Perpetuation of Francisella tularensis

Summary

Principal Investigator: Sam Telford
Abstract: Francisella tularensis is the causative agent of tularemia, an acute febrile infection with variable presentation and outcomes. Although the agent is said to be maintained in nature by cycles involving ticks and rodents or rabbits, its great infectivity and presumptiveenvironmental stability suggestsother modes of perpetuation. Our longterm goal is to determine the proximal determinants of risk for outbreaksof tularemia, and in particular,how the agent is maintained between epizootics. The specific hypothesis is that multiple modes of transmission are facilitated by a metapopulation structure of genetic variants within an enzootic focus;certain variants may be better adaptedto ticks as opposed to environmental reservoirs. We base our hypothesis on our investigationof the ongoing pneumonic tularemia outbreak on Martha's Vineyard, wherein we have found (1) that 11 F. tularensis variants circulate in our island study sites;and (2) that certain of these variants appear to be associated solely with ticks or with animals. Based on these observations, we now seek to determine experimentallywhether certain variants are more likely to be inherited by ticks, remain stable within the environment, or cause pulmonary pathology. The specific aims, therefore, are to: 1. Determine whether variants differ in their capacity to be transmitted by ticks, including maintenance by inheritance. We will clone strains from the multiple loci variable number tandem repeat analysis (MLVA)-defined genotypes, and measure the vector competence of various ticks for such clones. 2. Determine whether variants differ in their capacity to stably persist in the environment, including resistance to dessication, survival in water, and colonisation of freeliving or parasitic cyst-forming protozoa. We will measure the viability and survival of each genotype under simulated environmental stresses in vitro. 3. Determine whether variants differ in their infectivity to and virulence within rodents, including capacity to induce pulmonary pathology or hematogenously disseminate. Rats and mice will be infected by intratracheal instillation, as well as parenteral delivery, and tissues examined by histopathology,immunohistochemistry, PCR, cultivation, and cytokine mRNA expression. Taken together, these observations will provide a basis for understanding how the agent of tularemia is perpetuated on Martha's Vineyard, and why pneumonic human disease is prevalent there.
Funding Period: ----------------2006 - ---------------2012-
more information: NIH RePORT

Top Publications

  1. ncbi Pneumonic tularemia on Martha's Vineyard: clinical, epidemiologic, and ecological characteristics
    Bela T Matyas
    Massachusetts Department of Public Health, 305 South Street, Room 506, Boston, MA 02130, USA
    Ann N Y Acad Sci 1105:351-77. 2007
  2. pmc Molecular detection of Bartonella schoenbuchensis from ectoparasites of deer in Massachusetts
    Kotaro Matsumoto
    Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA
    Vector Borne Zoonotic Dis 8:549-54. 2008
  3. ncbi Rickettsia rickettsii (Rickettsiales: Rickettsiaceae) in Amblyomma americanum (Acari: Ixodidae) from Kansas
    Zenda L Berrada
    Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA
    J Med Entomol 48:461-7. 2011
  4. pmc Survival of Francisella tularensis Type A in brackish-water
    Zenda Lea Berrada
    Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine, 200 Westboro Road, Building 20, North Grafton, MA 01536, USA
    Arch Microbiol 193:223-6. 2011
  5. ncbi Histologic, immunohistochemical, microbiological, molecular biological and ultrastructural characterization of pulmonary tularemia
    Paula Navarro
    Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA
    Pathol Res Pract 207:63-6. 2011
  6. pmc Quantum of infection of Francisella tularensis tularensis in host-seeking Dermacentor variabilis
    Heidi K Goethert
    Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536, USA
    Ticks Tick Borne Dis 1:66-8. 2010
  7. pmc Bartonella spp. transmission by ticks not established
    Sam R Telford
    Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachussetts, USA
    Emerg Infect Dis 16:379-84. 2010
  8. ncbi Bartonella sp. Infection of voles trapped from an interior Alaskan site where ticks are absent
    Kotaro Matsumoto
    Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, Massachusetts 01536, USA
    J Wildl Dis 46:173-8. 2010
  9. pmc Burden of tick-borne infections on American companion animals
    Zenda L Berrada
    Division of Infectious Diseases and New England Regional Biocontainment Laboratory, Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA
    Top Companion Anim Med 24:175-81. 2009
  10. pmc Diversity of Francisella species in environmental samples from Martha's Vineyard, Massachusetts
    Zenda L Berrada
    Tufts Cummings School of Veterinary Medicine, North Grafton, MA, USA
    Microb Ecol 59:277-83. 2010

Scientific Experts

  • Sam Telford
  • G P Wormser
  • Heidi K Goethert
  • Zenda L Berrada
  • Kotaro Matsumoto
  • Zenda Lea Berrada
  • Paula Navarro
  • Bela T Matyas
  • Sam R Telford III
  • James H McMahon
  • Jenny Cunningham
  • Maria L Garcia-Moliner
  • Joseph Alroy
  • Driss Zoukhri
  • Joseph A Cook
  • Elissa Klinger
  • Henry S Nieder

