the European countries. In recent years, the G3P[8] RVAs emerged also in Europe as a predominant genotype and the viral strains detected revealed high similarities with equine-like G3P[8] RVA strains, resulting in a new variant circulating in humans and able to cause AGE in the paediatric population., Case Presentation: An 8-year-old boy was admitted to the Emergency Room because he had suffered from severe diarrhoea, vomiting, and high fever over the previous two days. Severe dehydration was evident based on low serum concentrations of potassium and sodium, low glycaemia, and pre-renal failure (creatinine 2.48 mg/dL, urea 133 mg/dL). Immunological tests were within normal range. Enzyme immunoassay for the detection of RV was positive, and a sample of faeces was collected in order to perform the molecular characterization of the viral strain. The phylogenetic trees revealed relatedness between the VP7 and VP4 genes of the G3P[8] RVA Italian strain (namely PG2) and those belonging to recent G3P[8] RVAs detected worldwide. The G3 VP7 belonged to the G3-I lineage and shared the highest nucleotide sequence identity (99.8%) with the equine-like G3 previously identified in other countries. The P [8] VP4 revealed a similar clustering pattern to that observed for the VP7. In addition, the molecular characterization of the 11 gene segments of strain PG2 revealed a G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genomic constellation., Conclusions: This case shows the first detection in Italy of a reassortant G3P[8] RVA associated with a severe AGE, which is unusual in a school-age child without any known severe underlying problems. The findings reported in this paper highlight the importance of continuously monitoring the RVA strains circulating in paediatric age in order to detect novel viral variants able to spread in the general population.

Background: Ewingella americana (Ea) is a Gram-negative, lactose-fermenting, oxidase-negative and catalase-positive bacterium that was first described in 1983 as a new genus and species in the family Enterobacteriaceae. It is not known whether Ea is a true pathogen or simply an opportunistic infectious agent, as most of the cases have been described in patients at risk., Case Presentation: A 4-year-old girl described here was hospitalized due to a productive cough over the previous 3 weeks and a fever > 38 °C associated with tachypnea over the previous 2 days. Her familial and personal medical histories were negative for relevant diseases, including respiratory infections. At admission, she was febrile (axillary temperature 39.2 °C) and had dyspnea with retractions, grunting and nasal flaring. A chest examination revealed fine crackling rales in the left upper field associated with bilateral wheezing. A chest X-ray revealed segmental consolidation of the lingula of the left lung. Laboratory tests revealed leukocytosis (15.,800 white blood cells/mm 3 with 50.3% neutrophils), a slight increase in serum C-reactive protein (11.9 mg/L) and normal procalcitonin values (< 0.12 ng/mL). A nasopharyngeal swab culture did not reveal viral or bacterial respiratory pathogens, including atypical bacteria. A blood culture revealed the presence of a Gram-negative, lactose-fermenting rod that was oxidase negative and catalase positive. The isolate was identified by means of the VITEK®2 identification system (bioMérieux, Firenze, Italy) as Ea. This identification was confirmed by sequencing the 16 s ribosomal deoxyribonucleic acid (rDNA). The pathogen was sensitive to aminoglycoside, fluoroquinolones, carbapenems, cefotaxime, and ceftazidime but was intermediate against sulfametoxazole/trimethoprim and resistant to amoxicillin-clavulanic acid, fosfomycin, and oxacillin. The child was immediately treated orally with amoxicillin-clavulanic acid and erythromycin. Based on the results of a blood culture and sensitivity tests, the amoxicillin-clavulanic acid medication was stopped after 3 days. Erythromycin was continued for a total of 10 days, and the child was discharged after 3 days in the hospital. Follow-up visit 1 month later did not reveal any respiratory problems., Conclusion: This case shows that Ea infections in healthy subjects are mild even in pediatric age, and the need for antibiotic therapy is debated. Cases occurring in subjects with underlying chronic disease can be significantly more complicated and require appropriate antibiotic therapy.

In otherwise healthy infants and young children, respiratory tract infections (RTIs) are extremely common. Clinical data have shown that OM-85 could prevent respiratory recurrences in children. However, further studies are needed to explore the true importance of OM-85 in clinical practice. In addition, an unsolved problem is the efficacy of OM-85 when it is administered for two consecutive years. Moreover, another open question is the safety of OM-85 when co-administered with the influenza vaccine. In order to solve these unanswered issues, 200 children aged three to six years with a history of recurrent RTIs, defined as at least six documented episodes of acute RTI in a single year, who had received OM-85 (Broncho-Vaxom ® ; OM Pharma, a Vifor Pharma Group Company, Geneva, Switzerland) for two consecutive years (3.5 mg once a day for 10 days for 3 months of each year) were selected and matched based on age, sex, and period of evaluation with children with recurrent RTIs who did not receive OM-85. In the group of children treated with OM-85, the number of patients who did not experience any new episode of RTI, as well as the number of RTIs, wheezing episodes, medical visits, and prescribed antibiotic courses, were significantly lower than that in the group not treated with OM-85. The results were similar in the first and second year of OM-85 administration. A minority of patients showed mild adverse events, and the safety profile was overall good, including in the 49 children who received the influenza vaccination within one month from the beginning of the first cycle of OM-85. Our data suggest that OM-85 can effectively and safely reduce the risk of new infective episodes in children with recurrent RTIs and that a second yearly course of lysate administration can be useful to maintain protection, particularly when the diagnosis of recurrent RTIs is made in younger children for whom it is likely that definitive maturation of the immune system still requires a long time.

