17. Allograft-Transmissible Infections Flashcards
Where do allografts rank in the most often transplanted tissue?
Musculoskeletal grafts are second behind blood
What are the three main characteristics of allograft infectious agents?
1) Asymptomatic infection in donor
2) Present in allograft
3) Can survive during subsequent storage/processing of the allograft
What microbes are transmitted via allograft?
Bacteria
Viruses
Protozoa
Prions
What factors increase risk to infection?
Increasing travel
Climate change - vectorborne diseases have widened distribution
What viruses can be transmitted via allografts?
HIV 1 and 2 HTLV (Human T-lymphotropic Viurs) Hep, B C and D Human cytomegalovirus CMV Herpes 6, 7 and 8 karposis sarcoma Human erythrovirus Herpes simplex virus - HSV1 and 2 Varicella Zoster Virus EBV - Epstein Barr virus Human Papilloma Virus West Nile Virus Rabies Virus Lymphocytic choriomeningitis virus
What are some examples of bacteria transmitted via allografts?
Primarily Gram negative or enterococcus
- Treponema Pallidum (Syphilis)
- Clostridium sordelli (Sepsis)
- Mycobacterium Sp (Tuberculosis)
- Balamuthia mandrillaris (Balamuthia - severe encephalitis)
What are some protozoa transmitted by allografts?
Plasmodium sp. malaria Toxoplasma gondi (toxoplasmosis) Trypanasoma cruzi (Chagas disease) Babesia microti (Babesiosis)
What are some prions transmitted via allografts?
Spongiform Encephalopathies - TSE (Creutzfeldt Jacob Disease - CJD and variant
What are the two main modes of transmission for allograft infection?
1) Donor was infected - acute or latent
2) Allograft is contaminated
- Cadaveric, gut organisms etc
- Exogenous - during allograft processing
What is an example of an acute donor infection?
Acute Hep C infection
Infected donor with no anti-HCV infected 8/40 individuals
What is an example of a latent or chronic donor infection?
Latent Creutfeltz jakob disease
- Fuarrrrk can lay dormant for up to 40 years
Has occured in corneal dura and pericardium transplants
What is an example of in situ allograft contamination?
1) Clostridium sordelli sepsis from cadaveric allograft
- Microorganisms pass through wall and populate
- Low oxygen selects anaerobes
- Nutrients low, clostridia sporulates
- Spores can evade detection/sterilisation
2) Exogenous contamination
- Staphlococcus sp most frequently encountered in post op infections
How can transmission be prevented?
1) Effective donor screening
2) Optimize microbial inactivation/reduction during retrieval and processing
3) Undertake comprehensive surveillance for known and emerging agents
How can donor screening be optimized?
Comprehensive screening
- Infectious diseases
- Minimum deferral period after cessation of symptoms
- Deferrals for high risk behaviour
Physical examinationWhat are donors tested for?
Syphilis Hep B (DNA cadaveric only) Hep C (RNA cadaveric donors only) HIV (HIV RNA cadaveric only) HTLV
Repeat testing performed on donors 6 months post operatively
How can contamination be reduced?
1) Aseptic technique at recovery
2) Bacteriological culture of tissue swabs and samples
3) Cadaveric donation time constraints
4) Allograft ‘bioburden’ reduction - gamma irradiation
- Soft tissue = 15kGy
- Bone = 25KG
How can one practice Aseptic technique at recovery?
Retrieval
- Operating theatres
Processing
- clean room
Equipment and surfaces cleaned
Compliance audited by the Therapeutic Goods Administration (TGA)
How can one effectively culture tissue swabs and samples?
Living Donors
- Milled bone - post saline wash sent for culture
Cadaveric Donors
- Single cadaveric donor material processed per sesh
- Allograft washed in sterile water, filtered
- Water sent for culture
How can cadaveric donation time constraints be followed?
Body refrigerated within 12 hours of death
Tissue retrieval must occur within 24 hours from time of death
How are novel/emerging agents surveyed?
Monitoring of post op infections (critical)
Rule out other sources of infection
Emerging infections - assess transmissibility of agent
- Research (animal models)
- Prevalence assessment in donors
- Surveillance for infection in recipients
How good are current serological tests for HIV, HCV etc?
Capable of detecting >99.9% of infectious donations
Not 100% due to “window period” time taken between point of infection to detection of pathogenic agent in blood
What is the window period?
Time taken between point of infection to detection of pathogenic agent in bloodstream
Is virus prevalence higher in musculoskeletal or blood donors?
Muskuloskeletal
Only bacterial reported in australia, 113/2321 (4.9%)
Skin infection rate = 15.7
Heart valve infection rate = 15.1
Staphylococcus sp most common
What are the proposed infection rates of viruses?
HIV = 1 / 161 000 HBV = 1 / 172 000 HCV = 1 / 55,000 HTLV = 1 / 118 000
What is the Calman scale?
Easily understood risk continuum or scale so patient can provide informed consent
Negligible (1 in 1 million) Minimal 100 000 Very low 10 000 Low 1000 Moderate 100 - 1000 High (1 in 100)
What are allograft risk estimates as defined by Calman scale?
1 in 55 000 (very low) to
1 in 172 000 (minimal)
What is Nucleic Acid Testing (NAT) and how does it reduce allograft transmission risk?
Reduces length of the Window Period
More sensitive to infection
HIV 22 - 9 days - 400 000 chance now HCV 66 - 7 days - 500 000 HBV 44 - 22 days 345 000
Many countries have not implemented screening
What are some drawbacks of NAT testing?
Can potentially compromise viability of the organ
Better in cadaveric donors
HIV/HCV NAT under consideration by TGA for corneal grafts
How can transmission risk be further reduced?
2) More stringent donor selection criteria
- Specific Qs - emerging/novel agents
3) Improved post transplant surveillance/report
4) Universal allograft bioburden reduction
- Number of bacteria on sample
