The pathogenesis of invasive mycosis caused by filamentous fungi is closely associated with tissue damage resulting from hyphal elongation. The morphological changes that occur during hyphal cell death induced by antifungal drugs, however, have not been extensively investigated. In this study, we cultured Aspergillus fumigatus and Rhizopus oryzae, two representative pathogenic molds, in the presence of isavuconazole and performed dynamic and detailed observations of morphological alterations in their hyphae. We observed cessation of hyphal elongation, degeneration of the cell membrane, and a continuous decrease in the fluidity of the intracellular matrix in both species. As evaluated by propidium iodide positivity, hyphal cell viability was reduced by 96.8% and 100% in A. fumigatus and R. oryzae, respectively. These results suggest that morphological changes in hyphae induced by isavuconazole result in cell death.

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Histopathological examination enables rapid identification of fungi at the genus level. However, only a few pathologists are familiar with the unusual morphological appearances of fungi by the host-parasite interaction and/or degeneration that may lead to the wrong diagnosis. Histopathological examination of vessels invaded by fungi is helpful in identifying Aspergillus or Mucorales species, in addition to examination of their mycelial morphology. However, there are many Aspergillus look-alikes that grow in tissues, and the presence of GMS-positive or PAS-positive filamentous materials sometimes leads to wrong diagnosis of mycosis.

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Pulmonary aspergillosis is a refractory infectious disease that occurs in patients with impaired immunity or pulmonary underlying diseases. It is roughly categorized into invasive pulmonary aspergillosis and chronic pulmonary aspergillosis depending on their clinical course or the type of underlying diseases. Diagnosing aspergillosis requires a review of background information or radiological findings. As the sensitivity of fungal culture is from sputum low, bronchoscopy must be performed to obtain specimen from the site of infection for fungal culture or pathological examination. However, bronchoscopy is usually avoided if the patient has poor general conditions. Hence, a better auxiliary diagnostic method is needed. Galactomannan antigen has good accuracy for the diagnosis of invasive pulmonary aspergillosis, but not for chronic pulmonary aspergillosis. Although the Aspergillus precipitating antibody test has a relatively good sensitivity and specificity for the diagnosis of chronic pulmonary aspergillosis, it is not covered by the Japanese medical insurance system. Approval of Aspergillus IgG EIA antibody tests or the development of new diagnostic methods for pulmonary aspergillosis is necessary.

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