Kugeler Kiersten J, Mead Paul S, Janusz Aimee M, Staples J Erin, Kubota Kristy A, Chalcraft Linda G, Petersen Jeannine M
Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases, Fort Collins, Colorado, USA.
Clin Infect Dis. 2009 Apr 1;48(7):863-70. doi: 10.1086/597261.
In the United States, tularemia is caused by Francisella tularensis subsps. tularensis (type A) and holarctica (type B). Molecular subtyping has further divided type A into 2 subpopulations, A1 and A2. Significant mortality differences were previously identified between human infections caused by A1 (14%), A2 (0%) and type B (7%). To verify these findings and to further define differences among genotypes, we performed a large-scale molecular epidemiologic analysis of F. tularensis isolates from humans and animals.
Pulsed-field gel electrophoresis with PmeI was performed on 302 type A and 61 type B isolates. Pulsed-field gel electrophoresis pattern and epidemiologic analyses were performed. Logistic regression was used to assess factors associated with human mortality.
Pulsed-field gel electrophoresis typing identified 4 distinct type A genotypes, A1a, A1b, A2a, and A2b, as well as type B. Genotypic and geographic divisions observed among isolates from humans were mirrored among isolates from animals, specifically among animal species that are linked to human infection and to enzootic maintenance of tularemia. Significant differences between human infections caused by different genotypes were identified with respect to patient age, site of organism recovery, and mortality. Human infections due to A1b resulted in significantly higher mortality (24%) than those caused by A1a (4%), A2 (0%), and type B (7%).
Three type A genotypes, A1a, A1b, and A2, were shown to be epidemiologically important. Our analysis suggests that A1b strains may be significantly more virulent in humans than A1a, A2, or type B strains. These findings have important implications for disease progression, disease prevention, and basic research programs.
在美国，兔热病由土拉热弗朗西斯菌亚种土拉热弗朗西斯菌（A 型）和全北区亚种（B 型）引起。分子分型进一步将 A 型分为两个亚群，即 A1 和 A2。先前已确定由 A1（14%）、A2（0%）和 B 型（7%）引起的人类感染之间存在显著的死亡率差异。为了验证这些发现并进一步明确不同基因型之间的差异，我们对来自人和动物的土拉热弗朗西斯菌分离株进行了大规模分子流行病学分析。
对 302 株 A 型和 61 株 B 型分离株进行了 PmeI 脉冲场凝胶电泳。进行了脉冲场凝胶电泳图谱分析和流行病学分析。采用逻辑回归评估与人类死亡率相关的因素。
脉冲场凝胶电泳分型确定了 4 种不同的 A 型基因型，即 A1a、A1b、A2a 和 A2b，以及 B 型。在人类分离株中观察到的基因型和地理分布差异在动物分离株中也有体现，特别是在与人类感染和兔热病自然疫源地维持相关的动物物种中。在患者年龄、病原体回收部位和死亡率方面，不同基因型引起的人类感染存在显著差异。由 A1b 引起的人类感染导致的死亡率（24%）显著高于由 A1a（4%）、A2（0%）和 B 型（7%）引起的感染。
三种 A 型基因型，即 A1a、A1b 和 A2，在流行病学上具有重要意义。我们的分析表明，A1b 菌株在人类中的毒性可能比 A1a、A2 或 B 型菌株显著更强。这些发现对疾病进展、疾病预防和基础研究项目具有重要意义。
