American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2020
Comparative StudyComparative Modeling of Tuberculosis Epidemiology and Policy Outcomes in California.
Rationale: Mathematical modeling is used to understand disease dynamics, forecast trends, and inform public health prioritization. We conducted a comparative analysis of tuberculosis (TB) epidemiology and potential intervention effects in California, using three previously developed epidemiologic models of TB. Objectives: To compare the influence of various modeling methods and assumptions on epidemiologic projections of domestic latent TB infection (LTBI) control interventions in California. ⋯ Conclusions: All models projected a stagnation in the decline of TB incidence, highlighting the need for additional interventions including greater access to LTBI diagnosis and treatment for non-U. S.-born individuals. Differences in model results reflect gaps in historical data and uncertainty in the trends of key parameters, demonstrating the need for high-quality, up-to-date data on TB determinants and outcomes.
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Am. J. Respir. Crit. Care Med. · Feb 2020
Respiratory Syncytial Virus Disease Severity Is Associated with Distinct CD8+ T-Cell Profiles.
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. ⋯ Patients with greater frequencies of Tc1, CD8+ T cells expressing IL-17 (Tc17), and CD4+ 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.
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Am. J. Respir. Crit. Care Med. · Feb 2020
Nasal Pneumococcal Density Is Associated with Microaspiration and Heightened Human Alveolar Macrophage Responsiveness to Bacterial Pathogens.
Rationale: Pneumococcal pneumonia remains a global health problem. Colonization of the nasopharynx with Streptococcus pneumoniae (Spn), although a prerequisite of infection, is the main source of exposure and immunological boosting in children and adults. However, our knowledge of how nasal colonization impacts on the lung cells, especially on the predominant alveolar macrophage (AM) population, is limited. ⋯ Similarly, AM-heightened opsonophagocytic capacity was correlated with nasopharyngeal pneumococcal density (r = 0.61, P = 0.025). Conclusions: Our findings demonstrate that nasal colonization with pneumococcus and microaspiration prime AMs, leading to brisker responsiveness to both pneumococcus and unrelated bacterial pathogens. The relative abundance of AMs in the alveolar spaces, alongside their potential for nonspecific protection, render them an attractive target for novel vaccines.