Recently, two vaccines against meningococcal serogroup B (MenB) have been developed. They are prepared according to the reverse vaccinology approach and contain 4 (4CMenB) and 2 (MenB-FHbp) cross-reactive surface proteins. In Italy 4CMenB vaccine has been included in the official vaccination schedule only recently and recommended only for infants and toddlers, whereas MenB-FHbp is not licensed. In order to collect information about the present carriage of Neisseria meningitidis serogroup B (MenB) in Italian adolescents and to evaluate the potential protection offered by the presently available MenB vaccines, 2,560 otherwise healthy, high school students aged 14-21 years (907 males, 35.4%, median age 16.2 years) were enrolled in Milan, Italy. A swab to collect posterior pharynx secretions was collected from each subject and meningococcal identification, serogrouping, multilocus sequence typing analysis, sequence alignments and phylogenetic analysis were performed. A total of 135 (5.3%) adolescents were meningococcal carriers. Strains belonging to serogroup B were the most common (n = 58; 2.3%), followed by MenY (n = 32; 1.2%), MenC (n = 7; 0.3%), MenW (n = 6; 0.3%) and MenX (n = 5; 0.2%). The remaining bacteria were not capsulated. The identified MenB strains belonged to eleven clonal complexes (CCs): ST-162 CC (n = 12; 20.7%), ST-865 CC (n = 12; 20.7%), ST-41/44/Lin.3 CC (n = 11; 19.0%), ST-35 CC (n = 6; 10.3%), ST-32/ET-5 CC (n = 4; 6.9%), ST-269 CC (n = 3; 5.2%), ST-213 CC (n = 2; 3.4%), ST-198 CC (n = 1; 1.7%), ST-461 CC (n = 1; 1.7%), ST-549 CC (n = 1; 1.7%), and ST-750 CC (n = 1; 1.7%). This study showed that MenB was the most commonly carried meningococcal serogroup found in adolescents living in Milan, Italy. The MenB vaccines presently licensed could have theoretically induced the production of antibodies effective against the greatest part of the identified MenB strains (100% in the case of 4CMenB and 95% in case of MenB-FHbp) Monitoring carriage remains essential to evaluate MenB circulation, but further studies are necessary to evaluate the effect on carriage and the final efficacy of both new MenB vaccines.

Background: In recent years, several outbreaks due to Enterovirus D-68 (EV-D68) have been reported, and it was confirmed that the virus can cause upper and lower respiratory tract diseases and be associated with the development of neurological problems., Objectives: The main aim of this research was to study the genetic characteristics of EV-D68 strains that were circulating in Italy identified during an outbreak of an EV-D68 infection that occurred in Italy during the period March-October 2016., Study Design: A retrospective study of the circulation of different types and subtypes of EV-D68 was performed. Nasopharyngeal swabs were collected from March 2016 through October 2016 in children admitted to the Emergency Room with respiratory diseases., Results: Among 390 children, 22 (59.1% males; mean age 47 months) were found to be infected by EV-D68 and most of them were immunocompetent (72.7%). Pneumonia was diagnosed in 12 (54.5%) children. Phylogenetic analysis of the VP1 region showed that all the strains identified in this study belonged to clade B3. Within B3 subclade, the Italian EV-D68 strains were most closely related to strains detected in Southern China in 2015 as well as to strains detected in US and the Netherlands in 2016., Conclusions: These results showed that EV-D68 infections are a common cause of lower respiratory illness in pediatric age. The circulation of one EV-D68 lineage has been proven in Italy and in the European region during 2016. However, further studies are required to investigate whether some strains or lineages may possess a higher affinity for the lower airway or central nervous system., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. The HAdVs were detected using a respiratory virus panel fast assay (xTAG RVP FAST v2) and with a HAdV-specific real-time polymerase chain reaction; their nucleotides were sequenced, and they were tested for positive selection. Among 307 nasopharyngeal samples, 61 (19.9%) tested positive for HAdV. HAdV was the only virus detected in 31/61 (50.8%) cases, whereas it was found in association with one other virus in 25 (41.0%) cases and with two or more viruses in 5 (8.2%) cases. Human Enterovirus/human rhinovirus and respiratory syncytial virus were the most common co-infecting viral agents and were found in 12 (19.7%) and 7 (11.5%) samples, respectively. Overall, the HAdV strain sequences analyzed were highly conserved. In comparison to HAdV-negative children, those infected with HAdV had a reduced frequency of lower respiratory tract involvement (36.1% vs 55.2%; p = 0.007), wheezing (0.0% vs 12.5%; p = 0.004), and hospitalization (27.9% vs 56.1%; p<0.001). Antibiotic therapy and white blood cell counts were more frequently prescribed (91.9% vs 57.1%; p = 0.04) and higher (17,244 ± 7,737 vs 9,565 ± 3,211 cells/μL; p = 0.04), respectively, in children infected by HAdV-C than among those infected by HAdV-B. On the contrary, those infected by HAdV-B had more frequently lower respiratory tract involvement (57.1% vs 29.7%) but difference did not reach statistical significant (p = 0.21). Children with high viral load were absent from child care attendance for a longer period of time (14.5 ± 7.5 vs 5.5 ± 3.2 days; p = 0.002) and had higher C reactive protein levels (41.3 ± 78.5 vs 5.4 ± 9.6 μg/dL; p = 0.03). This study has shown that HAdV infections are diagnosed more commonly than usually thought and that HAdVs are stable infectious agents that do not frequently cause severe diseases. A trend toward more complex disease in cases due to HAdV species C and in those with higher viral load was demonstrated. However, further studies are needed to clarify factors contributing to disease severity to understand how to develop adequate preventive and therapeutic measures.

Background: An increasing number of children infected by enterovirus D68 (EV-D68) and affected by severe respiratory illness, muscle weakness and paralysis were described in the USA and Canada in 2014 OBJECTIVES: To investigate the potential involvement of EV-D68 in determining community-acquired pneumonia (CAP) in hospitalised children in order to acquire information concerning the clinical problems associated with EV-D68 in Italy., Study Design: This prospective study of children hospitalised for CAP in the largest Pediatric Department in Milan, Italy, was carried out between 1 June and 31 December 2014. All of the children's admission nasopharyngeal swabs were investigated for the presence of EV-D68., Results: One hundred and seventy-six children with radiographically confirmed CAP were hospitalised during the 7-month study period: 97 (55.1%) had enterovirus/rhinovirus-positive nasopharyngeal samples, including four (2.3%) positive for EV-D68. These four samples were collected between 9 and 21 October, a month in which 21 cases of CAP were recorded. Phylogenetic analysis showed that all of the sequences fell into clade B. The most severe case was diagnosed in a 14-year-old girl with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS syndrome), who died after 12 days of hospitalisation., Conclusions: EV-D68 was detected in few children with usually mild-to-moderate lower respiratory tract infection, although the disease lead to the death of a girl with a severe chronic underlying disease. Further studies capable of better defining the epidemiological, genetic and pathogenetic characteristics of the virus are required in order to be able to prepare appropriate preventive and therapeutic measures., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In order to investigate the genetic diversity and patterns of the co-circulating genotypes of respiratory syncytial virus (RSV) and their possible relationships with the severity of RSV infection, we studied all of the RSV-positive nasopharyngeal samples collected from children during five consecutive winters (2009-2010, 2010-2011, 2011-2012, 2012-2013 and 2013-2014). The RSVs were detected using the respiratory virus panel fast assay and single-tube RT-PCR, their nucleotides were sequenced, and they were tested for positive selection. Of the 165 positive samples, 131 (79.4%) carried RSV-A and 34 (20.6%) RSV-B; both groups co-circulated in all of the study periods, with RSV-A predominating in all the seasons except for winter 2010-2011, which had a predominance of RSV-B. Phylogenetic analysis of the RSV-A sequences identified genotypes NA1 and ON1, the second replacing the first during the last two years of the study period. The RSV-B belonged to genotypes BA9 and BA10. BA9 was detected in all the years of the study whereas BA only desultorily. Comparison of the subjects infected by RSV-A and RSV-B types did not reveal any significant differences, but the children infected by genotype A/NA1 more frequently had lower respiratory tract infections (p<0.0001) and required hospitalisation (p = 0.007) more often than those infected by genotype A/ON1. These findings show that RSV has complex patterns of circulation characterised by the periodical replacement of the predominant genotypes, and indicate that the circulation and pathogenic role of the different RSV strains should be investigated as each may have a different impact on the host. A knowledge of the correlations between types, genotypes and disease severity may also be important in order to be able to include the more virulent strains in future vaccines.

