5/23/08- 5/30/08Weekly Bird Flu Thread:WHO confirms first bird flu case in Bangladesh

JPD

Inactive
WHO confirms first bird flu case in Bangladesh

http://www.straitstimes.com/Latest+News/Asia/STIStory_240294.html

GENEVA - THE World Health Organisation (WHO) on Friday confirmed the first human case of bird flu in Bangladesh, a baby boy who has recovered, bringing the number of countries which have recorded human infections to 15.

Bangladesh authorities announced the case on Thursday, and the WHO said it had been confirmed by a laboratory at the US Centers for Disease Control and Prevention (CDC) in Atlanta.

'The case was confirmed by CDC in Atlanta. It is the first in Bangladesh,' WHO spokesman Gregory Hartl said.

The 16-month-old boy was infected in January and has since recovered, he said.

Bangladesh authorities informed the United Nations agency promptly about the case but it took time for the international laboratory testing to be completed, Hartl said.

The H5N1 virus was first detected in Bangladesh in March last year and since then the authorities have culled around 2 million chickens and destroyed more than 2 million eggs.

Avian influenza has spread through 47 of Bangladesh's 64 districts, causing losses of about 45 billion taka (S$883.8 million) for the growing poultry sector, which accounts for 1.6 per cent of the impoverished nation's gross domestic product.

'When a disease is so widespread in poultry, it is really a matter of time before you get a human case. It shows the need to control the disease in animals if you are going to reduce the chances of transmission to humans,' Mr Hartl said.

The virus rarely infects people but experts fear it could mutate or combine with the highly contagious seasonal influenza virus and spark a pandemic, which could kill millions of people.

Prior to the Bangladesh case, 14 countries had reported 382 cases including 241 fatalities since 2003, according to the WHO. -- REUTERS
 

JPD

Inactive
S Korea to upgrade measures against bird flu

http://news.xinhuanet.com/english/2008-05/23/content_8237315.htm

SEOUL, May 23 (Xinhua) -- South Korea will upgrade its measures to deal with potential human bird flu infections and allocate funds to promote research into mad cow disease, South Korea's Yonhap News Agency said on Friday.

The national health promotion commission said 658.3 billion won (about 633 million U.S. dollars) will be allocated this year to address general public concerns and critical issues like avian influenza and mad cow disease.

The commission said the goal for this year is to stockpile sufficient Tamiflu drugs to treat at least 2.4 million people in case there is a outbreak involving humans.

South Korean quarantine officials confirmed 42 cases of the virulent H5N1 bird flu strain since April 1, which have resulted in millions of birds being culled and buried. This is the third outbreak to hit the country with the first and second cases happening in the winter months of 2003-2004 and 2006-2007.

No Korean national has been afflicted by avian influenza so far.
 

JPD

Inactive
E Nepal's 6 districts at risk of bird flu

http://news.xinhuanet.com/english/2008-05/23/content_8237329.htm

KATHMANDU, May 23 (Xinhua) -- Avian Influenza Control Project in Nepal has said six districts bordering India are at risk of bird flu, reported the local media house's website eKantipur Friday.

According to Dr Manas Kumar Banerjee, coordinator of Avian Influenza Control Project of Epidemiology and Disease Control Division under Ministry of Health and Population, Jhapa, Ilam, Panchthar, Taplejung, Sunsari and Morang districts in eastern Nepal are at risk of the flu.

"There is embargo on the import of poultry items but despite the ban, items like white eggs imported from India are sold in the local market of the mentioned districts," said Dr Banerjee.

He added that animal health and human health units of the government have been focusing on warning people against the risk of flu.

He said the government is equipped with Personal Protective Equipment. "We also have a stock of antiviral medicine 'Tamiflu' that is needed in case any human gets infection by flu," he added.
 

JPD

Inactive
Large Suspect H5N1 Cluster in Sulawesi Indonesia

http://www.recombinomics.com/News/05220805/H5N1_Sulawesi_Cluster.html

Recombinomics Commentary 18:27
May 22, 2008

Five Kendari inhabitants, South-East Sulawesi, were expected strong has terjangkit the bird flu virus.

They were treated in Daerah space of the Public
Hospital isolation (RSUD) South-East Sulawesi since last Tuesday.

Their condition currently the high fever, the cough, and breathless.

Before experiencing this sign, around their residence was gotten by 80 chickens died suddenly

The five residents who were expected terjangkit the virus of Avian Influensa (H5N1) itua was Asdar, 8 years, Andika Saputra (1.3), Sarminda (10), Nuraminah (4) as well as Dg Sholeh (53).

