Life-saving tests
29/07/2016 // Feature // Text: Martin Zoeller // Photo: Andreas Fechner

Tiziana Lazzarotto cares for people who have organ transplants - serving not at their hospital beds, but in the virology laboratory of one of Europe's most renowned transplant clinics. Valuable insights from QIAGEN tests help guide decisions critical to the patients' lives.

Shortly before you reach her office on the second floor of Building 11, the yellow warning signs grow more frequent, and the wooden doors are replaced by dramatic-looking steel ones, several centimeters thick, with little glass windows. It’s through windows like these that trapped characters in Hollywood movies throw their loved ones a final kiss. A sign on a door on the right says “Tiziana Lazzarotto.” The door opens and sunlight pours into the corridor.

“Ciao, I’m Tiziana!” Professor Tiziana Lazzarotto says with a friendly smile. The CV of this lively 58-year-old is so extensive you have to scroll right down your screen to read it all: Professor of Microbiology and Clinical Microbiology at the University of Bologna, Italy, with 180 scientific articles, countless medical congresses and six prizes. “I work with passion,” she says. The silent witnesses on her desk include a Paris pencil holder, an “I Love Berlin” glass and a miniature koala bear – all souvenirs from conferences.

Source: Global Observatory on Donation & Transplantation 2013.

With a CV like that, Tiziana Lazzarotto is clearly an authority in her field, a coryphaeus in clinical virology. As an Italian she might empathize with that Latin word, and in particular with one of its present-day English meanings: “leader of the chorus.” That is how Tiziana Lazzarotto sees her role – a facilitator who ensures the success of entire projects to help patients. Specifically by helping transplant patients live with a new organ. And even more specifically by collecting and evaluating data about their health status: “Diagnostics can assess if there’s a threat of infection, or even death.”

War! That is what Professor Lazzarotto is waging along with a team of serious yet friendly physicians and assistants; a war fought on the side of patients who need help to fight off the attacks of viruses and bacteria. The battlefield is the transplant patients’ immune system. “In the first 20 days after a transplant, it’s initially the risk of a bacterial infection that is high,” Professor Lazzarotto says. “Afterwards, it’s mainly the cytomegalovirus (CMV).” Over 80 % of transplant patients have to fight infection with CMV, a common virus that can cause severe symptoms or death in people with weakened immune systems.

Prof. Dr. Tiziana Lazzarotto is a professor of microbiology and clinical virology. Her work is mainly devoted to the cytomegalovirus, and to protecting transplant patients from it. Prof. Lazzarotto shows her support for the worldwide physicians' initiative #stopcmv by carrying a small silver loop on her lapel.

This is because after a transplant, the patient’s immune system must be suppressed; yet if it is suppressed too far, infection sets in. So how far is “too far”? Up till now, it has been difficult to individualize post-operative medication. Some patients have received too many immunosuppressants, and some too few. What has been lacking is insight into exactly how much medication each patient needs so that his or her immune system is weak enough to accept the new organ but strong enough to repulse dangerous viruses and bacteria.

“We have two types of monitoring tests and both must be carried out at the same time,” explains Professor Lazzarotto. Viral load tests such as QIAGEN’s artus PCR kits are used in Bologna to help determine the presence and concentration of a specific virus, and immunological tests like QuantiFERON-CMV add another layer of information by measuring the patient’s immune response to the infection. “Our task is to prevent the progression of a viral infection towards active disease,” says Professor Lazzarotto. “So if we diagnose an infection and see only a poor immune response to it, we need to help the patient by either reducing the immunosuppressant or initiating an antiviral therapy.” 

Now, a new tool, QuantiFERON Monitor, promises to further advance the management of post-transplant patients. The novel test helps to assess the strength of the immune system of patients who are given immunosuppression therapy after a transplant by measuring their individual cell-mediated immune response. For the first time ever, it is possible to decide on the right amount of medication based on a patient’s specific immune response. Up until now, clinics have only monitored the concentration of the medication, irrespective of its effect on the immune system.

In view of the fact that immunosuppression is responsible for 40–70 % of all deaths following an organ transplant, QuantiFERON Monitor meets a critical medical need by allowing doctors to assess an individual’s immune response, helping guide patient management and treatment decisions to reduce the risks of organ rejection and infection. The test was launched with a CE-mark in Europe in 2015, and a regulatory submission is planned for the U.S. as well.

