今後,注目すべき深在性真菌症―トリコスポロン症の病態と感染制御―  [in Japanese] Pathogenesis of Trichosporon asahii and Strategies for Infectious Control of Disseminated Trichosporonosis  [in Japanese]

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Abstract

<i>Trichosporon</i>属は易感染性宿主に発症する致死的な日和見感染症の起炎真菌の一つとして注目されている.深在性トリコスポロン症を惹起する菌種は最近の分離学的な再考の結果<i>T. asahii, T. mucoides</i>とされた.大分医科大学第二内科において過去20年間に13例の深在性トリコスポロン症を経験した.本症は抗癌化学療法を施行された血液悪性疾患患者において白血球の減少期に発症,重篤な臨床経過をとることが多い.我々は<i>T. asahii</i>と<i>T. mucoides</i>に特異性を認めるPCRプライマーを設定し,トリコスポロン症患者の保存血清を用いてPCR法を検討した結果,患者の血清中から<i>Trichosporon</i>のDNAが高率に,しかも血液培養陽性になる数日から数週前から検出されることを明らかにした.またマウスモデルにおける治療研究ではコロニー刺激因子(G-CSF)とフルコナゾールの併用療法が最も効果的であった.さらに新たなマウスモデルでの検討では,血液培養陰性にもかかわらず血清PCRが陽性を示す潜在的トリコスポロン血症ともいうべき状態が存在することが明らかになった.この時期における早期治療開始が深在性トリコスポロン症の感染制御には重要であると思われる.

Deep-seated trichosporonosis is a lethal opportunistic infection in immunocompromised patients. <i>Trichosporon asahii</i> and <i>T. mucoides</i> are the most common strains of fungi that cause disseminated trichosporonosis. Thirteen patients were diagnosed with disseminated trichosporonosis over a 20 year period in Oita Medical University Hospital. The majority of them had underlying hematologic malignancies, for which they received cytotoxic chemotherapy resulting in neutropenia. For the rapid diagnosis of this condition, we developed a novel nested-PCR assay that detected DNA specific for <i>Trichosporon asahii</i> and <i>Trichosporon mucoides</i> in the serum of patients with the condition. In a retrospective study using these serum samples, the specific DNA fragment was detected a few days to a few weeks earlier than blood culture. To treat this infection, we studied the efficacy of granulocyte colony-stimulating factor (GCS-F) alone and in combination with antifungal agents against disseminated trichosporonosis in neutropenic mice. The results suggested that GCS-F might be a useful immunomodulator against <i>Trichosporon</i> infections in neutropenic mice and the therapeutic outcome improved when used in combination with fluconazole. Furthermore our experimental animal model demonstrated that disseminated trichosporonosis is induced by immunosuppresion in hosts with latent trichosporonemia which was detectable by the nested PCR but not by blood culture. We found that there is a critical period for the progression of disseminated trichosporonosis after entry of fungi into the bloodstream.

Journal

  • Nippon Ishinkin Gakkai Zasshi

    Nippon Ishinkin Gakkai Zasshi 44(3), 181-186, 2003

    The Japanese Society for Medical Mycology

Cited by:  1

Codes

  • NII Article ID (NAID)
    130003672062
  • Text Lang
    JPN
  • Article Type
    Journal Article
  • ISSN
    0916-4804
  • Data Source
    CJPref  J-STAGE 
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