title: A murine model of Cryptococcus gattii meningoencephalitis.
abstract: OBJECTIVE
  Meningoencephalitis caused by Cryptococcus gattii is associated with significant morbidity and the need for aggressive therapy, and often necessitates neurosurgical intervention. We adapted a previously described murine model of cryptococcal meningoencephalitis due to Cryptococcus neoformans to that caused by C. gattii.
  
  
  METHODS
  Mice were inoculated intracranially with either C. gattii (genotype VGIIa) or C. neoformans. In virulence studies, different C. gattii infecting inocula were compared with a fixed inoculum of C. neoformans, and differences were assessed by survival, brain tissue fungal burden, serum antigen titres and histopathological changes within brain tissue. For treatment, fluconazole or posaconazole (10 mg/kg orally twice daily) was initiated 24 h post-inoculation.
  
  
  RESULTS
  C. gattii was more virulent than C. neoformans, as evident by shorter median survival, earlier histopathological changes and higher serum antigen titres. However, no differences in fungal burden or dissemination to other organs were observed among the various groups. In treatment studies, both fluconazole and posaconazole improved the median survival of mice infected with either species. However, neither regimen improved the percentage of animals surviving to the predetermined study endpoint.
  
  
  CONCLUSIONS
  These results demonstrate the virulence of C. gattii meningoencephalitis and the potential of this model for the assessment of new treatment strategies.
authors.affiliation: Department of Medical Microbiology and Immunology and Department of Internal Medicine the Division of Infectious Diseases, The University of California Davis, Davis, CA, USA. grthompson@ucdavis.edu
authors.forename: George R
authors.initials: GR
authors.lastname: Thompson
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Wiederhold
authors.forename: Laura K
authors.initials: LK
authors.lastname: Najvar
authors.forename: Rosie
authors.initials: R
authors.lastname: Bocanegra
authors.forename: William R
authors.initials: WR
authors.lastname: Kirkpatrick
authors.forename: John R
authors.initials: JR
authors.lastname: Graybill
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Patterson
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage; D000946:Antigens, Fungal / Q000097:blood; D001921:Brain / Q000382:microbiology; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology*; D056285:Cryptococcus gattii / Q000472:pathogenicity*; D003455:Cryptococcus neoformans / Q000472:pathogenicity; D004195:Disease Models, Animal; D015725:Fluconazole / Q000008:administration & dosage; D006651:Histocytochemistry; D008590:Meningoencephalitis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D016019:Survival Analysis; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000935:Antifungal Agents; D000946:Antigens, Fungal; D014230:Triazoles; C101425:posaconazole; D015725:Fluconazole