“Prevention and surveillance of donor-derivedinfections in solid organ transplant recipients”

Carlos Lumbreras

Infectious Diseases Unit

Instituto de Investigación

Hospital “12 de Octubre”. Madrid. Spain

London, 31/03/2012

EW01: State-of-the-art management of infections following solid organ transplantation

Fishman J. New Engl J Med 2007; 357:2601-14

Safety Availability

Donor-Derived Infections

Barriers for a Successful Organ Transplantation

70-80s 90s 21st Century

Organ shortage

Infection

Cancer

Surgery

Rejection

Surgery

Cancer

Rejection

Infection

Rejection

Cancer

Surgery

Infection

Organ shortage

Source: OPTN/SRTR 2009 Annual Report

Pruett T. Am J Transplant 2011: 11:1115-16

Donor-Derived Infections

� Epidemiology

� Prevention and management

� Future directions

Types of Donor-Derived Infections in relationship with donor screening

� Expected:

� CMV, Epstein-Barr, Toxo

� Some bacterial infections

� Unexpected:

� HIV, HCV, tuberculosis,

� West-Nile virus ….

FrequentRecognisedProphylaxisMinor damage

RareUnrecognisedNo prophylaxisMorbidity/Mortality

Epidemiology of Donor-Derived Infections: Limitations of Existing Data

� Lack of standardization of the evaluation of donors and recipients

� Difficulties in distinguishing from recipient-derived infections

� Incomplete reporting:

� Lack of standardized reporting systems (Underreporting!!)

� Publication bias: Transmission is more “appealing”

� Many case-reports, some retrospective studies, few prospective

studies.

Len O. Am J Transplant 2008; 8:2420-25

Incidence= 1,7%

Viral infections were not recorded

Epidemiology of Donor-derived infections:OPTN-DTAC 2006-2009

Ison MG. Am J Transplant 2011; 11:1123-30

106

13

10

26

26

31

Confirmedtransmission

29

4

2

8

7

7

Attributablerecipient deaths

201Total infections

21Parasitic

26Mycobacteria

30Fungus

38Bacteria

86Virus

Donor reportsOrganism

Incidence= 1%Mortality= 27%

Ison MG. Am J Transplant 2011; 11:1123-30Ison MG. Am J Transplant 2011; 11:1123-30

Donor-derived Infections

� Epidemiology

� Prevention and management

� Causes of DDI

� Donor screening

� Guidelines

� Future directions

Causes of Unexpected Donor-Derived Infections

� Undiagnosed latent asymptomatic infection in the donor

� Lack of adequate donor screening

� Failure of screening tests

� Misdiagnosis of an active infection

� As the cause of donor´s death

� Complicating donor clinical course (ICU stay, medical devices..)

� Contamination of preservation fluids

Fischer SA. New Engl J Med 2006; 354:2235-50

Toro C. Transplantation 2003; 75:102-104

� Donor: 29-year-old healthy man who died due to a traffic accident

� 3/5 recipients developed HTLV-1-related subacutemyelopathy in the first 2 years after transplantation

� Retrospective epidemiological background: Donor´smother was born in Venezuela and was infected by HTLV-1

� Donor was infected by vertical transmission

Causes of Unexpected Donor-Derived Infections

� Undiagnosed latent asymptomatic infection in the donor

� Lack of adequate donor screening

� Failure of screening tests

� Misdiagnosis of an active infection

� As the cause of donor´s death

� Complicating donor clinical course (ICU stay, medical devices..)

� Contamination of preservation fluids

Ison MG. Am J Transplant 2011; 11:1218-25

Failure of screening tests

� Plasma dilution

� Time constraints

� Diagnostic vs Screening tests

� Viral eclipse phase, “window” period

Failure of Screening Tests

Causes of Unexpected Donor-Derived Infections

� Undiagnosed latent asymptomatic infection in the donor

� Lack of adequate donor screening

� Failure of screening tests

� Misdiagnosis of an active infection

� As the cause of donor´s death

� Complicating donor clinical course (ICU stay, medical devices..)

� Contamination of preservation fluids

Maier T. Clin Infect Dis 2010; 50:1112-19

� Donor: a 26-year-old woman who died due tomeningoencephalitis

� Re-examination of brain stem: Negri bodies

� Background: Dog-bite on a recent trip to India

� Recipients:

� 2 cornea and 1 liver transplant recipients alive and well

� 1 lung and 2 kidney transplant recipients developedrabies and died

� Donor: a 26-year-old woman who died due tomeningoencephalitis

� Re-examination of brain stem: Negri bodies

� Background: Dog-bite on a recent trip to India

� Recipients:

� 2 cornea and 1 liver transplant recipients alive and well

� 1 lung and 2 kidney transplant recipients developedrabies and died

� Donor: a 26-year-old woman who died due tomeningoencephalitis

� Re-examination of brain stem: Negri bodies

� Background: Dog-bite on a recent trip to India

� Recipients:

� 2 cornea and 1 liver transplant recipients alive and well

� 1 lung and 2 kidney transplant recipients developedrabies and died

� Donor: a 26-year-old woman who died due tomeningoencephalitis

� Re-examination of brain stem: Negri bodies

� Background: Dog-bite on a recent trip to India

� Recipients:

� 2 cornea and 1 liver transplant recipients alive and well

� 1 lung and 2 kidney transplant recipients developedrabies and died

Causes of Unexpected Donor-Derived Infections

� Undiagnosed latent asymptomatic infection in the donor

� Lack of adequate donor screening

� Failure of screening tests

� Misdiagnosis of an active infection

� As the cause of donor´s death

� Complicating donor clinical course: BACTERIAL INFECTIONS

� Contamination of preservation fluids

Evidence of the Absence of Transmission: UNRECOGNIZED BACTEREMIA

Lumbreras C. Clin Infect Dis 2001; 33:721-26

Ruiz I. Am J Transplant 2006; 6:178-182

� 52% of infected donors (103/197):

