Epidemiology of respiratory syncytial virus in hospitalized children over a 9-year period and preventive strategy impact.

Background: Respiratory Syncytial Virus (RSV) is the primary cause of respiratory infections and hospitalizations in young children globally, leading to substantial disease burden and mortality. The aim of the present study was to review and provide updates on how the SARS-CoV-2 pandemic have significantly influenced RSV epidemiology on hospitalized children due to RSV infection. A potential impact of the available preventive strategies on the same population were provided. Methods: All children aged 0-6 years hospitalized at Meyer Children's Hospital IRCCS for RSV infection from September 2014 to March 2023 were retrospectively recorded. Seasonal trends before and after SARS-CoV-2 pandemic, age distribution, ICU admission and co-infections, comorbidities and prematurity were retrieved. Predictions on the number of hospitalizations avoided by the deployment of different preventive strategies were provided. Results: A total of 1,262 children with RSV infection were included in the study. The 70% of them had less than 1 year-of-age at the moment of hospitalization and almost 50% less than 3 months. In the post-pandemic seasons, a 317% increase in the number of hospitalizations was recorded with a significant increase in older children compared to the pre-pandemic seasons. ICU support was required for 22% of children, the majority of whom were under 3 months of age. Almost 16% of hospitalized children were born preterm and only 27% of hospitalized children had prior comorbidities. The rate of comorbidities among RSV hospitalized children increased with age. Nirsevimab prophylaxis could have prevented more than 46% of hospitalizations in this cohort. A preventive strategy addressing also children aged 7 months to 6 years of age with co-existing comorbidities would increase that rate above 57%. Discussion: The identification of RSV hospitalization-related features is informing the decision-maker for the deployment of the wisest preventive approach on a population scale.

COVID-19 in Pregnant Women and Neonates: A Systematic Review of the Literature with Quality Assessment of the Studies.

The SARS-CoV-2 virus emerged in December 2019 and then spread globally. Little is still known about the impact of COVID-19 on pregnant women and neonates. A review of the literature was performed according to the PRISMA guideline recommendations, searching the MEDLINE and EMBASE databases. Studies' quality assessments were performed using the JBI Critical Appraisal Checklist. A total of 37 studies were included, involving 275 pregnant women with COVID-19 and 248 neonates. The majority of pregnant women presented with mild to moderate symptoms, only 10 were admitted in the ICU, and one died. Two stillbirths were reported and the incidence of prematurity was 28%. Sixteen neonates were tested positive for SARS-CoV-2 by RT-PCR, and nine of them were born from mothers infected during pregnancy. Neonatal outcomes were generally good: all the affected neonates recovered. RT-PCR for SARS-CoV-2 yielded negative results on amniotic fluid, vaginal/cervical fluids, placenta tissue, and breast milk samples. SARS-CoV-2 infection in pregnant women appeared associated with mild or moderate disease in most cases, with a low morbidity and mortality rate. The outcomes of neonates born from infected women were mainly favorable, although neonates at risk should be closely monitored. Further studies are needed to investigate the possibility of vertical transmission.

Experts' opinion for improving global adolescent vaccination rates: a call to action.

Worldwide, lifestyle and resource disparities among adolescents contribute to unmet health needs, which have crucial present and future public health implications for both adolescents and broader communities. Risk of infection among adolescents is amplified by biological, behavioral, and environmental factors; however, infectious diseases to which adolescents are susceptible are often preventable with vaccines. Beyond these concerns, there is a lack of knowledge regarding adolescent vaccination and disease risk among parents and adolescents, which can contribute to low vaccine uptake. Promising efforts have been made to improve adolescent vaccination by programs with motivational drivers and comprehensive communication with the public. In May 2017, a multidisciplinary group of experts met in Amsterdam, Netherlands, to discuss adolescent vaccine uptake, as part of an educational initiative called the Advancing Adolescent Health Spring Forum. This article presents consensus opinions resulting from the meeting, which pertain to the burden of vaccine-preventable diseases among adolescents, reasons for low vaccine uptake, and common characteristics of successful strategies for improving adolescent vaccination.Conclusion: There is an urgent "call to action," particularly targeting healthcare providers and public health authorities, for the prioritization of adolescent vaccination as a necessary element of preventive healthcare in this age group.What is Known:• Despite increased risk of certain infectious diseases, adolescent vaccination uptake remains low.What is New:• Barriers to adolescent vaccine uptake include lack of information regarding vaccines and disease risk, health system inadequacies, and insufficient healthcare follow-up.• Successful efforts to improve adolescent vaccine uptake need cohesive leadership and involvement of multiple stakeholders, as well as youth-friendly messaging; healthcare providers and policymakers should prioritize adolescent vaccination and implement proven program strategies to improve adolescent health worldwide.

The burden of bacteremia and invasive diseases in children aged less than five years with fever in Italy.

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

Pneumococcal vaccination in Europe: schedule adherence.

