Sonia Bianchini

Characteristics and Their Clinical Relevance of Respiratory Syncytial Virus Types and Genotypes Circulating in Northern Italy in Five Consecutive Winter Seasons

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.

Vitamin D supplementation reduces the risk of acute otitis media in otitis-prone children

Background: The aim of this study was to evaluate whether a deficit in vitamin D (VD) is associated with an increased risk of recurrent acute otitis media (AOM) and whether VD supplementation is effective in reducing the number of AOM episodes in otitis-prone children. Methods: A total of 116 children with a history of recurrent AOM (≥3 episodes in preceding 6 months or ≥4 episodes in preceding 12 months) were prospectively and blindly randomized to receive oral VD 1000 IU/d or placebo for 4 months. Episodes of AOM were monitored for 6 months. Results: Fifty-eight children received placebo and 58 with similar characteristics were treated with VD. The number of children experiencing ≥1 AOM episode during the study period was significantly lower in the treatment group (26 versus 38; P = 0.03). There was a marked difference in the number of children who developed uncomplicated AOM (P < 0.001), but no difference in the number of children with ≥1 episode of spontaneous otorrhea. The likelihood of AOM was significantly reduced in the patients whose serum VD concentrations were ≥30 ng/mL. Conclusions: VD hypovitaminosis is common in children with recurrent AOM and associated with an increase in the occurrence of AOM when serum 25(OH)D levels are <30 ng/mL. The administration of VD in a dosage of 1000 IU/d restores serum values of ≥30 ng/mL in most cases and is associated with a significant reduction in the risk of uncomplicated AOM.

Medical Education and Attitudes About Acute Otitis Media Guidelines : A Survey of Italian Pediatricians and Otolaryngologists

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.

Efficacy of injectable trivalent virosomal-adjuvanted inactivated influenza vaccine in preventing acute otitis media in children with recurrent complicated or noncomplicated acute otitis media.

Background: Most cases of acute otitis media (AOM) follow an upper respiratory infection due to viruses, including influenza viruses. As effective and safe influenza vaccines are available, their use has been considered among the possible measures of AOM prophylaxis. Objectives: To evaluate the efficacy of an inactivated virosomal-adjuvanted influenza vaccine in preventing AOM in children with a history of noncomplicated recurrent AOM (rAOM) or rAOM complicated by spontaneous perforation. Methods: In this prospective, randomized, single-blinded, placebo-controlled study, 180 children aged 1 to 5 years with a history of rAOM and previously unvaccinated against influenza were randomized to receive the inactivated virosomal-adjuvanted subunit influenza vaccine (n = 90) or no treatment (n = 90), and AOM-related morbidity was monitored every 4 to 6 weeks for 6 months. Results: The number of children experiencing at least 1 AOM episode was significantly smaller in the vaccinated group (P < 0.001), as was the mean number of AOM episodes (P = 0.03), the mean number of AOM episodes without perforation (P < 0.001), and the mean number of antibiotic courses (P < 0.001); the mean duration of bilateral OME was significantly shorter (P = 0.03). The only factor that seemed to be associated with the significantly greater efficacy of influenza vaccine in preventing AOM was the absence of a history of recurrent perforation (crude odds ratio, P = 0.01; adjusted odds ratio, P = 0.006). Conclusions: The intramuscular administration of injectable trivalent inactivated virosomal-adjuvanted influenza vaccine in children with a history of rAOM significantly reduces AOM-related morbidity. However, the efficacy of this preventive measure seems to be reduced in children with rAOM associated with repeated tympanic membrane perforation.

A randomized clinical trial assessing immunogenicity and safety of a double dose of virosomal-adjuvanted influenza vaccine administered to unprimed children aged 6–35 months

This study evaluated the immunogenicity of a double dose of the seasonal virosomal-adjuvanted influenza vaccine (Inflexal V, Crucell, The Netherlands) in 65 previously unvaccinated children aged less than 3 years: 43 received double doses (two doses of 0.50 mL 4 weeks apart) and 22 standard doses (two doses of 0.25 mL 4 weeks apart). Both treatments evoked a response that satisfied the EMEA criteria for adequate immunogenicity for all three vaccine strains, but the double dose had a significantly greater effect on all of the studied parameters of humoral and cell-mediated immune response (p<0.05). This result was achieved without any increase in the incidence of local and systemic adverse events. This means that doubling the dose of the virosomal-adjuvanted influenza vaccine (i.e. administering the same dose as that usually given to older children) effectively and safely increases the immune response to inactivated influenza vaccine in unprimed children aged less than 3 years.

