Notification of Donor-Derived Tuberculosis — CDC’s Office of Blood, Organ, and Other - PowerPoint Presentation

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Notification of Donor-Derived Tuberculosis — CDC’s Office of Blood, Organ, and Other Tissue Safety

Jefferson Jones, MD MPHMedical Officer

California TB Controller Association ConferenceMarch 12, 2019

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Outline

Organ transplantation in the United StatesRegulation of organ transplantationReporting organ donor-derived diseaseCDC’s Office of Blood, Organ, and Other Tissue Safety (BOOTS)

Reporting organ donor-derived tuberculosisInteraction of BOOTS and partner organizationsCase studies

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Organ supply in United States

Number of deceased donors and transplants increasingWaiting list also increasing>124,000 on waiting list

~Additional 1 person per 10 minutes5,661 on waiting list died during 201820 deaths per day

https://optn.transplant.hrsa.gov/data/view-data-reports/

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Balancing Resources —Differences between blood and organs

SAFETY

AVAILABILITY

For blood, the emphasis is on safety, and availability is less of a concern.

For organs, the emphasis is on availability, and safety is less of a concern.

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National Organ Transplant Act

Passed in 1984Established Organ Procurement and Transplantation Network (OPTN)Directs organ allocationLinks all organizations involved in donation and transplantation

Establishes transplant policiesContracted by HRSA to United Network for Organ Sharing (UNOS)Established Organ Procurement OrganizationsEvaluate donor and recovers organsCoordinate matching organs to recipient

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Regulation of organ transplantation

Health Resources and Services Administration (HRSA) regulates solid organ transplantationOPTN forms policy and collects dataFood and Drug Administration regulates human cells, tissues, and cellular and tissue-based products (e.g., skin, muscle, bone, valves, corneas)

Regulate infectious disease testingHospital regulators (CMS, CMS-approved organization)

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Ad Hoc Disease Transmission Advisory Committee (DTAC)

Part of OPTN patient safety programExamine and classify potential donor-derived transmission of infection or malignancyEducate transplant communityHelp change policy and improve processes

Membership includes CDC, HRSA, transplant centers, transplant infectious disease, laboratory experts, organ procurement organizations

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Role of CDC

CDC not regulatory agencyThrough HRSA agreement member of DTAC, investigates potential infectious disease transmissionsNationally notifiable diseases in donor or recipientMultiple ill recipients

Encephalitis in donor or recipient(s)Unknown syndromeGoal is it determine whether infection was transmitted from donor to recipient(s)~ 50 case investigations annually are referred to CDC

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Reporting to DTAC

OPTN policy that all suspected donor-derived disease should be reportedPassive reporting by transplant centers and OPO’s to OPTN/UNOS (referred to DTAC for review)No standardized criteria for what specific data to reportAny infectious disease or malignancy suspected to be transmitted to an organ recipient from the organ donor (at discretion of clinical team or OPO)

Trigger to report can include recipient illness or in some cases, suspected donor disease (at time of organ recovery or retrospectively)

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Pathogens of special interest- reportable for suspected or confirmed donor or recipient illness

• Acute Flaccid Myelitis

• Amebic encephalitis

•

Anaplasma

or

Ehrlichiosis

• Anthrax

•

Arboviral

Infections

•

Babesiosis / Babesia microti • Brucellosis / Brucella species • California Serogroup Virus Diseases • Chagas / Trypanosoma cruzi (T. cruzi) • Chikungunya Virus Disease

•

Coccidioidomycosis

(

Coccidioides

species) /Valley Fever

• Enterovirus D68, A71

• Fungi/Mold (if growing from sterile site o e.g. blood culture excluding Candida species)

• Hantavirus

• Hepatitis A

• Hepatitis B (active only) *

• Hepatitis C (acute, past or present)2

• Histoplasmosis

• HIV Infection

• Influenza-associated pediatric mortality

• Lymphocytic

choriomeningitis

virus (LCMV)

• Leptospirosis / Leptospira Fever, Crimean-Congo Hemorrhagic Fever

•

Listeriosis

/ Listeria

monocytogenes

• Lyme disease /

Borrelia

species

• Malaria /

Plasmodium

species

• Measles /

Rubeola

• Microsporidia

• Middle East Respiratory Virus(MERS)

• Mumps

• New

WorldArenavirus

• Pandemic

Influenzastrains

• Plague /

Yersinia

pestis

• Poliomyelitis, paralytic

• Poliovirus

infection,nonparalytic

• Q fever /

Coxiella

burnetii

• Rabies, animal or human

• Rubella / German Measles

• Severe Acute Respiratory Syndrome (SARS)- Associated Coronavirus Disease

• Smallpox/

Variola

• Spotted Fever Rickettsiosis

• Strongyloides

•

Tuberculosis (TB)

o e.g. Identified through a culture or DNA probe in the organ donor or other evidence suggesting by active TB

• Tularemia /

Francisella

tularensis

• Varicella / Chickenpox

• Viral Hemorrhagic Fevers • West Nile Virus Disease

• Zika virus

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Determining donor-derived disease

