Clinical Virology Programs

Our research group has just published 2 research papers in peer-reviewed journals. The study by Vezina et al describes the pharmacokinetics of valganciclovir, which is being used to prevent herpesvirus infections in pediatric solid organ transplant patients. The research by Romain et al presents a novel method for determining the susceptibility of EBV strains–including those taken directly from patients with mono–to antiviral drugs. Visit the Dovepress website to read the articles:

• The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease - Heather E Vezina, Richard C Brundage, Thomas E Nevins, et al
• A method for evaluating antiviral drug susceptibility of Epstein-Barr virus - Charlotte A Romain, Henry H Balfour Jr, Heather E Vezina, et al.

Amy Karger MD PhD presented the results of 6 years of quantitative viral load monitoring for EBV infections at our institution  on October 30, 2009 at the 47th annual meeting of  the Infectious Diseases Society of America in Philadelphia. She reported that  EBV infections were more common in solid organ than hematopoietic cell transplants and was useful in distinguishing cases of the serious posttransplant lymphoproliferative disorder.  For more information, please see the complete poster.

Clinical Application of Real-time Quantitative Epstein-Barr Virus (EBV) Polymerase Chain Reaction Assay to Posttransplant Infection

The Surgery Department’s Transplant Program Project Grant (PPG) has just received 5 years of funding from National Institute of Diabetes and Digestive and Kidney Diseases.  Dr. Arthur Matas is the Principal Investigator.  Clinical Virology Programs has one of the two new projects in this PPG, entitled “Viral Infections and Posttransplant Morbidity.”  Details about our prospective research study in recipients of solid organ transplants will soon be available under the “Viruses and Transplantation” link.

The journal Science published a study last week that indicates xenotropic murine leukemia virus-related virus (XMRV) may cause chronic fatigue. The study found XRMV present in 68 of 101 patients with Chronic Fatigue Syndrome whereas only 8 of 218 healthy patients had the virus.

The New York Times also reported on the study.

The new suspect is a xenotropic murine leukemia virus-related virus, or XMRV, which probably descended from a group of viruses that cause cancer in mice. How or when XMRV found its way into humans is unknown. But it has also been linked to cancer in people: it was first identified three years ago, in prostate cancer, and later detected in about one-quarter of biopsies from men with that disease (and in only 6 percent of benign biopsies). It is a retrovirus, from the same notorious family that causes AIDS and leukemia in people.

However, the findings are preliminary and need to be confirmed by further research.

The valomaciclovir for treatment of Mono presentation in San Francisco last month was reported in the Neue Zürcher Zeitung (NZZ), which is a major German language Swiss daily newspaper based in Zürich.

Photo: Dr. John Besser of the CDC (left), Dr Balfour (middle), and Barbara Schenk, Illinois SCACM Director (right).

On Monday, September 28th, Dr. Balfour gave a talk about our EBV research at a symposium entitled “Happy Birthday (200) Charles Darwin, Change and Evolution in Microbiology.”  This was the annual fall meeting of the South Central Association for Clinical Microbiology held at the Loyola University Medical Center near Chicago. The symposium was attended by 90 clinical microbiologists from 6 states: Michigan, Illinois, Indiana, Ohio, Kentucky and West Virginia.

Influenza A H1N1 viruses resistant to zanamivir (relenza) have just been reported in the Journal of Virology. This was predictable, but we didn’t think it would happen so soon. These resistant viruses must still be considered rare.

For more information on influenza, see our article, New Flu Facts.

We have recently found using a relatively new technique called microarrays that primary EBV infection induces a reproducible alteration in the gene expression profile of blood cells. To find out if this gene expression profile is specific for EBV versus being shared with other viral infections, we have started to examine the pattern evoked by influenza immunization of some of our Mono 5 subjects who have not been infected by EBV and some who have. If the pattern is not seen among the subjects who have not been infected but is found in the subjects who have been infected, this would be evidence that it is specific for EBV infection. If it is not seen in either group, this would be evidence that it is specific for primary EBV infection. In other words, when this virus infects us, does it leave a calling card with our immune system?

In a study presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco, University of Minnesota researchers found that students who receive an antiviral medication early in the course of the illness become less sick than those offered the standard advice to rest for several weeks.

The results are similar to a previous study by the same researchers on a different antiviral drug. But whether doctors embrace treatment of mononucleosis may depend on how they view the illness.

“When you are in a health service at a university or a big high school, you appreciate how many patients there are and how sick kids can be,” said Dr. Henry H. Balfour, the lead author of the papers and a professor of laboratory medicine and pathology. “We have kids miss entire semesters, and their studies suffer. It’s not a trivial disease for people who are active.”

Read more.

On Monday, September 14, 2009, Dr. Balfour presented the preliminary results of our valomaciclovir for treatment of infectious mononucleosis (Mono 6) study as a “late breaker” advance at a major infectious diseases scientific meeting in San Francisco.  In a nutshell, the 11 subjects who received the antiviral drug valomaciclovir got better faster than the 10 volunteers who were given placebo tablets, and the drug significantly reduced the amount of virus in the oral cavity. “A specific treatment for mono has great potential,” Balfour said, “because mono often results in several weeks of reduced productivity in school or the workplace and shortening that would be a great boon.”  Also, mono is caused by the Epstein-Barr virus (EBV), which can produce serious disease in persons with weakened immunity, such as transplant recipients.  “Development of this drug could be important to them,” he said, “because there are presently very few treatment options for EBV infections.”

However, valomaciclovir is still in the experimental stage.  The number of subjects studied was small.  The dose used was associated with nausea, which suggests that a lower dose or a different formulation may be needed to optimize effectiveness and safety.

Clinical Virology Programs at the University of Minnesota headed by Dr. Henry Balfour conducted this clinical trial.  The researchers are now analyzing a mountain of clinical, viral, immune, and pharmacology data for the final medical report expected to be completed in December.  Assisting Balfour in this clinical research project are pharmacology scientists Heather Vezina and Richard Brundage, immunologists Kristin Hogquist and Dare Odumade, and Boynton Health Service physician B. J. Anderson.

The results of the Mono 6 study were reported at the 49th annual ICAAC, which stands for Interscience Conference on Antimicrobial Agents and Chemotherapy.  Approximately 8,000 scientists from the U.S. and many other countries attended this conference.