Background: Relatively common in adults, intestinal tuberculosis is considered rare in children and adolescents. The protean manifestations of intestinal tuberculosis mean that the diagnosis is often delayed (sometimes even for years), thus leading to increased mortality and unnecessary surgery. The main diagnostic dilemma is to differentiate intestinal tuberculosis and Crohn's disease because a misdiagnosis can have dramatic consequences., Case Presentation: A 13-year-old Caucasian, Italian female adolescent attended the Emergency Department complaining of abdominal pain, a fever of up to 38 °C, night sweats, diarrhea with blood in stool, and a weight loss of about three kilograms over the previous two months. Physical examination revealed a marked skin pallor and considerable abdominal distension with relevant discomfort in all the abdominal quadrant. Laboratory tests revealed a decreased white blood cell count with anemia and increased C-reactive protein levels. The Mantoux tuberculin skin test was negative. A chest X-ray and an abdominal ultrasonography did not reveal any significant findings. The patient underwent colonoscopy that showed diffuse mucosal congestion and significant blood loss, and laparatomy showed small bowel and colon loops with a whitish appearance. A biopsy of the ileal mucosa revealed inflammation with noncaseating granulomas possibly due to bacterial infection. Given the suspicion of an opportunistic bacterial infection in a child with chronic inflammatory bowel disease (possibly Crohn's disease), treatment with a third-generation cephalosporin was started. However, the abdominal pain, fever and poor general condition persisted and so, after 11 days, the patient underwent total body computed tomography and magnetic resonance imaging of the brain. On the basis of the radiological findings, miliary tuberculosis was suspected and bronchoscopy was performed and resulted positive for Mycobacterium tuberculosis. Miliary tuberculosis was confirmed and an effective treatment with four drugs was started., Conclusion: This case shows that the manifestations of intestinal tuberculosis can be very difficult to diagnose and mimic those of Chron's disease. Total body computed tomography and laparotomy with an intestinal biopsy for the detection of Mycobacterium tuberculosis are the means of avoid the risks of a misdiagnosis in children with unexplained chronic abdominal problems.

Objective: To evaluate whether physicians follow current guidelines for managing acute otitis media (AOM) and whether educational programs are needed to improve knowledge of AOM treatment among paediatricians (PEDs) and otolaryngologists (ENTs) Methods: A total of 1270 PEDs and 852 ENTs were randomly selected and interviewed with an anonymous questionnaire about how they managed AOM., Results: Inappropriate AOM approaches were identified among 60.2% of PEDs and 88.5% of ENTs (p < 0.001). Amoxicillin and amoxicillin with clavulanic acid were appropriately chosen as first-line drugs by the majority of PEDs and ENTs, although significantly more ENTs reported otherwise (15.8% PEDs vs 25.5% ENTs; p < 0.001). ENTs were significantly more likely than PEDs to report prescribing decongestants, mucolytics, anti-inflammatory drugs, and steroids (p < 0.001)., Conclusion: These results show that AOM prescriptions for antibiotics and adjunctive treatments are often inappropriate and highlight the need for educational strategies aimed at PEDs and ENTs to improve their compliance with evidence-based guidelines for AOM treatment.

Background: Air pollution has many negative health effects on the general population, especially children, subjects with underlying chronic disease and the elderly. The aims of this study were to evaluate the effects of traffic-related pollution on the exacerbation of asthma and development of respiratory infections in Italian children suffering from asthma or wheezing compared with healthy subjects and to estimate the association between incremental increases in principal pollutants and the incidence of respiratory symptoms., Methods: This prospective study enrolled 777 children aged 2 to 18 years (375 with recurrent wheezing or asthma and 402 healthy subjects). Over 12 months, parents filled out a daily clinical diary to report information about respiratory symptoms, type of medication used and healthcare utilization. Clinical data were combined with the results obtained using an air pollution monitoring system of the five most common pollutants., Results: Among the 329 children with recurrent wheezing or asthma and 364 healthy subjects who completed follow-up, children with recurrent wheezing or asthma reported significantly more days of fever (p=0.005) and cough (p<0.001), episodes of rhinitis (p=0.04) and tracheitis (p=0.01), asthma attacks (p<0.001), episodes of pneumonia (p<0.001) and hospitalizations (p=0.02). In the wheezing/asthma cohort, living close to the street with a high traffic density was a risk factor for asthma exacerbations (odds ratio [OR]=1.79; 95% confidence interval [CI], 1.13-2.84), whereas living near green areas was found to be protective (OR=0.50; 95% CI, 0.31 -0.80). An increase of 10 μg/m3 of particulates less than 10 microns in diameter (PM10) and nitrogen dioxide (NO2) increased the onset of pneumonia only in wheezing/asthmatic children (continuous rate ratio [RR]=1.08, 95% CI: 1.00-1.17 for PM10; continuous RR=1.08, 95% CI: 1.01-1.17 for NO2)., Conclusions: There is a significant association between traffic-related pollution and the development of asthma exacerbations and respiratory infections in children born to atopic parents and in those suffering from recurrent wheezing or asthma. These findings suggest that environmental control may be crucial for respiratory health in children with underlying respiratory disease.

