Transplantation: Laboratory Testing for Screening and Monitoring Infectious Diseases

Transplantation of solid organs, bone marrow, and other human tissues saves and improves thousands of lives every year. Approximately 40,000 transplants were performed in the United States in 2019.1 Unfortunately, demand exceeds supply—more than 109,000 men, women, and children were on the national transplant waiting list as of September 2020.1

Successful transplants are guided by laboratory testing, including pre- and post-transplant testing for infectious diseases.2-5 An organ or tissue with a latent infection can cause serious illness in the recipient and potentially donor organ or tissue rejection. Immunosuppressant drugs that help prevent rejection of the transplanted organ or tissue can lead to a latent infection becoming active.3,4

This article will discuss the importance of laboratory testing for patients who donate and receive transplants, with a focus on screening and monitoring for infectious diseases.

 
Overview of Transplantation and the Importance of Laboratory Testing
A transplant performed between 2 different persons is called an allograft transplant; tissue can be from a living or a deceased donor. Laboratory testing is used to determine if donor and recipient tissues are a “match;” examine general parameters of health (eg, tests of liver and renal function); monitor for signs of rejection of the transplanted tissue; and monitor levels of immunosuppressant drugs5-9 (see Sidebar).

Screening for infectious diseases prior to transplant and monitoring the recipient for the development of infections are also critically important to the transplant success.2-5

Donor and Recipient Pre-Transplant Infectious Disease Testing

Donor Testing
To avoid transmission of infectious diseases through the transplanted organ or tissue, the Centers for Disease Control and Prevention (CDC) and Organ Procurement and Transplantation Network (OPTN) require prospective organ and tissue donors be tested for certain infections (Table).3

Similar requirements have been published by professional organizations4 and the United States Food and Drug Administration (FDA).10 Importantly, the FDA requires that infectious disease donor testing be performed using assay kits that are FDA approved or FDA cleared specifically for donor testing and performed according to the manufacturer’s instructions.4 In many cases, the FDA requires that donor specimens be tested by both an antibody test and a nucleic acid amplification test (NAAT or NAT).4

Also important is a detailed donor social and medical history, which can be used to indicate the risk of various infectious diseases and other health problems.11

Recipient Testing
To avoid activation of latent or unrecognized infections by immunosuppressant drugs in transplant recipients, the American Society of Transplantation Infectious Diseases Community of Practice recommends testing for certain infections (Table).4

Post-Transplant Testing
Specific guidelines have been developed for post-transplant testing and vary with the type of transplant performed (eg, a solid organ such as a liver or kidney, or bone marrow transplant).5,8,9,12,13 However, all transplant recipients are at risk of infections and require monitoring for the same types of infectious diseases tested for prior to receiving the transplant.2,5,8,9,12,13 Post-transplant testing (Table) depends on the type of transplant and the recipient’s clinical condition.14

Table. Summary of donor, recipient, and post-transplant infectious disease testing3,4,10,14
Infection (s) Pre-transplant Post-transplant
Donor Recipient
CMV, HIV types 1 and 2, HBV, HCV, EBV ●a ● ●
Treponema pallidum (syphilis) ●a
Toxoplasmosis ●b ●
West Nile virus ●c
Human T-lymphotropic virus ●d
Chlamydia trachomatis and Neisseria gonorrhea ●e
Bacterialf ● ●
Mycobacterial (eg, tuberculosis) ● ●
Fungalg ● ●
Parasitic ● ●
Adenovirus ●
BK virus ●
Herpes virus ●
JC virus ●
Parvovirus ●
Varicella zoster ●
Pneumocystis jiroveci ●
Toxoplasma gondii ●
•, required testing; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV; human immunodeficiency virus; JC, John Cunningham; WBC, white blood cell.
a all
b deceased donor only
c living donor
d WBC-rich tissue
e reproductive tissue
f for example, colonization of an indwelling catheter
g based on endemicity, eg, histoplasmosis and coccidiodomycosis

