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“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
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Fishman J. New Engl J Med 2007; 357:2601-14
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Safety Availability
Donor-Derived Infections
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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
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Source: OPTN/SRTR 2009 Annual Report
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Pruett T. Am J Transplant 2011: 11:1115-16
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Donor-Derived Infections
� Epidemiology
� Prevention and management
� Future directions
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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
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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.
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Len O. Am J Transplant 2008; 8:2420-25
Incidence= 1,7%
Viral infections were not recorded
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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
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Donor-derived Infections
� Epidemiology
� Prevention and management
� Causes of DDI
� Donor screening
� Guidelines
� Future directions
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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
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Fischer SA. New Engl J Med 2006; 354:2235-50
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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
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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
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Ison MG. Am J Transplant 2011; 11:1218-25
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Failure of screening tests
� Plasma dilution
� Time constraints
� Diagnostic vs Screening tests
� Viral eclipse phase, “window” period
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Failure of Screening Tests
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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
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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
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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
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Evidence of the Absence of Transmission: UNRECOGNIZED BACTEREMIA
Lumbreras C. Clin Infect Dis 2001; 33:721-26
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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
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Evidence of the Absence of Transmission: MENINGITIS
Satoi S. Transplantation 2001; 72:1108-13
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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
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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.
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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
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Mai H. Transplantation 2006; 82:1163-67
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Donor-derived Infections
� Epidemiology
� Prevention and management
� Causes of DDI
� Donor screening
� Guidelines
� Future directions
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Data regarding eligibility of organ donors
Grossi P. Am J Transplant 2009; 9 (S4): s19-s26
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Standard Screening Tests for Organ Donors
Grossi P. Am J Transplant 2009; 9 (S4): s19-s26
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“Donors at Increased Risk of InfectionTransmission”
� Exclusion from transplantation
� Accepted for transplantation
� Additional tests (more sensitive)
� Improve consent process
� Close follow-up after transplantation
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Fishman J. Notity Project Brochure. 2011: 63
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Donor-derived Infections
� Epidemiology
� Prevention and management
� Causes of DDI
� Donor screening
� Guidelines
� Future directions
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� 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)
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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)
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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)
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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)
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Donor-derived Infections
� Epidemiology and causes
� Prevention and management
� Future directions
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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
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Leggieri N. Curr Opin Infect Dis 2010: 23:311-319
Improving Donor Screening
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Creation of Systems to Report and Operate DDI
Courtesy of Michael Ison
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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….
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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