The representative Kendari Mayor, Musaddar Mappasomba, stated his side would menangung all the medical treatment cost and the maintenance of the five residents.

Although the laboratory test was not yet known, according to Musaddar, his side already melakukan spraying disenvektan in the house of the five patients.

The above translation describes a large suspect H5N1 cluster in Sulawesi in Indonesia. The family members have bird flu symptoms and chickens near their residence died suddenly. Recently there have been three clusters including at least one confirmed case in each cluster, but all three have been denied because of lack of testing or mis-diagnosis.

The above cluster, if confirmed, would be the largest cluster this year in Indonesia, and would be cause for concern.
 

JPD

Inactive
Global Expansion of H5N1 Raises Pandemic Concerns

http://www.recombinomics.com/News/05220807/H5N1_Global.html


Commentary

Global Expansion of H5N1 Raises Pandemic Concerns
Recombinomics Commentary 22:26
May 22, 2008

Today’s report on more H5N1 confirmed whooper swans in Japan increases the likelihood of a significant global expansion of H5N1. These outbreaks of the Fujian strain in Japan are associated with record levels of H5N1 in South Korea, setting the stage for an expansion of H5N1 into new areas. H5N1 has not been previously confirmed in these northern areas of Japan or southeastern Russia. Movement into new areas parallels development almost exactly three years ago at Qinghai Lake, when H5N1 caused a massive wild bird outbreak leading to a dramatic global expansion of the Qinghai strain, which moved clade 2.2 into 50 countries west of China where H5N1 had not been previously reported.

In the current expansion, the Fujian strain (clade.2.3) is moving into new areas. However, the monitoring of this movement is punctuated with false negatives. One of the birds reported today died last month, but initially tested negative on the rapid test. This result mimics the data for the soldier in South Korea who tested positive in 2 or 3 lab tests, bit was declared negative because the N1 test was negative. The case was relatively mild, which raises concerns of more efficient transmission and undetected case.

The soldier in South Korea has parallels with the announcement of the first confirmed H5N1 case in Bangladesh. Although the child was infected in a Dhaka slum in January, he was not confirmed positive because in January he tested negative for H5, but has since tested positive in the testing by the CDC in Atlanta. Like the case in South Korea, or multiple mild cases in Egypt a year ago, such cases are easily missed in testing, if the testing is done at all. Such cases are more likely to spread H5N1 to others because they are more mobile because they are not as sick, and contacts are also not likely to be tested.

The infection in a slum in Dhaka, with no contact with domestic poultry raises transmission concerns. Dhaka had reported dead crows, which were confirmed H5N1 positive in multiple cities in Bangladesh. There were similar reports of dying wild birds in major cities in India, including Calcutta. In India, testing was minimal. Villagers who ate H5N1 infected birds and developed symptoms were watched, but not tested. The number of mild cases in India and Bangladesh was undoubtedly significantly higher than the one reported case.

Although mild H5N1 is a decided plus for patients who recover, the passage of H5N1 through mammalian hosts leads to adaptation, which is the greatest concern for H5N1. Moreover, since H5N1 can readily recombine with more aggressive strains of H5N1, the milder versions can acquire the ability to transmit efficiently, and the re-acquire virulence properties. These types of changes can be seen at the genetic level by characterizing acquire polymorphisms. In Israel, the H5N1 PB2 gene has acquired a number of human polymorphisms. Similarly, the H1N1 that is Tamiflu (oseltamivir) resistant has acquired a polymorphism, H274Y, which is found in H5N1. As noted, Florida isolates have acquired an additional NA polymorphism that is almost exclusively found in H5N1.

These cross species polymorphisms exchanges suggest that the prevalence of H5N1 in human hosts is far more common than is reflected in official WHO cases. Surveillance programs in humans and wild birds remains poor, so much of the H5N1 activity involves silent changes.

However, the movement of the Fujian strain into long range migratory birds is clear, and this strain will be co-circulating with the Qinghai strain, leading to more exchanges of genetic information and infections of more birds which are eaten by more mammals. Surveillance of mammals is even poorer than surveillance of wild birds and humans, lead to more silent spread of H5N1.

The geographic spread of H5N1 has become increasingly obvious, and the latest data from Japan, South Korea, and southeastern Russia signal a new advance into new regions such as northeastern Asia and North America.

This global expansion should become increasingly clear in the upcoming months.
 

