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Influenza A and methicillin-resistant Staphylococcus aureus co-infection in rhesus macaques – A model of severe pneumonia
- Source :
- Antiviral research
-
Abstract
- Background Influenza results in up to 500,000 deaths annually. Seasonal influenza vaccines have an estimated 60% effectiveness, but provide little or no protection against novel subtypes, and may be less protective in high-risk groups. Neuraminidase inhibitors are recommended for the treatment of severe influenza infection, but are not proven to reduce mortality in severe disease. Preclinical models of severe influenza infection that closely correlate to human disease are needed to assess efficacy of new vaccines and therapeutics. Methods We developed a nonhuman primate model of influenza and bacterial co-infection that recapitulates severe pneumonia in humans. Animals were infected with influenza A virus via intra-bronchial or small-particle aerosol inoculation, methicillin-resistant Staphylococcus aureus , or co-infected with influenza and methicillin-resistant S. aureus combined. We assessed the severity of disease in animals over the course of our study using tools available to evaluate critically ill human patients including high-resolution computed tomography imaging of the lungs, arterial blood gas analyses, and bronchoalveolar lavage. Results Using an intra-bronchial route of inoculation we successfully induced severe pneumonia following influenza infection alone and following influenza and bacterial co-infection. Peak illness was observed at day 6 post-influenza infection, manifested by bilateral pulmonary infiltrates and hypoxemia. The timing of radiographic and physiologic manifestations of disease in our model closely match those observed in severe human influenza infection. Discussion This was the first nonhuman primate study of influenza and bacterial co-infection where high-resolution computed tomography scanning of the lungs was used to quantitatively assess pneumonia over the course of illness and where hypoxemia was correlated with pneumonia severity. With additional validation this model may serve as a pathway for regulatory approval of vaccines and therapeutics for the prevention and treatment of severe influenza pneumonia.
- Subjects :
- Male
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine
Pneumonia, Viral
030106 microbiology
Disease
medicine.disease_cause
Article
03 medical and health sciences
Orthomyxoviridae Infections
Positron Emission Tomography Computed Tomography
Virology
Influenza, Human
Pneumonia, Staphylococcal
Influenza A virus
Animals
Humans
Medicine
Lung
Pharmacology
Vaccines
medicine.diagnostic_test
biology
Coinfection
business.industry
Pneumonia
medicine.disease
Macaca mulatta
Methicillin-resistant Staphylococcus aureus
Influenza
respiratory tract diseases
Co-infection
030104 developmental biology
Bronchoalveolar lavage
medicine.anatomical_structure
Influenza Vaccines
Therapies
Models, Animal
Immunology
biology.protein
business
Neuraminidase
Subjects
Details
- Language :
- English
- ISSN :
- 01663542
- Database :
- OpenAIRE
- Journal :
- Antiviral Research
- Accession number :
- edsair.doi.dedup.....794fcb37ff41c40fd45c5789962fc772
- Full Text :
- https://doi.org/10.1016/j.antiviral.2016.02.013