Open AccessIdentification of a Surrogate Marker for Infection in the African Green Monkey Model of Inhalation Anthrax
Author(s) -
Cynthia A. Rossi,
Melanie Ulrich,
Sarah L. Norris,
Douglas S. Reed,
M. Louise M. Pitt,
Elizabeth K. Leffel
Publication year - 2008
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00520-08
Subject(s) - bacillus anthracis , immunoassay , african green monkey , immunology , biology , bacteremia , antigen , disease , medicine , virology , microbiology and biotechnology , pathology , bacteria , antibiotics , antibody , virus , genetics
In 2001, a bioterrorism attack involvingBacillus 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 toB. 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 ofB. anthracis therapeutic development.