Date: September 14, 2009
Author: Shari Roan <shari.roan@latimes.com>
URL: =20
http://www.latimes.com/news/nationworld/nation/la-sci-mono15-2009sep15,0,594=
568.story
Ref: Katz et al. paper,
http://pediatrics.aappublications.org/cgi/content/abstract/124/1/189
Antiviral drug found to reduce severity of mono
-----------------------------------------------
The so-called kissing disease is commonly treated only with rest. But
in a study, young people who received an antiviral medication early
in the illness became less sick.
Mononucleosis, the curse of high school and college students, doesn't
have to bring social and academic lives to a screeching halt,
researchers reported today. Instead, the disease can be treated to
shorten the duration of the illness and reduce the chance of
transmission.
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."
Commonly known as the kissing disease, mononucleosis is caused by the
Epstein-Barr virus. About 140,000 people become ill with mononucleosis
each year in the United States, most of them between the ages of 15 and
25. Ninety percent of adults have been exposed to mono, but for reasons
that aren't clear, not everyone becomes sick when infected. People who
are infected as children, for example, often have only mild symptoms that
go unnoticed. People who are first infected as teenagers or adults become
much sicker.
Traditionally, rest is the only recommended treatment; medications are
offered simply to ease symptoms such as swollen glands and sore throat.
Opinions vary about whether the illness is worth treating. After several
weeks of extreme fatigue and flulike symptoms, most patients recover with
no lingering effects. But some recent research suggests mono is not so
innocuous. Studies show people who have been infected with Epstein-Barr
virus carry a moderately higher risk of developing multiple sclerosis. A
few types of cancers - as well as arthritis, lupus and chronic fatigue
syndrome - have also been linked to Epstein-Barr virus.
"I think there would be a lot of interest in treating mononucleosis if
we found something that worked," said Dr. Ben Katz, a pediatrics
professor at Northwestern University's Feinberg School of Medicine. In
a study published in July in the journal Pediatrics, Katz found that
about 10% of adolescents diagnosed with the illness still have symptoms
- mostly severe fatigue - six to 12 months later.
An antiviral treatment has long been of interest to doctors, Katz said.
But there is some research to suggest that medications would not help
patients get better faster. Although the virus causes the illness - and
antiviral medications would reduce levels of the virus - the symptoms of
sore throat, swollen lymph glands, headache and fever may be due to the
body's reaction to the virus. Antivirals may not have an effect on this
immune response.
"That's why adults who have mono are so much sicker," Katz said. "It may
be that you get sick from this robust immune-system response."
The study presented today involved 23 university students who had
mononucleosis and had been sick for less than two weeks. They were given
either an experimental antiviral drug called valomaciclovir or a placebo
for three weeks. The study showed the students receiving the drug had less
of the virus in their mouths and recovered faster than did those who
received no treatment. The students taking the antiviral medication reached
a 50% improvement in symptoms in 7.6 days compared with 11.1 days for the
placebo group.
"The drug gets rid of the virus. That's the first thing you have to show,"
Balfour said. "The clinical benefit is that the kids got better faster."
Because the load of virus in oral secretions is reduced, treating the
infection may also reduce person-to-person transmission, Balfour said.
Valomaciclovir is under development by Epiphany Biosciences of San
Francisco, which also funded the study. The medication is in phase 2
studies for mononucleosis and shingles, said Christian Hofmann, vice
president of business development. "Both mononucleosis and shingles are
sort of under-appreciated diseases in terms of how much they affect
quality of life," he said.
Balfour said more research is needed on the dosage and how the medication
dissolves in the stomach and intestines. He also reported that one student
who took the medication developed pancreatitis and was briefly hospitalized.
Because pancreatitis is sometimes a complication of mononucleosis, it's
unclear what role the drug played, if any, in the condition.
Previous studies suggest that a drug already on the market, valacyclovir
(Valtrex) is also effective against mononucleosis. Balfour presented data
at the 2005 meeting of the Interscience Conference on Antimicrobial Agents
and Chemotherapy - the annual infectious diseases meeting of the American
Society for Microbiology -- that found valacyclovir significantly lessened
the severity of the illness for 10 treated students compared with 10
untreated students. The treated students also had significantly less virus
in their saliva and throat after two weeks.