Bedaquiline and delamanid in tuberculosis

Introduction: In recent years, a pressing need to develop new, effective and safe drugs against tuberculosis (TB) has continued. Poor adherence to a long therapeutic regimen against TB, intermittent drug use, errors in medical prescriptions, low quality of old TB drugs and ineffective TB control have led to the emergence of resistant TB. Areas covered: Two new drugs have gained importance and seem promising against resistant TB: bedaquiline and delamanid. This review summarizes the main characteristics of these two drugs and their role in TB management. Expert opinion: Bedaquiline and delamanid appear to be promising new anti-TB drugs. Due to a mechanism of action that is different from that of other available drugs, their efficacy has appeared optimal in cases of adults with resistant pulmonary TB. Although their pharmacokinetic and pharmacodynamic profiles seem optimal, potential cardiologic side effects such as QT-interval prolongation have been associated with their use. However, specific studies performed in the pediatric population are needed to confirm these results. This seems particularly important considering the long duration of TB treatment required for resistant TB as well as the potential interactions with other drugs included in anti-TB regimens or administered for an underlying comorbidity.

Clinical and socioeconomic impact of pediatric seasonal and pandemic influenza

Influenza is frequent among otherwise healthy day-care and school-aged children. Recent studies have demonstrated its significant effect on various outcome factors, including significantly more school and parental work absenteeism, and secondary illnesses among family members. Other studies have shown that the potential benefit of vaccinating children against influenza extends to other members of their families, thus supporting earlier economic modeling analyses of immunization programs. Although there are some differences in the clinical and socio-economic impact of seasonal and pandemic influenza, the benefits of vaccination are similar in both cases. The vaccination of otherwise healthy children may significantly reduce direct and indirect influenza-related costs, which supports the recommendation to make wider use of influenza vaccine in healthy children of any age in order to reduce the burden of infection on the community.

Use of complementary and alternative medicine in children with recurrent acute otitis media in Italy

Controlling environmental factors, chemoprophylaxis, immunoprophylaxis and surgery are considered possible means of preventing recurrent acute otitis media (RAOM), but there are no available data concerning the paediatric use of complementary and alternative medicine (CAM). We evaluated the uses of CAM (homeopathy and/or herbal medicine) as means of preventing AOM in children with a history of RAOM. Eight hundred and forty Italian children with RAOM (⩾3 episodes in six months) aged 1–7 years were surveyed in 2009 using a face-to-face questionnaire, filled by parents or caregivers, that explored the prevalence, determinants, reasons, cost, and perceived safety and efficacy of CAM. About one-half (46%) of the children used CAM, significantly more than the number who used immunoprophylaxis (influenza vaccine 15%; p<0.05), PCV-7 34%; p< 0.05) or chemoprophylaxis (2%; p<0.001). Use of CAM in the family was the only important factor positively associated with the use of CAM in children (adjusted OR 7.94; 95% CI: 5.26–11.99). The main reasons for using CAM were a fear of the adverse effects of conventional medicine (40%) and to increase host defences (20%). CAM was widely seen as safe (95%) and highly effective (68%). CAM prescribers were paediatricians in 50.7% of cases; self-initiation was reported by 23% of respondents. CAM expenditure was between €25 and €50/month in 27.6% of cases and ⩾ €50/month in 16%. Children with RAOM should be considered among the categories of subjects likely to be using CAM. Together with the fact that paediatricians are the main prescribers, this is worrying because of the current lack of evidence regarding the efficacy, safety and cost-effectiveness of CAM in the prevention of RAOM.

Epidemiology and clinical characteristics of respiratory infections due to adenovirus in children living in Milan, Italy, during 2013 and 2014

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.

Effectiveness of a propolis and zinc solution in preventing acute otitis media in children with a history of recurrent acute otitis media

Recurrent acute otitis media (rAOM) is frequently encountered in infants and children and the lack of any definitive treatment has led parents and physicians to try complementary and alternative therapies. We evaluated the efficacy of a propolis and zinc suspension in preventing AOM in 122 children aged 1–5 years with a documented history of rAOM, who were prospectively, blindly, randomized 1:1 to receive the suspension plus elimination of environmental risk factors or elimination of environmental risk factors only. AOM- and respiratory-related morbidity were assessed at study entry and every four weeks. In the 3-month treatment period AOM was diagnosed in 31 (50.8%) children given the propolis and zinc suspension and in 43 (70.5%) controls (p=0.04). The mean number of episodes of AOM per child/month was 0.23 ± 0.26 in the propolis and zinc group and 0.34 ± 0.29 in controls (reduction 32.0%, p=0.03). The administration of a propolis and zinc suspension to children with a history of rAOM can significantly reduce the risk of new AOM episodes and AOM-related antibiotic courses, with no problem of safety or tolerability, and with a very good degree of parental satisfaction. No effect can be expected on respiratory infections other than AOM.