No abstract

Rationale: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Although T-helper type 2 (Th2) cell pathology is implicated in severe disease, the mechanisms underlying the development of immunopathology are incompletely understood.Objectives: We aimed to identify local immune responses associated with severe RSV in infants. Our hypothesis was that disease severity would correlate with enhanced Th2 cellular responses.Methods: Nasal aspirates were collected from infants hospitalized with severe (admitted to the pediatric ICU) or moderate (maintained in the general ward) RSV disease at 5 to 9 days after enrollment. The immune response was investigated by evaluating T-lymphocyte cellularity, cytokine concentration, and viral load.Measurements and Main Results: Patients with severe disease had increased proportions of CD8 (cluster of differentiation 8)positive T cells expressing IL-4 (Tc2) and reduced proportions of CD8 1 T cells expressing IFNg (Tc1). Nasal aspirates from patients with severe disease had reduced concentrations of IL-17. Patients with greater frequencies of Tc1, CD8 1 T cells expressing IL-17 (Tc17), and CD4 1 T cells expressing IL-17 (Th17) had shorter durations of hospitalization.Conclusions: Severe RSV disease was associated with distinct T-cell profiles. Tc1, Tc17, and Th17 were associated with shorter hospital stay and may play a protective role, whereas Tc2 cells may play a previously underappreciated role in pathology.

A national Scottish audit of 282 patients with HIV infection attending 11 clinics showed the following levels of performance against quality improvement Scotland Sexual Health Services Standards: syphilis serology was offered in the previous six months to 55% of patients (range: 12-97% of patients in individual clinics), sexual history documented within four weeks of initial HIV diagnosis in 67% (12-100%) and offer of tests for sexually transmitted infections (STIs) documented within four weeks of HIV diagnosis in 45% (4-96%). Considerable variation in performance exists between clinics. The audit prompted interventions to further improve the sexual health care of people living with HIV infection.

Most infants are infected with RSV by their second birthday. Despite known risk factors such as prematurity or congenital heart disease, most hospitalized infants are previously healthy. The mechanisms underlying the immunopathology of severe disease is incompletely understood. Our objective was to compare T cell profiles in nasal aspirates between infants with moderate and severe RSV disease hospitalized without immune deficiencies or congenital heart disease, during 2014–2017. Infants requiring intensive care were categorized as having severe disease, while infants maintained in the general ward were categorized as having moderate disease. The T cell profile in nasal aspirates collected 7 days after hospitalization (median 11 days after first symptom onset) was determined by flow cytometry. Nasal aspirates from patients with severe disease were characterized by a higher proportion of CD8+ T cells expressing IL-4 (Tc2) (P=0.024) and a lower proportion of CD8+ T cells expressing IFNγ (Tc1) (P=0.019) compared to patients with moderate disease. Patients with reduced frequencies of Tc1, Tc17, or Th17 cells had shorter durations of hospitalization (P=0.0023, P=0.0188, P=0.0437, respectively). Additionally, patients with severe disease had lower concentrations of IL-17 in nasal aspirates compared to patients with moderate disease (P=0.0133). These results suggest that RSV disease severity is associated with a specific T cell profile, and that Tc2 cells may play an underappreciated role in the development of RSV immunopathology.

It is unclear if surveillance bias (increased reports to Child Protective Services [CPS] related to program involvement) has a substantial impact on evaluation of home visiting (HV) prevention programs. We estimated surveillance bias using data from Connecticut’s HV program, birth certificates, CPS, and hospitals. Using propensity score matching, we identified 15,870 families similar to 4015 HV families. The difference-in-differences approach was used to estimate surveillance bias as the change in investigated reports from the last 6 months of program involvement to the next 6 months. The median age of the children at program exit was 1.2 years (range: 60 days, 5 years). We estimated that 25.6% of investigated reports in the HV group resulted from surveillance bias. We reviewed CPS reports of 194 home-visited families to determine if a home visitor made the report and found that 10% were directly from home visitors. Program evaluations should account for surveillance bias.