Transplant of Organs and Tissue From Donors Who Are Positive for HBV, HCV, and HIV
For many years, persons with HBV, HCV, and HIV infections were not considered eligible donors for organ and tissue transplants.15,16 However, with demand for transplants far exceeding supply, donors have been successfully matched to recipients with the same infectious diseases, with good outcomes.15-17

Furthermore, new therapies that suppress viral reproduction have enabled successful transplants of organs and tissue from donors with positive HBV, HCV, and HIV serology to persons negative for these diseases, greatly increasing the donor pool.15,16,18 In these cases, strategies can include prophylaxis or preemptive therapy.18 Using transplants from HCV-positive donors as an example, the prophylaxis method would begin therapy with a direct-acting antiviral (DDA) before or immediately after the transplant. With the preemptive method, a DAA would be begun once viremia is detected but before any signs of liver disease.

Transplantation and COVID-19
Organ and tissue transplants have been greatly affected by the COVID-19 pandemic.19,20 Testing is critically important to ensure both donor and recipient are negative for active SARS-CoV-2 infection at the time of transplant. After SARS-CoV-2 infection has resolved, it is unclear how long a transplant should be delayed; some professional organizations suggest a minimum of 3 months.19 The risk of poor outcomes for the patient by delaying the transplant must be balanced against potential complications of COVID-19. Whether transplant recipients receiving immunosuppressant medications are at increased risk for acquiring COVID-19, or how the medications may affect the disease course, is yet to be determined.19-21 Studies suggest transplant recipients who develop COVID-19 have a higher mortality rate, which may reflect a higher frequency of comorbidities in transplant patients compared with the general population.22

The role of COVID-19 vaccination for transplant recipients has not yet been established. However, a recent study of patients who had received solid organ transplants and either the Pfizer/BioNTech or Moderna mRNA vaccine found no adverse events other than those expected with any vaccination (eg, injection site pain).23  No evidence of transplant rejection was identified during short-term follow-up of COVID-19 vaccine recipients.23
 
Other Necessary Pre- and Post-Transplant Testing 

The success of organ and tissue transplant is largely due to the development of specialized laboratory testing. Testing necessary during the transplant process and follow-up of the recipient include
  • Determining donor and recipient compatibility6,7
  • Blood type-ABO compatibility
  • Tissue typing (human leukocyte antigens [HLA])
  • Serum crossmatch
  • Percent reactive antibody

  • Recipient testing post-transplant5,7,8
  • Immune cell function (monitor immunosuppression parameters)
  • Therapeutic drug monitoring (monitor levels of immunosuppressant drugs)
  • Monitoring for infections and infectious diseases

  •  Biochemical testing8,9
  • Tests of general health such as complete blood count and liver and kidney function of donor and recipient prior to transplant
  • Testing to identify possible rejection (eg, urine protein and serum creatinine after kidney transplant; transaminase, bilirubin, alkaline phosphatase after liver transplant)
How the Laboratory Can Help

Quest Diagnostics offers a comprehensive menu of tests necessary to identify infectious diseases in donors prior to transplant, and for the follow-up of transplant recipients. Consistent with FDA guidelines, Quest does not make any alteration to tests used for donor testing, maintains FDA registration to perform donor testing and complies with all FDA regulations, and has a dedicated facility for donor testing in Chantilly, Virginia, where all donor testing is performed.

Quest also offers testing necessary to determine donor–recipient compatibility and for the management of transplant recipients.  