JPD

Inactive
Global Expansion of Fujian H5N1 Confirmed

http://www.recombinomics.com/News/05230805/H5N1_Fujian_Global.html

Recombinomics Commentary 20:41
May 23, 2008

The match between the Fujian H5N1 sequences in Primorsky, Russia with multiple sequences from northern Japan and the record outbreak in South Korea leaves little doubt that a global expansion of Fujian clade 2.3 sequences has begun. H5N1 has never been reported in northern Japan or southeastern Russia and prior outbreaks in South Korea and Japan have been at the end of the year when birds are migrating into the region. The current outbreaks are in the spring, when birds are migrating out of the region.

The tracks of outbreaks (see satellite map) signal movement to the north and will likely migrate Fujian H5N1 into new regions. Although such movements may have happened previously, but not detected, the record levels in South Korea and the multiple locations in northern Japan suggest that the current levels are higher.

This expansion has much in common with the expansion of the Qinghai (clade 2.2) strain three years at Qinghai Lake. Those sequences migrated north to Siberia and Mongolia over the summer, and then spread to Europe, the Middle East, and Africa. To date, all H5N1 west of China has been clade 2.2. Clade 2.2 also expanded into south Asia as well as South Korea / Japan in 2006/2007.

The current outbreaks represent the first reports of the Fujian strain (clade 2.3) in Japan, South Korea, or Russia. The movement into northern Japan signals movement into North America in the upcoming weeks via the East asian flyway. Similarly, the movement into Russia signals migration into northeastern Russia, which will also feed into North America. The H5N1 in South Korea signals movement into Siberia, where there will be mixing with clade 2.2 from Europe, the Middle East, and Africa. This will lead to more rapid evolution via recombination between clade 2.2 and clade 2.3.

All public human sequences from China have been the Fujian strain, and the clade 2.3.4 sequences from the public sequences from Japan and Russia are most closely related to sequences from a human case in Guangdong province in 2006. Thus, these clade 2.3 sequences have been confirmed in human cases in China and the soldier in South Korea was H5 positive, although Korea has denied the infection because of false negatives for N1.

This global expansion has been confirmed with Fujian sequences in three countries that have never reported Fujian sequences previously. Surveillance programs, especially those that focus on healthy wild birds have been abysmal, in part because cloacal swabs are collected, and the methodologies used have been fatally flawed.

Recent results in Japan have also highlighted problems linked to false negatives generated by the rapid tests, which have a notoriously low sensitivity. Testing of dead and dying whooper swans in Japan has been successful, including testing on samples that have previously been negative by rapid test.

A more serious surveillance effort is required to accurately map the transport and transmission of Fujian H5N1 by long range migratory birds. The prompt release of sequences by labs in Japan and Russia should serve as a model for this surveillance.

The reliance on false negatives and the hoarding of sequences remain hazardous to the world’s health.
 

JPD

Inactive
H5N1 Confirmation Delays in Bangladesh Increase Concerns

http://www.recombinomics.com/News/05230803/H5N1_Dhaka_Delay.html

Recombinomics Commentary 16:24
May 23, 2008

The toddler became ill in January this year, and has since made a full recovery, said Hartl. Although the health authorities in Bangladesh reported the suspected case straight away, it took time for a sample from the baby to be sent and tested in the US, he said.

The above comments on the first confirmed H5N1 in Bangladesh raises serious surveillance concerns. The confirmed patient was a child with a relatively mild case of H5N1 in an overcrowded Dhaka slum with no clear connection to poultry. In January, 2008 H5N1 outbreaks in Bangladesh and West Bengal were widespread, and there was little doubt that human and poultry H5N1 were being under reported in both countries.

In West Bengal, villagers had been eating H5N1 infected birds since December, 2007 and were developing bird flu symptoms. However, India was using a “watchful waiting” approach, which kept the sick villagers under observation, but did not test. This lack of testing extended to wild birds that died in proximity to the dead poultry and delayed testing of poultry which led to delayed culling.

In Bangladesh H5N1 had been reported in 2007, but there were media reports suggesting the H5N1 in birds were being under-reported. By January reporting and culling began to increase, but those increases were accompanied by reports of wild birds dying and confirmation of H5N1 in birds literally falling out of trees in major population centers. H5N1 in crows was confirmed in densely populated Chittagong, and crows also began dying in Dhaka in late January, early February, when the above case was hospitalized. There were also reports of dead wild birds in Calcutta as well as H5N1 confirmed poultry in the suburbs.

The confirmed case in Bangladesh had tested positive for influenza A, but initial tests for H5 were negative. Consequently, the respiratory disease was not treated by Tamiflu, suggesting the infection was relatively mild although the child was hospitalized fro 14 days.

