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  1. 1. Aspergillosis<br />Diagnosis and Treatment<br />
  2. 2. Case<br />A 50 year old WM with ESRD secondary to diabetes on HD who<br />underwent a cadaveric renal transplant. <br />Immunosuppressive regimen consisted of prednisone, Mycophenolatemofetil, and cyclosporine. Patient developed thrombocytopenia and was taken off the Mycophenolatemofetil. Developed catheter-related sepsis and bacteremia due to <br />P. aeruginosa. <br />The catheter was removed and he received a 2-week course of <br />Meropenemand Ciprofloxacin then discharged.<br />
  3. 3. 1 month posttransplant he developed a nonproductive cough. He was maintained on prednisone and cyclosporine and was given Ganciclovir for CMV prophylaxis. He was again started on Mycophenolatemofetil. <br />2 months post-transplant he was readmitted to the hospital for possible rejection. <br />
  4. 4. ROS was negative for cough chest pain, hemoptysis, <br />SOB, fever and night sweats. <br />PE revealed that the patient was afebrile. Clear lungs. Heart sounds normal.<br />Abdomen non tender.<br />CBC: WBC 5.0, Hb10.5, Plt49<br />Serum Cr 3.4 BUN 70<br />What additional information or testing would you require?<br />
  5. 5. Additional testing<br />Serology/Antigen<br />EIA <br />CXR<br />High res-CT<br />Bronchoscopy<br />Micro<br />Biopsy<br />NegAspergillusAb<br />Galactomannan?<br />A new 3 cm round lesion in the Left lower Lung<br />3 well-defined round lesions in LLL<br />Washing Cx (+)<br />Biopsy slides<br />
  6. 6. Fig:1 Aspergilloma found at post-mortem in the lung of a child with leukemia.<br />
  7. 7. Fig 2: Aspergilloma found at post-mortem in the lung of a child with leukemia. Note fungus ball occupying cavity.<br />
  8. 8. Aspergillosis<br />Aspergillosis is a spectrum of diseases in humans and animals caused by members of the genus Aspergillus. <br />These include <br />Mycotoxicosisdue to ingestion of contaminated foods <br />Allergy and sequelae to the presence of conidia or transient growth of the organism in body orifices<br />Colonization without extension in preformed cavities and debilitated tissues<br />Invasive, inflammatory, granulomatous, necrotizing disease of lungs, and other organs <br />Systemic and fatal disseminated disease. <br />
  9. 9. The type of disease and severity depends upon the physiologic state of the host and the species of Aspergillus involved.<br />Distribution: World-wide.<br />Etiological Agents: <br />Aspergillusfumigatus, A. flavus, A. niger, A. nidulans and A. terreus. <br />
  10. 10. Invasive Aspergillosis DX<br />Histopathology<br />acute angle branching<br />septatednonpigmented hyphae, measuring 2-4 microns in width<br />culture yielding Aspergillus sp.<br />
  11. 11. Fig 3: Grocott’smethenamine silver (GMS) stained tissue section of lung showing fungal balls of hyphae of Aspergillusfumigatus.<br />
  12. 12. Aspergillus<br />Fig 4: Grocott’smethenamine silver (GMS) stained tissue sections showing Aspergillusfumigatus in lung tissue, note conidial heads forming in an alveolus. <br />
  13. 13. Fig 5: Microscopic morphology of Aspergillusniger showing large, globose, dark brown conidial heads, which become radiate, tending to split into several loose columns with age. Conidiophores are smooth-walled, hyaline or turning dark towards the vesicle. Conidial heads are biseriate with the phialides borne on brown, often septatemetulae. Conidia are globose to subglobose, dark brown to black and rough-walled.<br />
  14. 14. Fig 6: Aspergillusterreus on Czapekdox agar showing typical suede-like cinnamon-buff to sand brown colonies. Reverse yellow to deep dirty brown.<br />
  15. 15. Fig 7: Conidial head of Aspergillusterreus. Conidial heads are compact, columnar and biseriate. Conidiophores are hyaline and smooth-walled. Conidia are globose to ellipsoidal, hyaline to slightly yellow and smooth-walled.<br />
  16. 16. Treatment of Invasive Aspergillosis<br />IDSA Guidelines<br /><br />CID 2008:46 (Feb) <br />Primary agent: Voriconazole<br />Alternative agents: L-Amphotericin , Posaconazole, Micafungin, Caspofungin, Itraconazole<br />
  17. 17. Fig 8: Antifungal susceptibility disk test showing the in vitro activity of Voriconazole against Aspergillusfumigatus with Candida krusei as a control.<br />