Abstract
Bovine respiratory syncytial virus (RSV) has substantial morbidity in young calves, and closely parallels human RSV in infants. We performed a randomized controlled trial in five to six-week-old Holstein calves (Bos taurus). comparing fusion protein inhibitor (FPI) and non-steroidal anti-inflammatory drug (NSAID) singly and in combination at three and five days after experimental BRSV infection. Thirty-six calves received one of six treatments; Ibuprofen started on day 3, Ibuprofen started on day 5, FPI started on day 5, FPI and Ibuprofen started on day 3, FPI and Ibuprofen started on day 5, or placebo. We have previously reported significant clinical benefits when combined FPI and NSAID treatment was started at three and five days after bovine RSV infection. Necropsy was performed on Day 10 following infection and hematoxylin and eosin staining was performed on sections from each lobe. Histology was described using a four-point scale. We performed canonical discrimination analysis (CDA) to determine the structural level where differences between treatments occurred and mixed effects regression to estimate effect sizes. Separation from placebo was maximal for dual therapy at the levels of the alveolus, septum, and bronchus in CDA. We found that the clinical benefits of combined FPI and NSAID treatment of BRSV extend at least partially from histopathological changes in the lung when treatment was started three days after infection. We found decreased lung injury when ibuprofen was started as monotherapy on day 3, but not day 5 following infection. Combined therapy with both an FPI and ibuprofen was always better than ibuprofen alone. We did not prove that the clinical benefits seen starting FPI and ibuprofen five days after infection can be solely explained by histopathological differences as identified on H&E staining.
Highlights
Bovine respiratory syncytial virus (BRSV) has substantial morbidity and mortality alone or as the inciting agent in bovine respiratory disease complex in young calves [1, 2]
Bronchiolitis is a major cause of hospital admission in winter and spring in infants [4]
We found that clinical outcomes were improved when combined antiviral and nonsteroidal anti-inflammatory drug (NSAID) treatment were started at 3- and 5-days post BRSV inoculation [16]
Summary
Bovine respiratory syncytial virus (BRSV) has substantial morbidity and mortality alone or as the inciting agent in bovine respiratory disease complex in young calves [1, 2]. Infected calves who survive often develop recurring cough and poor weight gain in response to dusty environments, due to development of an enhanced hypersensitivity response to environmental antigens [1, 3]. Human respiratory syncytial virus (HRSV) is a closely related virus that is the most common inciting agent in bronchiolitis. HRSV precedes or triggers recurrent antigen induced wheezing following initial infection in 48% of infants [5]. HRSV in infants follows a similar clinical trajectory to BRSV in calves, has similar lung ultrasound manifestations, and demonstrate similar immunological characteristics [6,7,8,9]
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