title: A Non-Human Primate Model of Severe Pneumococcal Pneumonia.
abstract: BACKGROUND
  Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia.
  
  
  OBJECTIVE
  To develop a non-human primate model of pneumococcal pneumonia.
  
  
  METHODS
  Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily.
  
  
  RESULTS
  Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines.
  
  
  CONCLUSIONS
  We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes.
authors.affiliation: Division of Pulmonary Diseases & Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.|Division of Pulmonary Diseases & Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States of America.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Reyes
authors.affiliation: Division of Pulmonary Diseases & Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.|Division of Pulmonary Diseases & Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States of America.
authors.forename: Marcos I
authors.initials: MI
authors.lastname: Restrepo
authors.affiliation: Division of Pulmonary Diseases & Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.|Division of Pulmonary Diseases & Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States of America.
authors.forename: Cecilia A
authors.initials: CA
authors.lastname: Hinojosa
authors.affiliation: Division of Pulmonary Diseases & Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.|Division of Pulmonary Diseases & Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States of America.
authors.forename: Nilam J
authors.initials: NJ
authors.lastname: Soni
authors.affiliation: Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Anukul T
authors.initials: AT
authors.lastname: Shenoy
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Gilley
authors.affiliation: Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Norberto
authors.initials: N
authors.lastname: Gonzalez-Juarbe
authors.affiliation: Division of Pulmonary Diseases & Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.|Division of Pulmonary Diseases & Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States of America.
authors.forename: Julio R
authors.initials: JR
authors.lastname: Noda
authors.affiliation: Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.
authors.forename: Vicki T
authors.initials: VT
authors.lastname: Winter
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX, United States of America.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: de la Garza
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX, United States of America.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Shade
authors.affiliation: Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.
authors.forename: Jacqueline J
authors.initials: JJ
authors.lastname: Coalson
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX, United States of America.
authors.forename: Luis D
authors.initials: LD
authors.lastname: Giavedoni
authors.affiliation: Division of Pulmonary Diseases & Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.|Division of Pulmonary Diseases & Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States of America.
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.|Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Orihuela
mesh_terms: D000818:Animals; D015415:Biomarkers; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging / Q000382:microbiology / Q000473:pathology; D010215:Papio; D010641:Phenotype; D011018:Pneumonia, Pneumococcal / Q000175:diagnosis / Q000382:microbiology*; D011323:Primates; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000145:classification; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators