title: Characterization of lethal inhalational infection with Francisella tularensis in the common marmoset (Callithrix jacchus).
abstract: The intracellular Gram-negative pathogen Francisella tularensis is the causative agent of tularaemia and is prevalent in many countries in the northern hemisphere. To determine whether the common marmoset (Callithrix jacchus) would be a suitable non-human primate model of inhalational tularaemia, a pathophysiology study was undertaken. Ten animals were challenged with approximately 10(2) c.f.u. F. tularensis strain SCHU S4 (F. tularensis subsp. tularensis). To look for trends in the infection, pairs of animals were sacrificed at 24 h intervals between 0 and 96 h post-challenge and blood and organs were assessed for bacteriology, pathology and haematological and immunological parameters. The first indication of infection was a raised core temperature at 3 days post-challenge. This coincided with a number of other factors: a rapid increase in the number of bacteria isolated from all organs, more pronounced gross pathology and histopathology, and an increase in the immunological response. As the disease progressed, higher bacterial and cytokine levels were detected. More extensive pathology was observed, with multifocal lesions seen in the lungs, liver and spleen. Disease progression in the common marmoset appears to be consistent with human clinical and pathological features of tularaemia, indicating that this may be a suitable animal model for the investigation of novel medical interventions such as vaccines or therapeutics.
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Nelson
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Lever
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Dean
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Savage
authors.affiliation: Veterinary Laboratories Agency, Weybridge, Addlestone, Surrey KT15 3NB, UK.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Salguero
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Pearce
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stevens
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Andrew J H
authors.initials: AJH
authors.lastname: Simpson
mesh_terms: D000818:Animals; D002144:Callithrix; D004195:Disease Models, Animal; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D005604:Francisella tularensis / Q000472:pathogenicity*; D019570:Inhalation Exposure; D007668:Kidney / Q000382:microbiology; D007958:Leukocyte Count; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D013154:Spleen / Q000382:microbiology; D013997:Time Factors; D014406:Tularemia / Q000276:immunology / Q000382:microbiology* / Q000473:pathology