Streptococcus pneumoniae serotype 22F infection in respiratory syncytial virus infected neonatal lambs enhances morbidity

Abstract

Respiratory syncytial virus (RSV) is the primary cause of viral bronchiolitis resulting in hospitalization and a frequent cause of secondary respiratory bacterial infection, especially by Streptococcus pneumoniae (Spn) in infants. While murine studies have demonstrated enhanced morbidity during a viral/bacterial co-infection, human meta-studies have conflicting results. Moreover, little knowledge about the pathogenesis of emerging Spn serotype 22F, especially the co-pathologies between RSV and Spn, is known. Here, colostrum-deprived neonate lambs were divided into four groups. Two of the groups were nebulized with RSV M37, and the other two groups were mock nebulized. At day three post-RSV infection, one RSV group (RSV/Spn) and one mock-nebulized group (Spn only) were inoculated with Spn intratracheally. At day six post-RSV infection, bacterial/viral loads were assessed along with histopathology and correlated with clinical symptoms. Lambs dually infected with RSV/Spn trended with higher RSV titers, but lower Spn. Additionally, lung lesions were observed to be more frequent in the RSV/Spn group characterized by increased interalveolar wall thickness accompanied by neutrophil and lymphocyte infiltration and higher myeloperoxidase. Despite lower Spn in lungs, co-infected lambs had more significant morbidity and histopathology, which correlated with a different cytokine response. Thus, enhanced disease severity during dual infection may be due to lesion development and altered immune responses rather than bacterial counts.

Discovery of gem-Dimethyl-hydroxymethylpyridine Derivatives as Potent Non-nucleoside RSV Polymerase Inhibitors

“…Histopathology was performed on hematoxylin-eosin-stained FFPE sections as reported, 41 An integer-based score of 0−4 was assigned for each parameter (bronchiolitis, syncytial cells, epithelial necrosis, epithelial hyperplasia, alveolar septal thickening, neutrophils in bronchial lumen, neutrophils in alveolar lumen, alveolar macrophages, peribronchial lymphocytic infiltration, perivascular lymphocytic infiltration, lymphocytes in alveolar septa, fibrosis), with 4 as the highest score An integer-based score of 0−4 was assigned for each histological parameter, with 4 as the highest score, then a final score was calculated by adding up all measured scores to form a 0−48 score, with 48 as the highest, which is called the accumulative histopathological lesion score. Staining for RSV per field was performed as previously reported 38 and scored as follows: 0 = no positive cells, 1 = 1−10 positive cells, 2 = 11−39 positive cells, 3 = 40−99 positive cells, 4 = >100 positive cells.…”