Nonadherence to recommended pneumococcal conjugate vaccine (PCV) schedules may have implications for protection against pneumococcal disease. In this commentary, we have assessed adherence to the recommended dosing schedules (the completion of the primary PCV and booster series) in different European countries. We found that adherence with the PCV schedule was lower than that for diphtheria-tetanus-acellular pertussis (DTaP) and that higher adherence was observed in countries where PCV vaccination is recommended and funded. Adherence with the booster dose is often lower than that with the primary series completion, and it is often given after the recommended age. These data highlight the need to encourage timely vaccination of children with PCV, in line with local immunization schedules. There is no single solution to improve adherence; actions need to be tailored to the context of individual countries through initiatives at the national, regional, and local levels and should target different stakeholders.

Impact on disease incidence of a routine universal and catch-up vaccination strategy against Neisseria meningitidis C in Tuscany, Italy.

BACKGROUND: Invasive infections due to Neisseria meningitidis are still an important public health issue worldwide. In Europe, meningococcal meningitis is differently distributed in the EU countries, but most cases of meningococcal diseases are caused by serogroups B and C. In Italy, each year about 900 cases of bacterial meningitis occur, of whom one third are caused by N. meningitidis. In March 2005, the Regional Health Authority of Tuscany approved a policy of active offer of conjugate meningococcus C (MCC) vaccination with three doses to all newborns at 3, 5 and 13 months of age (subsequently turning to a single dose at 13 months as of 2008) and a catch-up until age 6 years with a single dose. OBJECTIVE: The aim of the present study was to evaluate the effectiveness of the vaccination strategy adopted by Tuscany in preventing cases of invasive meningococcal C disease. METHODS: Surveillance data for the calculation of disease incidence, immunization coverage with MCC vaccine and vaccination status of meningitis cases were collected from 2005 to 2011. RESULTS: Incidence rates of meningococcal meningitis and septicemia decreased in all age groups involved in the immunization campaign, as a result of the progressively increasing vaccination coverage. Since 2006, no cases of invasive meningococcal C infection in vaccinated subjects were observed in Tuscany. A herd immunity effect was measured in unvaccinated age groups. CONCLUSION: MCC vaccination implementation in Tuscany was successful in the prevention of meningococcal C disease. Our results should prompt all Italian Regions to consider introducing MCC vaccination in order to protect their population.

Economic and clinical evaluation of a catch-up dose of 13-valent pneumococcal conjugate vaccine in children already immunized with three doses of the 7-valent vaccine in Italy.

A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportunity of administering a further dose of PCV13 to children under 5 years of age who had already completed their vaccination with PCV7, with the aim of extending the serotype coverage, triggered an animated scientific debate. The purpose of this study was to perform a clinical/economic evaluation of the administration of a dose of PCV13, in a catch-up programme, for children under 5 years of age, who had already received 3 doses of PCV7. A mathematical model of the clinical/economic impact of the adoption of 4 catch-up strategies with PCV13 (children up to 24, 36, 48 and 60 months old) was set up, with a vaccination coverage of 80%, versus immunization with 3 doses of PCV7 without the catch-up programme. The time span covered by the simulation was 5.5 years. The following clinical outcomes of infection were evaluated: hospitalised meningitis/sepsis, hospitalised bacteraemic pneumonias (complicated and uncomplicated), hospitalised non-bacteraemic pneumonias, and non-hospitalised pneumonias. The administration of one dose of PCV13 to children up to 60 months of age significantly reduces the number of cases of pneumococcal diseases (especially, non-hospitalised pneumonias, 80% of all events prevented, and hospitalised cases of non-bacteraemic pneumococcal pneumonias, 15% of all events prevented) and, subsequently, the relative cost for medical treatment. This results in savings for medical costs amounting to more than 1,000,000 Euros when vaccinating children under 24 months of age (up to almost 3 million Euros for children up to 60 months). More than half of those savings are attributable to avoided hospitalised cases of non-bacteraemic pneumococcal pneumonias. Increasing the number of cohorts involved in the vaccination programme, the impact of immunization increases. The average cost per event avoided is 1674 Euros vaccinating children up to 24 months, and increases to 2522 Euros by vaccinating up to 60 months of age. The cost per year of life saved for different vaccination strategies is always acceptable (from 12,250 Euros to 22,093 Euros). The results of this study justify, even from the economic point of view, the recommendation of the Italian Ministry of Health to vaccinate children up to 24 months of life in a catch-up programme, as well as the administration of PCV13 children up to 36 months of age, already used in some Italian regions. Furthermore, a catch-up programme that provides the immunization of children under 60 months of age, is also justified from both the economic and clinical point of view.

Neonatal screening for severe combined immunodeficiency caused by an adenosine deaminase defect: a reliable and inexpensive method using tandem mass spectrometry.

