title: Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].
abstract: Orientia tsutsugamushi, the etiologic agent of scrub typhus, is a mite-borne rickettsia transmitted by the parasitic larval stage of trombiculid mites. Approximately one-third of the world's population is at risk of infection with Orientia tsutsugamushi, emphasizing its importance in global health. In order to study scrub typhus, Orientia tsutsugamushi Karp strain has been used extensively in mouse studies with various inoculation strategies and little success in inducing disease progression similar to that of human scrub typhus. The objective of this project was to develop a disease model with pathology and target cells similar to those of severe human scrub typhus. This study reports an intravenous infection model of scrub typhus in C57BL/6 mice. This mouse strain was susceptible to intravenous challenge, and lethal infection occurred after intravenous inoculation of 1.25 × 10(6) focus (FFU) forming units. Signs of illness in lethally infected mice appeared on day 6 with death occurring ∼ 6 days later. Immunohistochemical staining for Orientia antigens demonstrated extensive endothelial infection, most notably in the lungs and brain. Histopathological analysis revealed cerebral perivascular, lymphohistiocytic infiltrates, focal hemorrhages, meningoencephalitis, and interstitial pneumonia. Disseminated infection of endothelial cells with Orientia in C57BL/6 mice resulted in pathology resembling that of human scrub typhus. The use of this model will allow detailed characterization of the mechanisms of immunity to and pathogenesis of O. tsutsugamushi infection.
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Shelite
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Tais B
authors.initials: TB
authors.lastname: Saito
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Mendell
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Bin
authors.initials: B
authors.lastname: Gong
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Guang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Valbuena
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Donald H
authors.initials: DH
authors.lastname: Bouyer
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Sealy Center for Vaccine Development, Institute of Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Walker
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D012285:Orientia tsutsugamushi; D012612:Scrub Typhus