Respiratory Syncytial Virus (RSV) is associated with most of the acute viral respiratory tract infections causing hospitalization with a peak during the first months of life. Many clinical trials of RSV vaccine candidates are being carried out. The aim of this study was to obtain epidemiologic information to give suggestions on target populations and prevention strategies before the introduction of new vaccines or monoclonal antibodies. We retrospectively evaluated, over a 5-year period (September 2014–August 2019), a population of hospitalized Italian children aged 0–6 years with a laboratory confirmed diagnosis of RSV infection. Risk factors, seasonality of RSV infection, distribution according to age, cases of coinfections and reinfections and cases needing Intensive Care Unit were evaluated. Hospitalizations due to RSV were 624 in the period under study. The peak was found between November and April, with 80.4% of cases recorded between December and February. 62.5% of cases were found in children under three months of age and 41% in children under 30 days old. The need for intensive care was associated with younger ages, with 70.9% of cases in children below three months of age. Unless the incoming vaccines demonstrate a strong herd protection effect, preventive strategies should be aimed at newborns or at maternal immunization.

Background: A few years after the introduction in Italy of a four-component anti-meningococcal B vaccine (4CMenB), we evaluated the effectiveness and impact of vaccination in two regions using different schedules (2, 4, 6, 12 months in Tuscany vs. 7, 9, 15 months in Veneto) through an observational retrospective study. Methods: Vaccination started in 2014 in Tuscany and in 2015 in Veneto; the data collected referred to the period 2006–2018 for Tuscany and 2007–2018 for Veneto. Cases of invasive meningococcal disease due to N. Meningitidis B were identified by culture and/or real-time PCR. Results: In Tuscany, pre-vaccine incidence was 1.96 (95% CL 1.52; 2.40) and dropped to 0.62 (95% CL 0.60; 0.64) in the post-4CMenB era. Evaluating only vaccinated children, post-4CMenB incidence was 0.12 (95% CL 0.08; 0.15). In Veneto pre-vaccine incidence was 1.94 (95% CL 1.92; 1.96) and dropped to 1.34 (95% CL 1.31; 1.38) in the post-4CMenB era. In the vaccinated population, MenB incidence was 0.53 (95% CL 0.50; 0.56). Vaccine effectiveness was 93.6% (95% CL 55.4; 99.1) in Tuscany and 91.0% (95% CL 59.9; 97.9) in Veneto, with mean vaccine coverages of 83.9% and 81.7%, respectively. The overall impact (evaluating both vaccinated and unvaccinated children) was 0.68 (95% CL 0.10; 0.89) in Tuscany and 0.31 (95% CL −0.56; 0.69) in Veneto; the total impact (evaluating only vaccinated children) was 0.94 (95% CL 0.56; 0.99) and 0.90 (95% CL 0.57; 0.97), respectively. The relative case reduction (RCR) was 65% in Tuscany and 31% in Veneto. Considering the vaccinated population, the RCR was equal to 91% and 80%, respectively. Conclusion: In conclusion, 4CMenB appears to have a very high effectiveness in Italy; the impact of vaccination appears greater where the immunization program is started early.

Recently, human bocavirus (HBoV) has appeared as an emerging pathogen, with an increasing number of cases reported worldwide. HBoV is mainly associated with upper and lower respiratory tract infections in adults and children. However, its role as a respiratory pathogen is still not fully understood. It has been reported both as a co-infectious agent (predominantly with respiratory syncytial virus, rhinovirus, parainfluenza viruses, and adenovirus), and as an isolated viral pathogen during respiratory tract infections. It has also been found in asymptomatic subjects. The authors review the available literature on the epidemiology of HBoV, the underlying risk factors associated with infection, the virus’s transmission, and its pathogenicity as a single pathogen and in co-infections, as well as the current hypothesis about the host’s immune response. An update on different HBoV detection methods is provided, including the use of quantitative single or multiplex molecular methods (screening panels) on nasopharyngeal swabs or respiratory secretions, tissue biopsies, serum tests, and metagenomic next-generations sequencing in serum and respiratory secretions. The clinical features of infection, mainly regarding the respiratory tract but also, though rarely, the gastrointestinal one, are extensively described. Furthermore, a specific focus is dedicated to severe HBoV infections requiring hospitalization, oxygen therapy, and/or intensive care in the pediatric age; rare fatal cases have also been reported. Data on tissue viral persistence, reactivation, and reinfection are evaluated. A comparison of the clinical characteristics of single infection and viral or bacterial co-infections with high or low HBoV rates is carried out to establish the real burden of HBoV disease in the pediatric population.