Mild H5N1 is of great concern because patients are more likely to remain mobile and spread the infection. Moreover, mild cases are less likely to visit physicians, be tested, or test positive when tested.

Thus, a mild case of H5N1 in a crowded slum in Dhaka, Bangladesh in the absence of a poultry connection is a nightmare scenario, yet confirmation came almost four months after admission.

These delays have extended a recent trend in human cases. In Pakistan, one of the largest transmission chains began in October, 2007, but was not reported until December, 2007. The reports were made after the index case fatality infected one of his brothers, who then infected two more brothers. There were no reports until a after a second brother died. By then the samples has largely degraded and only the second fatal case was confirmed. Two surviving brothers were recently confirmed based on H5 antibody increases, but this cluster was also associated with a significant delay.

In Indonesia there have been clusters linked to three of the four recently confirmed cases, but those clusters are denied even after a cluster member has been H5N1 confirmed.

Similarly, a soldier in South Korea was denied after he had tested H5 positive in two or three lab tests. The soldier had pneumonia and lost consciousness after culling H5N1 infected poultry, yet was said to be negative because of a failure to confirm N1.

Testing and reporting of H5N1 in birds is also deficient. H5 in dead geese on a farm on Prince Edward Island is allowed to degrade prior to shipment for independent confirmation and North America is declared H5N1 free.

Recent H5N1 positive whooper swans in Japan are reported after initially testing negative.

Six travelers on a Canada train are said to be influenza A negative based on a rapid test, yet subsequently test positive for seasonal flu.

This long list of false negatives and delayed reporting creates a false sense of security regarding the spread of H5N1 in avian and human populations, which can be hazardous to the world’s health.
 

JPD

Inactive
Fatal Tamiflu Resistant H1N1 Cases in The Netherlands

http://www.recombinomics.com/News/05230801/H274Y_Fatal.html

Recombinomics Commentary 12:58
May 23, 2008

Both in Utrecht and Rotterdam is a deceased patient with flu, by resistance to oseltamivir (Tamiflu). The victims were young patients with a weakened immune system strong.

The above translation describes two patients in the Netherlands who died from infection with Tamiflu resistant H1N1. Their immune system was compromised, and the H1N1 was not susceptible to Tamiflu (oseltamivir) treatment.

The report highlights the limitations of using Tamiflu to treat seasonal flu when the H274Y status is unknown. H274Y is common in many European countries. In Norway, more H1N1 infections are Tamiflu resistant than wild type. High levels have also been reported in France and Russia, while many countries have frequencies between 10-20% of H1N1 cases.

Although these isolates are susceptible to Relenza, and some are still sensitive to amantadines, the reliance on Tamiflu can have deadly consequences.

Moreover, the widespread distribution of H274Y in H1N1 can impact H5N1 treatment if the polymorphism is acquired by recombination.

Recent mild H5N1 cases raise concerns that the level of H5N1 in human populations is significantly higher than the confirmed cases reported by the WHO.
 

JPD

Inactive
Concern over mystery of Bangladeshi baby with bird flu

http://www.news-medical.net/?id=38626

A case of bird flu in a young child in Bangladesh has raised concern. According to the Bangladeshi health authorities a 16-month-old boy has been confirmed as the country's first human case of the H5N1 strain of bird flu.

While the child has recovered following treatment there is concern as to how he contracted the infection.

The boy is from a poor crowded slum area in the capital Dhaka, nowhere near a chicken farm - the case was detected during a routine check-up.

A major culling programme is now underway and authorities say it was simply a matter of time before a person was infected by the H5N1 virus.

The health ministry says it will step up its monitoring of such areas.

The H5N1 strain of bird flu first appeared in Bangladesh just over a year ago, and has since spread alarmingly.

It has infected chickens, ducks and wild birds in more than two-thirds of country's districts, as well as neighbouring parts of India but while the impact has been massive, until now, the costs has been mainly economic, to the tune of $650m.

Two million birds have been culled and as many eggs and more than one and a half million people are now without work.

Because the domestic bird population is so large and many chicken farms are in close proximity to each other, the bird flu virus has spread rapidly.

Experts fear the H5N1 strain will eventually mutate or combine with the highly contagious seasonal influenza virus and trigger a pandemic, especially in countries such as Bangladesh where people live in close proximity to backyard poultry.

While the virus rarely infects people, there have been 382 human cases worldwide since 2003, including 241 deaths, according to the World Health Organisation - most traced to contact with infected birds.
 

