TRANSPLANT ID: A PRACTICAL APPROACH - PowerPoint PPT Presentation

Loading...

PPT – TRANSPLANT ID: A PRACTICAL APPROACH PowerPoint presentation | free to download - id: 3b8a0d-ZmJjO



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

TRANSPLANT ID: A PRACTICAL APPROACH

Description:

TRANSPLANT ID: A PRACTICAL APPROACH Atul Humar Transplant Infectious Diseases University of Alberta SUMMARY Infectious complications continually evolve in transplant ... – PowerPoint PPT presentation

Number of Views:277
Avg rating:3.0/5.0
Slides: 71
Provided by: transplan1
Learn more at: http://transplants.med.ualberta.ca
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: TRANSPLANT ID: A PRACTICAL APPROACH


1
TRANSPLANT ID A PRACTICAL APPROACH
  • Atul Humar
  • Transplant Infectious Diseases
  • University of Alberta

2
WHATS NEW?
  • Changing immunosuppression
  • Widespread prophylaxis
  • Emerging infections
  • Evolving infections
  • Donor Derived infection
  • Molecular diagnostics
  • Host-pathogen interactions

3
INFECTION BASIC PRINCIPLES
  • Inflammatory response attenuated by immunosup.
  • may abolish typical signs/symptoms
  • decreased sensitivity of serological,
    radiological tests
  • Efffects of established infection may be
    devastating
  • Treatment may have more toxicities
  • Rifampin - decrease CNI
  • Erythromycin, azoles increase CNI
  • Synergistic nephrotoxicity - aminoglycosides,
    AmB, high dose septra,

4
INFECTION BASIC PRINCIPLES
  • Determinants of infection
  • Technical issues with transplantation
  • Vascular anastomoses leak, thrrombosis,
    stricture
  • Non-vascular anastomoses- leak, stricture
  • Net state of immunosuppression
  • Epidemiologic exposures

5
(No Transcript)
6
(No Transcript)
7
(No Transcript)
8
(No Transcript)
9
INFECTIONS IN TRANSPLANTATION
  • Major determinants of the risk of infection

The net state of Immunosuppression
Epidemiological exposures
10
NET STATE OF IMMUNOSUPPRESSION
  • Immunosuppressive therapy dose, duration,
    temporal sequence - area under the curve
  • Induction therapy especially ALG, Alemtuzimab
  • Mucocutaneous barrier integrity intubation,
    drains, catheters, central lines
  • Neutropenia, lymphopenia
  • Viral co-infection CMV, HCV, HIV

11
NET STATE OF IMMUNOSUPPRESSIONCAN WE MEASURE?
  • Non-specific immunoassays
  • Intracellular ATP, biomarkers, proteomic-based
    technologies
  • Pathogen-specific immunity
  • ICS
  • IFN-g assays,
  • HLA tetramers
  • Elispot

12
EPIDEMIOLOGICAL EXPOSURES
  • Overlapping but distinct exposures
  • Community CAP, CA-MRSA, Endemic mycosis,
    respiratory viruses, enteric viruses
  • Nosocomial MRSA, aspergillus, MDR gram
    negatives, VRE
  • Donor latent or active infection
  • Recipient latent or active infection

13
AN EXAMPLE OF EPIDEMIOLOGIC EXPOSURE
  • 61 y.o. male heart transplant 1991
  • Stable immunosuppression x years
  • cylosporin, prednisone
  • 3 week history of progressive leg cellulitis,
    fever unresponsive to antibiotics
  • Intermittent confusion

14
(No Transcript)
15
(No Transcript)
16
What was the exposure?
  • This patient generally will not get an OI unless
    some excess exposure
  • Exposure
  • Delivery of topsoil to his home
  • Legs knee deep in topsoil while he was spreading
    it

17
(No Transcript)
18
Tx ID TIMELINE 0-1 MONTH
  • Post-op Infections
  • Technical / anastomotic related infection
  • nosocomial pneumonia, wound, etc
  • MRSA, VRE, Candida, C. difficile
  • Donor Derived Infection
  • These are rare but diagnosis can be missed
  • Recipient derived infection
  • Ongoing pneumonia
  • Colonization to infection
  • Most OI absent exceptions include certain
    fungal infections, HSV, occasional others

19
(No Transcript)
20
(No Transcript)
21
Tx ID TIMELINE 1-6 MONTH
  • Account for CMV, PCP prophylaxis
  • BK viruria viremia. BKVAN
  • CMV D/R- month 3-6 augmented
    immunosuppression
  • EBV viremia D/R-
  • HCV recurrence (OLTx)
  • C. difficile, Fungal, mycobacterial, respiratory
    virus
  • VZV post-prophylaxis

22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
BRONCHOSCOPY TESTS
  • Gram stain and culture
  • Fungal stain and culture
  • AFB smear and culture
  • Legionella DFA, culture
  • CMV shell vial culture
  • Respiratory viruses culture DFA for HSV,
    Influenza, parainfluenza, RSV, adenovirus
  • stain for PCP
  • Cytology
  • Molecular testing replacing traditional testing

