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 104 to 2.5 X 105 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 103 bacteria exhibited mild non-specific signs of illness and were culture negative. One marmoset inoculated with 2.5 X 103 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.
Highlights
Burkholderia mallei is a non-motile Gram negative bacillus that does not persist in the environment outside of its natural equine reservoir
We demonstrate that the common marmoset is susceptible to intranasal infection with B. mallei
We document the median lethal dose that causes acute disease by the intranasal route of inoculation and detail pathologic changes induced by B. mallei during infection
Summary
Burkholderia mallei is a non-motile Gram negative bacillus that does not persist in the environment outside of its natural equine reservoir. The organism causes the highly contagious and debilitating zoonotic disease glanders, which primarily affects horses, mules and donkeys. By the 2nd half of the 19th century, glanders was widespread due to the Civil War, when it was readily transmitted to thousands of cavalry horses passing through remount stations. In response to this epidemic, industrial countries implemented vigorous eradication programs that entailed financial incentive to owners, destruction of infected animals, and disinfection of affected facilities. Despite the success of eradication efforts, naturally occurring glanders is still found in parts of Asia, Africa, the Middle East and South America. The disease is closely monitored by the World Organization for Animal Health (OIE) as it is considered a serious safety and biosecurity threat
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