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15 September 2006

Volume 43, Number 6
Clinical Infectious Diseases 2006;43:711–716
1058-4838/2006/4306-0008
DOI: 10.1086/506348
MAJOR ARTICLE

Live Vaccine Strain Francisella tularensis Is Detectable at the Inoculation Site but Not in Blood after Vaccination against Tularemia

Matthew J. Hepburn,1

Bret K. Purcell,2

James V. Lawler,1

Susan R. Coyne,3

Patricia L. Petitt,1

Karen D. Sellers,1

David A. Norwood,3 and

Melanie P. Ulrich3

Divisions of 1Medicine, 2Bacteriology, and 3Diagnostic Systems, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland

Introduction.Live vaccine strain (LVS) Francisella tularensis is a live, attenuated investigational tularemia vaccine that has been used by the US Army for decades to protect laboratory workers. Postvaccination bacterial kinetic characteristics of LVS at the inoculation site and in the blood are unknown and, therefore, were assessed in a prospective study. LVS vaccination of laboratory workers provided the opportunity to compare culture with polymerase chain reaction (PCR) for the detection of F. tularensis in human clinical samples.

Methods.Blood and skin swab samples were prospectively collected from volunteers who received the LVS tularemia vaccine at baseline (negative controls) and at 5 specified time points (days 1, 2, 7 or 8, 14 or 15, and 35 after vaccination). Bacterial culture and PCR of whole blood samples (17 volunteers) and inoculation site swabs (41 volunteers) were performed.

Results.The culture and PCR results of all blood samples were negative. Results of real‐time PCR from the inoculation site samples were positive for 41 (100%) of 41 volunteers on day 1, for 40 (97.6%) of 41 volunteers on day 2, for 24 (58.5%) of 41 on day 7 or 8, for 6 (16.7%) of 36 on day 14 or 15, and for 0 (0%) of 9 on day 35. Positive results of bacterial cultures of the inoculation site samples occurred significantly less frequently, compared with PCR testing, with 4 (9.8%) of 41 volunteers having positive results on day 1 ( ) and 4 (9.8%) of 41 on day 2 ( ); all results from subsequent days were negative.

Conclusions.F. tularensis LVS genomic DNA was detected in the majority of samples from the inoculation site up to 1 week after LVS vaccination, with real‐time PCR being more sensitive than culture. Our data suggest that bacteremia does not occur after LVS vaccination in normal, healthy human volunteers.

Received 7 December 2005; accepted 16 May 2006; electronically published 10 August 2006.

Reprints or correspondence: Dr. Matthew J. Hepburn, PSC 821 Box 84, FPO, AE 09421 ().

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D.S. Francy, R.N. Bushon, A.M.G. Brady, E.E. Bertke, C.M. Kephart, C.A. Likirdopulos, B.E. Mailot, F.W. Schaefer III, H.D. Alan Lindquist. (2009) Comparison of traditional and molecular analytical methods for detecting biological agents in raw and drinking water following ultrafiltration. Journal of Applied Microbiology
Online publication date: 1-May-2009.
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Matthew J Hepburn, Andrew JH Simpson. (2008) Tularemia: current diagnosis and treatment options. Expert Review of Anti-infective Therapy 6:2, 231-240
Online publication date: 1-May-2008.
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(2007) Arbobakterien (über Arthropoden übertragbare Bakterien). Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 50:9, 1192-1207
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Colin A. Forestal, Meenakshi Malik, Sally V. Catlett, Anne G. Savitt, Jorge L. Benach, Timothy J. Sellati, and Martha B. Furie. (2007) Francisella tularensis Has a Significant Extracellular Phase in Infected Mice. The Journal of Infectious Diseases 196:1, 134-137
Online publication date: 1-Jul-2007.
  • The opinions and assertions contained herein are those of the authors and are not to be construed as official policy or as reflecting the views of the Department of the Army or the Department of Defense.

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