26
(No Transcript)
27
Tx ID TIMELINE gt6 MONTH
  • Depends on outcome good vs. bad graft function.
    Tapering immunosuppression vs. ongoing high level
    problems with rejection
  • Some patients at ongoing risk of OI despite
    minimal exposures
  • Others only get OI if significant exposure

28
Tx ID TIMELINE gt6 MONTH
  • Late viral infections
  • CMV (colitis, recurrence), BKVAN, PTLD, HCV
  • Community acquired infection
  • Respiratory virus, CA-MRSA, atypical mould
    infection,
  • Other OI based on exposures

29
(No Transcript)
30
(No Transcript)
31
EMERGING TRENDS IN INFECTION
EMERGING TRENDS
CHANGING OLD INFECTIONS
NOVEL INFECTIONS
Respiratory viruses
Bacteria Fungus Viruses
Vector borne viruses
Blood/body fluid transmitted
Enteric transmitted
32
More potent immunosuppression
Widespread prophylaxis
KNOWN PATHOGEN
  • Modified presentation
  • Symptoms
  • Timing
  • Spectrum

Drug resistance
33
MOULD INFECTIONS in ORGAN TRANSPLANT RECIPIENTS
Hyalohyphomycetes
Husain et al. Clin Infect Dis 2003
34
Gan, valgan, prophylaxis
Potent Immunosuppression
CMV
  • Modified presentation
  • Symptoms
  • Timing

Drug resistance
35
(No Transcript)
36
TIME to CMV DISEASE UP to 6 MONTHS (n364)
100
90
364 D/R- SOT patients
80
70
  • May present with atypical symptoms (no fever
    malaise, fatigue) diagnosis can be missed
  • Patient may not be followed by primary center or
    may not be followed as closely

60
50
Patients with no CMV Disease
40
30
20
Prophylaxis period
10
0
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
Time (days)
Paya et al. Am J Transplant 2004 4 611
37
CMV RESISTANCE
  • Overall resistance rates low in most transplant
    populations
  • In certain subpopulations, resistance rates of up
    to 10 described in some studies
  • Especially lung transplant
  • Bharade et al. JHLT 2002, Limaye et al. JID 2002
  • D/R- lung recipients at highest risk
  • The two alternative therapies are
  • Foscarnet and cidofovir
  • Both have significant toxicities

38
NOVEL INFECTIONS TRANSPLANTATION
Emerging Infections
New Pathogen New disease
Old Pathogens New disease (in transplant pts)
Old Pathogens Previouslyunrecognized
H1N1 influenza Xenotransplantion
BKVAN West Nile virus
HHV-6/7 adenovirus
39
DWI
ADC
HHV-6 encephalitis
Viral load 1.2 million copies/ml
HHV-6 pneumonitis
40
Clinical reactivation
Subclinical reactivation
41
NEW PATHOGENS and the Transplant Patient
  • 1. More likely to develop symptomatic disease if
    exposed to a pathogen
  • 2. Once exposed, more rapidly progressive lethal
    disease

SENTINEL CHICKEN CONCEPT
42
NEW PATHOGENS and the Transplant Patient
  • 3. Higher viral burden longer viral shedding
    with increased amounts of virus
  • Increased infectivity
  • Super-spreaders
  • 4. Lack of response to therapeutic measures
  • Standard antiviral may have less efficacy
  • Decreased immunogenicity of vaccines

43
EMERGING INFECTIONS AND TRANSPLANT
  • Transplant patients can potentially acquire a new
    pathogen in 3 ways

Transfusion- transmitted
Organ- transmitted
Community- acquired
44
WNV and TRANSPLANTATION
  • Numerous case reports/series of TTWNV
  • High mortality ( 30)
  • Two instances of organ donor transmission of WNV
    (2003, 2005)
  • Most common is community acquired WNV
  • Immunocompetent severe disease in 1140

45
816 TRANSPLANT PATIENTS
WNV IgG/IgM
Seroprevalence study (0.25 95CI 0.03-0.88)
Estimated risk of severe neuroinvasive
disease 40 (95CI 16-80)
Kumar D et al. Am J Transplant 2004 41883
46
Kumar/Humar Am J Transplant 2005
47
Pandemic (Novel) H1N1 virus
  • AST ID COP 25 center study of epidemiology of
    H1N1 in transplantation (Kumar et al. ATC 2010)

48
Figure 1 Time of onset of symptoms during the
pandemic.
49
Table 1 Demographics of solid organ transplant
recipients with Influenza A
BMI Body Mass Index
50
Table 2 Clinical presentation and complications
of Influenza A in adult and pediatric solid organ
transplant recipients.
51
Table 3 An analysis of factors associated with
admission to the intensive care unit (ICU)
52
DONOR DERIVED INFECTION
PARASITIC Malaria Chagas disease Strongyloides Sch
istosomiasis Flukes
VIRAL Hepatitis A, B, C, D HIV HHV 1 -
8 Rabies West Nile Virus LCMV
PATHOGENS
FUNGAL Candida Cryptocococcus Coccidioides Histopl
asma Aspergillus
BACTERIAL Gram positive Gram negative Mycobacteria
l Spirochetes
PRION vCJD
53
DDI Frequency - USA (CDC)
  • Organs
  • 25 cases from 2002-2007
  • 20,000 transplants/yr
  • Tissues
  • 20 cases from 1998-2006
  • 1 million transplants/yr
  • RARE EVENTS!
  • 75 mortality SOT
  • How many not diagnosed?