Detail Information

Publications14

  1. ncbi Pneumonic tularemia on Martha's Vineyard: clinical, epidemiologic, and ecological characteristics
    Bela T Matyas
    Massachusetts Department of Public Health, 305 South Street, Room 506, Boston, MA 02130, USA
    Ann N Y Acad Sci 1105:351-77. 2007
    ..Why tularemia is prevalent on Martha's Vineyard and why it commonly presents as a pneumonic disease there remain undescribed...
  2. pmc Molecular detection of Bartonella schoenbuchensis from ectoparasites of deer in Massachusetts
    Kotaro Matsumoto
    Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA
    Vector Borne Zoonotic Dis 8:549-54. 2008
    ..Five of 6 keds were found to contain B. schoenbuchensis DNA, and 2 deer ticks cofeeding on deer with such keds did as well. The detection of Bartonella DNA in deer ticks probably represents contamination by infected deer blood...
  3. ncbi Rickettsia rickettsii (Rickettsiales: Rickettsiaceae) in Amblyomma americanum (Acari: Ixodidae) from Kansas
    Zenda L Berrada
    Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA
    J Med Entomol 48:461-7. 2011
    ..We conclude that lone star ticks may be epidemiologically significant vectors of Rocky Mountain spotted fever and of spotted fever group rickettsiae...
  4. pmc Survival of Francisella tularensis Type A in brackish-water
    Zenda Lea Berrada
    Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine, 200 Westboro Road, Building 20, North Grafton, MA 01536, USA
    Arch Microbiol 193:223-6. 2011
    ....
  5. ncbi Histologic, immunohistochemical, microbiological, molecular biological and ultrastructural characterization of pulmonary tularemia
    Paula Navarro
    Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA
    Pathol Res Pract 207:63-6. 2011
    ..Our study demonstrates the usefulness of microbiological studies followed by morphological evaluation and the limitation of the molecular biology analysis of posttherapy samples...
  6. pmc Quantum of infection of Francisella tularensis tularensis in host-seeking Dermacentor variabilis
    Heidi K Goethert
    Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Rd, North Grafton, MA 01536, USA
    Ticks Tick Borne Dis 1:66-8. 2010
    The American dog tick, Dermacentor variabilis, is fundamental to the perpetuation of Francisella tularensis tularensis on Martha's Vineyard, Massachusetts, U.S.A...
  7. pmc Bartonella spp. transmission by ticks not established
    Sam R Telford
    Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachussetts, USA
    Emerg Infect Dis 16:379-84. 2010
    ..by ticks, to animals or humans, has not been established. We are unaware of any well-documented case of B. henselae transmission by I. scapularis ticks...
  8. ncbi Bartonella sp. Infection of voles trapped from an interior Alaskan site where ticks are absent
    Kotaro Matsumoto
    Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, Massachusetts 01536, USA
    J Wildl Dis 46:173-8. 2010
    ..rutilus sampled in this study. We conclude that Bartonella species may commonly infect M. rutilus in a site where ticks are absent...
  9. pmc Burden of tick-borne infections on American companion animals
    Zenda L Berrada
    Division of Infectious Diseases and New England Regional Biocontainment Laboratory, Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA
    Top Companion Anim Med 24:175-81. 2009
    ....
  10. pmc Diversity of Francisella species in environmental samples from Martha's Vineyard, Massachusetts
    Zenda L Berrada
    Tufts Cummings School of Veterinary Medicine, North Grafton, MA, USA
    Microb Ecol 59:277-83. 2010
    ..tularensis and Francisella novicida were detected from samples collected from the brackish-water pond. We conclude that diverse Francisella spp. are present in the environment where human cases of pneumonic tularemia occur...
  11. pmc Metapopulation structure for perpetuation of Francisella tularensis tularensis
    Heidi K Goethert
    Division of Infectious Diseases, Tufts Cummings School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536, USA
    BMC Microbiol 9:147. 2009
    ..During times of increased transmission, the foci would merge and a larger scale epizootic would occur, with greater likelihood that humans become exposed...
  12. pmc Status of the "East Side hypothesis" (transovarial interference) 25 years later
    Sam R Telford
    Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, Massachusetts 01536, USA
    Ann N Y Acad Sci 1166:144-50. 2009
    ....
  13. pmc Nonrandom distribution of vector ticks (Dermacentor variabilis) infected by Francisella tularensis
    Heidi K Goethert
    Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA
    PLoS Pathog 5:e1000319. 2009
    ..We conclude that we have identified a microfocus where the agent of tularemia stably perpetuates and that this area is where genetic diversity is generated...
  14. pmc Differential mortality of dog tick vectors due to infection by diverse Francisella tularensis tularensis genotypes
    Heidi K Goethert
    Division of Infectious Diseases, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA
    Vector Borne Zoonotic Dis 11:1263-8. 2011
    The factors involved in the long-term perpetuation of Francisella tularensis tularensis in nature are poorly understood...