April 1, 2005

Impact of MPV on children with serious, chronic illnesses studied

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John Williams, M.D., reviews a scan with 5-year-old Lucas Koonce.
photo by Mary Donaldson

Impact of MPV on children with serious, chronic illnesses studied

Researchers at the Monroe Carell Jr. Children's Hospital at Vanderbilt are trying to define the impact of a newly described virus on children with chronic and life-threatening illness and injuries. Human metapneumovirus, or MPV, is also the target of a number of other ongoing research projects, keeping VCH at the forefront of international efforts to investigate this new virus.

John V. Williams, M.D., assistant professor of Pediatrics in Infectious Diseases, is working with research fellows Jennifer Domm, M.D., and Mercedes Judkins, M.D., on similar studies to find out MPV's impact on seriously ill children. Domm is studying the children seen at VCH's Hematology/Oncology clinic, and Judkins is working with children in the pediatric critical care unit (PCCU).

“We're getting nasal swab samples from all the children in the Hematology/Oncology clinic with Dr. Domm, and Dr. Judkins is getting similar samples from the children in the PCCU,” Williams said. “If the sample tests positive for MPV, we perform an extra step of sequencing the virus genes, something like a viral fingerprint to find out if the viruses are likely being spread more in the community, or inside the hospital.”

In this current double study, Williams and his researchers will look not just at the scope of the problem, that is, the number of chronically and critically ill children who have MPV, but also whether the presence of the virus correlates with major interventions, like bronchoscopies or surgeries. They will also document whether MPV is associated with bacterial or fungal infections that require the use of strong antibiotics or antifungal medications.

“If we can prove MPV causes these problems, the scientific community may consider the use of antivirals to help these patients,” Domm said. “The goal is to prove a need for a treatment.”

MPV is already associated with pneumonia as often as the flu is in healthy children and it is second only to RSV as a cause of bronchiolitis. Williams and James Crowe, M.D., professor of Pediatric Infectious Diseases, published those findings in the New England Journal of Medicine last year (Reporter, Jan. 30, 2004). That study marked Children's Hospital as a leader in the study of MPV. But the virus may be especially dangerous for children with suppressed immune systems, like those undergoing treatment for cancer, and those who have critical illnesses or injuries in the critical care unit.

Rebecca Koonce's 5-year-old son, Lucas, is one of the children who participated in the study in the Hematology/Oncology clinic. His nasal swab was positive for MPV. Just finding that out doesn't really change anything for Lucas, yet, but his mother says she is excited to have a name for what caused his pneumonia last year. She hopes the next step leads to a treatment.

“I just don't want any other kids to be as sick as he's been,” she said. “Knowing what to expect and knowing what it is is important. It helps me to feel more in control. Lucas has never been an explainable child.”

The same goes for dozens of families inside the PCCU. They are slowly getting information about this secondary infection and what effect it can have on their already seriously ill children.

Judkins' research is meant to describe both the frequency and the severity of the disease in the critically ill children. The study is funded by MedImmune Inc., a company based in Gaithersburg, Md., that is sponsoring similar trials in five other communities. It is hoped the findings will be released later this spring.

Grants in this area of research are growing. The first funding at Vanderbilt for this work came from a Discovery Grant award in 2002 to Crowe for $50,000, an investment that Crowe says has returned over $3 million in funding in the last two years. For example: Williams was awarded two grants from the NIH worth $500,000 total; Crowe was recently awarded a $750,000 Burroughs Wellcome Fund award to study the immunology and cell biology of MPV; the team was awarded a $1.3 million grant from the National Institutes of Health (NIH) to develop and test vaccine candidates for the virus; two pharmaceutical grants from MedImmune support epidemiology studies; and Tim Peters, M.D., assistant professor of Pediatrics in Infectious Diseases, was awarded a $350,000 grant from the NIH to study MPV basic science over the next three years.

“We’re also collaborating with David Wright, Ph.D., in the Chemistry department on structural studies of MPV proteins,” Williams said. “Vanderbilt scientists are investigating the clinical, cellular, molecular, structural and immunological aspects of MPV, so we are truly one of the top five centers in the world for the study of this new virus.”