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. 1997 Nov;65(11):4701–4704. doi: 10.1128/iai.65.11.4701-4704.1997

Development of a model of low-inoculum Streptococcus pneumoniae intrapulmonary infection in infant rats.

R A Saladino 1, A M Stack 1, G R Fleisher 1, C M Thompson 1, D E Briles 1, L Kobzik 1, G R Siber 1
PMCID: PMC175674  PMID: 9353053

Abstract

We have developed a model of low-inoculum Streptococcus pneumoniae infection in infant rats. We challenged 4-day-old Sprague-Dawley pups via intraperitoneal or intrapulmonary injection of S. pneumoniae serotypes 1, 3, 4, 5, 6b, 7f, 9v, 14, 19f, and 23f. To achieve bacteremia with low inocula, it was necessary to passage the isolates in rats. Inocula of the 10 S. pneumoniae serotypes producing bacteremia in 50% or more animals ranged from 1 to 400 CFU. Virulence was similar by intraperitoneal and intrapulmonary routes. Lung specimens from animals challenged by the intrapulmonary route grew S. pneumoniae and demonstrated histologic evidence of focal infection. Meningitis was detected in 20 to 50% of bacteremic animals, and mortality invariably followed bacteremia within 24 to 48 h. This model of intrapulmonary infection uses low inocula of S. pneumoniae and results in bacteremia, meningitis, and death in infant rats.

