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.
Over many years, OM-85, a lysate of 21 common bacterial respiratory pathogens, has been demonstrated to prevent respiratory recurrences in children. However, further studies are needed to explore the ...true importance of OM-85 in the prevention of respiratory tract infections (RTIs) in children. This study was planned to further contribute to the evaluation of the role played by OM-85 in prevention of recurrent RTIs in children.
This study was a randomized (3:3:1), placebo-controlled, double-blind, single-centre, phase IV trial carried out in Italy to assess the efficacy of OM-85 (Broncho-Vaxom
; Vifor Pharma; Meyrin 2/Geneva, Switzerland) in reducing the number of new RTI episodes in 288 children aged 1 to 6 years with a history of recurrent RTIs and to compare the efficacy of the standard 3-month regimen with that of administration of OM-85 for 6 months during a 6-month study period.
The number of RTIs and of children who experienced at least one RTI were significantly lower among patients receiving OM-85 for 3 months than among those given placebo (33% vs 65.1%, p < 0.0001). Differences were statistically significant for upper RTIs (i.e., common cold/viral pharyngitis and acute otitis media; p < 0.0001 and p = 0.006, respectively). Days of absence from day-care for children and working days lost by parents were significantly lower in the group with children treated with OM-85 for 3 months than in the placebo group (p = 0.007 and p = 0.004, respectively). No difference was seen between children who received OM-85 for 3 and those who received OM-85 for 6 months. The prevalence of atopy as well as the history of recurrent wheezing and age of the study child did not influence the results. Benefit was maximally evident among children with a history of frequent recurrences. OM-85 was well tolerated and safe, even in children who received an influenza vaccination.
The use of OM-85 for 3 months in 3 series of 10 consecutive days each time reduces the risk of recurrent RTIs in children, with a favourable safety profile. The greater effect observed in children prone to several respiratory episodes than in non-prone children seems to indicate that this lysate should be administered especially to children with a proven high susceptibility to RTIs.
Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality. Among these, Respiratory ...Syncytial Virus (RSV) represents the main cause of lower respiratory tract infections (LRTIs) in young children worldwide. RSV manifestation can range widely from mild upper respiratory infections to severe respiratory infections, mainly bronchiolitis and pneumonia, leading to hospitalization, serious complications (such as respiratory failure), and relevant sequalae in childhood and adulthood (wheezing, asthma, and hyperreactive airways). There are no specific clinical signs or symptoms that can distinguish RSV infection from other respiratory pathogens. New multiplex platforms offer the possibility to simultaneously identify different pathogens, including RSV, with an accuracy similar to that of single polymerase chain reaction (PCR) in the majority of cases. At present, the treatment of RSV infection relies on supportive therapy, mainly consisting of oxygen and hydration. Palivizumab is the only prophylactic method available for RSV infection. Advances in technology and scientific knowledge have led to the creation of different kinds of vaccines and drugs to treat RSV infection. Despite the good level of these studies, there are currently few registered strategies to prevent or treat RSV due to difficulties related to the unpredictable nature of the disease and to the specific target population.
A statement of consensus was formulated after reviewing available literature on pediatric treatment strategies for COVID-19 by the Steering and Scientific Committee of the Italian Society of ...Infectious Pediatric Diseases in connection with the Italian Society of Paediatrics.
Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients ...hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP) as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP.
To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the ...different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009-2010, 2011-2012, and 2013-2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1-2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.
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.
Acute gastroenteritis (AGE) due to group A rotavirus (RVA) agent is one of the major causes of hospitalization in paediatric age. The G3P8 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 G3P8 RVAs emerged also in Europe as a predominant genotype and the viral strains detected revealed high similarities with equine-like G3P8 RVA strains, resulting in a new variant circulating in humans and able to cause AGE in the paediatric population.
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 G3P8 RVA Italian strain (namely PG2) and those belonging to recent G3P8 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-P8-I2-R2-C2-M2-A2-N2-T2-E2-H2 genomic constellation.
This case shows the first detection in Italy of a reassortant G3P8 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.
Acute respiratory infections (ARIs) are extremely common in children, especially those under 5 years old. They can lead to complications, super-infection, respiratory failure, and even compromised ...respiratory function in adulthood. For some of the responsible pathogens, vaccines are available. This review reports current issues about vaccines against the main respiratory pathogens to highlight the available strategies to reduce the burden of paediatric respiratory disease. The optimal use of influenza, pneumococcal, pertussis and measles vaccines is required in order to reduce ARI burden. Vaccination coverage rates must be improved to achieve the full benefits of these vaccines. Recently, advances in the knowledge of respiratory syncytial virus structural biology and immunology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines even against this harmful pathogen.
Several studies have shown that in recent years incidence of acute otitis media (AOM) has declined worldwide. However, related medical, social, and economic problems for patients, their families, and ...society remain very high. Better knowledge of potential risk factors for AOM development and more effective preventive interventions, particularly in AOM-prone children, can further reduce disease incidence. However, a more accurate AOM diagnosis seems essential to achieve this goal. Diagnostic uncertainty is common, and to avoid risks related to a disease caused mainly by bacteria, several children without AOM are treated with antibiotics and followed as true AOM cases. The main objective of this manuscript is to discuss the most common difficulties that presently limit accurate AOM diagnosis and the new approaches and technologies that have been proposed to improve disease detection. We showed that misdiagnosis can be dangerous or lead to relevant therapeutic mistakes. The need to improve AOM diagnosis has allowed the identification of a long list of technologies to visualize and evaluate the tympanic membrane and to assess middle-ear effusion. Most of the new instruments, including light field otoscopy, optical coherence tomography, low-coherence interferometry, and Raman spectroscopy, are far from being introduced in clinical practice. Video-otoscopy can be effective, especially when it is used in association with telemedicine, parents' cooperation, and artificial intelligence. Introduction of otologic telemedicine and use of artificial intelligence among pediatricians and ENT specialists must be strongly promoted in order to reduce mistakes in AOM diagnosis.