Background: It has been shown that nasal saline irrigation (NSI) alone can be effective in children with infectious and/or allergic respiratory problems, but no study has assessed the awareness or clinical use of NSI among practising pediatricians. The main aim of this study was to evaluate the use of NSI in pre-school children by primary care pediatricians working in northern Italy., Methods: Nine hundred randomly selected National Health Service primary care pediatricians with an e-mail address were sent an e-mail asking whether they were willing to respond to a questionnaire regarding the use of NSI. The 870 who answered positively were sent an anonymous questionnaire by post and e-mail that had 17 multiple-choice items., Results: Completed questionnaires were received from 860 of the 870 primary care pediatricians (98.8%). NSI was used by almost all the respondents (99.3%), although with significant differences in frequency. It was considered both a prophylactic and a therapeutic measure by most of the respondents (60.3%), who prescribed it every day for healthy children and more frequently when they were ill. Most of the primary care pediatricians (87%) indicated an isotonic solution as the preferred solution, and the most frequently recommended administration devices were a nasal spray (67.7%) and bulb syringe (20.6%). Most of the pediatricians (75.6%) convinced parents to use NSI by explaining it could have various beneficial effects, and two-thirds (527/854; 61.7%) thought that most of the parents agreed about the importance of NSI. Analysis of possible associations between NSI prescribing behaviour and the demographic data revealed an associations with age and gender, with pediatricians aged <50 years prescribing NSI more frequently than their older counterparts (p < 0.01), and females prescribing NSI more frequently than males (p < 0.01)., Conclusions: In Northern Italy, most primary care pediatricians prescribe NSI for both the prophylaxis and therapy of upper respiratory tract problems in pre-school children. However, many aspects of the procedure are not clarified, and this reduces parental compliance. Given the medical and economic advantages of NSI, this situation should be changed as soon as possible.

To evaluate whether norovirus (NoV) can be a possible cause of respiratory tract infection, 562 nasopharyngeal samples collected from children admitted for influenza-like illness were tested for NoV. Three (0.5%) were positive NoV GII.4. The data show that NoV can be found in the respiratory secretions of children with respiratory symptoms and that respiratory involvement can precede gastrointestinal manifestations.

Before a protein vaccine is introduced into a country, it is essential to evaluate its potential impact and estimate its benefits and costs. The aim of this study was to determine the genetic characteristics of Neisseria meningitidis B (NmB) in the pharyngeal secretions of 1375 healthy adolescents aged 13-19 y living in Milan, Italy, in September 2012, and the possible protection offered by the two currently available NmB protein vaccines. Ninety-one subjects were Nm carriers (6.6%), 29 (31.9%) of whom carried the NmB capsular gene. The 29 identified strains belonged to eight clonal complexes (CCs), the majority of which were in the ST-41/44/Lin.3 CC (n = 11; 37.9%). All of the identified strains harboured ƒHbp alleles representing a total of 15 sub-variants: the gene for NHBA protein was found in all but three of the studied strains (10.3%) with 13 identified sub-variants. There were 15 porA sub-types, seven of which were identified in just one CC. The findings of this study seem to suggest that both of the protein vaccines proposed for the prevention of invasive disease due to NmB (the 4-protein and the 2-protein products) have a composition that can evoke a theoretically effective antibody response against the meningococcal strains currently carried by adolescents living in Northern Italy. The genetic characteristics of NmB strains can be easily evaluated by means of molecular methods, the results of which can provide an albeit approximate estimate of the degree of protection theoretically provided by the available vaccines, and the possible future need to change their composition.

Background: In 2009, the Italian Pediatric Society developed national guidelines for management of fever in children for health care providers and parents/caregivers; an update of these guidelines was scheduled after 2 years., Objective: This article summarizes the update of Italian guidelines on managing fever in children, focusing specifically on measuring body temperature and using antipyretic agents., Methods: Relevant publications in English and Italian were identified through searches of MEDLINE and the Cochrane Database of Systematic Reviews from January 1, 2008, to May 1, 2012. On the basis of consensus of a multidisciplinary expert panel, evidence levels and strength of recommendations were reviewed., Results: Axillary temperature measurement using a digital thermometer is recommended in children younger than 4 weeks. In the hospital or ambulatory care setting, axillary temperature measurement using a digital or infrared thermometer (tympanic or skin contact or nocontact) is recommended in children older than 4 weeks. Paracetamol and ibuprofen are the only antipyretic drugs recommended for use in children; however, combined or alternating use of these agents is not recommended., Conclusions: Recent scientific evidence mainly supports previous recommendations. The aim of the present article was to support pediatric knowledge and stimulate application of guidelines in daily clinical practice., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

Background: This study was designed to determine the proportion of bacteremic pneumococcal cases in a group of pediatric subjects with community-acquired pneumonia (CAP), the importance of the different serotypes and the impact of the currently available pneumococcal conjugate vaccines (PCVs)., Methods: The study involved children who were ≤5 years with radiographically confirmed CAP admitted to hospital in Italy between September 2008 and March 2011. A diagnosis of laboratory-confirmed bacteremic pneumococcal CAP was made in the presence of a culture and/or real-time polymerase chain reaction (PCR) positive for Streptococcus pneumoniae., Results: A total of 510 children were included in the study. Pneumococcal CAP was diagnosed in 73 cases (14.3%): S. pneumoniae was identified by means of positive real-time PCR in 67 cases (91.8%), a positive blood culture in 1 (1.4%) and both in 5 (6.8%). Complicated pneumonia was observed significantly more often in the pneumococcal-positive cases (P=0.02) and empyema was the main complication (P=0.007). Serotype 19A was most frequently encountered (17 cases; 25.8%), followed by serotypes 14 (10 cases, 15.1%), 4 (5 cases, 7.6%) and 3 (4 cases, 6.1%). The theoretical coverage offered by the available PCVs was calculated to be 31% for PCV7, 37% for PCV10 and 71% for PCV13., Conclusions: In Italy, bacteremic pneumococcal CAP accounts for a significant number of CAP cases in children who were ≤5 years, with serotypes 19A and 14 being the most frequent. This suggests that PCV13 is the best means of preventing pneumococcal CAP.

