FATAL ACUTE HEMOLYSIS FOLLOWING TRIAZOLE THERAPY IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS)

Area of Science:

• Veterinary Medicine
• Toxicology
• Avian Pathology

Background:

• Aspergillosis is a significant health concern in penguins, often managed with triazole antifungal drugs.
• Liquid formulations of itraconazole and voriconazole are commonly used for prophylaxis and treatment in penguins.
• Stressful events in penguins may predispose them to adverse drug reactions.

Purpose of the Study:

• To investigate the association between liquid azole antifungal administration and fatal hemolysis in African penguins.
• To evaluate the in vitro hemolytic potential of itraconazole, voriconazole, and their vehicle components.

Main Methods:

• Retrospective case review of 15 fatal cases in African penguins treated with liquid itraconazole or voriconazole.
• Postmortem examination to identify pathological findings.
• In vitro hemolytic assays using chicken whole blood exposed to azole drugs and vehicle ingredients (sorbitol, hydromellose).
• Spectrophotometric measurement of plasma hemoglobin.

Main Results:

• Fifteen African penguins died following administration of liquid itraconazole or voriconazole, exhibiting signs of hemolysis and hemoglobinuric nephrosis.
• Neither itraconazole nor voriconazole alone caused hemolysis in vitro.
• Vehicle ingredients sorbitol and hydromellose induced hemolysis in vitro, but at concentrations lower than predicted in vivo levels.
• The exact cause of hemolysis in vivo remains undetermined, with potential roles for unmeasured metabolites or species-specific sensitivities.

Conclusions:

• Liquid formulations of itraconazole and voriconazole are linked to fatal hemolysis in African penguins.
• While vehicle ingredients showed in vitro hemolytic activity, they may not fully explain the in vivo cases.
• Further research is crucial to elucidate the mechanisms of azole antifungal toxicosis and identify safer formulations for avian species.