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Usefulness of β-Glucan Assay

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1 Usefulness of β-Glucan Assay
Taminori Obayashi, M.D. Department of Medical Laboratory Higashi Saitama General Hospital, Japan The 3rd Global Fungal Infection Forum, Kampala, March 10-12, 2018

2 Useful in three ways. fungal infections.
1. Assists the physician in decisions in the diagnosis of invasive fungal infections. 2. Allows the physician to know the response to antifungals. 3. Avoids the inappropriate use of antifungals, and has the potential to contain the emergence of resistant strains and to reduce the medical cost.

3 Plasma (1→3)-β-D-glucan (pg/ml)
(1→3)-β-D-glucan concentrations in blood in microbiologically documented infections and unexplained fever Sensitivity 90%; Specificity 100% 1,000 500 Plasma (1→3)-β-D-glucan (pg/ml) 10 G-testを深在性真菌症の早期診断に利用できないか、動物モデルを含む予備検討をもとに、国内10施設で臨床試験を実施、その成績がLancet誌に掲載された。カンジダ症、アスペルギルス症患者の血中BG値は他の疾病に比べ著しく高値を示し、臨床的感度、特異度とも90%を超える画期的な血清診断薬が誕生。国内外の反響は大きく、欧米におけるグローバルな展開の原動力となった。Gテストは販売名ファンギテックGテストとして1995年に製造承認を取得、保険適用された。2003年以降、現在まで、我が国における深在性真菌症の診断と治療ガイドラインで推奨、first-line の診断薬として高い評価を得ている。 1 Healthy adults (n=60) IFI (n=41) Non fungal infections (n=59) FUO (n=102) Obayashi T, Yoshida M et al. Lancet 1995:345:17-20.

4 Sensitivity and Specificity Base on Autopsy-verified Cases Obayashi et al CID 46: 1864-1870, 2008
  Sensitivity: 97%  (n = 40) Specificity: 86% (n = 63)

5 Meta-analyses on the Sensitivity and Specificity of Serum β-Glucan Assay with Respect to Invasive Fungal Infection Sensitivity Specificity Obayashi, et al. (Lancet, 1995) 90% 100% Obayashi, et al.  (CID, 2008) 97% 86% Lu, et al. (Intern Med, 2011) 13 reports 76% 85% Karageorgopoulos, et al. (CID, 2011) 23 reports 77% Onishi, et al. (J Clin Microbiol, 2012) 36 reports 80% 82% Colorimetry Meta-analysis   Colorimetry     +   Turbidimetry

6 Given the sensitivity 80% and specificity 80 %, PPV and NPV are as follows:
Pretest Probability   50%  P.P.V.   80%  N.P.V.

7 77 y.o. Myelodysplastic syndrome
2003 Nov CTM Dec CRP(mg/dl) Glucan(pg/ml) Geni Q-Asp(copy/ml) Plateria Aspergillus 0.5 MCFG Feb Jan 2004 ITCZ Am B 0.6 0.8 Mar MEPM TEIC 1 10 100 1000 4070 1.6 4.3 4.7 7.2 1.5 8.6 2.0 2.1 5.7 - 14.9 This is the clinical course of this patients. Combination of Micafungin and Ampho was effective, and the response of BDG was observed. Because of the side effect of AMPH, namely renal dysfunction, the dose was reduced. In this case, Aspergillus DNA using real-time PCR was negative. GM, using Plateria aspergillus was slightly elevated.

8 Discontinuation of Empirical Antifungal Therapy in ICU Patients Using 1,3-β-D-Glucan Marcio Nucci e.ty al J Antimicrob Chemother 2016, June. Conclusion: Early discontinuation of echinocandin therapy In high risk ICU patients based on consecutive negative BDG tests may be a reasonable strategy, with a great potential to reduce the overuse of echinocandins in ICU patients.

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10 Utility of two glucan test kits with respect to PCP in 253 consecutive HIV-infected patients over 19 months at AIDS Care Center at The National Center for Global Health and Medicine in Tokyo Kobayashi Y, et al. Proceedings of the 30th annual meeting of the Japanese Society for AIDS Research, 2016.         Fungitell Sensitivity (n=34) % Specificity (n=219) % Fungitec 100% 87%   

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12 Thank you for your attention.
The 3dr Global Fungal Infection Forum, April 10-12, 2018, Kampala, Uganda

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15 Correlation of the Glucan Test Kits
(Yoshida K, et al J Infect Chemother, online, Jan 2011) Wako Fungitec Wako Fungitell

16 Correlation of the Glucan Test Kits
(Yoshida K, et al J Infect Chemother, online, Jan 2011) Fungitec Fungitell

17 Contaminated methylprednisolone acetate
米国における神経ブロック、硬膜外ステロイド注射による真菌性髄膜炎アウトブレイクー2012年9月に最初の症例が報告され、2013年10月には全米20州で患者数752名、死亡者64名に達し大きな衝撃を与えている。起因菌はExserohilm Rostratum(エクセロヒルム ロストラタム)という真菌で環境中に広く分布する黒色真菌。CDCの検討によれば、これらの患者の髄液中にはカンジダやアスペルギルスと同様、微量の(1→3)-β-D-グルカンが検出され、培養やPCRに比べ早期診断に有用との成績が示された。βグルカンは血清診断だけでなく、真菌による汚染薬剤の見張り役としても大きな注目を集めている。 補足 酢酸メチルプレドニゾロン  腐葉土や水中など Exserohilum rostratum

18 Gray Scale for β-Glucan Test 30 80 pg/ml


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