Dr. Luciano Potena, a 43-year-old cardiologist at the Sant’Orsola-Malpighi University Hospital in Bologna, presently cares for 500 heart transplant patients, of whom 100 are already being observed using the QuantiFERON Monitor: “We have fewer organ donations these days and the patients who are waiting are consequently in an increasingly poor state of health. So it is all the more important to perfect each individual transplant and post-operative care,” he says. That means individualization. After all, a majority of Italians carry the cytomegalovirus, which post-operative immunosuppressing therapy can set off again.

Professor Lazzarotto and Dr. Potena are on first-name terms. That is typical for Bologna, as the laboratories here are allies cultivating constant interaction with physicians. “We are in a continuous dialogue about the management of individual patients as well as clinical research projects,” explains Dr. Potena. “Thanks to this close collaboration and the diagnostic tools provided by QIAGEN, we’ve been able to develop a clinical management system that is tailor-made to the needs of our patients.”

Dr. Luciano Potena is a cardiologist. His department currently cares for about 500 outpatients who have undergone a heart transplant and whose immunosuppressants are constantly being customized. An additional 800 patients from all over Italy are under observation for a possible transplant.

Above all, patients are the ones who benefit from precise monitoring of immune response, says Professor Lazzarotto: “Antiviral medication is very effective, but also very aggressive,” she explains. “It is important to reduce the number of tablets.” What’s more, the clinic also benefits: “By measuring the strength of a patient’s immune system, the QuantiFERON Monitor test may provide important insights to assess how much medication we really need in order to be effective.” That saves money and reduces the number of days in which beds are occupied. “We are given targets like reducing the number of bed-days. A good laboratory and good, reliable tests help everyone, patients and the clinic alike,” she says.

Nowadays, consumer products from chocolates to gym shoes and teddy bears are all personalized. But in medicine, personalization still has a lot of catching up to do. Up until now, it has been extremely challenging to individualize the management of post-transplant patients due to the lack of adequate diagnostics to measure the specific status of their immune system. QuantiFERON Monitor holds great promise to fill this gap. “Personalization is the future and I see great potential here,” says Professor Lazzarotto. She carries the battle against CMV around with her in the form of a silver loop on her lapel. That is how you recognize supporters of the worldwide physicians’ initiative #stopCMV. That is her passion.

In the first quarter of 2016 alone, Tiziana Lazzarotto had three conferences where she passed on her experience – in Venice, Amsterdam, and China. Any suggestions for souvenirs? A small gondola, a wooden shoe, a Chinese paper dragon? They would certainly look good on this professor’s desk on the second floor of Building 11.

Dr. Luciano Potena discusses transplants...

What are the main challenges you face in your work today?

My area of expertise is heart transplants. We see an ongoing decline in the number of organ donations all across Europe, so we find ourselves transplanting patients in worse conditions than those a few years ago. This makes the post-transplant management more complex because weakened patients are at higher risk of post-surgical infection. At the same time, we face increasing pressure to optimize resources while providing every patient the best treatment possible.

What’s so difficult about managing the infection risk? 
We have highly effective antiviral drugs to treat potential infections, but those medicines are very costly and can have severe side effects. Considering that every single patient responds differently to an infection, our goal is to customize the therapeutic strategy as much as possible. But to achieve this we need to measure exactly what we are doing, we need to understand how the patient’s immune system is responding to a treatment. For instance, if I knew that a patient’s immune system is already responding to a CMV infection, I could use a lower dose of the medicine or for a shorter period of time, effectively reducing the risk of side effects and saving money.  

How do QIAGEN products help you to achieve this vision?
Thanks to the close collaboration with Professor Lazzarotto and QIAGEN, we were able to develop different strategies to monitor the immune system and effectively manage our patients. We’ve been using the QuantiFERON-CMV test for several years now on patients suffering from side effects of antiviral therapy to determine if their immune system is responding to the CMV infection. QuantiFERON Monitor is still fairly new, but I think that it will be important for the future. I believe monitoring is an essential next step in customizing therapy. We’re currently running a study with around 100 patients and receiving very interesting initial results. They suggest that I can identify patients at greatest risk of infection and monitor them more closely, or modulate the immunosuppressant therapy to avoid a clinical event. These results need to be confirmed in a follow-up phase of our study, but we are expecting a great deal from this test going forward and I believe that this is essential as the next step in customizing therapy.