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Infection and Immunity, December 2008, p. 5790-5801, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00520-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of a Surrogate Marker for Infection in the African Green Monkey Model of Inhalation Anthrax{triangledown}

Cynthia A. Rossi,1 Melanie Ulrich,1,{dagger} Sarah Norris,2 Douglas S. Reed,3,{ddagger} Louise M. Pitt,3 and Elizabeth K. Leffel3*

Diagnostics Systems Division,1 Research Support Division,2 Center for Aerobiological Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland3

Received 26 April 2008/ Returned for modification 6 June 2008/ Accepted 2 October 2008

In 2001, a bioterrorism attack involving Bacillus anthracis spore-laced letters resulted in 22 cases of inhalation anthrax, with five fatalities. This incident identified gaps in our health care system and precipitated a renewed interest in identifying both therapeutics and rapid diagnostic assays. To address those gaps, well-characterized animal models that resemble the human disease are needed. In addition, a rapid assay for a reliable diagnostic marker is key to the success of these efforts. In this study, we exposed African green monkeys to B. anthracis spores; examined clinical signs and physiological parameters, including fever, heart rate, complete blood count, and bacteremia; and evaluated the PCR assay and electrochemiluminescence (ECL) immunoassay for the biomarkers protective antigen and capsule. The results demonstrated that although there were neither objective clinical nor physiological signs that consistently identified either infection or the onset of clinical anthrax disease, the African green monkey is a suitable animal model exhibiting a disease course similar to that observed in the rhesus model and humans. We also demonstrated that detection of the biomarkers protective antigen and capsule correlated with bacterial loads in the blood of these nonhuman primates. The ECL immunoassay described here is simple and sensitive enough to provide results in one to two hours, making this assay a viable option for use in the diagnosis of anthrax, leading to timely initiation of treatment, which is a key component of B. anthracis therapeutic development.

* Corresponding author. Present address: Battelle National Biodefense Institute, National Biodefense Analysis and Countermeasures Center, 110 Thomas Johnson Dr., Suite 200, Frederick, MD 21702. Phone: (301) 620-7544. Fax: (301) 682-5268. E-mail: leffele{at}nbacc.net

{triangledown} Published ahead of print on 13 October 2008.

Editor: S. R. Blanke

{dagger} Present address: Hagerstown Community College, Mathematics and Science Division, 11400 Robinwood Drive, Hagerstown, MD 21742.

{ddagger} Present address: University of Pittsburgh, Center for Vaccine Research, 8039 BST3, 3501 Fifth Ave., Pittsburgh, PA 15261.

Infection and Immunity, December 2008, p. 5790-5801, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00520-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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