BACKGROUND: Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is an SCID caused by a defect in the enzyme adenosine deaminase. It is usually fatal in infancy because of severe recurrent infections. When diagnosis is made, permanent damage caused by infections or by metabolites is often present. Gene therapy, bone marrow transplantation, or enzyme therapy might be effective if performed early. ADA-SCID complies with all the criteria for inclusion in a newborn screening program. However, screening methods are still expensive or provide a non-negligible number of indeterminate results. OBJECTIVE: The aim of the present study was to develop a simple, reliable, and inexpensive method for diagnosis of ADA-SCID by using dried blood spot (DBS) samples taken at birth. Cost per test was calculated, including the cost for reagents, equipment, and operators. METHODS: DBS samples from 4 patients with genetically confirmed ADA-SCID and 12,020 DBS samples from healthy newborns were examined. Adenosine and 2'-deoxyadenosine were tested by using tandem mass spectrometry (PCT EP2010/070517). RESULTS: The mean levels of adenosine and 2'-deoxyadenosine were 7.8 ± 3.1 and 8.5 ± 6.0 µmol/L, respectively, in affected children; adenosine was found at 0.23 ± 0.09 µmol/L, whereas 2'-deoxyadenosine was never detected in healthy control subjects (adenosine: P < 10(-6) [95% confidence limit, 7.59-7.78] and 2'-deoxyadenosine: P < 10(-6) [95% confidence limit, 8.65-8.82] for control subjects vs patients with ADA-SCID). No indeterminate or false-positive results were found. Cost per test was €0.01 ($0.013). A pilot population-based newborn screening for ADA-SCID has started in Tuscany, Italy. CONCLUSION: Tandem mass spectrometry can be used for diagnosis of one of the most frequent form of SCID at a negligible cost.

Assessment and validation of bronchodilation using the interrupter technique in preschool children.

OBJECTIVE: To determine and validate a cut-off value for bronchodilation using the interrupter resistance (Rint) in preschool children. PATIENTS AND METHODS: Rint was measured in 60 healthy children (age range 2.7-6.4 years) before and after salbutamol inhalation (200 microg). Four potential methods for assessing BDR were evaluated: percent change from baseline, percent change of predicted values, absolute change in Rint, and change in Z-score. These cut-off values, determined as the fifth percentile of the healthy group, were applied to children referred for the assessment of recurrent wheezing, classified on the basis of acute symptoms and/or abnormal chest examination into symptomatic (n = 60, age range 2.9-6.1 years) and asymptomatic (n = 60, age range 2.5-5.7 years) groups. RESULTS: The cut-off values for bronchodilation calculated in healthy children were: -32% baseline; -33% predicted; -0.26 kPa L(-1) sec; and -1.25 Z-scores. Assessing BDR in children with a history of wheezing by either a decrease in absolute Rint or a decrease in Z-score gave sensitivity, specificity, negative predictive value, and positive predictive value all >80% for detecting children with current respiratory symptoms. CONCLUSIONS: Both a decrease in Rint > or =0.26 kPa L(-1) sec and a decrease in Z-score of > or =1.25 are appropriate for assessing BDR in preschool children with a history of recurrent wheezing. As Z-score is a more general solution, we recommend using a change in Z-score to determine BDR in preschool children. Further longitudinal studies will be required to determine the clinical utility of measuring BDR in managing lung disease in such children.

Hepatitis C virus infection in children coinfected with HIV: epidemiology and management.

Mothers with hepatitis C virus (HCV) and HIV coinfection are the major source of HCV/HIV coinfection in infancy and childhood. There is no known intervention capable of interrupting HCV spread from mother to child, while the majority of infant HIV infections occurring in the developed world can be prevented by antiretroviral prophylaxis in the mother and child, elective caesarean section, and formula-feeding. In the era preceding treatment of HIV infection with highly active antiretroviral therapy, HCV coinfection was of little concern because the short-term survival of patients with HIV infection prevented the slowly developing consequences of chronic hepatitis C. As the life expectancy of patients with HIV infection increased with therapy, HCV has emerged as a significant pathogen. Several lines of evidence in adult patients suggest that liver disease may be more severe in patients coinfected with HIV and that progression of HIV disease may be accelerated by HCV coinfection. Whether coinfected children may share these clinical patterns remains a matter of speculation. Chronic hepatitis C in otherwise healthy children is usually a mild disease; liver damage may be sustained and fibrosis may increase over the years, suggesting slow progression of the disease. Interferon-alpha has been the only drug used in the past decade to treat hepatitis C in children and adolescents, with average response rates of 20%. Preliminary results of treatment with interferon-alpha and ribavirin suggest that the efficacy would be greater with combined therapy. These treatment protocols have not yet been applied to children coinfected with HIV, but the increasing number of long-term survivors will probably prompt further investigation in the near future. At present, treating HIV disease and monitoring HCV infection and hepatotoxicity induced by antiretroviral drugs seem to be the more reasonable approach to HCV/HIV coinfection in childhood.