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Selected References

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  1. Alexander J. E., Lock R. A., Peeters C. C., Poolman J. T., Andrew P. W., Mitchell T. J., Hansman D., Paton J. C. Immunization of mice with pneumolysin toxoid confers a significant degree of protection against at least nine serotypes of Streptococcus pneumoniae. Infect Immun. 1994 Dec;62(12):5683–5688. doi: 10.1128/iai.62.12.5683-5688.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alonso De Velasco E., Dekker B. A., Verheul A. F., Feldman R. G., Verhoef J., Snippe H. Anti-polysaccharide immunoglobulin isotype levels and opsonic activity of antisera: relationships with protection against Streptococcus pneumoniae infection in mice. J Infect Dis. 1995 Aug;172(2):562–565. doi: 10.1093/infdis/172.2.562. [DOI] [PubMed] [Google Scholar]
  3. Austrian R. Some observations on the pneumococcus and on the current status of pneumococcal disease and its prevention. Rev Infect Dis. 1981 Mar-Apr;3 (Suppl):S1–17. doi: 10.1093/clinids/3.supplement_1.s1. [DOI] [PubMed] [Google Scholar]
  4. Breiman R. F., Spika J. S., Navarro V. J., Darden P. M., Darby C. P. Pneumococcal bacteremia in Charleston County, South Carolina. A decade later. Arch Intern Med. 1990 Jul;150(7):1401–1405. [PubMed] [Google Scholar]
  5. Briles D. E., Nahm M., Schroer K., Davie J., Baker P., Kearney J., Barletta R. Antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 streptococcus pneumoniae. J Exp Med. 1981 Mar 1;153(3):694–705. doi: 10.1084/jem.153.3.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Friedland I. R., McCracken G. H., Jr Management of infections caused by antibiotic-resistant Streptococcus pneumoniae. N Engl J Med. 1994 Aug 11;331(6):377–382. doi: 10.1056/NEJM199408113310607. [DOI] [PubMed] [Google Scholar]
  7. Hofmann J., Cetron M. S., Farley M. M., Baughman W. S., Facklam R. R., Elliott J. A., Deaver K. A., Breiman R. F. The prevalence of drug-resistant Streptococcus pneumoniae in Atlanta. N Engl J Med. 1995 Aug 24;333(8):481–486. doi: 10.1056/NEJM199508243330803. [DOI] [PubMed] [Google Scholar]
  8. Käyhty H., Ahman H., Rönnberg P. R., Tillikainen R., Eskola J. Pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine is immunogenic in infants and children. J Infect Dis. 1995 Nov;172(5):1273–1278. doi: 10.1093/infdis/172.5.1273. [DOI] [PubMed] [Google Scholar]
  9. MacLEOD C. M., KRAUS M. R. Relation of virulence of pneumococcal strains for mice to the quantity of capsular polysaccharide formed in vitro. J Exp Med. 1950 Jul 1;92(1):1–9. doi: 10.1084/jem.92.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. McCracken G. H., Jr Emergence of resistant Streptococcus pneumoniae: a problem in pediatrics. Pediatr Infect Dis J. 1995 May;14(5):424–428. doi: 10.1097/00006454-199505001-00004. [DOI] [PubMed] [Google Scholar]
  11. McLinn S., Williams D. Incidence of antibiotic-resistant Streptococcus pneumoniae and beta-lactamase-positive Haemophilus influenzae in clinical isolates from patients with otitis media. Pediatr Infect Dis J. 1996 Sep;15(9 Suppl):S3–S9. doi: 10.1097/00006454-199609009-00001. [DOI] [PubMed] [Google Scholar]
  12. Nielsen S. V., Sørensen U. B., Henrichsen J. Antibodies against pneumococcal C-polysaccharide are not protective. Microb Pathog. 1993 Apr;14(4):299–305. doi: 10.1006/mpat.1993.1029. [DOI] [PubMed] [Google Scholar]
  13. Pomat W. S., Lehmann D., Sanders R. C., Lewis D. J., Wilson J., Rogers S., Dyke T., Alpers M. P. Immunoglobulin G antibody responses to polyvalent pneumococcal vaccine in children in the highlands of Papua New Guinea. Infect Immun. 1994 May;62(5):1848–1853. doi: 10.1128/iai.62.5.1848-1853.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ramisse F., Binder P., Szatanik M., Alonso J. M. Passive and active immunotherapy for experimental pneumococcal pneumonia by polyvalent human immunoglobulin or F(ab')2 fragments administered intranasally. J Infect Dis. 1996 May;173(5):1123–1128. doi: 10.1093/infdis/173.5.1123. [DOI] [PubMed] [Google Scholar]
  15. Siber G. R. Pneumococcal disease: prospects for a new generation of vaccines. Science. 1994 Sep 2;265(5177):1385–1387. doi: 10.1126/science.8073278. [DOI] [PubMed] [Google Scholar]
  16. Tart R. C., McDaniel L. S., Ralph B. A., Briles D. E. Truncated Streptococcus pneumoniae PspA molecules elicit cross-protective immunity against pneumococcal challenge in mice. J Infect Dis. 1996 Feb;173(2):380–386. doi: 10.1093/infdis/173.2.380. [DOI] [PubMed] [Google Scholar]
  17. Vella P. P., Marburg S., Staub J. M., Kniskern P. J., Miller W., Hagopian A., Ip C., Tolman R. L., Rusk C. M., Chupak L. S. Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex. Infect Immun. 1992 Dec;60(12):4977–4983. doi: 10.1128/iai.60.12.4977-4983.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Voss L., Lennon D., Okesene-Gafa K., Ameratunga S., Martin D. Invasive pneumococcal disease in a pediatric population, Auckland, New Zealand. Pediatr Infect Dis J. 1994 Oct;13(10):873–878. doi: 10.1097/00006454-199410000-00005. [DOI] [PubMed] [Google Scholar]
  19. Zangwill K. M., Vadheim C. M., Vannier A. M., Hemenway L. S., Greenberg D. P., Ward J. I. Epidemiology of invasive pneumococcal disease in southern California: implications for the design and conduct of a pneumococcal conjugate vaccine efficacy trial. J Infect Dis. 1996 Oct;174(4):752–759. doi: 10.1093/infdis/174.4.752. [DOI] [PubMed] [Google Scholar]

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