Etiology and serotyping of parapneumonic effusion (PPE) and the impact of vaccination was evaluated over a 12-year period, before and after the PCV13 introduction (2011) for Italian children From 0 to 16 years of age. Five hundred and two children were evaluated; 226 blood and 356 pleural fluid samples were obtained and tested using Realtime-PCR and culture. In the pre-PCV13 era S. pneumoniae was the most frequent pathogen identified (64/90; 71.1%) with a large predominance of serotypes 1 (42.4%), 3 (23.7%), 7F (5.1%) and 19A (11.9%). The impact of vaccination, calculated on children 0-8 years of age, demonstrated a significant reduction of PPE: with an incidence rate of 2.82 (95%CL 2.32-3.41) in the pre-PCV13 era and an age-standardized rate (ASR) of 0.66 (95% CL 0.37-1.99) in the post-PCV13 era, p < 0.0001. No increase in non-PCV13 serotypes was recorded. S. pneumoniae remained the most frequent pathogen identified in the post-PCV13 era in unvaccinated children with an unchanged serotype distribution: respectively 26/66 (39.4%), 25/66 (37.9%), 5/66 (7.6%), and 4/66 (6.1%) for 1, 3, 7F and 19A. On the other hand 7F and 19A disappeared in vaccinated children and serotype 1 and 3 decreased by 91.8% and 31.5%, respectively. Realtime PCR was significantly more sensitive than culture both in pleural fluid (79.7% vs 12.5%) and in blood (17.8% vs 7.4%). In conclusion, our findings indicate that routine immunization with PCV13 has significantly reduced the burden of childhood PPE in vaccinated children, without increasing PPE due to other bacteria and without serotype shift. Moreover, the impact of PCV13 may be underestimated due to the increase in pneumococcal surveillance in Italy. Data has also shown that Real-time PCR is an essential tool to better define the etiology of PPE and to monitor vaccination plans. Longer studies will be necessary to evaluate the role of herd protection in PPE prevention.

Invasive meningococcal disease (IMD) is a highly lethal disease. Diagnosis is commonly performed by culture or Realtime-PCR (qPCR). Our aim was to evaluate, retrospectively, whether culture positivity correlates with higher bacterial load and fatal outcome. Our secondary aim was to compare culture and qPCR sensitivity. The National Register for Molecular Surveillance was used as data source. Cycle threshold (CT), known to be inversely correlated with bacterial load, was used to compare bacterial load in different samples. Three-hundred-thirteen patients were found positive for Neisseria meningitidis by qPCR, or culture, or both; 41 died (case fatality rate 13.1%); 128/143 (89.5%) blood samples and 138/144 (95.8%) CSF were positive by qPCR, 37/143 (25.9%) blood samples and 45/144 (31.2%) CSF were also positive in culture. qPCR was 3.5 times (blood) or 3.1 times (CSF) more sensitive than culture in achieving a laboratory diagnosis of IMD (OR 24.4; 95% CI 12.2–49.8; p < .10⁻⁴; Cohen’s κ 0.08 for blood and OR 49.0; 95% CI 19.1–133.4; p<10⁻⁴; Cohen’s κ 0.02; for CSF). Positivity of culture did not correlate with higher bacterial loads in blood (mean CT 27.7±5.71, and CT 28.1±6.03, p = 0.739 respectively in culture positive or negative samples) or in CSF (mean CT 23.1±4.9 and 24.7±5.4 respectively in positive or negative CSF samples, p = 0.11).CT values in blood from patients who died were significantly lower than in patients who survived (respectively mean 18.0, range 14–23 and mean 29.6, range 16–39; p<10⁻¹⁷). No deaths occurred in patients with CT in blood over 23. Positive blood cultures were found in 10/25 (40%) patients who died and in 32/163 (19.6%) patients who survived, p = 0.036, OR 2.73; 95% CL 1.025–7.215), however 60% of deaths would have remained undiagnosed with the use of culture only. In conclusion our study demonstrated that qPCR is significantly (at least 3 times) more sensitive than culture in the laboratory confirmation of IMD. The study also demonstrated that culture negativity is not associated with lower bacterial loads and with less severe cases. On the other side, in patients with sepsis, qPCR can predict fatal outcome since higher bacterial load, evaluated by qPCR, appears strictly associated with most severe cases and fatal outcome. The study also showed that molecular techniques such as qPCR can provide a valuable addition to the proportion of diagnosed and serotyped cases of IMD.

This is the first case of NBAS disease detected by NBS for primary immunodeficiency. NBS with KRECs is revealing unknown potentialities detecting conditions that benefit from early recognition like NBAS deficiency. Immune phenotyping should be mandatory in patients with NBAS deficiency since they can exhibit severe immunodeficiency with hypogammaglobulinemia as the most frequent finding. Fever during infections is a known trigger of acute liver failure in this syndrome, so immune dysfunction, should never go unnoticed in NBAS deficiency in order to start adequate therapy and prophylaxis.