Experimental animals are an obligate screen to investigate microorganism pathogenicity. Numerous animal models have been used to analyse the virulence of the opportunistic human pathogen Aspergillus fumigatus but none of the experimental models used previously have been satisfactory. This report discuss these models and presents a murine model of pulmonary aspergillosis that is very easy and the most adapted to compare the pathogenicity of A. fumigatus strains. Strains to be tested are inoculated intranasally and synchronously to mice and strains isolated from the lung of mice killed by the infection are typed. The number of colonies recovered is directly correlated to the virulence of the strain.

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深在性真菌症, とくに Candida および Aspergillus に起因する侵襲性感染は, 好中球減少症その他のリスク因子をもつ易感染患者の病態と予後を悪化させる大きな原因となっている. 侵襲性病型のカンジダ症やアスペルギルス症の診断は, 主として臨床診断および真菌学的検査に依存してきたが, それぞれ特異度および感度の点で限界がある. これを補助する目的で導入された診断法が, 非培養検査による血清診断と遺伝子診断である. 血清診断用の検査は, 病原真菌特異的な抗原, 抗体, 代謝物または細胞壁成分の検出を基本とし, これらの診断マーカーを高感度に検出するシステムを必要とする. こうした検査法の幾つかはすでに製品化され, 日常検査に使用されている. しかしいずれの検査法も感度および(または)特異度に限界があり, より信頼性の高い検査法の実用化を目指して新しい診断マーカーの探索や高感度検出法の開発が進められている. この総説では, 研究の歴史的経緯を含めて血清診断の現状と将来について, とくに技術面と臨床面を中心として解説と論考を行う.

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深在性真菌症の血清診断は欧米に比較して本邦において研究開発が進み, その有用性に関する多くの臨床データの集積が報告されている. しかしながら, このように血清診断が広く臨床応用されることによって, 偽陽性症例の問題や血清診断のみに基づく不必要な抗真菌薬の投与などの新たな臨床的問題も現れている. (1,3)-β-D-グルカンは深在性真菌症が疑われた患者のスクリーニング検査として有用である. しかし, 血清中の極めて微量な(1,3)-β-D-グルカンを測定するため, 偽陽性がときに問題となる. 原因真菌に応じた血清診断としては抗原検出法が有用である. カンジダ症ではマンナン抗原, クリプトコックス症では爽膜多糖抗原, アスペルギルス症ではガラクトマンナン抗原などの検出は原因真菌の推定にも有用である. しかし, クリプトコックス症の莢膜多糖抗原検出法を除いては, 感度が不十分であり, 臨床的な有用性には疑問があった. 近年, 主にELISA法を用いた高感度な抗原検出系の研究開発により, より微量の抗原を血清中から検出可能となったが, 特異性や偽陽性症例の問題などからも今後多くの臨床例で検討する必要がある.

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この総説は第45回日本医真菌学会総会で行われたパネルディスカッション「深在性真菌症治療薬開発の問題点-創薬から臨床試験まで-」において発表された7つの演題の抄録集である. このうち最初の3つの演題は創薬に関するもので, aureobasidin A を中心とした抗真菌抗生物質のスクリーニングと化学構造の解析および作用機作の解明等について, また選択的作用標的をもつ新規物質の探索・創製に関して(1→3)-β-glucan synthase を阻害するFK463 (micafungin)について, またトリアゾール系薬剤の構造活性相関から新規誘導体の展開に関してCS-758を例にあげての発表であった. 残りの4演題では血液疾患および呼吸器疾患における臨床試験の現状と問題点に関する発表と, 企業サイドからの新薬開発の問題点並びに行政の立場から新薬承認審査に関する諸問題が提示された.

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A female four-toed hedgehog probably imported from Africa and kept as a pet by a family suffered from depilation and mite (Caparinia tripilis) infection. Depilated quills were inoculated on a commercially available medium and an isolate of the dermatophytes was obtained. A giant colony after 14 days incubation on yeast extract Sabouraud's agar had a central umbo with white granular surface and a yellow pigment ring in the reverse. The hedgehog isolate produced numerous elongated microconidia singly attached along the sides of hyphae. Macroconidia were somewhat irregular in shape and size and 2-6 septa. Abundant intermediate sized spores between micro- and macro conidia and few spirals were observed. Hair perforation and urease activity tests were positive. Maximum growth temperature was 40. In the mating tests using the tester strains of both African and Americano-European races of Arthroderma benhamiae, the strain produced numerous gymnothecia only when paired with the African race mating type minus (-). In addition, 591 bases of the internal transcribed spacer region of the ribosomal RNA gene including the 5.8S region (ITS1-5.8S-ITS2) were sequenced and corresponded to those of T. mentagrophytes var. erinacei (DDBJ/EMBL/GenBank accession numbers Z97996 and Z97997) by more than 99.7%. Therefore, our case is the first isolation of A. benhamiae with T. mentagrophytes var. erinacei anamorph in Japan.

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Restriction fragment length polymorphism (RFLP) in mitochondrial DNA (mtDNA) from 25 environmental isolates of Sporothrix schenckii from northeastern China was investigated. Based on the mtDNA-RELP patterns with Hae III, 6 isolates were confirmed to be S. schenckii, while the other 19 isolates were confirmed to be species distinct from S. schenckii. The mtDNA RFLP patterns of the 19 non-S. schenckii were identical to each other.
The non-S. schenckii isolates could not be discriminated from S. schenckii by their macro- or micro-morphological features, and were not pathogenic in guinea pigs. Serological and delayed hypersensitivity cross-reactions were found between S. schenckii and the non-S. schenckii species, suggesting antigenic similarity. These results indicate that RFLP analysis of mtDNA is essential for the identification of environmental isolates of S. schenckii.

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Exophiala spinifera, a black yeast, rarely causes systemic infection, and only a very few cases of its infection by the invasion of internal organs or bones have been reported. We examined the ability of E. spinifera to invade bone tissues in vitro. The fungus was inoculated on the surface of murine bones, and then these bones were incubated at 30°C for 2, 4, and 12 weeks on water agar plates and on brain heart infusion agar supplemented with 1 % glucose (BHIA) plates. Histopathological examination demonstrated that the fungus was initially found in the non-calcified parts of the bone tissue, such as the growth plate and articular cartilage. Thereafter, the fungus invaded the calcified parts: cancellous and cortical bones. Our experiments showed that the capability of E. spinifera to invade bone tissue is higher than that of Candida albicans or other black fungi. E, spinifera grew in the mycelial form and C. albicans in the yeast form in these experiments. Our results suggest that E. spinifera may have a high potential to invade bone tissues, and that the mycelial form can invade bone more deeply than the yeast form. Therefore, bone degeneration should/ must be carefully monitored in any systemic infection with E. spinifera.

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