title: Use of the common marmoset to study Burkholderia mallei infection.
abstract: Burkholderia mallei is a host-adapted bacterium that does not persist outside of its equine reservoir. The organism causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by B. mallei typically occurs via the respiratory or percutaneous route, and the most common manifestations are life-threatening pneumonia and bacteremia. Glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. There is no vaccine to protect against B. mallei and there is concern regarding its use as a biothreat agent. Thus, experiments were performed to establish a non-human primate model of intranasal infection to study the organism and develop countermeasures. Groups of marmosets (Callithrix jacchus) were inoculated intranasally with B. mallei strain ATCC 23344 and monitored for clinical signs of illness for up to 13 days. We discovered that 83% of marmosets inoculated with doses of 2.5 X 10(4) to 2.5 X 10(5) bacteria developed acute lethal infection within 3-4 days. Signs of disease were severe and included lethargy, inappetence, conjunctivitis, mucopurulent and hemorrhagic nasal discharges, and increased respiratory effort with abdominal lifts. Burkholderia mallei was cultured from the lungs, spleen and liver of these animals, and pathologic examination of tissues revealed lesions characteristic of glanders. Challenge experiments also revealed that 91% of animals infected with doses ranging from 25 to 2.5 X 10(3) bacteria exhibited mild non-specific signs of illness and were culture negative. One marmoset inoculated with 2.5 X 10(3) organisms developed moderate signs of disease and reached humane end-points 8 days post-infection. The liver and spleen of this animal were colonized with the agent and pathological analysis of tissues showed nasal, splenic and hepatic lesions. Taken together, these data indicate that the marmoset is a suitable model to study respiratory infection by B. mallei.
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America; Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Tomislav
authors: T
authors: Jelesijevic
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Shawn M
authors: SM
authors: Zimmerman
authors: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Stephen B
authors: SB
authors: Harvey
authors: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Daniel G
authors: DG
authors: Mead
authors: Department of Microbiology, Franklin College of Arts and Sciences, University of Georgia, Athens, Georgia, United States of America.
authors: Teresa L
authors: TL
authors: Shaffer
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: D Mark
authors: DM
authors: Estes
authors: Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Frank
authors: F
authors: Michel
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Frederick D
authors: FD
authors: Quinn
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America; Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Robert J
authors: RJ
authors: Hogan
authors: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors: Eric R
authors: ER
authors: Lafontaine
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D058491:Bacterial Load; D042726:Burkholderia mallei / Q000472:pathogenicity*; D002144:Callithrix / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D005896:Glanders / Q000209:etiology* / Q000473:pathology / Q000635:transmission; D006736:Horses; D006801:Humans; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D013045:Species Specificity; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D015047:Zoonoses / Q000209:etiology / Q000473:pathology / Q000635:transmission