Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

Epidemiological and clinical characteristics of pertussis in children and their close contacts in households: A cross-sectional survey in Zhejiang Province, China.

Background: Despite the expanded immunization programs, the "re-emergence of pertussis" has become a global concern in recent years. At present, the prevalence of pertussis in China is seriously underestimated, and the role of close contact on the disease spreading in children remains unclear. Objectives: Our study aimed to investigate pertussis's epidemiological and clinical characteristics in children and their close contacts in households, as well as the antimicrobial resistance of Bordetella pertussis (B. pertussis) in Zhejiang Province, China. Methods: We have collected the retrospective and prospective data of children who were suspected of pertussis and their close contacts in households from January 1, 2018, to December 31, 2020, in the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Nasopharyngeal swabs were collected and cultured for B. pertussis. Antibiotics susceptibility test was determined by using E-test methods. Clinical information was collected from the medical records systems. Results: A total of 350 index patients and their 946 family members (close contacts in households) from 350 families were recruited. B. pertussis strains were isolated from 130 (37.1%) index patients and 116 (12.3%) close contacts. 37 index patients had negative culture results for B. pertussis while their close contacts were positive. A higher positive rate was found in female adults than that in male adults (16.3% vs. 5.1%, P < 0.01). The positive rate in index patients from multi-child families was significantly higher than that from one-child families (51.7% vs. 37.7%, P < 0.05). 53.3% of the pertussis patients were under 6 months of age. 98 (75.4%) isolates had MICs ≥ 256 mg/L to erythromycin, azithromycin, and clindamycin, and 127 (97.7%) had MICs < 0.016 mg/L to piperacillin. Conclusion: Infants under 6 months of age are at high risk of pertussis, and close contacts in households are prone to cluster infection. Culture for B. pertussis both in children and their close contacts contributes to improving the diagnosis rate of pertussis in children. Isolates of B. pertussis in China are highly resistant to macrolides.

Effect of Macrolides and ß-lactams on Clearance of Bordetella pertussis in the Nasopharynx in Children With Whooping Cough.

OBJECTIVE: The purpose of the current study is to investigate the bactericidal effect of macrolides and ß-lactams on Bordetella pertussis (B. pertussis) in the nasopharynx and provide guidance for treating macrolides-resistant B. pertussis infections. METHODS: Patients with whooping cough was diagnosed by culture of nasopharynx swabs between January 2016 to December 2018. B. pertussis was identified using specific antisera against pertussis and parapertussis. Drug susceptibility test was carried out using the E-test method. The clearance of B. pertussis in nasopharynx at 7 and 14 days into and posttreatment with macrolides, and ß-lactams was compared. RESULTS: A total of 125 B. pertussis samples were collected from patients who received single antibiotic treatment. Among those isolates, 62.4% (78/125) had high resistance with minimum inhibitory concentrations greater than 256 mg/L for erythromycin and azithromycin. The MIC90 of piperacillin, cefoperazone-sulbactam, meropenem, ampicillin, ceftriaxone, ceftazidime and trimethoprim-sulfamethoxazole for these isolates was <0.016, 0.094, 0.094, 0.19, 0.19, 0.25 and 0.75 mg/L, respectively. The clearance rate with ß-lactams treatment (68.8%, 44/64) was significantly higher than that with macrolides treatment at 14 days posttreatment (50.8%, 31/61) (χ2 = 4.18, P = 0.04). Macrolides had a better clearance rate at 7 days posttreatment than ß-lactams (χ2 = 4.49, P = 0.03) for macrolides-sensitive isolates and a worse clearance rate for macrolides-resistant isolates. CONCLUSION: B. pertussis isolates had a high-resistant rate for macrolides in our study. Macrolides are the first choice for treating pertussis caused by macrolides-sensitive strains, and some ß-lactams such as piperacillin should be considered as alternative antibiotics for treatment of macrolides-resistant B. pertussis infection.

TNF-α increases Staphylococcus aureus-induced death of human alveolar epithelial cell line A549 associated with RIP3-mediated necroptosis.

AIM: To explore the role of tumor necrosis factor-alpha (TNF-α) on Staphylococcus aureus-induced necroptosis in alveolar epithelial cells. MAIN METHODS: The A549 alveolar epithelial cell line was pretreated with small interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then stimulated by S. aureus, where some cells were pretreated with TNF-α or TNF-α with anti-TNF-α antibody simultaneously. A549 cell death was assessed using lactate dehydrogenase (LDH) leakage and flow cytometry analyses. The protein expressions of RIP1, RIP3, cleaved caspase-1, and cleaved caspase-8 were analyzed by western blot. KEY FINDINGS: S. aureus-induced LDH release was increased significantly by TNF-α. In addition, flow cytometry showed that TNF-α increased A549 cell apoptosis and necrosis in S. aureus-infected cell cultures. Levels of RIP3 and cleaved caspase-1 protein in A549 cells infected with S. aureus increased at 12 h post-infection, as shown by western blot. Significant additional increases in RIP3 expression were observed following the addition of TNF-α. Decreasing RIP3 levels by siRNA significantly suppressed the release of LDH induced by TNF-α and S. aureus. RIP3 siRNA also significantly suppressed A549 cell necrosis induced by S. aureus and TNF-α at 6 and 12 h post-infection as shown by flow cytometry analysis. SIGNIFICANCE: TNF-α enhances the damage of S. aureus on lung epithelial cells, and its mechanism is associated with RIP3 mediated necroptosis.