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Infection and Immunity, June 2007, p. 2954-2958, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.00090-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Assessment of the Kinetics of Treponema pallidum Dissemination into Blood and Tissues in Experimental Syphilis by Real-Time Quantitative PCR

Juan C. Salazar,^1,# Asha Rathi,^2,#, Nelson L. Michael,³ Justin D. Radolf,^4,5 and Linda L. Jagodzinski^3*

Department of Pediatrics, Connecticut Children's Medical Center, Division of Pediatric Infectious Diseases, Hartford, Connecticut 06106,¹ Henry M. Jackson Foundation, 1600 East Gude Drive, Rockville, Maryland 20850,² Walter Reed Army Institute of Research, 1600 East Gude Drive, Rockville, Maryland 20850,³ Departments of Medicine,⁴ Genetics and Developmental Biology, the University of Connecticut Health Center, Farmington, Connecticut 06030⁵

Received 16 January 2007/ Returned for modification 23 February 2007/ Accepted 2 April 2007

Little is known about the size and kinetics of treponemal burdens in blood and tissues during acquired or experimental syphilitic infection. We used real-time quantitative PCR to measure Treponema pallidum DNA levels in rabbits infected intratesticularly with the prototype Nichols strain. At the outset, we performed a series of in vitro blood spiking experiments to determine the effect of blood processing procedures on the distribution of treponemes in various blood components. T. pallidum DNA levels in plasma and whole blood were approximately 10-fold higher than those in serum and more than 200-fold greater than those in peripheral blood mononuclear cells (PBMCs). Ten rabbits were inoculated intratesticularly with doses of treponemes ranging from 4 x 10⁷ to 2 x 10⁸ organisms. In five rabbits, T. pallidum DNA levels were measured sequentially in serum, plasma, whole blood, and PBMCs until sacrifice at peak orchitis, at which time brain, kidney, liver, spleen, and testicles were harvested; blood and organs were also harvested at orchitis from the other five rabbits. T. pallidum DNA was detected in plasma within 24 h postinfection. Treponeme levels in whole blood and blood components increased significantly with the development of peak orchitis. Overall, levels in serum and PBMCs were lower than those in plasma and whole blood; this disparity was particularly marked at early time points. Significantly greater numbers of spirochetes were found in the spleen than in liver, kidney, or brain tissue at the time of sacrifice. Our findings highlight the remarkable capacity of T. pallidum to disseminate from the site of infection to blood and tissues, and they identify the spleen as a prime target for treponemal invasion.

Published ahead of print on 16 April 2007.

Editor: D. L. Burns

^# The first two authors contributed equally to this work.

Present address: Aerotek, 2400 Research Blvd., Suite 200, Rockville, MD 20850.