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Evaluation of an experimental animal model for testing antifungal substances
Abstract:
Accumulated evidence indicates that infection by fungi capable of causing systemic disease usually results in a relatively strong acquired resistance. The working hypothesis for this study was that an antifungal substance, even one with only slight fungistatic activity, could be an effective chemotherapeutic agent by arresting progression of the infection until acquired resistance became effective. The present study involved establishing and evaluating an experimental animal model (coccidioidomycosis in mice) which could be used to test this hypothesis. This model was reasonably similar to the natural disease. Results with infected nontreated animals indicated that the plot of mortality frequency against survival time did not follow a normal distribution curve. Thus, nonparametric procedures were used for evaluation. Use of this model with an established antibiotic (amphotericin B), with a crude preparation of a new antibiotic (CB-310), and with synthetic organoselenium compounds demonstrated that even low levels of antifungal activity could be detected. The model should be useful not only to test the original hypothesis but also to screen antifungal substances for their potential as chemotherapeutic agents.
Insights
A new mouse model for coccidioidomycosis effectively detects low-level antifungal activity. This research suggests even slight fungistatic drugs can aid treatment by allowing the immune system to develop resistance.
Area of Science:
- Mycology
- Immunology
- Pharmacology
Background:
- Systemic fungal infections typically elicit a robust acquired immune response.
- Antifungal chemotherapy aims to control infection until host immunity is established.
Purpose of the Study:
- To establish and validate an experimental animal model for coccidioidomycosis in mice.
- To test the hypothesis that even weakly fungistatic agents can be effective chemotherapeutics.
Main Methods:
- Developed a mouse model of coccidioidomycosis.
- Utilized nonparametric statistical methods due to non-normal mortality data.
- Evaluated amphotericin B, a new antibiotic (CB-310), and organoselenium compounds.
Main Results:
- The mouse model reasonably mimicked natural coccidioidomycosis.
- Demonstrated the model's ability to detect low levels of antifungal activity.
- Confirmed the potential of fungistatic agents in chemotherapy.
Conclusions:
- The established mouse model is suitable for testing antifungal chemotherapy hypotheses.
- The model can effectively screen novel antifungal substances for therapeutic potential.
- Even minimal fungistatic activity may be clinically relevant in treating systemic fungal infections.