JPD

Inactive
Bird flu scare

http://www.thestatesman.net/page.news.php?clid=6&id=205398&theme=

SILIGURI, May 24: Panic spread in areas beyond Kumartuli, ward number four of the Siliguri Municipal Corporation today following the random death of over 50 chickens. According to the locals, chickens in the area started dying yesterday. The death toll increased today turning people apprehensive of bird flu. ARD officials sent samples of the dead birds to Kolkata for tests. SNS
 

JPD

Inactive
Farmers keep bird flu at bay

http://vietnamnews.vnagency.com.vn/showarticle.php?num=03AGR240508

LONG AN — While the avian flu epidemic spreads nationwide, many big chicken farms in Mekong Delta provinces are still safe from the scourge due to their self-contained chicken raising process and the automatic system of cooling.

This model is being employed by farmers in the Mekong Delta provinces of Can Tho, Vinh Long, Tien Giang and Kien Giang in co-operation with C.P Breeding Limited Liability Company.

Each province has between 100,000 and 450,000 chickens being raised at any given time according to this model.

Chickens are kept in self-contained coops equipped with cooling systems, suitable for every kind and age of chickens.

These cooling systems include fans with a diameter of 1.5m moving air over cold water, said Vo Van Thach, the owner of the biggest farm in An Phuoc Commune worth VND1.2 billion.

The temperature of each coop is regulated automatically and adjusted according to each type and age of chicken.

It is these systems that create a fresh living environment for the chickens, sheltered from pathogens such as the H5N1 virus.

"My chicken flocks are safe from the epidemic," said Tran Thanh Dai in Soc Trang City.

Moreover, the company helps the farmers by providing the breed, necessary techniques and veterinary support to help the farmers at every stage of the chicken-raising process.

"I’m no longer worried about either the input or the output," said Dai.

The farmers only need to pay attention to ensuring the technical standards of their coops.

After 45 days, when the chicken weighs 2.7 kg, the company will collect it and pay VND5,000 per chicken.

"By feeding 15,000 chickens, I can earn VND 72 million after a month and a half," said Thach.

In 2008, the company plans to co-operate with more farmers to increase the number of chickens raised in self-contained coops with cooling systems, said Duong Van Phan, the director of the company’s branch in Vinh Long Province. — VNS
 

JPD

Inactive
Evolution of flu strains points to higher risk

http://www.khaleejtimes.com/Display...008/May/theworld_May1165.xml&section=theworld

26 May 2008


CHICAGO - Some strains of bird flu are coming ever closer to developing the traits they need to cause a human pandemic, a study released Monday said.

Researchers who analysed samples of recent avian flu viruses found that a few H7 strains of the virus that have caused minor, untransmissible infections in people in North America between 2002 and 2004 have increased their affinity for the sugars found on human tracheal cells.

Subsequent tests in ferrets suggested that these viral strains were not readily transmissible.

But one strain of the H7N2 virus, a low pathogenic avian flu strain isolated from a man in New York in 2003, replicated in the ferret's respiratory tract and was passed between infected and uninfected ferrets suggesting it could be transmissible in humans.

The investigators said the evidence suggests that the virus could be evolving toward the same strong sugar-binding properties of the three worldwide viral pandemics in 1918, 1957 and 1968.

"These findings suggest that the H7 class of viruses are partially adapted to recognize the receptors that are preferred by the human influenza virus," said Terrence Tumpey, a senior microbiologist with the US Centers for Disease Control and Prevention in Atlanta.

The authors said that if the viruses continue to evolve in this direction, the avian flu viruses could travel more easily between other animals and humans. They called for strict surveillance of avian flu viruses and continuing federal preparations for a possible future pandemic.

The study appears in the Proceedings of the National Academy of Sciences.
 

JPD

Inactive
G743A Acquired by Vaccine Resistant H5N1 in Egypt

http://www.recombinomics.com/News/05270801/G743A_Vaccine_Egypt.html

Recombinomics Commentary 09:11
May 27, 2008

New HA and NA sequences from Egypt have been released. Two of the 2008 HA sequences, A/chicken/Egypt/1709-5/2008 and A/chicken/Egypt/1709-6/2008 are closely related to a sub-clade which was first reported in Egypt from isolates collected between mid-December, 2007 and mid-January, 2008. This sub-clade was easily distinguished from earlier isolates, although it had the regional markers defined by earlier isolates from 2006 and 2007. The majority of these isolates were from vaccinated flocks, indicating this sub-clade was vaccine resistant. The clade also had a large number of non-synonymous changes.

