1. Exciting Cases in Transplant Infectious Diseases Wanessa Clemente Digestive Transplant Service University of Minas Gerais - Brazil

2. Outline Case Presentation Question Literature information

3. Case Presentation Time of transplantation 31 yo female, DM since age 17 y Hemodialysis (9 mo before transplantation) Kidney-pancreas transplant (Enteric drainage) IS regimen: Steroid + FK + MMF Hematoma (reopperated), Urinary fistula + UTI (clinical approach) E. coli MS Length of stay: 1 month Prophylaxis: – GCV, trimethoprim-sulfamethoxazole, ivermectin +albendazole

4. ~ 18 months after transplantation: Persistent diarrhea + vomiting of 2 weeks duration. Sore throat: 4 weeks before hospital admission. Distended and diffused painful abdomen. No cutaneous lesions. During hospitalization: Fever  Cefepime Admission Laboratory Findings: Case Presentation CMV antigenemia Negative Clostridium toxinNegative Acid-staining test (Cryptosporidium and Isospora) Negative Blood culturesNegative Urine culture>100,000 UFC K pneumoniae StoolNegative, including Baermann-Moraes method Blood examHemoglobin 11.8g/dL; WBC 6630/mm 3 Eosinophilia 21%/1390/mm 3 Platelets 376,000/ mm 3

5. Upper intestinal obstruction

6. Esophagogastroduodenoscopy Normal esophagus, mild pangastritis, nonspecific duodenitis. Diffusely ulcerated duodenal mucosa. Duodenal wall thickening with obstruction of the lumen.

7. Abdominal CT Pancreas and kidney grafts with usual appearance. Absence of lymphadenomegaly. Marked thickening of theduodenum and jejunum wall with reduction of the lumen. Significant dilation of the stomach.

8. Biopsy

9. Chest radiograph

10. Follow-up Immunosuppresion was reduced Ivermectin (200 μg/kg/d for 30 days) Control EGD (after 2 wk): GI CMV  Gancyclovir Hospital discharge: Day 31

11. On the other hand... TID, Vilela 2008 Fatal case of SS hyperinfection in 43 yo LT recipient. Two weeks after IS treatment for graft rejection. Cause of death: alveolar hemorrhage + secondary sepsis

12. Questions Q1: What is the Ss epidemiology? Q2: When to suspect? Q3: Should prophylaxis or empiric treatment be done? Q4: Which treatment regimen is better?

13. Epidemiological aspects Strongyloidiasis is a worldwide infection, but unusually reported in SOT recipients Schwartz & Mawhorter AJT 2013 SS hyperinfection syndrome is more frequent within 3 mo of transplantation Classically follows corticosteroid therapy Fardet Journal of Infection 2007 Diagnostic methods lacks in sensitivity and specificity Buonfrate CMI 2015 Mortality can approach 70% DD Ss infection is rare but recognized transplant complication Le AJT 2014

14. Geographic Distribution Plos 2013

15. Which drug should be chosen? Preferred: Ivermectin Alternative: Thiabendazole/ Albendazole (Second-line drugs) Consider intermittent treatment in high-risk patients Which regimen? Daily oral ivermectin 5 - 7d  30 d Veterinary preparations Consider adjuvant ATM therapy Fox Curr Opin Infect Dis 2006

16. Patients who have lived in an endemic region should be screened before procedure/ IS (stool examination and eosinophilia) or treated without screening (e.g. false negative testing) Antibody testing may be useful in non-endemic setting DDI has been documented, mainly intestinal and pancreatic transplant recipient Considerations Ahead of print Transplantation. Wright et al