title: Establishment of lethal inhalational infection with Francisella tularensis (tularaemia) in the common marmoset (Callithrix jacchus).
abstract: Susceptibility and lethality studies of inhalational tularaemia were undertaken using the common marmoset (Callithrix jacchus) to determine its suitability as a non-human primate model. Pairs of marmosets were exposed to varying challenge doses of Francisella tularensis by the airborne route and monitored for up to 14 days postchallenge (p.c.). Lethal infection was achieved following a retained dose of less than 10 bacterial colony-forming units (CFU). However, precise LD(50) determination was not possible. The model was characterized using a target challenge dose of approximately 100 CFU. Increased core body temperature was the first indicator of disease, at approximately 2.5 days p.c. Overt clinical signs were first observed 12-18 h after the temperature increase. Significantly decreased activity was observed after approximately 3 days. All animals succumbed to infection between 4.5 and 7 days p.c. At postmortem examination, gross pathology was evident in the liver, spleen and lungs of all animals and high bacterial numbers were detected in all the organs assessed. Bacteraemia was demonstrated in all animals postmortem. Histopathological observations included severe suppurative bronchopneumonia, severe multifocal pyogranulomatous hepatitis, splenitis and lymphadenitis. Tularaemia disease progression in the common marmoset therefore appears to be consistent with the disease seen in humans and other animal models. The common marmoset may therefore be considered a suitable model for further studies of inhalational tularaemia.
authors.affiliation: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, UK. mnelson@dstl.gov.uk
authors.forename: Michelle
authors.initials: M
authors.lastname: Nelson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Lever
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Savage
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Salguero
authors.forename: Peter C
authors.initials: PC
authors.lastname: Pearce
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stevens
authors.forename: Andrew J H
authors.initials: AJ
authors.lastname: Simpson