Allergic rhinitis (AR) is a very common childhood disease that is associated with a significant reduction in the patients' quality of life. Its treatment combines educating the patients and their parents, immunotherapy and drug administration. However, even the best approach does not relieve the symptoms of a number of patients. Alternative therapies are particularly needed for children because the fear of adverse events frequently reduces parental compliance to the prescribed drugs, and immunotherapy is less easy to administer than in adults. In this prospective investigator-blinded study we evaluated whether children, with a documented history of seasonal grass pollen-related AR, benefit from nasal irrigation by assessing the effects on nasal signs and symptoms, on middle ear effusion and on adenoidal hypertrophy. We randomized children aged 5 to 9 years (median age 82 months) to normal saline or hypertonic saline (a 2.7% sodium chloride solution), administered twice-daily using a disposable 20 ml syringe, or no treatment. Nasal symptoms (rhinorrhea, itching, sneezing, nasal obstruction), swelling of turbinates, adenoid hypertrophy or middle ear effusion were assessed at baseline and after 4 weeks of treatment. Two hundred and twenty children (normal saline: 80; hypertonic saline: 80; no treatment: 60) completed the study. After four weeks, all the considered items were significantly reduced in the group receiving hypertonic saline (P < 0.0001), whereas in the group receiving normal saline only rhinorrhea (P = 0.0002) and sneezing (P = 0.002) were significantly reduced. There was no significant change in any of the items in the control group. The duration of oral antihistamines was significantly lower in the children receiving hypertonic saline than in those treated with normal saline or in controls. No adverse events were reported and parental satisfaction and compliance with the procedure were globally very good, regardless of the solution used. Using our procedure, hypertonic saline is effective, inexpensive, safe, well tolerated and easily accepted by children with seasonal grass pollen-related AR and their parents. Our data suggest that nasal irrigation with hypertonic saline might be included in the wide spectrum of therapies recommended for grass-pollen AR.

Background: In infants, vitamin B12 deficiency may be due to an inborn error of absorption and metabolism, or nutritional problems., Case Presentation: An exclusively breastfed 5-month-old Italian male infant, who was born after a normal full-term pregnancy to a vegan mother who was apparently daily treated with a multivitamin oral preparation during the second and third trimester, was hospitalised because of poor weight gain, feeding difficulties, severe pallor, muscle hypotonia and somnolence. Upon admission, his weight, length and head circumference were below the third percentile, he had an enlarged liver and spleen, and showed a significant delay in developmental milestones and communicative reactions. He had a hemoglobin level of 4.7 g/dL with an MCV of 84.2 fL, a white blood cell count of 4,680/mm3, and a platelet count of 45,000/mm3. His serum vitamin B12 level was 57 pg/mL (normal value 180-500 pg/mL) and serum folate level 12.8 ng/mL (normal value >3 ng/mL). The results of metabolic examinations excluded a cobalamin C disorder, whereas nutritional screening showed a serum iron concentration of 9 μg/dL and serum ferritin of 4 ng/mL. Magnetic resonance imaging of the brain showed mild dilatation of the lateral ventricles with diffuse delayed myelination. The child was diagnosed as having vitamin B12 and iron deficiency due to nutritional inadequacy and was immediately treated with packed red blood cells, intramuscular vitamin B12 injections, and iron supplementation. A few days after the start of therapy, his hemoglobin levels and other hematological parameters rapidly improved, and a clinical improvement was observed within few weeks. There was an increase in his achievement of developmental milestones, but his development was still retarded seven months after the start of therapy., Conclusion: This case underlines the importance of adequately controlling maternal vitamin B12 intake during pregnancy by means of supplementation which, in the case of vegan mothers, should be significantly greater than that usually given. Moreover, the supplementation should be continued during lactation in order to avoid the development of signs of deficiency that may be associated with persistent neurological problems in infants. The case also highlights the need to consider vitamin B12 deficiency in infants with severe anemia even if their hematological parameters do not indicate megaloblastic anemia because the concomitant presence of substantial iron deficiency may modify the characteristics of the anemia.

Background: Discrepancies in the management of pharyngitis in children have been reported in Europe and the United States, and recommendations concerning the use of clinical scores, rapid antigen diagnostic tests (RADTs) or throat cultures, and the indications for antibiotic treatment largely differ., Objective: This article summarizes the Italian guidelines on the management of pharyngitis in children issued by the National Institute of Health., Methods: A multidisciplinary panel of experts (the Guidelines Development Group) developed and used a set of key questions to conduct a systematic review of the literature. Relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through April 30, 2011. Final recommendations were scaled according to the Italian National Guidelines Program grading., Results: Eighteen clinical questions were defined, and 44 recommendations were issued. None of the available scoring systems is sufficiently accurate to identify group A β-hemolytic streptococci (GABHS) pharyngitis in settings with low prevalence for rheumatic disease. RADT should be performed by trained personnel in every child with a history and signs/symptoms suggestive of GABHS pharyngitis. RADT is not recommended in children with a McIsaac score of 0 or 1 with ≥2 signs/symptoms suggestive of viral infection. Backup culture in children with negative RADT result is not recommended. Culture test with antibiotic susceptibility assay should be performed exclusively for epidemiologic purposes. Streptococcal antibody titers are of no value in diagnosing acute pharyngitis. Antibiotic therapy is recommended in microbiologically documented GABHS pharyngitis. Because penicillin V is not available in Italy, amoxicillin (50 mg/kg/d in 2-3 doses orally) for 10 days is the first choice of treatment. In noncompliant cases, benzathine penicillin may be administered. Although not routinely recommended due to the high cost and wide spectrum of activity, a 5-day course with a second-generation cephalosporin may be used in noncompliant cases. Macrolides should be limited to children with demonstrated type I hypersensitivity to penicillin. Ibuprofen or paracetamol is recommended for relief of pain or fever associated with discomfort. Because the carrier state is not associated with increased risk of suppurative complications and risk of GABHS transmission to contacts is minimal, the carrier state should never be investigated and treated. Recommendations for the management of suppurative complications are given., Conclusions: This guideline provides a comprehensive, evidence based, tool for the diagnosis and therapy of acute pharyngitis in children., (Copyright © 2012. Published by EM Inc USA.)

In order to evaluate the immunogenicity, safety, and tolerability of the MF-59 adjuvanted seasonal influenza vaccine in children and adolescents with juvenile idiopathic arthritis (JIA) treated with different anti-rheumatic drugs, 60 pediatric patients with JIA (30 treated with disease-modifying anti-rheumatic drugs [DMARDs] and 30 with etanercept) were compared with 30 healthy controls of similar gender and age. All of the patients received a single dose of the MF59-adjuvanted seasonal influenza vaccine (Fluad, Siena, Italy). Immunogenicity was assessed at baseline, and 1 and 3 months post-vaccination; safety and tolerability were also evaluated during the study period. The JIA patients treated with etanercept showed significantly lower geometric mean titres (GMTs) against the A/H1N1 strain than those treated with DMARDs (p<0.05) and the healthy controls (p<0.05), who had similar GMTs. The etanercept-treated JIA patients also showed a significant reduction in GMTs against the A/H1N1 and A/H3N2 strains from 1 to 3 months after vaccination (p<0.05). Furthermore, their seroconversion and seroprotection rates, and B antigen GMTs, were all significantly lower than those of the subjects in the other two groups (p<0.05). The safety and tolerability of the vaccine were good and similar between the groups. The results of this study indicate a reduced immune response to MF59-adjuvanted seasonal influenza vaccine in JIA children and adolescents treated with etanercept in comparison with those treated with DMARDs and healthy controls. The safety and tolerability of the vaccine appeared to be good in all of the study population., (Copyright © 2011. Published by Elsevier Ltd.)

