Alberto Villani

Restricted replication of respiratory syncytial virus in human alveolar macrophages

The cellular factors that regulate infection and replication of respiratory syncytial virus (RSV) in human alveolar macrophages were examined. RSV-exposed alveolar macrophages demonstrated a time-dependent expression of viral glycoproteins, maximal by 24 h post-infection resulting in infection of approx. 38% of the cells. Essentially all (33%) of these freshly isolated alveolar macrophages replicated RSV as shown by infectious centre assays. This RSV-permissive subpopulation of alveolar macrophages consisted primarily of major histocompatibility class II-expressing cells as determined by fluorescence-activated cell sorting. Re-infection of alveolar macrophages did not significantly alter the number of cells infected or capable of replicating RSV. However, in vitro differentiation of alveolar macrophages prior to infection resulted in a significant (P < 0.05), time-dependent decrease (approx. sevenfold) in the number of cells that replicated virus. The mechanism by which cellular differentiation restricted RSV replication is unknown. Production of defective interfering particles did not account for this decrease. Alveolar macrophages infected with RSV produce a variety of cytokines potentially contributing to this restricted viral replication. Pretreatment with several of these cytokines did not affect viral infection or replication. However, tumour necrosis factor (TNF alpha) significantly (P < 0.05) decreased viral replication but only by 30 to 60%. Thus RSV replication is reduced by in vitro differentiation of alveolar macrophages and, to a lesser degree, by pretreatment with TNF.

Bronchoalveolar lavage in children with chronic diffuse parenchymal lung disease

The aim of the present study was to compare cellular and noncellular components of bronchoalveolar lavage fluid (BAL) in a group of children with a diagnosis of chronic diffuse parenchymal lung disease (cDPLD) and a group of children without parenchymal lung disease undergoing BAL for various clinical indications (control group). We evaluated cellular and noncellular components (total proteins, albumin, hyaluronic acid, and fibronectin) in BAL fluid from 14 children (7 boys and 7 girls; mean age 9.2 years, range 5 months to 18.4 years) fulfilling the clinical and radiological diagnosis of chronic cDPLD, and in 19 controls without evidence of lung disease. The 14 patients were assigned to two study groups: early‐stage cDPLD (6 patients; age range 5 months to 5.2 years; duration of illness, 5–7 months) and long‐standing cDPLD (8 patients; age range 9.6–18.4 years; duration of illness, 1.2–17.6 years).

Does Breastfeeding Protect Young Infants from Pertussis? Case-Control Study and Immunologic Evaluation

Background: Pertussis infection can be severe in unvaccinated infants. A case-control study was conducted to investigate the potential role of breastfeeding in protecting young, unvaccinated infants from pertussis. Methods: Hospitalized infants <6 months of age with positive real time polymerase chain reaction for pertussis on nasopharyngeal aspirate were enrolled as cases; healthy controls were enrolled among patients admitted for ultrasound screening. Vaccinated infants were excluded. Sociodemographic, clinical and feeding information were collected. The effect of breastfeeding on pertussis was investigated through multivariable analysis. Breast milk and blood samples were obtained from mothers of patients. IgA and bacterial binding against Bordetella pertussis and other bacteria were tested in breast milk. IgG against pertussis toxin (PT) was tested in serum. Results: We enrolled 296 patients (61 cases and 235 controls). Exclusive breastfeeding was not associated with pertussis compared with partial breastfeeding/artificial feeding [odds ratio: 1.2; 95% confidence interval (CI): 0.31–4.67]. Children with siblings were at higher risk for pertussis (odds ratio: 2.5; 95% CI: 1.21–5.35). IgA against pertussis antigens were not higher in cases (IgA anti-PT median = 0.24 optical density) compared with controls (IgA anti-PT median = 0.21 optical density). Though bacterial binding to B. pertussis, measured in breast milk, was higher in cases (median = 4.35%) compared with controls (median = 2.8%; P = 0.004), bacterial binding to B. pertussis was low compared with other pathogens. IgG titers were higher in mothers of cases, but no correlation was found between serum IgG and breast milk IgA. Conclusion: Breastfeeding remains a mainstay of prevention for numerous diseases, though it does not seem to play a role against pertussis. Alternative strategies to protect unvaccinated infants from pertussis should be considered.