� Graft Colonization 63%

� Preservation fluid Contamination 29%

� Bacteremia 8%

� 8% (15 cases) of donor-to-host transmission

� Donor bacteremia (2 cases)

� Graft Colonization (13 cases)

� 2 patients died (Aspergillus, MRSA)

Prophylaxis:A/C + Aztreonam IV Antibiotics according to isolates

Evidence of the Absence of Transmission: MENINGITIS

Satoi S. Transplantation 2001; 72:1108-13

Donor-Derived Bacterial InfectionsDTAC Database (2006-2009)

� There were 25 recipients with transmitted DDBI

� 22 recipients received grafts from infected donors

and appropriate therapy WAS NOT administered

� 8 recipients died and 2 lost grafts

� 34 recipients received grafts from infected donors

and appropriate therapy WAS administered

� No infection transmission

Blumberg E. 48th IDSA 2010. Vancouver. Abstract 193

Donor-Derived Bacterial Infections

� Bacterial infection can be transmitted by organ

transplantation.

� Appropriate antibiotic therapy (donor and

recipient) greatly reduces the impact of bacterial

infection transmission.

� Early recognition and timely communication of

donor bacterial infection is essential.

Causes of Unexpected Donor-Derived Infections

� Unidiagnosed latent asymptomatic infection in the donor

� Lack of adequate donor screening

� Failure of screening tests

� Misdiagnosis of an active infection

� As the cause of donor´s death

� Complicating donor clinical course (ICU stay, medical devices..)

� Contamination of preservation fluids

Mai H. Transplantation 2006; 82:1163-67

Donor-derived Infections

� Epidemiology

� Prevention and management

� Causes of DDI

� Donor screening

� Guidelines

� Future directions

Data regarding eligibility of organ donors

Grossi P. Am J Transplant 2009; 9 (S4): s19-s26

Standard Screening Tests for Organ Donors

Grossi P. Am J Transplant 2009; 9 (S4): s19-s26

“Donors at Increased Risk of InfectionTransmission”

� Exclusion from transplantation

� Accepted for transplantation

� Additional tests (more sensitive)

� Improve consent process

� Close follow-up after transplantation

Fishman J. Notity Project Brochure. 2011: 63

Donor-derived Infections

� Epidemiology

� Prevention and management

� Causes of DDI

� Donor screening

� Guidelines

� Future directions

� DO NOT USE

� Disseminated infection as the cause of death

� Bacterial sepsis with shock

� Meningitis caused by Listeria and TBC

AST-2009-GuidelinesManagement of Donor-Derived infections

Am J Transplant 2009; 9 (suppl 4)

AST-2009-GuidelinesManagement of Donor-Derived infections

� Any active infection should be treated before Tx (II-3)

� Obtain cultures (II-3)

� Organs known to be infected should not be used (II-3)…..

but others can

� Give antimicrobials if donor is bacteremic (II-2), with a

contaminated perfusate (II-3) or has died due to

bacterial meningitis (III)……but accept the donor

Am J Transplant 2009; 9 (suppl 4)

AST-2009-GuidelinesManagement of Donor-derived Infections

� Lung Transplantation: Obtain cultures from graft and

give antibiotics based on isolates (III)

� Donor with active TBC should be excluded (II-2)

� Isoniazid warrants consideration for PPD- recipients

of PPD + donors (III)

Am J Transplant 2009; 9 (suppl 4)

AST-2009-GuidelinesManagement of Donor-derived infections

IIIMonitoring recipientsLeishmania (sero +)

IIIProphylaxis in the recipientsHistoplasma

II-2 ExcludeHIV, HTLV-1, Rabies, WNV, Chikunguya…

II-2Use only in HCV + recipientHCV

II-2ExcludeHBV (HbsAg +)

IIIProphylaxis in the recipientsCoccidiodes

II-3Prophylaxis or treatment in recipientsPlasmodium

IIIExclude heart transplantationChagas

II-2Prophylaxis in seronegative heart TxToxoplasma

II-3Accept and treat recipientSyphilis (RPR +)

II-2Monitoring in EBV - recipientEBV

GradeInterventionOrganism

Am J Transplant 2009; 9 (suppl 4)

Donor-derived Infections

� Epidemiology and causes

� Prevention and management

� Future directions

Future Directions

� Improve donor screening

� Reliable and FAST assays

� A multidisciplinary approach (include a TID doctor!!!)

� Create reliable systems to report and operate DDI:

� Unexpected to expected donor-derived infections

Leggieri N. Curr Opin Infect Dis 2010: 23:311-319

Improving Donor Screening

Creation of Systems to Report and Operate DDI

Courtesy of Michael Ison

Directive 2010/45/EU (“Transplantation Law”).European Parliament and EU Council. July 2010

� Article 11:

� Member States shall ensure there is a reportingsystem…..concerning serious adverseevents…..connected to transplantation

� Member States shall ensure there is an operatingprocedure…..for the management of serious adverseevents….

� Article 31:

� Member States shall bring into force the laws….tocomply with this directive by 27/12/2012….

Conclusions

� Unexpected donor-derived infections are a rare but serious

complication of organ transplantation

� Timely recognition is, often, critical to reduce adverse

events related to infection transmission (unexpected to

expected)

� Improved screening platforms are needed

� Reliable systems to report and manage transmission events

during transplantation should be mandatory