A 50-year-old man with a history of end-stage renal disease and diabetes underwent a kidney transplant. He later developed a nonproductive cough. Additional testing showed a new lung lesion and biopsy revealed Aspergillus fungus. Invasive pulmonary aspergillosis was diagnosed. Treatment guidelines recommend the antifungal drug voriconazole as the primary treatment, with alternative options including other antifungals depending on the patient's condition and test results.

1. Aspergillosis Diagnosis and Treatment

2. Case A 50 year old WM with ESRD secondary to diabetes on HD who underwent a cadaveric renal transplant. 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 P. aeruginosa. The catheter was removed and he received a 2-week course of Meropenemand Ciprofloxacin then discharged.

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. 2 months post-transplant he was readmitted to the hospital for possible rejection.

4. ROS was negative for cough chest pain, hemoptysis, SOB, fever and night sweats. PE revealed that the patient was afebrile. Clear lungs. Heart sounds normal. Abdomen non tender. CBC: WBC 5.0, Hb10.5, Plt49 Serum Cr 3.4 BUN 70 What additional information or testing would you require?

5. Additional testing Serology/Antigen EIA CXR High res-CT Bronchoscopy Micro Biopsy NegAspergillusAb Galactomannan? A new 3 cm round lesion in the Left lower Lung 3 well-defined round lesions in LLL Washing Cx (+) Biopsy slides

6. Fig:1 Aspergilloma found at post-mortem in the lung of a child with leukemia.

7. Fig 2: Aspergilloma found at post-mortem in the lung of a child with leukemia. Note fungus ball occupying cavity.

8. Aspergillosis Aspergillosis is a spectrum of diseases in humans and animals caused by members of the genus Aspergillus. These include Mycotoxicosisdue to ingestion of contaminated foods Allergy and sequelae to the presence of conidia or transient growth of the organism in body orifices Colonization without extension in preformed cavities and debilitated tissues Invasive, inflammatory, granulomatous, necrotizing disease of lungs, and other organs Systemic and fatal disseminated disease.

9. The type of disease and severity depends upon the physiologic state of the host and the species of Aspergillus involved. Distribution: World-wide. Etiological Agents: Aspergillusfumigatus, A. flavus, A. niger, A. nidulans and A. terreus.

10. Invasive Aspergillosis DX Histopathology acute angle branching septatednonpigmented hyphae, measuring 2-4 microns in width culture yielding Aspergillus sp.

11. Fig 3: Grocott’smethenamine silver (GMS) stained tissue section of lung showing fungal balls of hyphae of Aspergillusfumigatus.

12. Aspergillus Fig 4: Grocott’smethenamine silver (GMS) stained tissue sections showing Aspergillusfumigatus in lung tissue, note conidial heads forming in an alveolus.

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.

14. Fig 6: Aspergillusterreus on Czapekdox agar showing typical suede-like cinnamon-buff to sand brown colonies. Reverse yellow to deep dirty brown.

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.

16. Treatment of Invasive Aspergillosis IDSA Guidelines www.idsociety.org CID 2008:46 (Feb) Primary agent: Voriconazole Alternative agents: L-Amphotericin , Posaconazole, Micafungin, Caspofungin, Itraconazole

17. Fig 8: Antifungal susceptibility disk test showing the in vitro activity of Voriconazole against Aspergillusfumigatus with Candida krusei as a control.