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.

Live attenuated tularemia vaccines: Recent developments and future goals

“…While mice have largely served as the primary animal model for attenuation and protection studies, they are far more sensitive to type B strains than humans, and thus are not an ideal model for tularemia. Recent advances have been made in modeling human tularemia infection in rabbits, rats, and monkeys [11, 51–56]. One recent non-human primate study demonstrated that Schu S4 mutants of the dsbB and pdpB genes were shown to be attenuated in rhesus macaque monkeys and partially protective against an i.n.…”

Antibodies Contribute to Effective Vaccination against Respiratory Infection by Type A Francisella tularensis Strains

“…Rather, the effects of IRS on bacterial growth were most clearly observed in the infected liver and spleen. The liver is a major site of F. tularensis colonization and replication (9), and pneumonic tularemia is associated with hepatocellular damage in multiple experimental animal models, including the F344 rat (8,32,42,45). Although the level of damage falls short of liver failure and may be reversible, such damage may nevertheless compromise the liver's ability to perform essential metabolic functions and to utilize its many innate immune mechanisms to control systemic bacterial growth (22,25).…”

Francisella Tularensis : Tularemia

“…Some information is also provided by experimental infections [40][41][42][43]. Primates, lagomorphs, and rodents are very susceptible and sensitive to the disease.…”