Background: Little is known about the proportion of pediatric pandemic A/H1N1/2009 influenza cases who showed seroconversion, the magnitude of this seroconversion, or the factors that can affect the antibody level evoked by the pandemic A/H1N1/2009 influenza. Aims of this study were to analyse antibody responses and the factors associated with high antibody titres in a cohort of children with naturally acquired A/H1N1/2009 influenza infection confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR)., Results: Demographic, clinical and virologic data were collected from 69 otherwise healthy children with pandemic A/H1N1/2009 influenza (27 females, mean age ± SD: 5.01 ± 4.55 years). Their antibody levels against pandemic A/H1N1/2009 and seasonal A/H1N1 influenza viruses were evaluated by measuring hemagglutination-inhibiting antibodies using standard assays. Sixty-four patients (92.8%) with pandemic A/H1N1/2009 influenza had A/H1N1/2009 antibody levels of ≥ 40, whereas only 28/69 (40.6%) were seroprotected against seasonal A/H1N1 influenza virus. Those who were seroprotected against seasonal A/H1N1 virus were significantly older, significantly more often hospitalised, had a diagnosis of pneumonia significantly more frequently, and were significantly more often treated with oseltamivir than those who were not seroprotected (p < 0.05). The children with the most severe disease (assessed on the basis of a need for hospitalisation and a diagnosis of pneumonia) had the highest antibody response against pandemic A/H1N1/2009 influenza virus., Conclusions: Otherwise healthy children seem to show seroprotective antibody titres after natural infection with pandemic A/H1N1/2009 influenza virus. The strength of the immune response seems to be related to the severity of the disease, but not to previous seasonal A/H1N1 influenza immunity.

Streptococcus pneumoniae is a leading cause of severe life-threatening infections. Laboratory identification and serotyping of this pathogens is desirable to monitor vaccine impact and coverage; however, especially in pediatric patients, the yield of traditional microbiological diagnostic procedures can be very low. The aim of this study was to develop real-time polymerase chain reaction (PCR)-based assays to be performed directly on blood samples to identify the most common capsular serotypes causing pneumonia in Italian children (≤ 5 years of ages) after the introduction of the 7-valent conjugate vaccine. Our real-time PCR-based assays showed high sensitivity (at least 35 fg of pneumococcal DNA), and they were validated with 49 well-characterized pneumococcal isolates, 8 nonpneumococcal isolates, 13 simulated blood clinical samples loaded with S. pneumoniae of known serotypes, and 46 blood clinical samples. All the strains tested and the simulated blood clinical samples were correctly typed by the technique. Real-time PCR allowed serotyping in 37/46 children ≤ 5 years of age (80.4%) in whom pneumonia was diagnosed in four Italian hospitals. Non-PCV7 serotypes accounted for at least 47.8% (22/46) of cases, serotype 19A being the most common (34.7%, 16/46). Although, it is not known at present whether the incidence of 19A serotype is attributable to the use of PCV7 only, expanding pneumococcal serotype coverage has clearly the potential to prevent a larger number of pneumonias in Italian children less than ≤ 5 years of age. Molecular methods are of increasing importance in the diagnosis of pneumococcal pneumonia and in monitoring serotype distribution and replacement.

Background: Oxygen administration, aerosol devices and drugs, or the use of chest physiotherapy are common practices in pediatrics; however, little is known about the knowledge of pediatric healthcare workers concerning the right utilization of these tools. The aim of this study was to fill this gap as a preliminary step in the implementation of appropriate educational programs., Methods: This cross-sectional survey of a nationally representative sample of Italian pediatricians and nurses was carried out between September 1 and October 8, 2008. A self-administered, anonymous questionnaire concerning the approach to respiratory disease in infants and children was distributed to all of the participants at the Annual Congress of the Italian Society of Pediatrics, together with a stamped envelope addressed to the trained study researchers., Results: Of the 900 distributed questionnaires, 76.7% were completed and returned by 606 physicians (199 primary care pediatricians, 245 hospital pediatricians, and 162 pediatric residents) and 84 pediatric nurses. The vast majority of the respondents did not know the percentage of hemoglobin saturation indicating hypoxemia that requires oxygen administration. Most of the nurses admitted to overusing mucolytics and inhalatory corticosteroids, did not know the role of ipratropium bromide, were unable to indicate the first-line drug for respiratory distress, and did not know the correct dose of salbutamol. Only a minority of the respondents were able to specify the indications for chest physiotherapy. The nurses gave the fewest correct answers regardless of their age, gender, work setting, or the frequency with which they cared for children with respiratory distress in a year cared., Conclusions: The knowledge of primary care pediatricians, hospital pediatricians, and pediatric nurses in Italy concerning the use of pulse oximetry, aerosol devices and drugs, and chest physiotherapy is far from satisfactory and should be improved. Educational programs are therefore required for both nurses and pediatricians.

Objective: This study was designed to evaluate the immunogenicity, safety, and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children aged 6 to 23 months who had different gestational ages (GAs) at birth., Methods: The study involved 105 children: 35 preterm subjects with a GA of <32 weeks; 35 preterm subjects with a GA of 32 to 36 weeks; and 35 term subjects with a GA of 37 to 42 weeks. Each child received 2 intramuscular vaccine doses (Focetria [Novartis, Siena, Italy]): dose 1 at enrollment and dose 2 after 4 weeks (28 ± 2 days). Serum samples for antibody measurements were collected immediately before administration of dose 1, before administration of dose 2 (28 ± 2 days after baseline), and 4 weeks later (56 ± 2 days after baseline). Local and systemic reactions were assessed during the 14 days after each vaccination., Results: Of the 101 children who completed the study 32 out of 34 preterm subjects with a GA of <32 weeks, all of the preterm subjects with a GA of 32 to 36 weeks, and all of the term subjects seroconverted and were seroprotected after the first vaccine dose. Local and systemic tolerability was good in all of the groups, but fever was significantly more common after the first dose than after the second dose (P < .05), and there were no between-group differences., Conclusions: A single dose of 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine evoked a significant immune response against pandemic influenza A/H1N1 virus in children aged 6 to 23 months even if their GA was <32 weeks. The vaccine had a good safety and tolerability profile.