54
HOW DO YOU RECOGNIZE UNUSUAL DONOR TRANSMITTED
INFECTION?
  • These infections often (but not always) occur
    early post-transplant
  • They are often clinically very aggressive and may
    be difficult to diagnose
  • Rare or unexpected infection, unusual
    presentation, lack of seroconversion
  • Infections in multiple recipients of a common
    donor is often the best (or only) clue

55
Standard Donor Testing
  • Step 1. Screening by history
  • Step 2. Screening by laboratory results
  • HIV antibody
  • Hepatitis B surface antibody and antigen, HepB
    core Ab
  • Hepatitis C antibody
  • RPR (syphilis)
  • CMV antibody
  • EBV antibody
  • HTLV-I and II
  • Toxoplasma antibody
  • Cultures
  • Step 3. Screening by intra-operative exam

56
ENCEPHALITIS
  • Four recipients of kidneys, liver, and of an
    illiac artery graft died of encephalitis of
    unknown cause.
  • Onset within 21-27 days of surgery
  • Donor presented 4 days prior (fever, mental
    status changes)
  • Cocaine-induced subarachnoid hemorrhage
  • In retrospect had a bat bite earlier

Rabies virus inclusions
Srinivasan et al. NEJM 2005
57
YET ANOTHER UNUSUAL DONOR TRANSMITTED PATHOGEN
  • In 2003, 2005, 2-clusters of unusual infections
  • 8 patients (2 donors) mental status changes,
    fever, rash, graft dysfunction, multi-organ
    failure (7/8 died 9-76 days)
  • In 2005 cluster, donor had pet hamster
  • IHC staining, RT-PCR, ELISA and culture
  • Lymphocytic Choriomeningitis (LCMV).

Fischer et al. NEJM 2006
58
Notable Organ Transplant-Transmitted Infections
Published Literature
  • HIV, 1985
  • Hepatitis C, 2000
  • Chagas Disease (T. cruzi), 2001
  • West Nile Virus (WNV), GA 2002
  • Lymphocytic Choriomeningitis Virus (LCMV),
    WI 2003 and MA/RI 2005
  • Rabies, 2004
  • WNV, NY/PA 2005
  • Chagas, 2006
  • HIV/HCV 2007
  • Arenavirus 2007

59
Additional Donor Testing?
  • NAT testing
  • HIV - reduction in window period from 21 to 7
    days
  • HCV - reduction in window period - 70 to 7 days
  • HBV
  • West Nile Virus
  • Other
  • TB, Fungal, Chagas/T.cruzi, Strongyloides

60
FUNGAL INFECTIONS
  • With improved strategies against CMV, fungal
    infection have become the most important cause of
    infectious mortality
  • Candida and Aspergillus account for 80 of
    invasive fungal infections
  • Other 20 cryptococcus, other moulds, and endemic
    mycosis

61
Incidence of Invasive fungal infection
  • Renal 0-14
  • Heart 2-21
  • Liver 4-42
  • Lung 15-35
  • Intestinal 40-59
  • Pancreas 18-38

62
ASPERGILLUS IN LUNG TRANSPLANT
  • Several unique features
  • Direct communication of the allograft with the
    local environment
  • Aberrant immune response in the allograft
    (including mucociliary clearance)
  • Bronchial blood supply to the anastamosis is
    disrupted during surgery
  • The transiently devascularized anastamotic site
    is susceptible to ischemia, necrosis, infection
    with aspergillus

63
(No Transcript)
64
(No Transcript)
65
(No Transcript)
66
(No Transcript)
67
SUMMARY
  • Infectious complications continually evolve in
    transplant patients
  • Changes in well-known infections occur due to
    novel immunosuppression and antimicrobial
    prophylaxis. (modified symptoms and timing of
    infection and drug resistance).
  • Transplant patients are also at risk of novel or
    emerging pathogens akin to the sentinel chicken
    concept community, blood, donor acquired.

68
PREVENTION OF INFECTION
  • PCP, UTI, others
  • CMV disease
  • Toxoplasmosis
  • Other herpes viruses
  • Candida
  • Aspergillus
  • Strongyloides
  • Tuberculosis
  • Endemic mycosis
  • Septra
  • Multiple strategies
  • Septra, pyrimethamine
  • acyclovir
  • Azoles, echinocandins
  • Voriconazole, candins, others
  • Albendazole
  • INH, ?others
  • Vori, others

69
Vaccines
No live vaccines post-tx (MMR, Varivax,
Zostavax, YF, Intranasal flu)
70
SUMMARY
  • Therapeutic prescription for transplantation has
    2 components
  • Immunosuppressive component - to prevent and
    treat rejection
  • Antimicrobial component - to make the first
    component safe
  • The two major barriers to successful
    transplantation, infection rejection, are
    closely related
  • progress in one will benefit the other
About PowerShow.com