The same sub-clade was found in Israel in early 2008, A/chicken/Israel/1055/2008. Full sequences from this isolate were released and the NA sequence did not have G743A. The NA sequences from the two Egyptian isolates described above were closely related to the NA sequence from Israel. These three NA sequences differed from each other at two positions, One of the two positions (in A/chicken/Egypt/1709-6/2008) was G743A.

G743A had attracted interest in isolates collected form the beginning of 2007. It had been appended onto multiple genetic backgrounds in Egypt. In the same time frame, G743A was alos appended onto easily distinguished sequences in Moscow and Ghana. This concurrent acquisition was most easily explained by homologous recombination because like the vaccine resistant isolates describe above, the number of changes between those isolates with G743A and earlier precursors was minimal (2-6 changes), yet one of those small number of changes was G743A. It was also found in clade 2.2.3 isolates from Kuwait, also collected in early 2007. Sequence related to the Kuwait isolates were subsequently found throughout Europe from the summer of 2007 to early 2008. All published NA sequences from these related isolates have G743A. A similar acquisition was also seen in Nigerian isolates from early 2007.

Thus, the addition of G743A to the vaccine resistant sub-clade in Egypt and Israel is yet another example of a distinct clade 2.2 sub-clade with G743A appended. This type of acquisition by recombination involving the appending of the same polymorphism onto multiple genetic backgrounds has important applications for vaccine development.
 

JPD

Inactive
North American bird flu viruses becoming more adapted to humans: study

http://www.mytelus.com/ncp_news/article.en.do?pn=regional/ontario&articleID=2928005

Helen Branswell, Medical Reporter, THE CANADIAN PRESS

TORONTO - North American avian flu viruses of the H7 subtype - like the H7N3 viruses responsible for British Columbia's massive poultry outbreak in 2004 - seem to have adapted to more easily invade the human respiratory tract, a new American study suggests.

The adaptation is still only partial and the findings do not suggest the viruses are imminently poised to trigger a pandemic. But experts say they underscore the fact that H7 flu viruses need to be watched and studied.

"I think this is certainly amongst the most dangerous (avian flu) viruses out there," said virologist Dr. Ron Fouchier, with the Erasmus Medical Centre in Rotterdam, the Netherlands.

"And I think we need to continue to develop vaccines for H7 just as well as H5(N1)."

Fouchier was commenting on a scientific paper published Monday by the journal Proceedings of the National Academy of Sciences. Fouchier's research on avian influenza includes study of the H7N7 outbreak in the Netherlands in 2003, but he was not involved in this work.

Scientists from the U.S. Centers for Disease Control reported on their research on a number of H7 viruses, looking both at the types of receptor cells - bird or human - each was more inclined to latch onto and whether the viruses transmitted from infected to uninfected ferrets.

Of all available animal models, influenza infection in ferrets is considered to mirror most closely the course the disease takes in humans.

Human flu viruses that circulate every winter have adapted to be able to bind to the receptors that predominate in the human respiratory tract, known as alpha 2-6 receptors. Avian viruses, on the other hand, prefer the alpha 2-3 receptors found in the guts of wild birds (their natural host) and domestic poultry. Those receptors are scarce in the human upper respiratory tract.

It is assumed that an avian virus would need to make this kind of adaptation - learning to latch onto the human-type receptors - before it could transmit easily to and among humans.

Among the H7 viruses the CDC scientists studied were H7N3 viruses recovered from the two British Columbians infected during an outbreak in the poultry farm-dense Fraser Valley in 2004. More than 17 million chickens were destroyed in the efforts to stop that outbreak.

Also tested was a virus recovered from a strange H7N2 infection in the Yonkers area of New York City. A man who had no known contact with poultry was hospitalized in November 2003. Because he was suffering from other ailments, the fact that he was also harbouring an avian flu virus was not detected at the time. In fact, it was thought he had human flu.

Several months later testing at the CDC revealed the rare infection. How the man caught the virus remains a mystery.

Of all the H7 viruses studied for this work, the New York man's seemed most adapted to humans. It bound more easily to the receptors found in the lining of the human upper respiratory tract and had decreased binding to bird receptor cells. And when ferrets were inoculated with the virus, it spread from the infected animals to healthy animals placed in the same cages.

But in general H7 viruses from North America that have been isolated from about 2002 onwards seem to have developed an increasing affinity for the human-type receptors, said Dr. Terrence Tumpey, the CDC scientist who led the work.

"These viruses are partially adapted to recognize the receptors preferred by human influenza viruses, but not completely," he said in an interview from Atlanta.

