Donor-Derived Infections in the Transplant Patient

Claire E. Magauran

Donor-derived infections are those that are transmitted from a donor to one or more recipients.

BACKGROUND

Twenty-one thousand three hundred and fifty-four solid organ transplants were performed in the United States from January-September 2011 utilizing 10,556 donors.¹ Seven thousand and twelve allogeneic and 9,778 autologous hematopoietic stem cell transplants (HSCTs) were performed in the United States in 2009.
Up to eight lives can be saved with a single organ donor. Eighteen people die daily awaiting an organ.²
Sixteen percent of unrelated donor recipients died due to infection compared to 12% of human leukocyte antigen (HLA)-identical sibling recipients between 2008 to 2009.³
Despite a large number of transplants performed, the rate of donor-derived infection is reported to be <1%.⁴ Any transmission of infection can have devastating consequences for the recipient, leading to significant morbidity and mortality.

DONOR SCREENING FOR SOLID ORGAN TRANSPLANT AND HEMATOPOIETIC STEM CELL TRANSPLANT

A thorough history and physical examination including exposures, travel history, and history of prior transfusions is required.
In HSCT, donor screening is performed within 8 weeks of donation; serologic testing is done within 30 days or less and followed by repeat testing within a week prior to transplant.5 The purpose of such screening is to rule out active infection in donors and assess risk for possible infection.

Lab Testing

SOT	HSCT
FDA-licensed HIV 1 and 2 antibody	FDA-licensed HIV 1 and 2 antibody^a
Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb)	Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (HBcAb) Hepatitis C antibody (anti-HCV)^a
Hepatitis C antibody (anti-HCV)	CMV antibody (CMV IgG)
CMV antibody (CMV IgG)
EBV antibody (EBV IgG)	EBV antibody (EBV IgG)
Rapid plasma reagin (RPR) or VDRL	Rapid plasma reagin (RPR) or VDRL
Purified protein derivative (PPD) or interferon-gamma release assay (IGRA) in potential living donors	Herpes simplex virus (HSV IgG) antibody^b
	HTLV-I/II antibodies^b
^aNucleic acid testing (NAT) used for HIV and HCV. ^bTested in HSCT not SOT.

Other specific tests depending on organ or exposure history may be performed (e.g., Toxoplasma or Strongyloides antibody testing if the donor is from an endemic area).

Deceased Donors

Blood cultures, urine cultures, and sputum or bronchoalveolar lavage cultures from hospitalized patients should be obtained in addition.⁶

Deceased Donor Screening Problems

Limited information about deceased donors
Short time frame to accept or reject donor organ from deceased donors
Lack of rapid, sensitive, specific, and cost-effective testing

High-Risk Donor (CDC Classification)⁷

Donors that are considered high risk for possible HIV transmission include: (1) Men who have sex with men in the last 5 years; (2) nonmedical intravenous, intramuscular, or subcutaneous injection of drugs in the last 5 years; (3) persons with hemophilia or other clotting disorders who have received human-derived clotting factor concentrates; (4) men and women engaging in sex in exchange for money or drugs in the last 5 years; (5) sexual exposure in the last 12 months with any person described above or with known or suspected HIV; (6) exposure in the last 12 months to known or suspected HIV-positive blood through percutaneous inoculation or through contact with an open wound, nonintact skin, or mucus membrane; (7) inmates of a correctional facility

The risks of rejecting a donor need to be weighed against those of possibly transmitting an infection, and informed consent from the potential recipient is required.

TIMELINE OF INFECTION AFTER SOLID ORGAN TRANSPLANTATION

0- to 1-Month Posttransplant

Infections related to surgery or indwelling devices are common. This includes wound infection, anastomotic leak, urinary tract infection (UTI), catheter-related bloodstream infection, ventilator-associated pneumonia, and Clostridium difficile colitis.
Nosocomial or health care-related infections including multidrug-resistant organisms (MDRO) such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, MDR gram-negative bacilli, and Candida species also occur.
Donor-derived infections: Any febrile illness early after transplant should be considered to be possibly donor-derived. These include known or unknown infections prior to transplant such as donor CMV IgG (+) in CMV IgG (−) recipient; donor with UTI, bacteremia, or meningoencephalitis (e.g., lymphocytic choriomeningitis virus [LCMV], West Nile virus [WNV], rabies).
Recipient infections: previously undiagnosed or insufficiently treated colonization or infection

1- to 6-Months Posttransplant

Antimicrobial prophylaxis has led to decreases in infections due to Pneumocystis, Nocardia, Toxoplasma, and Listeria; however, these opportunistic infections are still possible.
Prior to antiviral prophylaxis human herpes virus infections (CMV, EBV, HSV, VZV, HHV 6 and 7) were frequently seen during this time frame.
Infection due to BK virus, recurrent HCV, Cryptococcus, tuberculosis, adenovirus, influenza, and HBV (without prophylaxis) are possible.
Complications related to anastomosis are common in this time period.
Reactivation of latent donor or recipient infections may occur among patients who received prophylaxis.

>6-Months Posttransplant

Community-acquired infections such as respiratory viruses, pneumonia, and UTI are common.
Late viral infections may occur such as HBV, HCV, or CMV after the prophylaxis period (e.g., colitis).
Infections due to atypical pathogens such as Nocardia and Rhodococcus species may occur as well as fungal infections due to Aspergillus, Mucor, or other molds.
Posttransplant lymphoproliferative disorder (PTLD) which may be EBV related may occur.
Reactivation of latent infections when treating for acute graft dysfunction may surface during this time period.