Tuberculosis Control Program TRANSPLANT CASE STUDY Jeanne Soukup, RN, PHN Nurse Manager County of Los Angeles Tuberculosis Control Program

DISCLAIMER The speaker has no commercial or financial conflict of interest The use of fluoroquinolone for TB is not currently FDA approved.

OBJECTIVES Describe the epidemiologic and clinical features of tuberculosis disease in California’s organ transplant population Understand current TB screening practices for organ transplant donors and recipients Become familiar with pathway for reporting transplant-associated TB

INDEX PATIENT/TRANSPLANT RECIPIENT PMH: Rheumatoid Arthritis/ Interstitial Lung Disease w/ combined pulmonary fibrosis and emphysema, pulmonary HTN Hx of + QFT and had been on INH 11/23/17 underwent bilateral lung transplant Donor lung with swab + for rare AFB, MTB PCR –MTB detected

INDEX PATIENT/TRANSPLANT RECIPIENT Date/Time Specimen Smear PCR Culture 11/18/2017 0443pm Resp, lower Trach suction negative 11/23/2017 1048am Resp lower Bronchial wash* 1+ positive MTBc 11/24/2017 118pm BAL positive  11/27/2017 1016 11/29/2017 1630 N/D  12/01/2017 0953 1/11/2018   N/D

INDEX PATIENT/TRANSPLANT RECIPIENT Medications Dosage Start Isoniazid 300 11/25/2017 Rifabutin Ethambutol 1600 Pyrazinamide 2000 B6 25 Additional medications: Azithromycin, Moxifloxacin, Vancomycin, Prednisone 40 mg qday, decreased to 25 mg Tacrolimus 1 mg BID Posaconazole 300mg

INDEX PATIENT/TRANSPLANT RECIPIENT Patient discharged 12/15/17 to home Culture conversion 1/11/18 Isolate pan-sensitive Patient continued treatment with his private provider with public health oversight PZA and EMB discontinued after 8 weeks Patient did well in the outpatient setting with monthly home visits by the PHN completed treatment 5/31/18

DONOR 18 year old Hispanic male, born in the US History of incarceration in both juvenile and adult setting 9/27/17 CXR taken in jail as part of booking process read as normal 11/17/17 Suffered traumatic brain injury, emergently intubated, progressed to brain death Family consented to organ donation

DONOR No documented history of prior test for TB infection Family reportedly denied patient had travel within 6 months 11/18/17 CXR Significant lucency throughout the abdomen suspicious for pneumoperitoneum. No acute lung parenchymal or pleural abnormalities. 11/21/17 Pre-transplant BAL smear negative, no PCR performed; culture later grew MTBc 11/22/17 CXR Mild right lower lobe infiltrate.

DONOR Pre Accident CXR 9/27/2017

NOTIFICATION AND FOLLOW UP 11/27/17 case report received at TBCP 11/28/17 TBCP notified State TB Control Branch Liaison 11/29/17 informed by hospital transplant coordinator appropriate transplant agencies were notified of positive PCR; formal report filed Informed that the transplant agency would notify CDC 12/15/17 contacted by California TB Control Branch regarding BOOTS request for genotyping

Genotyping Isolates were requested to be sent for genotyping Needed to wait for donor isolate to grow but eventually MTBc was identified and isolate was sent Confusion as to the source of the isolates as the 11/23/18 donor specimen was labeled with recipient’s name Confirmed the source of 3 isolates Isolates sent for genotyping

Genotyping Isolates submitted for genotyping 11/21/17 donor pre-harvest BAL isolate 11/23/17 donor post-harvest, pre-transplant BAL 11/24/17 post transplant isolate (recipient) All three isolates had matching Gentype

Molecular Detection of Drug Resistance Request for MDDR testing from another State LAC had not requested MDDR since an initial GeneXpert did not identify Rif resistance This jurisdiction was treating with a quinolone and was awaiting MDDR results MDDR requested and no mutations associated with resistance detected pncA mutation was detected however the effect of this mutation on PZA resistance is unknown

Conventional DST Conventional second line DSTs performed by CDC found isolate sensitive to all drugs tested including PZA

Other Organ Recipients Heart Recipient: Prior to transplant had negative IGRA (QFT-TB-G) Post-transplant had positive IGRA (QFT-TB-G) CXR-negative Started on INH, Rifabutin, EMB and PZA Remained asymptomatic for TB

Other Organ Recipients Right Kidney No pre-transplant test for TB Infection Post-transplant indeterminate QFT-TB-G Multiple urine samples for AFB negative Started on INH, EMB, PZA and Moxi PZA stopped after 2 months with plan to treat for 12 months No concern for active TB

Other Organ Recipients Left Kidney/Pancreas Prior to transplant had negative IGRA (QFT-TB-G) Post transplant negative IGRA (QFT-TB-G) No TB symptoms

Other Organ Recipients Liver No pre-transplant test for TB Infection Post-transplant negative IGRA (QFT-TB-G) Started on Moxifloxacin, INH, EMB, PZA EMB and PZA stopped after 6 weeks Moxifloxacin and INH stopped after 6 months

Take Home Points Notify your State Liaison early in the process as they can provide valuable assistance Clarify which agencies have been notified and the role they will take in the investigation Order PCR, MDDR and expedite genotyping Notify exposed contacts

Questions????