Objective: Antibiotics are the drugs most frequently prescribed for children, and most of them lack patent protection. The aim of this study was to evaluate off-label antibiotic use in three European countries., Methods: Data relating to all patients admitted to the neonatal intensive care units (NICUs) and paediatric wards of the participating centres were collected by the same investigator over a 2-week survey period between February and May 2009. The data included age, date of birth, weight, relevant medical history and diagnosis, together with details of all of the antibiotics prescribed (compound, route of administration, dose, and indication for use)., Results: The study involved 616 children (110 admitted to NICUs: 62 in the UK, 38 in Italy and 10 in Greece; 506 admitted to general paediatric wards: 265 in the UK, 94 in Italy and 147 in Greece). A total of 1,244 antibiotic prescriptions were issued (290 in NICUs and 954 in paediatric wards). The results showed that off-label antibiotic use is very common among European paediatric patients, with generally only slight, but sometimes significant differences between countries. However, this use relates almost exclusively to doses and indications, and rarely to age. The only antibiotics found to be used off-label in an age-related manner in paediatric clinical practice are meropenem for neonates and quinolones or linezolid for older children, which represent priorities for future studies., Conclusion: European-wide educational programmes are urgently needed to meet the objectives of improving paediatricians' working knowledge of the recommendations surrounding licensed antibiotics-use in children, and of reducing uncontrolled patterns of prescribing.

A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild-type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population.

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.

A 13-valent pneumococcal conjugate vaccine (PCV13) has been developed to improve protection against pneumococcal disease beyond that possible with the licensed 7-valent vaccine (PCV7). This study compared the safety and immunogenicity of PCV13 with those of PCV7 when given as part of the pediatric vaccination schedule recommended in Italy. A total of 606 subjects were randomly assigned to receive either PCV13 or PCV7 at 3, 5, and 11 months of age; all subjects concomitantly received diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B (DTaP-HBV-IPV/Hib) vaccine. Vaccine reactions were monitored. Antibody responses to DTaP-HBV-IPV/Hib antigens, serotype-specific anticapsular polysaccharide IgG responses, and antipneumococcal opsonophagocytic assay (OPA) activity were measured 1 month after the two-dose primary series and 1 month after the toddler dose. Overall, the safety profile of PCV13 was similar to that of PCV7. The response to DTaP-HBV-IPV/Hib antigens was substantially the same with both PCV13 and PCV7. PCV13 elicited antipneumococcal capsular IgG antibodies to all 13 vaccine serotypes, with notable increases in concentrations seen after the toddler dose. Despite a lower immunogenicity for serotypes 6B and 23F after the primary series of PCV13, responses to the seven common serotypes were comparable between the PCV13 and PCV7 groups when measured after the toddler dose. PCV13 also elicited substantial levels of OPA activity against all 13 serotypes following both the infant series and the toddler dose. In conclusion, PCV13 appeared comparable to PCV7 in safety profile and immunogenicity for common serotypes, demonstrated functional OPA responses for all 13 serotypes, and did not interfere with immune responses to concomitantly administered DTaP-HBV-IPV/Hib vaccine.

Objective: This article summarizes the Italian Pediatric Society guideline on the management of the signs and symptoms of fever in children, prepared as part of the National Guideline Program (NGLP)., Methods: Relevant publications in English and Italian were identified through searches of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through December 31, 2007. Based on the consensus of a multidisciplinary expert panel, the strength of the recommendations was categorized into 5 grades (A-E) according to NGLP methodology., Summary: In the health care setting, axillary measurement of body temperature using a digital thermometer is recommended in children aged <4 weeks; for children aged > or =4 weeks, axillary measurement using a digital thermometer or tympanic measurement using an infrared thermometer is recommended. When body temperature is measured at home by parents or care-givers, axillary measurement using a digital thermometer is recommended for all children. Children who are afebrile when seen by the clinician but are reported to have had fever by their caregivers should be considered febrile. In special circumstances, high fever may be a predictive factor for severe bacterial infection. Use of physical methods of reducing fever is discouraged, except in the case of hyperthermia. Use of antipyretics-paracetamol (acetaminophen) or ibuprofen-is recommended only when fever is associated with discomfort. Combined or alternating use of antipyretics is discouraged. The dose of antipyretic should be based on the child's weight rather than age. Whenever possible, oral administration of paracetamol is preferable to rectal administration. Use of ibuprofen is not recommended in febrile children with chickenpox or dehydration. Use of ibuprofen or paracetamol is not contraindicated in febrile children with asthma. There is insufficient evidence to form any recommendations concerning fever in children with other chronic conditions, but caution is advised in cases of severe hepatic/renal failure or severe malnutrition. Newborns with fever should always be hospitalized because of the elevated risk of severe disease; paracetamol may be used, with the dose adjusted to gestational age. Use of paracetamol or ibuprofen is not effective in preventing febrile convulsion or the adverse effects of vaccines.

Background: Medical education and guidelines have been advocated as major means of improving the management of otitis media. Limited data are available concerning medical education in acute otitis media (AOM), and the association between medical education and attitudes about AOM guidelines has never been explored., Objectives: To assess the prevalence of medical education concerning AOM, of a positive attitude toward AOM guidelines and of appropriate diagnostic methods in a large sample of Italian pediatricians (PEDs) and otolaryngologist (ENTs) and to look for possible associations between them., Subjects and Methods: This cross-sectional survey was based on the responses of 2012 physicians (1160 PEDs and 852 ENTs) to a mailed anonymous questionnaire., Results: Very few (9%) of the responders had received any AOM medical education during medical school, but the number increased during residency (38%) and peaked in the postresidency period (53%) with slight differences between PEDs and ENTs. Forty percent reported a positive attitude toward AOM guidelines, with PEDs having a better attitude than ENTs (46% vs. 32%, P < 0.001). An appropriate diagnostic method for AOM was reported by only 21% of the physicians (PEDs 11% vs. ENTs 35%, P < 0.001). AOM medical education during postresidency and reporting the use of appropriate diagnostic methods were significantly associated with a positive attitude about AOM guidelines., Conclusions: Specific educational programs concerning AOM should be implemented and rigorously evaluated, before physicians become fully trained PEDs and ENTs, and maintained during postresidency. Evidence-based guidelines should be further incorporated into everyday practice of both PEDs and ENTs.

