A large animal model of invasive pulmonary aspergillosis in...

A - Human Necessities – 01 – K

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A01K 67/027 (2006.01) C12Q 1/02 (2006.01)

Patent

CA 2379311

A model of systemic mold/Aspergillus infection in a profoundly immunocompromised host has been established in the beagle dog. The beagle was rendered immunosuppressed using a combination of total body irradiation and daily steroids, which provided a window of time where the mold could be successfully inoculated through a bronchoscope. This created a localized infection in one lung lobe, which subsequently spread diffusely throughout the lung parenchyma, and uniformly resulted in the animal's death. The invention contemplates the further study of the pathophysiology of opportunistic mold infections in vivo and also provides examples for the development of new antifungal agents and more effective combinations of agents. Finally, the invention contemplates the development of technology for the early detection of systemic mold infections. The inventors envisions, that the use of the model should help save patients from clinical trials of antifungal drugs that may be effective in vitro without living up to the expectations in a clinical setting.

La présente invention concerne un modèle d'infection systémique par moisissure/Aspergillus chez un hôte profondément immunodéprimé, établi chez un chien beagle. Le beagle est immunodéprimé grâce à l'utilisation d'une combinaison d'irradiation complète corporelle et d'administration journalière de stéroïdes, laissant un intervalle de temps permettant d'inoculer successivement la moisissure via un bronchoscope. Cela permet d'obtenir une infection localisée dans un lobe pulmonaire, qui se propage ensuite par diffusion à travers le parenchyme pulmonaire, pour finir par causer la mort de l'animal. La présente invention concerne l'étude plus poussée de la pathophysiologie des infections opportunistes par moisissure in vivo ainsi que des exemples de mise au point de nouveaux agents antifongiques et de combinaisons plus efficaces d'agents. Pour finir, cette invention concerne la mise au point d'une technique de détection précoce d'infections systémiques par moisissure. Les inventeurs veulent que ce modèle puisse être utilisé pour éviter à des patients d'avoir à subir des essais cliniques de médicaments antifongiques qui pourraient s'avérer efficaces in vitro sans l'être en conditions cliniques.

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