Cambodian study hints at subclinical H5N1 cases
- From: Chim <ChimS1@xxxxxxx>
- Date: Fri, 25 Jan 2008 19:48:04 -0800 (PST)
Cambodian study hints at subclinical H5N1 cases
Jan 25, 2008 (CIDRAP News) - A recent study in Cambodia suggests that
some human cases of infection with the H5N1 avian influenza virus
escape detection because symptoms are mild or absent, according to a
report from an international avian flu conference this week in
Bangkok.
The meeting drew about 500 experts from 40 countries to discuss
research and ideas on a wide range of topics. Some other topics
discussed included the idea of stockpiling vaccine adjuvants to
prepare for a pandemic, the use of engineered human antibodies as a
defense against the H5N1 virus, and the high H5N1 case-fatality rate
in Indonesia.
Cambodian study
The Cambodian researchers tested 674 people in two villages who were
exposed to the virus and found that seven of them, all between the
ages of 4 and 18, had antibodies signaling previous infection,
according to a Jan 24 Bloomberg News report.
The finding contrasts with previous serologic studies of people in
areas affected by H5N1 outbreaks. A review published Jan 16 in the New
England Journal of Medicine (NEJM) said the few serologic studies
since 2003 of people with potential exposure to H5N1 suggest that
asymptomatic or mild cases are rare. The studies involved people
living with backyard poultry, workers in live-bird markets, and
healthcare workers.
More cases of mild disease might suggest that the virus is improving
its ability to spread among humans, while becoming less virulent.
Based on the current global count of 353 cases with 221 deaths, the
case-fatality rate is almost 63%.
The Cambodian researchers, led by Sirenda Vong of the Pasteur
Institute of Cambodia in Phnom Penh, conducted their study in early
2006, according to the Bloomberg story. The researchers asked
villagers about their exposure to poultry and tested their blood for
antibodies to H5N1.
The median age of the seven people who had antibodies was 12 years,
compared with 27 years for those who had no antibodies, the story
said.
Vong and colleagues had conducted a similar study of 351 Cambodian
villagers in 2005 and found that none had antibodies to the virus. The
study was published in Emerging Infectious Diseases in 2006.
Malik Peiris, a microbiology professor at the University of Hong Kong,
told Bloomberg that the latest study supports findings from the 1997
H5N1 outbreak in Hong Kong, in which human cases were first reported.
The virus infected 18 people, 6 of whom died. Peiris said children
were less severely affected than adults and had a better survival
rate, Bloomberg reported.
"Most of the children diagnosed in Hong Kong in 1997 had a very mild
course of infection; they basically had a mild flu-like illness and
they recovered," Peiris was quoted as saying. "I don't think there is
any evidence to say the situation has changed."
The recent NEJM review said H5N1 infections involving febrile upper
respiratory illnesses without pneumonia in children have been reported
more often since 2005, but early antiviral treatment may account for
this.
Stockpiling of adjuvants
Another topic raised at the meeting was the idea of separately
stockpiling adjuvants, immune-boosting chemicals that enable vaccine
producers to reduce the dose of antigen in a vaccine without reducing
immune response. Global health officials, including those at the World
Health Organization (WHO), hope this dose-sparing approach could
dramatically increase the world supply of pandemic vaccine.
Albert Osterhaus, a virologist at Erasmus Medical Center in the
Netherlands who spoke at the conference on Jan 23, said stockpiling
adjuvants would be useful if the pandemic strain turned out to be a
subtype other than H5N1, according to a Jan 23 Reuters report.
"There's a lot of discussion to vaccinate people against H5N1 with
adjuvanted vaccines," Osterhaus said. "We might do that, but it's very
expensive and it might well be that the pandemic outbreak may not be
caused by H5N1 but by H7, H9, or H2 [viruses]."
Osterhaus said adjuvants should be stockpiled separately from
antigens, Reuters reported. "Adjuvants can be stockpiled and H5
antigen as well," he said. "So if the pandemic is going to be H5N1,
you just mix them and you get a vaccine. If not, you rapidly produce
the antigen and add it together with the adjuvant."
Currently, the United States has no licensed influenza vaccines that
contain adjuvants, according to a previous CIDRAP News report.
However, a few studies of influenza vaccines with alum-based adjuvants
have shown acceptable protection levels. In August, researchers
working on a GlaxoSmithKline vaccine reported positive results for a
split-virus vaccine combined with a proprietary oil-and-water
adjuvant. A month later, Sanofi Pasteur reported promising results for
its inactivated vaccine paired with its own adjuvant.
Using engineered antibodies
In other developments, a researcher from Crucell, a Dutch
biotechnology company, reported at the conference today that
engineered human monoclonal antibodies to the H5N1 virus protected
mice from several strains of the virus, according to a Reuters
report.
Crucell created the human antibodies by mixing antibody fragments
taken from nine blood donors with antigens from two H5N1 strains found
in Vietnam and Indonesia, Reuters reported.
Mark Throsby, project director for antibody discovery at Crucell, told
the conference that in vitro studies showed that one line of the
engineered antibodies neutralized several strains of the H5N1 virus,
including strains isolated in Hong Kong in 1997, Indonesia in 2005,
and Vietnam in 2003, Reuters reported.
In the animal studies, he said, researchers injected the engineered
antibodies into mice that had been given normally lethal doses of H5N1
virus 3 days earlier. "We were able to protect all the animals,"
Throsby was quoted as saying. "It reduced their disease and they
became well again."
Drug resistance in Indonesia?
Yesterday Menno de Jong, a virologist at an Oxford University clinical
research unit in Ho Chi Minh City, Vietnam, spoke on the topic of drug
failure in the treatment of patients who have H5N1 infections. The
case-fatality rate for the disease in Indonesia is especially high--
82%, compared with about 63% overall, based on WHO figures.
De Jong told the conference that researchers are conducting studies to
see if H5N1 patients in places like Indonesia, Thailand, and Vietnam
require higher doses of antiviral medications, Reuters reported
yesterday.
"It could be they are treated later, or the virus is different, more
virulent," de Jong told a Reuters reporter. "There are many maybes,
including differences in the susceptibility of the virus."
He told Reuters that the H5N1 viruses in Indonesia appear less
susceptible to osteltamivir, the antiviral recommended as first-line
treatment for H5N1 infections. "It's not a resistant virus, it's just
that a bit more drug [may be] needed to inhibit these [H5N1] clade 2
viruses," he said.
De Jong was a member of the WHO expert panel that wrote the recent
review in the NEJM on human H5N1 cases. In line with de Jong's
observations at the Bangkok meeting, that article said clade 1 viruses
appear to be 15 to 30 times more susceptible to oseltamivir than clade
2 viruses from Turkey and Indonesia. However, the panel wrote that the
clinical relevance of this difference in oseltamivir susceptibility
"remains to be determined."
.
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