Severe pertussis infection in infants less than 6 months of age: Clinical manifestations and molecular characterization

ABSTRACT We conducted a study to determine the main traits of pertussis among unimmunized infants less than 6 months of age. From August 2012 to March 2015, 141 nasopharyngeal aspirates (NPAs) were collected from infants with respiratory symptoms attending 2 major hospitals in Rome. Clinical data were recorded and analyzed. Lab-confirmation was performed by culture and realtime PCR. B. pertussis virulence-associated genes (ptxP, ptxA and prn), together with multilocus variable-number tandem repeat analysis (MLVA), were also investigated by the sequence-based analysis on the DNAs extracted from positive samples. Antibiotic susceptibility with Etest was defined on 18 viable B. pertussis isolates. Samples from 73 infants resulted positives for B. pertussis. The median age of the patients was 45 d (range 7–165); 21 infants were treated with macrolides before hospital admission. Cough was reported for a median of 10 d before admission and 18 d after hospital discharge among infected infants, 84% of whom showed paroxysmal cough. No resistance to macrolides was detected. Molecular analysis identified MT27 as the predominant MLVA profile, combined with ptxP3-ptxA1-prn2 associated virulence genes. Although our data may not be generalized to the whole country, they provide evidence of disease severity among infants not vaccinated against pertussis. Moreover, genetically related B. pertussis strains, comprising allelic variants of virulence associated genes, were identified.

Media devices in pre-school children: the recommendations of the Italian pediatric society

BackgroundYoung children are too often exposed to mobile devices (MD) and most of them had their own device. The adverse effects of a early and prolonged exposure to digital technology on pre-school children has been described by several studies.Aim of the study is to analyze the consequences of MD exposure in pre-school children.MethodsWe analyzed the documented effects of media exposure on children’s mental and physical health.ResultsAccording to recent studies, MD may interfere with learning, children development, well being, sleep, sight, listening, caregiver-child relationship.DiscussionPediatricians should be aware of both the beneficial and side effects of MD and give advice to the families, according to children’s age.ConclusionIn according to literature, the Italian Pediatric Society suggest that the media device exposure in childhood should be modulated by supervisors.

Delayed puberty versus hypogonadism: a challenge for the pediatrician.

Constitutional delay of growth and puberty (CDGP) is the most common cause of delayed puberty (DP), is mainly found in males, and is characterized by short stature and delayed skeletal maturation. A family history of the subject comprising the timing of puberty in the parents and physical examination may provide clues regarding the cause of DP. Delayed onset of puberty is rarely considered a disease in either sex. In fact, DP usually represents a common normal variant in pubertal timing, with favorable outcomes for final height and future reproductive capacity. In adolescents with CDGP, a linear growth delay occurs until immediately before the start of puberty, then the growth rate rapidly increases. Bone age is often delayed. CDGP is a diagnosis of exclusion; therefore, alternative causes of DP should be considered. Functional hypogonadotropic hypogonadism may be observed in patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions including celiac disease, inflammatory bowel diseases, kidney insufficiency, and anorexia nervosa. Permanent hypogonadotropic hypogonadism (pHH) showing low serum value of testosterone or estradiol and blunted follicle-stimulating hormones (FSH) and luteinizing hormones (LH) levels may be due to abnormalities in the central nervous system. Therefore, magnetic resonance imaging is necessary to exclude morphological abnormalities and neoplasia. Moreover, pHH may be isolated, as observed in Kallmann syndrome, or associated with other hormone deficiencies, as found in panhypopituitarism. Baseline or gonadotropin-releasing hormone pituitary stimulated gonadotropin level is not sufficient to easily differentiate CDGP from pHH. Low serum testosterone in male patients and low estradiol values in female patients, associated with high serum FSH and LH levels, suggest a diagnosis of hypergonadotropic hypogonadism. A genetic analysis can reveal a chromosomal abnormality (e.g., Turner syndrome or Klinefelter syndrome). In cases where the adolescent with CDGP is experiencing psychological difficulties, treatment should be recommended.

Correction to: Neuropsychological and internalizing problems in acute central nervous system infections: a 1 year follow-up

CorrectionThe original article [1] contained an error mistakenly carried forward by the Production department handling this article whereby all authors’ names were incorrectly inverted.The original article has now been corrected to reflect the correct names of all authors.