In another study published in the journal International Pediatrics in 2003,
researchers treated 45 children with mononucleosis using either valacyclovir
and a steroid or a placebo. After 20 days, more than three-quarters of the
children receiving the medications showed significant improvement while no
children receiving placebo drugs had significant improvement. Valacyclovir
has been used safety for many years for the treatment of herpes infections.
All of the studies have been small, however, and much larger numbers will be
needed to confirm a benefit from antiviral treatment, Balfour said. Further,
he added, more attention should be paid to the consequences of mononucleosis
infection in order to assess the value of treating people with the infection=
.
He is conducting another study, trying to assess the effect of mononucleosis
on college students and determine whether certain characteristics are linked
to a more severe illness. Freshmen who screen negative for Epstein-Barr viru=
s
will be followed for four years to see what happens if they develop the
illness.
"We think it's worth treating," Balfour said. "But not everyone thinks so."
--------
(c) 2009 The Los Angeles Times
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - =
-
Source: Interscience Conference on Antimicrobial Agents and Chemotherapy
Date: September 14, 2009
URL: http://www.icaac.org
=20
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=3D756c7db9-a28d-4=
68e-ac8a-5825ad125848&cKey=3D5e61e22f-32bd-4fed-8e3c-75a9b60a2467
[Presentation Abstract]
Session: 146-Herpes Viruses and Other Viral Infections in
Immunocompromised Hosts
Monday, Sep 14, 2009, 8:30 AM -11:00 AM
Presentation Title: V-1256a - Randomized, Placebo-controlled, Double-blind
Trial of Valomaciclovir (VALM) for Infectious Mononucleosis (IM)
Location: Marriott Salon 7
Presentation Number: V-1256a
Pres. Time: Monday, Sep 14, 2009, 10:15 AM -10:30 AM
Category: V
Keywords: Epstein-Barr virus; infectious mononucleosis; valomaciclovir
Author(s): H.H. BALFOUR JR, H.E. VEZINA, K.A. HOGQUIST, R.C. BRUNDAGE,
B.J. ANDERSON, O.A. ODUMADE;
Univ. of Minnesota, Minneapolis, MN.
Financial Disclosures: H.H. Balfour,
Epiphany Biosciences Role(s): Grant Investigator, Received: Research Grant.
Abstract
Background
IM causes substantial loss of productivity in teenagers and young adults.
We conducted an investigator-initiated clinical trial of the guanosine
nucleoside prodrug VALM for IM under an investigator IND.
Methods
Subjects over the age of 15 with acute IM were randomized to 21 days of
VALM 4 g/day or placebo (PBO) and followed for 6 mo. Clinical, virologic,
immunologic and pharmacologic observations were made during 10 visits.
Results
21 subjects ages 16 to 24 yr (median age, 19.6 yr) enrolled a median of
6 days after onset of IM confirmed due to primary Epstein-Barr virus
(EBV) infection. 11 were assigned to VALM and 10 to PBO. VALM subjects
had significantly faster clinical improvement than PBO recipients as
documented by comparing the slopes of the plots of their physical exam/
symptom scores from each visit during the treatment period (95%
confidence intervals did not overlap; P<0.05). Severity of illness and
SF12 scores improved faster in VALM subjects but rates were not
statistically significant. VALM produced a significant decrease in
median EBV load in the oral compartment vs PBO (oral cell pellet, P=3D0.03;
oral supernatant, P=3D0.001, unpaired t test, 2-sided). The proportion of
subjects who had at least a 2 log10 decrease in EBV load in the oral
compartment was also significantly different (VALM 8/11; PBO 2/10; P=3D0.03,
Fisher exact test, 2-sided). No differences were found in clearance of EBV
DNAemia, CD8:CD4 ratios, CD8 lymphocytosis, or CD8 responses to lytic and
latent EBV tetramers in the VALM vs PBO subjects. 9/11 VALM subjects had
at least 1 plasma concentration of H2G, the parent compound of VALM, above
the in vitro IC50 for EBV in subject-derived lymphoblastoid cells, which
is 2.1 micromolar.
Conclusions
This is the first demonstration of a clinical benefit and an in vivo
antiviral effect of VALM in acute IM due to primary EBV infection. This
study encourages additional investigation of the role of VALM in the
management of diseases associated with EBV.
--------
(c) 2009 American Society for Microbiology
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