13.1 The Graft Recipient and the Presentation of Allograft-Associated Infections

The efficiency of disease transmission is likely due to a number of factors, including graft type, processing (for many types of tissue allografts), and recipient immunocompetence, which is the greatest issue in immunosuppressed transplant recipients (solid organs, hematopoietic stem cells) who have enhanced susceptibility to infections of all types. As a result, these individuals act as sentinels for transmissible disease. In immunosuppressed hosts, symptoms of infection are often decreased and the classic signs of infection (leukocytosis, erythema) are replaced by non-specific signs (altered mental status, elevation of blood liver function tests, wound dehiscence, unexplained hypotension). In immunosuppressed hosts, the transmission of blood or organ-derived infection due to West Nile Virus, for example, more often manifests as neurological disease with poor clinical outcomes than in normal hosts.

Multiple clusters of infection associated with organ transplantation (multiple recipients from the same donor) have included tuberculosis, Candida and Aspergillus (and other fungal) species, herpes simplex virus (HSV) and human herpes virus 8, lymphocytic choriomeningitis virus (LCMV), rabies virus, Chagas disease, HIV and hepatitis C virus. Detection of these unusual transmission events is dependent upon the suspicion of the clinicians caring for the transplant recipients, availability of pathology specimens, access to advanced microbiologic testing including nucleic acid amplification technologies (NAT), recognition of epidemiologic risks, and assistance with investigation of the outbreaks by public health authorities.

Infections have also been reported more uncommonly due to tissue and eye tissue transplantation. This lower frequency is likely a reflection of chemical or radiation processing (disinfection) of some tissue grafts as well as the normal inflammatory and immune function of the hosts, and possibly improved healing and vascular supply in many recipients of such grafts. The risk of transmission varies, depending on the graft type and the extent of processing for the graft; some grafts are heavily processed (e.g., bone chips), while some grafts are minimally processed (e.g., cardiovascular tissue). Tissue transplants have been associated with transmission of Candida albicans and other fungi, Chryseobacterium meningosepticum, now Elizabethkingia meningoseptica, Clostridium species, HCV, Epstein-Barr Virus (EBV), and group A Streptococcus. These infections may present with local signs of graft failure, purulence, unexplained erythema, persistent pain, or systemic infection.

Adverse reactions associated with eye tissues have been associated with primary graft failures (PGF), bacterial and fungal endophthalmitis and keratitis, corneal dystrophy/degeneration, and scleral graft rejection. Often, although infection is suspected, microbiological cultures may not be obtained routinely and/or a specific pathogen is not identified. A significant reduction in adverse events resulted from use of 5% ophthalmic povidone-iodine solution by eye banks prior to recovery of eyes or corneas.
Despite screening and processing, hematopoietic stem cells (HPCs) have also been associated uncommonly with transmissions of a wide range of viral, bacterial, fungal, and parasitic infections.

Response to Possible Allograft–associated Transmission Event

  1. The clinician must be suspicious that transmission of infection may occur in association with allograft implantation.
  2. In the setting of unexpected graft dysfunction, local signs (e.g., erythema, edema, pain) of infection or inflammation, fluid collections or bleeding, recipient samples must be obtained for diagnostic analysis. These include analysis of both fresh and fixed tissue. Concerning microbiologic methods, Gram stain and culture, bacterial and fungal cultures, and, if appropriate, mycobacterial smears and cultures. Special assays may be indicated based on the nature of the graft or reaction. Complete blood counts with differential counts should also be obtained.
  3. Systemic signs of infection or inflammation (fever, leukocytosis, hypotension, confusion, pneumonia, meningismus) merit blood cultures, and sputum or cerebral spinal fluid cell counts, glucose and protein, microbiological cultures and fixed tissue specimens as appropriate to the site of infection.
  4. Donor screening assays must be performed according to local requirements with consideration of the certification of the laboratory performing the assays, special testing based on the epidemiologic history of the donor, and laboratory quality control measures. Donor autopsies should be encouraged, and autopsy specimens and other fixed tissue from biopsy should be accessed if there is a transmission investigation.
  5. Notification of the organ, eye or tissue bank (as appropriate) of the possibility or demonstration of infection in the allograft donor must be achieved within 24 hours of recognition of potential disease transmission.
  6. Notification of the appropriate public health authorities must be made to ensure appropriate investigation of transmission event.