In order to evaluate the infectious agents associated with the first episode of severe acute wheezing in otherwise healthy infants and to define the role of each of them in recurrences, 85 patients in Italy, aged <12 months, hospitalized because of a first acute episode of wheezing, were prospectively enrolled between 1 October 2005 and 31 March 2006. Upon enrollment, nasopharyngeal swabs were collected for the real-time PCR detection of respiratory syncytial virus (RSV) types A and B, influenza virus types A and B, adenovirus, parainfluenza viruses types 1, 2, 3 and 4, rhinovirus, human metapneumovirus, human coronavirus types 229E, OC43, NL63, and HKU1, bocavirus, enterovirus, and paraechovirus; nasopharyngeal aspirates were also obtained to detect atypical bacteria. At least one infectious agent was identified in 76 children (89.4%). RSV was the most frequently detected pathogen and its prevalence was significantly higher than that of the other pathogens in both age groups, and significantly higher in the children aged 3-12 months than in those aged <3 months. Only the children with RSV infection experienced recurrent wheezing. Viral load was significantly higher in children with than in those without recurrent wheezing. This study shows that RSV is the main reason for hospitalization during the first wheezing episode in infants, and that it appears to be the only pathogen associated with a high frequency of recurrences. A high viral load seems to be strictly related to the likelihood of recurrence.

This study was planned to investigate the prevalence and clinical features of the illnesses associated with human bocavirus (hBoV) in children with acute disease. We prospectively enrolled all subjects aged less than 15 years attending an emergency room in Milan, Italy, on Wednesdays and Sundays between 1 November 2004 and 31 March 2005 for any acute medical reason, excluding surgical diseases and trauma. Nasopharyngeal swabs were collected at admission to detect hBoV; influenza A and B viruses; respiratory syncytial virus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; rhinovirus; adenovirus; and coronaviruses 229E, OC43, NL63, and HKU1 by real-time PCR. Among the 1,332 enrolled children, hBoV was the fifth most frequently detected virus (7.4%). The rate of hBoV coinfections with other viruses was significantly higher than for the other viruses (50.5% versus 27.5%; P < 0.0001). Eighty-nine of the 99 hBoV-positive children (89.9%) had a respiratory tract infection, and 10 (10.1%) had gastroenteritis. hBoV coinfections had a significantly greater clinical and socioeconomic impact on the infected children and their households than hBoV infection alone. In conclusion, these findings show that the role of hBoV infection alone seems marginal in children attending an emergency room for acute disease; its clinical and socioeconomic importance becomes relevant only when it is associated with other viruses.

The development of children who have syndromes with mental retardation and/or language delay can be worsened by sensorineural or conductive hearing loss (HL). Given the existing scarcity of data, we investigated the prevalence of otitis media with effusion and/or HL in 50 children with Cornelia de Lange syndrome (CdLS) aged 1-18 years, and its impact on the children's performance. The children underwent otological and audiological examinations in order to ascertain the relative frequencies of otitis media with effusion and/or hearing impairment; their demographic and clinical data were obtained by questionnaires and from information in their medical charts. Otitis media with effusion was diagnosed in 94%, and its prevalence was similar in all age groups; HL was detected in 40 children (80%). Conductive HL due to middle ear effusion was the main cause of hearing impairment alone (60%) or in combination with sensorineural deficit (20%). HL had a negative impact on performance regardless of the type. A history of routine audiological and/or otological assessments was reported by a minority of parents. Our findings indicate that otitis media with effusion and/or HL is an important feature of children with CdLS and may negatively affect their performance. Careful follow-up throughout childhood is necessary to detect and treat any hearing loss in children with CdLS in order to minimize its impact on performance.

Between 1 September and 8 October 2006, we used a self-administered, anonymous questionnaire in order to evaluate knowledge and attitudes regarding HPV disease and its prevention in a nationally representative sample of Italian pediatricians. Three hundred and eleven of the 400 enrolled physicians (175 primary care pediatricians, 160 hospital pediatricians and 65 residents in pediatrics) returned completed surveys (227 females; mean age+/-standard deviation, 45.3+/-11.61 years). The results showed a lack of knowledge concerning HPV disease and its prevention, with marginal differences between the subgroups, even though the majority would recommend HPV vaccination. These findings highlight an urgent need to improve pediatrician information in order to ensure the optimal implementation of HPV vaccination, and the adequate acceptability of HPV vaccines to adolescents and their parents.

This cross-sectional study of 340 obstetrics/gynecology, 123 neonatology, and 244 pediatric health care workers (HCWs) was designed to evaluate compliance with recommendations concerning the use of influenza vaccine during pregnancy and among pediatric subjects. The results clearly show that only a marginal number of the HCWs in all three fields currently recommend vaccine use for pregnant women and healthy young children. Moreover, all of the HCWs were seriously deficient in terms of their general knowledge of influenza prevention and their own personal vaccination coverage was low. Extensive and sustained efforts to overcome cultural limitations concerning influenza and its prevention are urgently required among HCWs caring for women and children in order to ensure effective compliance with the current recommendations.

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Spontaneous clearance of HPV infection occurs in most cases, but chronic infection with high risk genotypes is associated with the development of cervical cancer. In particular, HPV 16 and 18 are responsible for 70% of cancers of the cervix and, in variable proportions, for cancers of the vagina, vulva, anus, penis and oropharinx. Low risk HPV genotypes, such as HPV 6 and 11, cause genital warts. Two prophylactic vaccines using virus like particles (VLPs) of L1 capside protein of HPV 16 and 18 have been developed. Of these, one also containing VLPs of HPV 6 and 11, has been approved by FDA, EMEA and AIFA for use in 9-26 year-old females. Large scale studies have shown that these vaccines are safe, well tolerated, elicits high levels of neutralizing antibodies, prevent chronic HPV infections due to genotypes present in the vaccine, and associated cervical lesions (and genital wars for the quadrivalent vaccine). To be effective the vaccines should be given prior to sexual debut. In Italy, the vaccination will be offered to 12 year-old girls. This article is the result of a targeted Consensus Conference by a panel of experts, which reviews the cornerstones of HPV infection, its association with cervical cancer, the advances in prophylactic vaccines, and the primary role of the paediatrician for the optimal adoption of this new preventive strategy.

Background: The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiology-related. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent., Study Design: In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children., Results: Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus., Conclusions: These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.