More information is available at    

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References
  1. Organ donation statistics. Health Resources & Services Administration. Reviewed September 2020. Accessed February 27, 2021. https://www.organdonor.gov/statistics-stories/statistics.html
  2. Guenette A, Husain S. Infectious complications following solid organ transplantation. Crit Care Clin. 2019;35(1):151-168. doi:10.1016/j.ccc.2018.08.004
  3. Donor screening and testing. Centers for Disease Control and Prevention. Reviewed January 30, 2019. Accessed March 3, 2021. https://www.cdc.gov/transplantsafety/protecting-patient/screening-testing.html
  4. Malinis M, Boucher HW; AST Infectious Diseases Community of Practice. Screening of donor and candidate prior to solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13548. doi:10.1111/ctr.13548
  5. Centers for Disease Control and Prevention; Infectious Disease Society of America; American Society of Blood and Marrow Transplantation. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Recomm Rep. 2000;49(RR-10):1-128. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr4910a1.htm
  6. Blood tests for transplant. National Kidney Foundation. Reviewed January 31, 2017. Accessed March 3, 2021. https://www.kidney.org/atoz/content/BloodTests-for-Transplant
  7. Tiercy JM. How to select the best available related or unrelated donor of hematopoietic stem cells? Haematologica. 2016;101(6):680-687. doi:10.3324/haematol.2015.141119
  8. Schinstock CA, Gandhi MJ. Maintaining the health of the renal allograft: laboratory and histologic monitoring after kidney transplantation. Clin Lab Med. 2018;38(4):607-621. doi:10.1016/j.cll.2018.07.003
  9. Cimino FM, Snyder KA. Primary care of the solid organ transplant recipient. Am Fam Physician. 2016;93(3):203-210.
  10. Guidance for industry: eligibility determination for donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps). US Food and Drug Administration. Updated May 16, 2019. Accessed March 3, 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/eligibility-determination-donors-human-cells-tissues-and-cellular-and-tissue-based-products
  11. Jones JM, Kracalik I, Levi ME, et al. Assessing solid organ donors and monitoring transplant recipients for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection — US Public Health Service Guideline, 2020. MMWR Recomm Rep. 2020;69(4):1-16. doi:10.15585/mmwr.rr6904a1.
  12. Zhong D, Liang SY. Approach to transplant infectious diseases in the emergency department. Emerg Med Clin North Am. 2018;36(4):811-822. doi:10.1016/j.emc.2018.06.010
  13. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(suppl 3):S1-155. doi:10.1111/j.1600-6143.2009.02834.x
  14. Fishman JA. Infection in organ transplantation. Am J Transplant. 2017;17(4):856-879. doi:10.1111/ajt.14208
  15. Botha J, Fabian J, Etheredge H, et al. HIV and solid organ transplantation: where are we now. Curr HIV/AIDS Rep. 2019;16(5):404-413. doi:10.1007/s11904-019-00460-7
  16. Crismale JF, Ahmad J. Expanding the donor pool: hepatitis C, hepatitis B and human immunodeficiency virus-positive donors in liver transplantation. World J Gastroenterol. 2019;25(47):6799-6812. doi:10.3748/wjg.v25.i47.6799
  17. Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13499. doi:10.1111/ctr.13499
  18. Prakash K, Aslam S. New updates in the world of hepatitis C virus infected organ transplantation. Curr Opin Organ Transplant. 2020;25(4):364-370. doi:10.1097/MOT.0000000000000785
  19. Ljungman P, Mikulska M, de la Camara R, et al. The challenge of COVID-19 and hematopoietic cell transplantation; EBMT recommendations for management of hematopoietic cell transplant recipients, their donors, and patients undergoing CAR T-cell therapy. Bone Marrow Transplant. 2020;55(11):2071-2076. doi:10.1038/s41409-020-0919-0
  20. Kumar D, Manuel O, Natori Y, et al. COVID-19: a global transplant perspective on successfully navigating a pandemic. Am J Transplant. 2020;20(7):1773-1779. doi:10.1111/ajt.15876
  21. Poulsen NN, von Brunn A, Hornum M, et al. Cyclosporine and COVID-19: risk or favorable? Am J Transplant. 2020;20(11):2975-2982. doi:10.1111/ajt.16250
  22. Alfishawy M, Elbendary A, Mohamed M, et al. COVID-19 mortality in transplant recipients. Int J Organ Transplant Med. 2020;11(4):145-162.
  23. Boyarsky BJ, Ou MT, Greenberg RS, et al. Safety of the first dose of SARS-CoV-2 vaccination in solid organ transplant recipients. Transplantation. February 4, 2021. Published online ahead of print. doi:10.1097/TP.0000000000003654
Content reviewed 4/2021
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