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Major cause of infant pneumonia described by Vanderbilt Children’s experts

Jan. 28, 2004, 4:00 PM

Researchers at Vanderbilt Children’s Hospital have nailed down a clear
picture of a newly described virus that is a leading cause of pneumonia
in babies. A study in this week’s New England Journal of Medicine
defines the "who, how, and how much" of the impact of human
metapneumovirus (MPV) on children.

"Our findings show human metapneumovirus is the second most common
cause of serious respiratory illness in young children," said Dr. James
E. Crowe, the senior author of the article and associate professor of
Pediatric Infectious Diseases at Vanderbilt Children’s Hospital. "This
appears to be more important than influenza for babies."

After examining samples and data from more than 2,000 infants and
children, seen over the course of 25 years at the Vanderbilt Pediatric
Vaccine Clinic, Crowe and his team found MPV was an apparent cause of
up to 12 percent of lower respiratory illnesses in the first year of
life, rivaling the No. 1 culprit, respiratory syncytial virus or RSV.

"It’s amazing to think as pediatricians we’ve been seeing this virus
for decades, and now it’s exciting to know what it is." Crowe said.

"We do see a lot of bronchiolitis, or lower respiratory illness, that
doesn’t test positive for viruses," said lead author, Dr. John V.
Williams, assistant professor of Pediatric Infectious Diseases. "That’s
why this research is so important, because it gives a name and
description to a lot of serious infections."

Of the 2,000 children in the study, 321 had symptoms of lower
respiratory tract illness, including pneumonia, for which no viral
agent could be identified; but 20 percent of those samples tested
positive for MPV, which meant that 12 percent of all wheezing and
pneumonia seen in the clinic was due to MPV.

"That was surprising to find one virus was the cause of such a large
proportion of disease that previously tested negative for anything
else," Williams said.

The study supports previous findings that the leading cause of lower
respiratory infection in infants is respiratory syncytial virus, or
RSV. Fifteen percent of children in this study with lower respiratory
illness tested positive for RSV. Parainfluenza accounted for 10 percent
of the infections; influenza accounted for 5 percent and adenovirus for
4 percent.

"This study goes beyond just defining the scope of the problem, it
gives us the first good clinical definition of MPV," Williams said. "We
now know it is most severe in children younger than one, we know that
in two-thirds of cases it causes bronchiolitis, 10 percent will get
pneumonia, 20 percent croup and 14 percent of these children were
diagnosed with an asthma exacerbation."

The asthma connection is one element of the study’s results that will likely be scrutinized by further studies.

"One of the intriguing things we found in this study is that MPV is
three times more likely to trigger an asthma attack than RSV or similar
viruses," Williams said. "We’re not sure what it means, but the
association is robust and we believe will be duplicated in more
studies."

Williams says funding for studies to find preventions or treatments for
MPV will come quickly because this study suggests this illness is quite
costly to society; he has two NIH-funded grants to study the virus.

"It is a major cause of ear infection," Williams said. "Forty percent
of children in this study with MPV also had ear infections."

Hospitalization rates for infants infected with MPV were similar to the
rates for RSV, but more evenly disbursed throughout the year. RSV
normally appears in November and peaks in January.

"This study told us what we can expect MPV to do to healthy kids, the
next step is to find out how serious the most severe cases can be,"
Williams said. "We’re currently conducting studies at Vanderbilt
Children’s Hospital to see what MPV does to children with a depressed
immune system, like cancer or transplant patients, or to children
already in the intensive care units either because of prematurity, or
other medical issues."

Crowe is excited by the speed with which this research is heading toward prevention or treatment.

"This virus was only discovered by a virus hunter in the Netherlands
about two years ago," Crowe said. "And already we have been able to
define its clinical effects. The only virus that has moved more quickly
through research is the SARS virus."

Crowe says the National Institutes of Health is already funding studies
to develop candidate vaccines. He already has funding from a drug
company to look at an animal model to develop a vaccine.

"This virus is a good candidate for quick development of a monoclonal
antibody, much like the Synagis antibody for RSV," Crowe said. "That’s
the kind of drug that could be given to babies and children at the very
highest risk for MPV, like premature babies and cancer patients."

One of the major drawbacks right now is the lack of a standardized test to detect MPV.

"The test we used is a good one, but is hasn’t been through the
required standardization so that physicians can use it in their
day-to-day operations. We may still be two years from that," Crowe
said.

While we’re waiting for tests, prevention techniques, and treatment for
the human metapneumovirus, there are some common-sense tactics that can
be used to protect against this common cause of
pneumonia.

"Given what we know from related viruses, we can suggest that MPV is
probably spread through nasal secretions," said Crowe. "Good hand
washing is the best prevention."

Contact: Carole Bartoo, (615) 322-4747
carole.bartoo@vanderbilt.edu

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