Each year, more than 180,000 people1 receive a desperately needed gift – donated human organs or stem cells that can help them live healthier, more normal lives. But to keep the body’s immune system from rejecting the transplant, recipients must take drugs that suppress their immune system for the rest of their lives. This means they are more likely to develop infections that can be deadly. And one of most dangerous infections for people who have received transplants is cytomegalovirus, or CMV.

CMV belongs to the herpesvirus group, which also includes the viruses that cause chicken pox, herpes simplex, and mononucleosis (“mono”). It is spread by close contact with someone who has CMV in their saliva, urine or other body fluids. Researchers believe that up to 100% of some populations may be infected2; the infection rate in the United States is estimated to be between 50% and 80%. 3 It’s a chronic infection that, once acquired, stays in the body for life.

For most people with healthy immune systems, CMV is a quiet invader that causes no symptoms. They can live their entire lives completely unaware they have the virus. But when the immune system weakens, this normally dormant virus can re-awaken with life-threatening potential.

Transplant patients are among those most vulnerable to CMV infection, especially in the critical few months after the transplant. Between 20% and 60% of people with a solid organ transplant develop a symptomatic CMV infection4. These symptoms are similar to the flu – fever, body aches, sore throat – and may be difficult to control.

“CMV is one of the most dangerous infections for transplant patients,” said Paul Baum, MD, PhD, Head, Clinical Science, Roche Molecular Diagnostics. “You can treat it but you can’t cure it and there are no approved vaccines against CMV.”

Transplant types

The two most common types of transplants are solid organ transplants and hematopoietic stem cell transplants5. People receive solid organ transplants to replace organs that have failed due to disease or injury. Examples include lungs in cystic fibrosis patients, kidneys in patients with diabetes, and the liver in patients with chronic hepatitis. Hematopoietic stem cell transplants are used to treat leukaemias, lymphomas and some non-cancerous disorders like severe immunodeficiencies.

A solid organ patient’s transplant journey is complex. First, a medical specialist determines that the patient needs the transplant. The patient undergoes extensive testing and may spend months, even years, on a transplant waiting list. For people needing an organ transplant, testing provides essential information about the urgency of the need for the organ, the patient’s blood and tissue type, and body size – this data helps the donor computer programme find the best match. 

CMV testing for donor and patient

CMV testing plays a vital role for both the patient needing the transplant and the donor. Generally, organ transplant patients are tested for CMV at least twice before the transplant. The first test normally occurs a few months before the transplant or after the patient has been placed on the transplant waiting list. When a donor organ becomes available, another CMV test takes place hours before surgery so that the transplant team has the most current information about the patient’s CMV status.

The pre-transplant test is a blood (serology) test that identifies whether the donor or patient receiving the transplant has already been infected with CMV and provides information about the level of potential risk to the recipient from the virus (see chart). The type of transplant also affects the CMV risk – lung, heart and multi-organ transplants carry the highest risk, kidney and stem cell transplants the lowest. Because CMV infection is so common worldwide, healthy people who test positive for CMV can usually still become donors. 

A pre-transplant test provides information about the level of potential risk to the recipient from the virus
The level of potential risk to the recipient depends on whether the donor or patient receiving the transplant has already been infected with CMV

After the transplant, patients begin their lifelong immunosuppressant therapy – usually a combination of many different drugs. This therapy reduces the immune system’s function to make sure it doesn’t reject the organs or stem cells. Unfortunately, this immunosuppressant therapy also means that the CMV virus is more likely to multiply and become symptomatic.  

“In transplant patients, CMV disease can damage many organs including the lung, liver, kidney, gastrointestinal tract and the eyes,” Paul said. To help prevent and minimise this damage, patients normally receive prophylactic antiviral therapy following their transplant

Testing for CMV therefore continues after the transplant, however the type of testing changes. Post-transplant patients normally undergo polymerase chain reaction (PCR) testing for the first three months after the transplant to measure “viral load” – that is, how much CMV is in the body. This testing is important in four ways:

  • assessing CMV risk and severity
  • helping guide therapy decisions
  • diagnosing CMV quickly and
  • monitoring the effectiveness of therapy and the development of antiviral resistance 

Polymerase Chain Reaction (PCR) is a method of rapidly making many copies of a sample of DNA from, for example, blood or saliva. Once enough DNA has accumulated, automated tests can reveal the presence of a specific bacterium or virus. 

While transplants save the lives of thousands of people around the world each year, the transplant recipients face a permanent threat from infections - with CMV as one of the most dangerous. Testing before and after the transplant plays a significant role in helping clinicians manage the risk to patients from CMV.

References:

  1. The 2014 data are based on the Global Observatory on Donation and Transplantation (GODT) data, produced by the WHO-ONT collaboration. http://www.transplant-observatory.org/
  2. Vilibic-Cavlek, T. (2015). Prevalence and dynamics of cytomegalovirus infection among patients undergoing chronic hemodialysis. Indian Journal of Nephro, 25(2), 95-98.
  3. https://medlineplus.gov/cytomegalovirusinfections.html
  4. Hibberd, PL, Tolkoff-Rubin NE, Cosimi AB, Schooley RT, Isaacson D, Doran M, et al. Symptomatic cytomegalovirus disease in the cytomegalovirus antibody seropositive renal transplant recipient treated with OKT3. Transplantation 1992; 53:68-72.
  5. Razonable RR. Epidemiology of cytomegalovirus disease in solid organ and hematopoietic stem cell transplant recipients. Am J Health Syst Pharm 2005; 62 (Suppl1): S7-S13

Tags: Patients, Science