Development of a novel preclinical model of pneumococcal pneumonia in nonhuman primates

American Journal of Respiratory Cell and Molecular Biology
Bryan D KraftK E Welty-Wolf

Abstract

Pneumococcal pneumonia is a leading cause of bacterial infection and death worldwide. Current diagnostic tests for detecting Streptococcus pneumoniae can be unreliable and can mislead clinical decision-making and treatment. To address this concern, we developed a preclinical model of pneumococcal pneumonia in nonhuman primates useful for identifying novel biomarkers, diagnostic tests, and therapies for human S. pneumoniae infection. Adult colony-bred baboons (n = 15) were infected with escalating doses of S. pneumoniae (Serotype 19A-7). We characterized the pathophysiological and serological profiles of healthy and infected animals over 7 days. Pneumonia was prospectively defined by the presence of three criteria: (1) change in white blood cell count, (2) isolation of S. pneumoniae from bronchoalveolar lavage fluid (BALF) or blood, and (3) concurrent signs/symptoms of infection. Animals given 10(9) CFU consistently met our definition and developed a phenotype of tachypnea, tachycardia, fever, hypoxemia, and radiographic lobar infiltrates at 48 hours. BALF and plasma cytokines, including granulocyte colony-stimulating factor, IL-6, IL-10, and IL-1ra, peaked at 24 to 48 hours. At necropsy, there was lobar consolidation with frequ...Continue Reading

References

Jul 1, 1975·Laboratory Animals·J C Kim, S S Kalter
Dec 1, 1975·The Journal of Infectious Diseases·R F BerendtJ S Walker
Dec 1, 1991·Journal of Applied Physiology·P J FracicaJ D Crapo
Oct 1, 1990·The Pediatric Infectious Disease Journal·B WolachN Sadan
Feb 25, 1983·JAMA : the Journal of the American Medical Association·E W HookD R Schaberg
Sep 1, 1994·American Journal of Respiratory and Critical Care Medicine·M S DehouxM Aubier
Jan 1, 1996·American Journal of Respiratory and Critical Care Medicine·A BouttenM Aubier
Jan 1, 1995·Scandinavian Journal of Infectious Diseases·A OrtqvistM Kalin
Mar 14, 1998·Chest·J M TorresD Schlossberg
Aug 12, 1998·American Journal of Respiratory and Critical Care Medicine·K E Welty-WolfC A Piantadosi
Oct 3, 1999·Critical Care Medicine·C MontónJordi Puig de la Bellacasa
Mar 18, 2000·Thorax·J F Cordier
Jan 21, 2004·Respiration; International Review of Thoracic Diseases·Mustafa KolsuzOmer Colak
Apr 9, 2004·Critical Care Medicine·Malina IoanasAntoni Torres
Apr 26, 2005·Archives of Medical Research·Slavica DodigIvana Cepelak
Oct 4, 2005·Vaccine·Krishna K MurthyJean L Patterson
Jul 11, 2006·Archives of Medical Research·Vasiliki Vlacha, Gavriela Feketea
Sep 15, 2009·Lancet·Katherine L O'BrienHib and Pneumococcal Global Burden of Disease Study Team
Sep 30, 1924·The Journal of Experimental Medicine·H A Reimann
Jan 14, 2011·Journal of Medical Primatology·Yugendar R BommineniGene B Hubbard
Apr 7, 2011·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·G VernetK P Klugman
Jan 19, 2012·Infection and Immunity·Jason M WarfelTod J Merkel
Mar 27, 2012·The Journal of Infectious Diseases·Peter C WroeSusan S Huang
Feb 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Junhee SeokInflammation and Host Response to Injury, Large Scale Collaborative Research Program

Citations

Jul 7, 2015·Expert Review of Molecular Diagnostics·Emily R KoEphraim L Tsalik
Jan 9, 2015·American Journal of Respiratory Cell and Molecular Biology·Jesmond DalliCharles N Serhan
Nov 18, 2016·PloS One·Luis F ReyesCarlos J Orihuela
Feb 8, 2019·Critical Care Medicine·Bryan D KraftK E Welty-Wolf
Aug 31, 2019·International Journal of Molecular Sciences·Noemi BorsaMarcos I Restrepo
Aug 4, 2020·Veterinary Pathology·Katelin L DavisEdward J Dick
Sep 14, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Masakazu ShinoharaCharles N Serhan
Sep 1, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·Laura E FredenburghC A Piantadosi
Dec 8, 2017·ILAR Journal·Lisa A MillerEdward S Schelegle
Jan 16, 2019·Lab Animal·Lingye ChenBryan D Kraft

Related Concepts

Bronchoalveolar Lavage Fluid
Interleukins
Lung
Papio
Streptococcal Pneumonia
Primates
Streptococcus pneumoniae
Granulocyte Colony-Stimulating Factor
Klebsiella pneumoniae
Autopsy

Related Feeds

American Thoracic Association Journals

Discover the latest respiratory research published by the journals from the American Thoracic Society.

Bacterial Pneumonia

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Bacterial Pneumonia (ASM)

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.