Respiratory Syncytial Virus-Load Kinetics and Clinical Course of Acute Bronchiolitis in Hospitalized Infants: Interim Results and Review of the Literature.

Respiratory Syncytial Virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. The role of RSV load in disease severity is still debated. We present the interim results of a prospective monocentric study enrolling previously healthy infants hospitalized for RSV bronchiolitis, collecting nasopharyngeal aspirates every 48 h from admission to discharge, and evaluating RSV load dynamics in relation to clinical outcome measures of bronchiolitis severity, including: need, type and duration of oxygen therapy, length of hospitalization, and the bronchiolitis clinical score calculated at admission. The results showed that the highest viral replication occurs within the first 48 hours after admission, with a significant decrease at subsequent time points (p < 0.0001). Moreover, higher RSV-RNA values were associated with the need for oxygen therapy (p = 0.03), particularly high-flow nasal cannula type (p = 0.04), and longer duration of respiratory support (p = 0.04). Finally, higher RSV load values were correlated with lower white blood cells, especially lymphocyte counts and C-reactive protein levels (p = 0.03, p = 0.04, and p = 0.01, respectively), as well as with patients of a younger age (p = 0.02). These data suggest that RSV may actively contribute to the clinical severity of bronchiolitis, together with other potential non-viral factors.

Gut, oral, and nasopharyngeal microbiota dynamics in the clinical course of hospitalized infants with respiratory syncytial virus bronchiolitis.

Introduction: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospitalization in infants worldwide. The nasopharyngeal microbiota has been suggested to play a role in influencing the clinical course of RSV bronchiolitis, and some evidence has been provided regarding oral and gut microbiota. However, most studies have focused on a single timepoint, and none has investigated all three ecosystems at once. Methods: Here, we simultaneously reconstructed the gut, oral and nasopharyngeal microbiota dynamics of 19 infants with RSV bronchiolitis in relation to the duration of hospitalization (more or less than 5 days). Fecal samples, oral swabs, and nasopharyngeal aspirates were collected at three timepoints (emergency room admission, discharge and six-month follow-up) and profiled by 16S rRNA amplicon sequencing. Results: Interestingly, all ecosystems underwent rearrangements over time but with distinct configurations depending on the clinical course of bronchiolitis. In particular, infants hospitalized for longer showed early and persistent signatures of unhealthy microbiota in all ecosystems, i.e., an increased representation of pathobionts and a depletion of typical age-predicted commensals. Discussion: Monitoring infant microbiota during RSV bronchiolitis and promptly reversing any dysbiotic features could be important for prognosis and long-term health.

The Relationship between Gut Microbiota and Respiratory Tract Infections in Childhood: A Narrative Review.

Respiratory tract infections (RTIs) are common in childhood and represent one of the main causes of hospitalization in this population. In recent years, many studies have described the association between gut microbiota (GM) composition and RTIs in animal models. In particular, the "inter-talk" between GM and the immune system has recently been unveiled. However, the role of GM in human, and especially infantile, RTIs has not yet been fully established. In this narrative review we provide an up-to-date overview of the physiological pathways that explain how the GM shapes the immune system, potentially influencing the response to common childhood respiratory viral infections and compare studies analysing the relationship between GM composition and RTIs in children. Most studies provide evidence of GM dysbiosis, but it is not yet possible to identify a distinct bacterial signature associated with RTI predisposition. A better understanding of GM involvement in RTIs could lead to innovative integrated GM-based strategies for the prevention and treatment of RTIs in the paediatric population.

Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics.

Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens' reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide.

Diagnosis, treatment, and follow-up of a case of Wolman disease with hemophagocytic lymphohistiocytosis.

Wolman Disease (WD) is a severe multi-system metabolic disease due to lysosomal acid lipase (LAL) deficiency. We report on a WD infant who developed an unusual hemophagocytic lymphohistiocytosis (HLH) phenotype related to WD treated with sebelipase alfa. A male baby came to our attention at six months of life for respiratory insufficiency and sepsis, abdominal distension, severe hepatosplenomegaly, diarrhea, and severe growth retardation. HLH was diagnosed and treated with intravenous immunoglobulin, steroids, cyclosporine, broad-spectrum antimicrobial therapy, and finally with the anti-IL-6 drug tocilizumab. WD was suspected for the presence of adrenal calcifications and it was confirmed by LAL enzyme activity and by molecular analysis of LIPA. Plasma oxysterols cholestan-3ß,5α,6ß-triol (C-triol), and 7-ketocholesterol (7-KC) were markedly increased. Sebelipase alfa was started with progressive amelioration of biochemical and clinical features. The child died from sepsis, 2 months after sebelipase discontinuation requested by parents. Our case shows the importance of an early diagnosis of WD and confirms the difficulty to reach a diagnosis in the HLH phenotype. Sebelipase alpha is an effective treatment for LAL deficiency, also in children affected by WD. Further data are necessary to confirm the utility of measuring plasma c-triol as a biochemical marker of the disease.

Utility of tuberculin skin test and IGRA for tuberculosis screening in internationally adopted children: Retrospective analysis from a single center in Florence, Italy.

BACKGROUND: Most of internationally adopted children (IAC) come from countries in which tuberculosis (TB) is endemic. Interpretation of discordant Tuberculin Skin Test (TST) and Quantiferon-Gold In Tube (QFT) results is under debate. METHODS: Children consecutively referred to our IAC Center between 2009-2017 were prospectively evaluated and screened with protocol recommended by the America Academy of Pediatrics, including TST and QFT. TB infection prevalence was evaluated and possible risk factors associated with discordant TST/QFT results were investigated. RESULTS: 1775 IAC were enrolled (median age: 5.8; IQR:3.3-8.2; 1065 [60.0%] males). Most of the children came from a European country (715; 40.3%) and, among them, 428 (59.9%) from Russia. Active pulmonary TB was diagnosed in 7 (0.4%) children while LTBI was diagnosed in 255 (14.4%) children. Concordant TST-/QFT-result was observed in 1520 (85.6%) children, concordant TST+/QFT + result in 63 children (3.5%), while 169 children (9.5%) displayed TST+/QFT-result and the remaining 23 children (1.3%) TST-/QFT+. Factor significantly associated with discordant TST+/QFT-result was BCG vaccination (aOR:2.62; 95%CI. 1.12-6.12; P = 0.026) and age <5 years (aOR: 5.59; 95%CI:2.27-12.18; P < 0001). . No significant association was evidenced with, continent of origin, eosinophilia or gender. CONCLUSIONS: Our data suggest that QFT might be used as unique screening assay in IAC, but further studies are needed at this regard.

Auxo-endocrinological features in a cohort of internationally adopted children in Italy.

BACKGROUND: Internationally adopted children (IAC) can present growth impairment at arrival, which usually recovers over time. Moreover, a major prevalence of precocious puberty has been reported in this group. METHODS: All IAC referred to a tertiary level hospital in Italy from January 2016 to June 2017, underwent a standardized screening protocol and were prospectively enrolled in the study. The analyses of possible risk factors for growth impairment and precocious puberty were performed. RESULTS: Overall, 422 children were included (males 59.5%), with median age of 6.5 years (IQR 9.4-3.9), 29.9% adopted from Europe, 26.8% from Asia, 23.9% from Africa and 19.4% from Latin America. Children were in Italy from a median of 75 days (IQR 137.0-38.7). Stunting was observed in 12.9% of children, wasting in 4.3%, underweight in 12.9%. Precocious puberty was diagnosed in 2.2% of children. 17.1% IAC had diagnosis of special needs. Fetal alcohol spectrum disorders represented the 41.7% of children with special needs and 48.1% of Russian children. Independent predictive factors for stunting were age < 5 years, a diagnosis of special need and having been living in Italy for < 60 days since the arrival. CONCLUSION: Stunting among IAC is a frequent finding especially in children < 5 years and in those with special needs, independently from their geographical origin.

Internationally adopted children: not only infectious diseases!

Information on prevalence of special needs in internationally adopted children (IAC) is incomplete. We reviewed data from 422 IAC screened at a single Centre in Italy in 2015-16. Prevalence of special needs reached 17.1% (n = 72). Among these children, the most frequent conditions were fetal alcohol spectrum disorders (FASD; n = 30; 7.1%), cleft lip palate (n = 8; 1.9%) and other congenital malformations (n = 20; 4.7%). Worrisomely, 25 out of 52 (48.1%) Russian children presented with FASD.