"It needs to be adapted further. But I think it shows that potentially that these viruses are changing."

"Because we can look at an older North American H7 or Eurasian H7s or H5s and they have the characteristic avian influenza binding properties. Whereas these seem to be different and possibly changing."

At this point it is unclear what additional changes would be needed for an H7 virus to fully adapt to a human host - or whether H7 viruses could acquire all those changes.

When H7 viruses have caused human cases, the ensuing disease has typically been mild, with people suffering conjunctivitis (pink eye) and-or mild respiratory symptoms. There is one exception - a veterinarian infected with an H7N7 virus died during the Dutch outbreak.

The mildness of the disease may have lulled some people into a sense of complacency about H7 viruses, said Dr. Danuta Skowronski, an influenza expert at the British Columbia Centre for Disease Control.

But she insisted the fact that H7 viruses don't induce the life-threatening disease seen in H5N1 infection doesn't mean they shouldn't be viewed as a serious pandemic threat.

"H7, with its mildness, may be more - I hate to anthropomorphize - but more devious. Because through surreptitious spread - because it's milder, it's unrecognized, people might dismiss it more - it may actually have more opportunity to adapt to the human respiratory tract," she said from Vancouver.

"And even though it may be mild today, even though it may not transmit easily today, the potential is always there for it to change. And basically we don't want new (flu) subtypes in the human population. We've got enough to deal with the humanized strains."
 

JPD

Inactive
New bird flu dangers investigated

http://www.upi.com/NewsTrack/Science/2008/05/28/new_bird_flu_dangers_investigated/3949/

ATLANTA, May 28 (UPI) -- A study led by U.S. researchers suggests H5N1 is not the only strain of bird flu that could cause a pandemic.

Terrence Tumpey of the U.S. Centers for Disease Control and Prevention said more than one H7 strain of the flu virus has evolved traits needed to easily infect humans, The Times of London reported Tuesday.

While the H5N1 strain is considered the most deadly strain, it is not yet able to move from person to person. A 2003 case in New York, however, showed the H7N2 virus can replicate in the respiratory tract of mammals. A study with ferrets suggests the strain can be passed from animal to animal, the newspaper said.

Researchers said the findings suggest the virus could be acquiring an ability to bind to sugars on the cells of the human windpipe.
 

JPD

Inactive
Human H7N2 Ressortant Sequences Withdrawn from Genbank

http://www.recombinomics.com/News/05280801/H7N2_Pulled.html

Recombinomics Commentary 06:18
May 28, 2008

Here, we use glycan microarray technology to determine the receptor-binding preference of H7 influenza viruses of both Eurasian and North American lineages and assess the transmissibility of selected H7 influenza viruses using the ferret model. Surprisingly, we found that recently isolated H7N2 and H7N3 viruses of the North American lineage possess increased binding to 2–6 SA, with several strains exhibiting preferential binding characteristic of human influenza viruses. One of these was an H7N2 virus, A/NY/107/03, associated with respiratory disease in an adult male, which we found to be capable of efficient direct contact transmission in the ferret model.

The above comments describe increased affinity of North American H7 isolates for “human” receptors, as described in this week’s PNAS paper. The one isolate that has been efficiently transmitted in a ferret model has been discussed previously.

The isolate is from a patient in New York who was diagnosed March 17, 2003 after presenting in November, 2002. Sequences for seven of the eight gene segments were deposited at Genbank on March 24, 2008, 3 days after the PNAS paper was accepted for publication. The deposited sequences represented a clear human / avian reassortant. Three genes (HA, NA, NP) were avian and from a North American H7N2 source. The other four genes (PB1, PA, MP, NS) were clearly human, most closely related to H3N2 isolates from New York, circa 2003.

The sequences were accessible at the end of last month, but have since been withdrawn.

More information on why these sequences were withdrawn, and the status of the sequences, including PB2 which was not released earlier, would be useful.
 

JPD

Inactive
Boy recovers from bird flu: WHO

http://www.gulf-times.com/site/topi...=221209&version=1&template_id=44&parent_id=24

Published: Thursday, 29 May, 2008, 07:03 AM Doha Time
GENEVA: An infant in Bangladesh contracted H5N1 bird flu and survived, in the South Asian country’s first human infection with the virus, the World Health Organisation (WHO) said yesterday.

In a statement released in Geneva, the United Nations agency said a 16 month-old boy from Komalapur, Dhaka, developed symptoms in late January and then recovered.

“The case was exposed to live and slaughtered chickens at his home,” the WHO said. “Specimens have been collected from his family members and neighbours. All remain healthy to date.”

