Transplant transmitted infections

End-stage organ failure is estimated to affect more than six million people worldwide.⁴ Due to the high demand for organs and cells, every potential donor should be considered. However, this can open the possibility of transmitting infections, and to a lesser extent malignancy, from the donor organ to the recipient. Post-transplantation immunosuppressive regimes are critical in controlling organ rejection, but opportunistic infection can cause complications if not managed.

Common infections found in people of all ages, which generally do not cause problems for those with healthy, functioning immune systems, can have serious consequences for immunocompromised people and are a leading cause of morbidity and mortality in patients following transplantation. Examples include: 

Cytomegalovirus (CMV)

CMV is a major cause of infections post-transplant, with incidence varying by transplant type, donor-recipient match, and immunosuppressive regimen. Some 20%-60% of solid organ transplant recipients develop a symptomatic CMV infection, typically during the first few months after transplantation.⁵ Patients can be infected through the donor organ, or the virus can be reactivated if previously present, or a new infection may be acquired during the transplant process.⁶

Epstein-Barr virus (EBV)

EBV infection in immunocompromised transplant patients can result in malignant B cell lymphoproliferations, such as post-transplant lymphoproliferative disorder (PTLD). In EBV-seronegative transplant recipients, EBV infection rates are high, approaching therefore, the incidence of PTLD is greater in children who are more likely EBV-seronegative than adults  Incidence varies by organ transplanted, but can be as high as 20% of recipients.⁷

BK polyomavirus (BKV)

BKV is a member of the polyomavirus family. Infection in immunocompromised individuals, such as patients who receive solid-organ transplants can cause complications. For kidney transplant patients, BKV infection is considered the most common viral complication, causing polyomavirus nephropathy (PVN) in up to 10% of kidney transplant recipients, and about 50% of PVN-affected patients will experience transplant graft failure.⁸

Herpes simplex virus (HSV) / Varicella Zoster virus (VZV)

HSV and VZV are ubiquitous yet important human pathogens that can have very similar and wide-ranging clinical presentations.⁸ Transplant recipients are more susceptible to severe manifestations of HSV infection and may be slower to respond to therapy.⁹ HSV is the second most common cause of viral infection after transplantation, whereas VZV has been shown to cause symptomatic infections in up to 20% of solid organ transplants, and more than 40% of hematopoietic stem cell transplants.¹⁰

Human adenoviruses (HAdVs)

 HAdVs cause asymptomatic-to-mild respiratory infections in children and young adults. However, in patients undergoing transplantation who are immunocompromised, HAdV can cause severe symptoms, such as hepatitis, nephritis, meningoencephalitis, and pneumonia.¹¹ AdV infection has been found to occur in 5-22% of solid organ transplant patients, usually within the first six months post-transplantation.¹² Once established, HAdV infections are difficult to cure and can result in organ failure and death.¹³

Toxoplasma gondii

Toxoplasma gondii is a relatively common infection and can be transmitted via organ transplant from an infected donor, or reactivation of a latent Toxoplasma infection can occur as a result of immunosuppression in organ transplant recipients. Reactivated disease in immunocompromised hosts frequently presents with brain lesions and can be associated with high morbidity and mortality.^14-16

Overall, about 50% to 65% of transplant recipients will develop symptomatic viral infection within 90 days post–solid organ transplant without prophylaxis, and infections account for about 20% of the deaths within 100 days after hematopoietic stem cell transplant. The earlier these infections can be detected, the higher the likelihood that clinicians can place patients on treatment to produce better outcomes.^17,18

Pre- and post-transplantation laboratory testing is critical to making the most out of every donation, and ensuring patients get the life-saving surgeries they need. Early intervention with best-in-class monitoring tools provides actionable results that enable informed treatment decisions.

Comprehensive and reliable testing requirements
The success of transplant programs depends on comprehensive and reliable pre- and post-transplant testing to minimize risk. From initial screening to post-transplantation follow-up, labs must process multiple samples and run numerous tests to detect potential pathogens.

Ensuring consistency across institutions
Labs are tasked with ensuring that diagnostic testing is consistent and comparable across institutions and throughout the continuum of care. Variability in practices can create challenges in maintaining uniform diagnostic standards.

Variability among viral load thresholds to guide treatment decisions
Treatment decisions for viral infections heavily rely on viral load.  However,  there is an absence of universal viral load thresholds to guide treatment decisions.¹⁹ Coupled with differences in assay availability and performance, standardization and consistency in testing remains a challenge.

Delays in test result turnaround
For some laboratories, send-out testing can result in delays of several days, slowing down critical treatment decisions and impacting patient care during time-sensitive situations.²⁰

Limited Access to Accurate Testing
Restricted availability of accurate viral monitoring tests and results makes it challenging for clinicians to determine optimal treatment plans. This limitation increases the risk of adverse outcomes for patients due to delayed or inappropriate treatment decisions.²¹

Appropriate testing for infectious diseases pre-transplant, which assesses all the risks associated with the transplant, is essential for success.

Serologic testing is an integral part of clinical management, helping to:

• Identify infections that may disqualify the recipient or the donor
• Match the right donor with the right recipient
• Implement strategies to mitigate the risk of infection post-transplant

Roche serology assays and instruments can be used to perform a broad range of immunoassays and offer various options to suit throughput needs. Roche Elecsys® assays include highly specific and sensitive serology tests to detect infectious diseases, including:^27-30

• Testing based on ECL (ElectroChemiLuminescence) technology to deliver reliable results
• Serology screening assays that detect the major viral genotypes and variants found worldwide
• Very high seroconversion sensitivity
• Very high specificity and clear cut-off separation of positive and negative results to reduce the need for retesting

The widespread application of polymerase chain reaction (PCR) testing for the detection of viral nucleic acid (DNA or RNA) is the most important innovation in laboratory diagnosis and clinical management of post-transplant infections.³¹

Nucleic acid amplification testing (NAT) techniques, like PCR testing, are commonly used to:

• Aid in the diagnosis and management of transplant transmitted infections
• Measure viral load to inform the need for treatment or change in immunosuppression
• Monitor a patient’s response to therapy

To optimize viral load monitoring and elevate patient care, Roche offers the first FDA-cleared and approved molecular transplant portfolio - the cobas® CMV, cobas® EBV, and cobas® BKV tests. The portfolio provides:^22-24

• Critical transplant viral tests that can run from a single patient sample on the fully automated cobas® 5800, 6800, and 8800 systems
• Fast, trustworthy results in a streamlined workflow for laboratories
• Ready-to-use reagents and controls calibrated to WHO international standards that ensure result comparison across healthcare institutions no matter where the tests are run^22-24