There are no available vaccines for dengue, the most important mosquito-transmitted viral disease. Mechanistic studies with anti-dengue virus (DENV) human monoclonal antibodies (hMAbs) provide a rational approach to identify and characterize neutralizing epitopes on DENV structural proteins that can serve to inform vaccine strategies. Here, we report a class of hMAbs that is likely to be an important determinant in the human humoral response to DENV infection. In this study, we identified and characterized three broadly neutralizing anti-DENV hMAbs: 4.8A, D11C, and 1.6D. These antibodies were isolated from three different convalescent patients with distinct histories of DENV infection yet demonstrated remarkable similarities. All three hMAbs recognized the E glycoprotein with high affinity, neutralized all four serotypes of DENV, and mediated antibody-dependent enhancement of infection in Fc receptor-bearing cells at subneutralizing concentrations. The neutralization activities of these hMAbs correlated with a strong inhibition of virus-liposome and intracellular fusion, not virus-cell binding. We mapped epitopes of these antibodies to the highly conserved fusion loop region of E domain II. Mutations at fusion loop residues W101, L107, and/or G109 significantly reduced the binding of the hMAbs to E protein. The results show that hMAbs directed against the highly conserved E protein fusion loop block viral entry downstream of virus-cell binding by inhibiting E protein-mediated fusion. Characterization of hMAbs targeting this region may provide new insights into DENV vaccine and therapeutic strategies.

Rationale: Postsepsis care recommendations target specific deficits experienced by sepsis survivors in elements such as optimization of medications, screening for functional impairments, monitoring for common and preventable causes of health deterioration, and consideration of palliative care. However, few data are available regarding the application of these elements in clinical practice.Objectives: To quantify the delivery of postsepsis care for patients discharged after hospital admission for sepsis and evaluate the association between receipt of postsepsis care elements and reduced mortality and hospital readmission within 90 days.Methods: We conducted a retrospective chart review of a random sample of patients who were discharged alive after an admission for sepsis (identified from International Classification of Diseases, 10th Revision discharge codes) at 10 hospitals during 2017. We used a structured chart abstraction to determine whether four elements of postsepsis care were provided within 90 days of hospital discharge, per expert recommendations. We used multivariable logistic regression to evaluate the association between receipt of care elements and 90-day hospital readmission and mortality, adjusted for age, comorbidity, length of stay, and discharge disposition.Results: Among 189 sepsis survivors, 117 (62%) had medications optimized, 123 (65%) had screening for functional or mental health impairments, 86 (46%) were monitored for common and preventable causes of health deterioration, and 110 (58%) had care alignment processes documented (i.e., assessed for palliative care or goals of care). Only 20 (11%) received all four care elements within 90 days. Within 90 days of discharge, 66 (35%) patients were readmitted and 33 (17%) died (total patients readmitted or died, n = 82). Receipt of two (odds ratio [OR], 0.26; 95% confidence interval [95% CI], 0.10-0.69) or more (three OR, 0.28; 95% CI, 0.11-0.72; four OR, 0.12; 95% CI, 0.03-0.50) care elements was associated with lower odds of 90-day readmission or 90-day mortality compared with zero or one element documented. Optimization of medications (no medication errors vs. one or more errors; OR, 0.44; 95% CI, 0.21-0.92), documented functional or mental health assessments (physical function plus swallowing/mental health assessments vs. no assessments; OR, 0.14; 95% CI, 0.05-0.40), and documented goals of care or palliative care screening (OR, 0.52; 95% CI, 0.25-1.05; not statistically significant) were associated with lower odds of 90-day readmission or 90-day mortality. Conclusions:In this retrospective cohort study of data from a single health system, we found variable delivery of recommended postsepsis care elements that were associated with reduced morbidity and mortality after hospitalization for sepsis. Implementation strategies to efficiently overcome barriers to adopting recommended postsepsis care may help improve outcomes for sepsis survivors.

Two hundred seventy nasopharyngeal aspirates were tested in duplicate with the Ortho Diagnostics, Inc. (Raritan, N.J.), respiratory syncytial virus antigen enzyme-linked immnunosorbent assay. The test was sensitive

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children. Rapid identification of RSV infections would allow for specific chemotherapy. We evaluated a means of rapid diagnosis, the Abbott enzyme immunoassay (EIA), by using 314 stored nasopharyngeal aspirates. RSV antigens were identified in 62 of 66 RSV culture-positive specimens. An additional 37 specimens from which RSV was not isolated were positive in the EIA. Of these, 29 were confirmed as truly positive by a blocking assay, for a total of 95 (66 + 29) positive specimens. The sensitivity of the EIA for total positive samples was 96% (91/95) versus 69% (66/95) for cell culture. The specificity of the EIA was 96% (211/219). In these stored specimens, Abbott EIA was superior to cell culture for the detection of RSV.

Immediate inoculation of HEp-2 cells is generally advocated for the isolation of respiratory syncytial virus. However, delayed laboratory inoculation of properly transported specimens obtained by aspiration of nasopharyngeal mucus provided an isolation rate similar to that obtained with immediate inoculation.