Animal models of Aspergillus infection in preclinical trials, diagnostics and pharmacodynamics: What can we learn from them?

Abstract

Animal models of aspergillosis, particularly those studied in rodents, are an integral part of antifungal drug development. The capacity to control different variables is beneficial, allowing a well defined model system to be used to address various issues of efficacy with monotherapy, combinations, or immunotherapy. One beneficial aspect of the use of animal models is that they enable us to investigate novel indications of drugs prior to a clinical trial or where a clinical trial is impractical. Included in these types of studies is the testing of potentially preventative vaccines. Animal models also are useful for studying diagnostic assays, as well as pharmacology and toxicity. Thus, because of the ability of the best models to mimic human diseases, and our ability to infect genetically identical cohorts of the same age, sex, co-morbidities and risk factors, with an identical challenge inoculum at the same time, we are able to address issues in vivo that cannot be answered by in vitro tests. We also can have sufficient numbers of subjects for statistical analyses, can vary the severity of infection at will and can choose to terminate the experiments to enable using survival or clearance of residual infection as the efficacy end-point. Are these animal models predictive of clinical efficacy, pharmacology and toxicity of an antifungal drug? No single model should be relied upon, as different models of aspergillosis in mice or other animals sometimes show somewhat different results. However, the accumulated wealth of experience has demonstrated the utility of these models in predicting clinical efficacy, pharmacology and toxicity.