Animal models of aspergillosis - also useful for vaccination strategies?

The attempt to establish vaccination strategies against infections caused by Aspergillus fumigatus seems to be questionable. Invasive aspergilloses are opportunistic diseases of the immunocompromised host and only a passive immunization with immunoglobulins could be taken into consideration. Until now there have been no preclinical and/or clinical data available concerning the efficacy of specific immunoglobulins; animal experiments could offer an approach for the preclinical assessment of this topic. Generally, A. fumigatus is an opportunistic pathogen. Birds show a relatively high susceptibility to infections caused by A. fumigatus. In laboratory animal species, rabbits seem to have the highest susceptibility followed by mice, rats and guinea-pigs. Mice are easy to handle in all-day laboratory use, and infections are mostly established by the intravenous, intranasal or intraperitoneal route. The main target organs of infection are the kidneys by all three infection routes. Forty clinical isolates of A. fumigatus tested showed a comparable virulence in systemic infections in the intravenously infected mouse model. By using histopathological techniques, we also observed infectious lesions within the central nervous system in all cases. Only A. fumigatus strains lacking green pigmentation showed a significantly lower virulence. Histopathological examinations are of great benefit in the study of these animal models as they give detailed information about the infectious process. Measuring colony-forming units in tissues is only of minor use in prediction as it cannot discriminate between infective tissue lesions and cavity-infections/persistence, e.g. in the kidney pelvis. Quantitative methods for measuring fungal organ burdens, e.g. by chitin-enzyme-linked immunosorbent assays, have also been described and offer an alternative towards solely measuring colony-forming units in tissues.