Levels include proven, probable, possible, unlikely, and excludedDepends on presence of disease in single or multiple recipient(s), pretransplant studies, and molecular testingProven: Same disease in donor and recipient and either

Proof of identical disease (e.g., molecular testing) OREvidence of negative disease pretransplant and in multiple recipients

OPTN/UNOS Disease Transmission Advisory Committee

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Disease reporting by transplant centers and OPOs

Variable by centerBronchoscopy, blood, urine culture reported Certain organisms frequent, treated by standard antimicrobial prophylaxis, and no associated with significant morbidity/mortality

Donor infection might be unrecognized Some diseases are rare and infrequently encounteredSome donors have no evidence of infectious cause of deathDifficulty in linking donor and recipient infections

Suspecting donor-derived disease responsibility of transplant centers/OPO

Some infections difficult to recognize and diagnose in recipient

Geographic distance

Timeliness of information

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Variability of Reporting Suspected Donor-derived Diseases by Organ Procurement Organizations

OPTN/UNOS DTAC-Cases reported through 2013.

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DTAC reports 2008–2012

Deceased Donors

N (%)

Donors

recovered

40,223

Donors with PDDTE

763 (

1.9%)

Donors

with proven/probable PDDTE

141

(

0.4%)

Total recipient transplants performed

110,402

Recipients with proven/probable

disease

177

(

0.2%)

Recipient deaths due

to proven/probable d

isease

39

(

0.04%)

PDDTE: Potential donor-disease transmission events

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Suspected Donor-derived disease reports to the DTAC: 2005-2011

Disease

Number of Donor Reports

Number of Recipients with Confirmed Transmission

Number of DDD-Attributable Recipient Deaths

Virus

166

48

16

Bacteria

118

34

9

Fungus

75

31

10

Mycobacteria*

53

10

3

Parasite

35

22

7

Total Infections

447

145

45

DTAC: Disease Transmission Advisory Committee DDD: Donor-derived disease

Data includes cases classified as possible, probable or proven from 2005-2007 as published in AJT, and all reviewed cases from 2008-2011.

*Including TB, non-TB mycobacteria

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Reporting donor-derived TB to DTAC

Laboratory performs TB test and result is positiveLaboratory or transplant center reports result to local health departmentIf transplant center suspects donor-derived disease, it reports to OPTNOPTN refers to DTAC

If CDC Office of Blood Organ and Other Tissue (BOOTS) accepts, it coordinates investigation

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CDC BOOTS TB investigation partners

Public health jurisdictions for donor and each recipientState epidemiologistState TB controllerOrgan Procurement OrganizationTransplant Centers

CDC Division of TB EliminationCDC Infectious Disease Pathology Branch

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CDC BOOTS TB Investigation Points of Contact

Public health agencies for donor and each recipientOrgan Procurement Organization (Donor information)Clinical history

Next-of-kin interviewLaboratory testingTransplant CentersCDC Division of TB EliminationCDC Infectious Disease Pathology Branch

Autopsy results

Tissue specimens

Donor medical records

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CDC BOOTS TB Investigation Points of Contact

Public health agencies for donor and each recipientOrgan Procurement Organization Transplant Centers (recipient information)

Clinical history, symptoms, laboratory results, imagingConfirm public health informedCDC Division of TB EliminationCDC Infectious Disease Pathology Branch

Recipient medical records

Tissues for testing

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CDC BOOTS TB Investigation Points of Contact

To determine if recipient disease is donor-derivedRisk factors for TBCase provided by health department

Organ Procurement OrganizationTransplant CentersCDC Division of TB EliminationCDC Infectious Disease Pathology Branch

If isolate available, confirm isolate sent for genotyping

Public health agencies for donor and each recipient

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CDC BOOTS TB Investigation Points of Contact

Public health agencies for donor and each recipientOrgan Procurement Organization Transplant CentersCDC Division of TB Elimination

Provide genotyping results and interpretationLiaison to state/local health departmentsCDC Infectious Disease Pathology Branch

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CDC BOOTS TB Investigation Points of Contact

Public health agencies for donor and each recipientOrgan Procurement Organization Transplant CentersCDC Division of TB Elimination

CDC Infectious Disease Pathology BranchTesting of available donor and recipient tissues

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Case study

Lung recipient with positive MTB PCR of BAL. Liver and kidney recipient hospitalized for fever of unknown origin.Confirm liver and kidney (and other organs) recipient transplant teams aware of possible exposure. Recipients have symptoms or TB? TB risk factors?

Donor have symptoms or TB? TB risk factors?Genotype of isolates match? Genotype specific to geographic location or population?Any donor tissue available for testing?

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Case study

Lung recipient has positive MTB PCR of BAL. No other recipients with positive tests or symptoms.How many months after transplant?Lung recipient have symptoms or TB? TB risk factors?Lung donor have symptoms or TB? TB risk factors?

Genotype of lung recipient specific to geographic location?Any donor tissue available for testing?

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