A novel experimental intraperitoneal infection model for Haemophilus parasuis in neutropenic guinea pigs

J Pharmacol Toxicol Methods. 2019 Jan-Feb:95:27-35. doi: 10.1016/j.vascn.2018.11.008. Epub 2018 Nov 23.

Abstract

Introduction: Haemophilus parasuis, one of the major swine pathogens, has at least fifteen different types, all of which have significant economic effects on the global swine industry. The aim of this study was to establish an experimental intraperitoneal infection model for H. parasuis in neutropenic guinea pigs.

Methods: Intraperitoneal administration of cyclophosphamide and Haemophilus parasuis was conducted in guinea pigs. Clinical signs, gross pathology, and histopathology were observed in neutropenic guinea pigs infected with H. parasuis.

Results: Intraperitoneal administration of 100 mg/kg cyclophosphamide led to immunosuppression with white blood cells, lymphocytes, and neutrophils all <1000 mm3, while no histological tissue damage was observed. Intraperitoneal administration of 109 colony-forming units (CFU) of H. parasuis led to typical respiratory symptoms, 90% morbidity, and 20% mortality in a 72 h-period. Bacteriological screening revealed that multiple organs, including the heart, liver, spleen, lungs, kidneys, and blood, were infected with H. parasuis. The threshold loads of bacteria in blood and the lungs were (7.04 ± 0.53)log10 CFU/mL and (6.24 ± 0.62)log10 CFU/g, respectively, at 3 d after infection. Gross pathology examination showed celiac effusion, intestinal mucosal hemorrhage, and liver, spleen, or lung swelling, necrosis, and hemorrhage. Congestion, mild interstitial pneumonia, inflammatory exudation, and endothelial cell proliferation were observed in the histological examination.

Discussion: All the results suggest that we have established an experimental intraperitoneal infection model for H. parasuis in neutropenic guinea pigs. It is especially useful as a tool for pharmacokinetics, pharmacodynamics, or a pharmacokinetics/pharmacodynamics (PK/PD) model of antimicrobial agents against respiratory disease.

Keywords: Guinea pig; Haemophilus parasuis; Intraperitoneal; Model; Neutropenic.

MeSH terms

  • Animals
  • Cyclophosphamide / administration & dosage
  • Disease Models, Animal*
  • Female
  • Guinea Pigs
  • Haemophilus Infections / immunology*
  • Haemophilus Infections / microbiology
  • Haemophilus Infections / veterinary
  • Haemophilus parasuis / immunology*
  • Haemophilus parasuis / pathogenicity
  • Immunosuppressive Agents / administration & dosage*
  • Injections, Intraperitoneal
  • Lung
  • Male
  • Mice
  • Models, Animal*
  • Neutropenia / chemically induced*
  • Neutropenia / immunology
  • Swine

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide