Editor's note: The Proceedings of the National Academy of
Sciences of the United States of America published "Emergence and
predominance of an H5N1 influenza variant in China" last week.
The paper contains "ungrounded statements," Chen Hualan,
director of the National Avian Influenza Reference Laboratory, and
Shu Yuelong, director of the National Influenza Centre under the
Chinese Centre for Disease Control and Prevention, told China
Daily in an interview. The following is the transcript of the
interview.
Q: The article, "Emergence and predominance of an H5N1 influenza
variant in China," claims there is a "previously unidentified H5N1
virus sub-lineage" - the Fujian-like strain in China. Is that
true?
Chen: I have read the article and found its viewpoints and
conclusion regarding the so-called "Fujian variant" lacks
scientific evidence.
The authors alleged that the prototype virus of the "Fujian-like (FJ-like) variant" was first
detected in March 2005, and that viruses from this sub-lineage have
replaced the multiple sub-lineages of the H5N1 virus in southern
China and emerged among live-poultry markets in Fujian, Guangdong, Yunnan, Guizhou and Hunan provinces and the Guangxi Zhuang Autonomous Region.
The article further asserted the virus had already been
transmitted to Hong Kong, Laos, Malaysia and Thailand, resulting in
a new transmission and outbreak wave.
But in fact, the so-called "Fujian-like variant" was by no means
a new variant. Its gene sequence is highly more than 99 percent
similar to the H5N1 subtype virus isolated in Hunan and other
provinces during the bird flu outbreak in early 2004.
China's Ministry of Agriculture has prescribed that the samples
of all suspected cases of highly pathogenic avian influenza should
be delivered to the National Avian Influenza Reference Laboratory
for virus isolation and gene sequence analysis.
Over the past two years, our laboratory has isolated some
viruses from the waterfowl in southern China, and reported the
results to such international organizations as the Food and
Agriculture Organization (FAO) of the United Nations and the World
Organization for Animal Health (OIE).
The genotype of these viruses was fairly stable, showing no big
variance in antigenicity (the ability to trigger an immune
response).
The Ministry of Agriculture isolated only one new mutant virus
of avian influenza during a surveillance campaign early this year
in Shanxi Province and the Ningxia Hui Autonomous Region in North China.
But no new virus was discovered in southern China.
We have already posted the sequence of the newly-found virus to
the GenBank - international public genetic database, and the
ministry has also notified the case to the FAO and the OIE.
Experiments showed that the virus strain was of low
pathogenicity to mammals. My laboratory has already developed
diagnostic reagents and vaccines against the strain, and new
vaccines have been applied in Shanxi and Ningxia, which has put
infections under effective control.
Q: The article claims that the vaccine is less effective to the
"Fujian-like variant," which emerged due to the massive vaccination
in poultry in China.
As an inventor of China's avian influenza vaccine, what are your
comments on that claim?
Chen: Our laboratory has investigated the vaccine efficacy to
all representative isolates in different places at different times,
and confirmed that the vaccine currently in use is effective.
The antibody tests conducted by the Ministry of Agriculture on 3
million to 4 million samples each year have shown that the antibody
level has reached the internationally accepted protection
level.
In line with international common practice for evaluating
vaccine efficacy, we first vaccinate the animals before testing
them and observing for symptoms, deaths and virus shedding.
We have been carrying out virus tests on animals for our
vaccines, which have provided sound protection to vaccinated
poultry and proven effective in controlling all the viruses
isolated in southern China in recent years.
Furthermore, judging from the outcome of present immunization
efforts in China, it is evident that all the vaccine products in
use are effective.
As indicated in the article, the authors, conducting tests on 76
poultry sera collected from live-poultry markets in southern China
it was unclear what kind of vaccination these birds had been given
discovered that these sera are less effective in neutralizing the
so-called "Fujian-like variant" than in neutralizing other H5N1
viruses.
They concluded that the poultry vaccine currently used in China
is less effective in preventing the "Fujian-like strain."
It is unscientific to evaluate a vaccine in such a way, which is
flawed both in testing materials and methods.
What's more, the testing results described in the article do not
support its conclusion that China's massive vaccination has caused
mutation of the virus and impaired the effectiveness of the
vaccines.
?
Because even though these serum samples were collected randomly,
they still have quite high neutralizing titers against the
so-called "Fujian-like strain."
Q: What is the effect of the measure for prevention and control
of bird flu by "vaccination plus culling" that has been adopted
here in the country?
Chen: Poultry vaccination commenced in some key areas in China
right after the outbreak of bird flu in parts of the country in
2004. A compulsory program for the vaccination of all poultry began
in the second half of 2005, along with culling of all the infected
birds and the flocks at risk to eradicate the epidemic sources.
Vaccination density was maintained at more than 95 percent
between January and October this year, according to Ministry of
Agriculture statistics.
It appears that along with the increased density of vaccination,
the number of cases has reduced significantly.
For example, China reported only 10 outbreaks of H5N1 bird flu
in the January-October period this year, compared with 50 cases in
2004 and 31 in 2005, a testimony that the "vaccination plus
culling" strategy is effective.
This strategy has received the acknowledgement of many
international organizations, including the FAO and the OIE.
Q: The article states viruses from this "Fujian-like"
sub-lineage caused the five recent human H5N1 infections in
southern China. Is that true?
Shu: The Chinese mainland has confirmed 20 human infection cases
since October 2005. The infections, seven in 2005 and 13 in 2006,
are all separate cases involving 12 provinces, regions and
municipalities. The majority of the contagion, or 18 cases, were
discovered in southern China, while only two were reported in the
north.
The disease usually breaks out in the winter and spring when
there is a high incidence of respiratory diseases.
The gene sequence analysis of 16 H5N1 strains isolated from
samples collected from all cases indicated that the 15 strains
isolated from southern China cases belong to the same group. There
is no ground for five of the human cases to be caused by so-called
mutated strains in southern China.
The remaining strain isolated from the human case in northern
China (the Xinjiang Uygur Autonomous Region) belongs to
the same virus group as the strain isolated from domestic poultry
in Heishan of Liaoning Province and the strain isolated from
migratory birds in Qinghai Province.
In comparison, viruses isolated from the cases in the south are
quite different from those in the north, and also from the cases in
Viet Nam and Thailand.
As the entire gene segments of the 16 strains isolated from
cases in the mainland are from poultry sources, there has not been
a biological basis for human-to-human transmission.
For the purpose of strengthening international exchange and
co-operation, the Chinese Centre for Disease Control and Prevention
provided the WHO with two strains of human bird flu viruses in
December 2005 and four in May 2006.
This centre has also delivered some part of gene sequence of
human bird flu viruses to the GenBank.
?
Q: The article claims that "Fujian-like variant" has already
initiated a third wave of transmission throughout Southeast Asia.
What's your comment?
Chen: I've noticed that the article has repeatedly said that the
"Fujian-like" H5N1 influenza virus sub-lineage has resulted in a
new transmission wave in Southeast Asia. However, the data in the
article itself does not support this claim.
Some authors of the paper claimed two years ago that the
so-called "genotype Z virus" might lead to a worldwide pandemic.
Their claims and predictions have turned out to be all subjective
and groundless.
Predictions about major animal diseases, especially those
related to the development of avian influenza, often exert a
dramatic impact on society and people's minds.
Therefore, a responsible scientist must adopt a very cautious
attitude when making any predictions about the development tendency
of any diseases. Such predictions should be based upon extensive
scientific research and actual and reliable data.
Although the "genotype Z virus" claim of the authors was hyped
by the media, in the academic circle, however, it was not
accepted.
Just as an official of the WHO said, the "genotype Z virus" is
rather bewildering because during the avian influenza outbreak of
2004, it was not identified in countries in Southeast Asia or in
China.
Recently, one expert participating in the research of this
article told the media that there was no data indicating the
"Fujian-like" virus maintains a higher virulence, or poses higher
threat to trigger avian influenza pandemic compared with other
genotype viruses.
(China Daily November 10, 2006)
