Cytomegalovirus: A little-known virus that can cause big problems
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.
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.
Things you might not know about organ transplants
Watch the journey of Masahiko Sato and experience what it is like to receive an organ transplant.
[00:02]
[Music] My name is Masahiko Satō, but my friends call me Mos. I'm an immigrant. I am a son. I am now a loving husband. I’m a father. I was surprised to find myself
[Music] in a hospital in November of 2006. By January of 2008, I was dying of stage four congestive heart failure. During this time, I spent at least a year not knowing if I would be alive each time I went to bed. Then my wife received a phone call from the hospital in September of 2008. We had been waiting months for a donor heart, so we were excited — but we were also a little apprehensive.
[01:15]
We were required to get to the hospital within four hours of receiving the call. The heart transplantation procedure required me to stay in the hospital for at least two weeks, followed by a three-month isolation period at home. After that, I was required to wear a mask, and I wasn’t allowed to hug or touch anyone. Even today, I still need to avoid crowds in an effort to minimize the risk of infection. Before and after my heart transplant surgery, I had up to 10 doctors. Before each doctor’s visit, I had blood tests that were critically important to inform the doctors about what was happening inside my body.
[02:11]
These results were essential. Currently, I have a cardiologist, a pulmonologist, an endocrinologist, a GI/liver specialist, an ophthalmologist, and a dermatologist — and I see these specialists every 6 to 12 months. Since my transplant, I’ve been on immunosuppressants, antibiotics, steroids, vitamins, calcium, antifungal agents, and stomach medication. Post-transplant, I was on 16 prescriptions that I had to take three times a day. Today, as I’ve improved, I’m now down to 10 medications, still taken three times a day.
[03:13]
The high doses of immunosuppressants I take come with serious side effects. My doctors are concerned about metabolic syndrome, cardiovascular disease, diabetes. I also have osteopenia, stage one renal disease, and my doctors are monitoring me for cataracts. I have hand tremors. So, I continue to see about seven doctors every 6 to 12 months. I’d like to thank everyone who helps make test results available to physicians — every little thing you do matters. Every detail truly impacts patient outcomes.
[04:14]
As a result of my heart transplant, we are dreaming again, and we are actively planning for the future. I’ve lived to see my son graduate from law school. I’ve seen my daughter graduate with honors from college and recently defend her PhD thesis. As my recovery has progressed, we are always painfully aware that another family had to suffer the loss of a loving daughter for me to be alive today. I am determined to be as disciplined and compliant as I possibly can, because I hope to one day meet this family — and I want to be able to say to them: I’ve done everything I possibly can to honor their sacrifice and the kindness of their daughter.
[06:00]
So, a hero of mine is a young woman I don’t know — who was willing to share her gift of life with me. For those of you who are watching, I would ask you to consider potentially becoming a hero to another critically ill patient like
[Music] me.
References
The 2014 data are based on the Global Observatory on Donation and Transplantation (GODT) data, produced by the WHO-ONT collaboration.
Vilibic-Cavlek, T. (2015). Prevalence and dynamics of cytomegalovirus infection among patients undergoing chronic hemodialysis. Indian Journal of Nephro, 25(2), 95-98.
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.
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