Dual infection by respiratory syncytial virus and Streptococcus pneumoniae in an experimental lamb model

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 intense in the RSV/Spn group characterized
by increased interalveolar wall thickness accompanied by
neutrophil and lymphocyte infiltration. 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.