Hepburn Matthew J, Purcell Bret K, Lawler James V, Coyne Susan R, Petitt Patricia L, Sellers Karen D, Norwood David A, Ulrich Melanie P
Division of Medicine, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Clin Infect Dis. 2006 Sep 15;43(6):711-6. doi: 10.1086/506348. Epub 2006 Aug 10.
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.
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.
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 (P<.001) and 4 (9.8%) of 41 on day 2 (P<.001); all results from subsequent days were negative.
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.
活疫苗株（LVS）土拉弗朗西斯菌是一种减毒活的实验性兔热病疫苗，美国陆军已使用数十年以保护实验室工作人员。接种部位及血液中LVS接种后的细菌动力学特征尚不清楚，因此，在一项前瞻性研究中进行了评估。实验室工作人员接种LVS疫苗提供了一个机会，可比较培养法与聚合酶链反应（PCR）在人类临床样本中检测土拉弗朗西斯菌的效果。
前瞻性地收集了在基线时（阴性对照）以及接种疫苗后5个特定时间点（接种后第1、2、7或8、14或15、35天）接受LVS兔热病疫苗的志愿者的血液和皮肤拭子样本。对全血样本（17名志愿者）和接种部位拭子（41名志愿者）进行了细菌培养和PCR检测。
所有血液样本的培养和PCR结果均为阴性。接种部位样本实时PCR结果显示，第1天41名志愿者中有41名（100%）呈阳性，第2天41名志愿者中有40名（97.6%）呈阳性，第7或8天41名中有24名（58.5%）呈阳性，第14或15天36名中有6名（16.7%）呈阳性，第35天9名中无1名（0%）呈阳性。与PCR检测相比，接种部位样本细菌培养阳性结果出现的频率显著更低，第1天41名志愿者中有4名（9.8%）呈阳性（P<0.001），第2天41名中有4名（9.8%）呈阳性（P<0.001）；后续各天的所有结果均为阴性。
在接种LVS疫苗后长达1周的时间里，接种部位的大多数样本中检测到了土拉弗朗西斯菌LVS基因组DNA，实时PCR比培养法更敏感。我们的数据表明，正常、健康的人类志愿者接种LVS疫苗后不会发生菌血症。
