Molecular Epidemiology ofFrancisella tularensisin the United States

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.