The H5N1 virus has infected millions of birds in much of Asia, Africa, and some parts of Europe. Public health experts fear it could spark a human pandemic if it mutates into a form that passes easily between people.

A total of 383 humans are known to have been infected with the virus since 2003, and 241 have died, according to the WHO.

The Bangladeshi infection was flagged during surveillance activities by the International Centre for Diarrhoeal Disease Research Bangladesh, the WHO said. – Reuters
 

JPD

Inactive
Unclear Origins of Human H7N2 Sequences from New York

http://www.recombinomics.com/News/05280805/H7N2_Unclear.html

Recombinomics Commentary 23:56
May 28, 2008

Jessica Belser et al. analyzed the binding strength between several recent avian flu viruses and the sialic acid sugar molecules found on the surface of human and ferret cells. The authors found that a few of the H7 strains that caused minor, untransmissible viral infections in individuals in North America between 2002 and 2004 have increased their affinity for the sialic acids found on human tracheal cells. They show that one strain of the H7N2 virus, isolated from a man in New York in 2003, replicated in the ferret respiratory tract and was capable of transmission through direct contact with other ferrets. Belser et al. suggest that these viruses could be evolving toward the same strong, sugar-binding properties that characterized the three pandemic viruses of the 20th century. If this evolution continues, avian flu viruses could potentially travel easily between animals and humans, according to the authors.

The above comments by PNAS highlight the potential importance of A/New York.107/2003(H7N2) isolated from a patient in New York who presented in November, 2002. This paper was accepted for publication on March 21, 2008, and sequences from seven of the eight gene segments were deposited at Genbank on March 24, 2008. These sequences became public a month later. Three of the sequences (HA, NA, NP), were avian H7N2, while four of the sequences (PB1, PA, MP, NS) were human H3N2 (most closely related to New York sequences circa 2003). The sequence data clearly indicated the virus was an avian / human reassortant. However, the characterization sheets were entitled “A Human Case of Influenza A (H7N2) in New York State, 2003” and made no mention of the reassorted nature of the sequences, which had never been previously reported for H7N2.

A year earlier the isolate was used in a Journal of Virology paper, “Pathogenesis of Avian Influenza (H7) Virus Infection in Mice and Ferrets: Enhanced Virulence of Eurasian H7N7 Viruses Isolated from Humans” and although the sequence of the HA was used in the HA1 phylogenetic tree, there was no mention of human gene sequences. Similarly, this week’s PNAS paper also describes the sequence of HA, but also does not mention the human genes.

The lack of any discussion of human sequences in either paper suggests the sequences of the human genes had not been generated or analyzed prior to the publication of these two papers.

The removal of the sequences from Genbank within a month of release suggests that the validity of the human sequences is uncertain. If the human sequences are due to lab generation of the reassortants via contamination, then the previously described results from the mouse ands ferret studies would not be applicable to the H7N2 isolated from the patient. However, the human sequences are most closely related to sequences from New York isolated in 2003, suggesting that the reassortant was naturally formed in the patient or another patient in the area around the time of infection in 2002.

The removal of the sequences suggests the origin of the sequences is uncertain.

More information on the history of these sequences as well as the sequence of PB2, would be useful.
 

JPD

Inactive
Frequency of Human H7N2 Infections Remains Cloudy

http://www.recombinomics.com/News/05280804/H7N2_Cloudy.html

Recombinomics Commentary 19:29
May 28, 2008

Also tested was a virus recovered from a strange H7N2 infection in the Yonkers area of New York City. A man who had no known contact with poultry was hospitalized in November 2003. Because he was suffering from other ailments, the fact that he was also harbouring an avian flu virus was not detected at the time. In fact, it was thought he had human flu.

Several months later testing at the CDC revealed the rare infection. How the man caught the virus remains a mystery.

Of all the H7 viruses studied for this work, the New York man's seemed most adapted to humans. It bound more easily to the receptors found in the lining of the human upper respiratory tract and had decreased binding to bird receptor cells. And when ferrets were inoculated with the virus, it spread from the infected animals to healthy animals placed in the same cages.

The above comments summarize some of the recent data on A/New York/107/2003(H7N2), which was recently characterized in two journal articles, one in Journal of Virology last year, and one in the Proceedings of the National Academy of Sciences this week. Both articles highlight the H7N2 isolate because of its association with respiratory disease in mouse and ferret models, as well as changes in affinity for human flu receptors. The ability to cause and transmit respiratory disease in mammals is of concern, because avian viruses generally do not cause such diseases in humans. Other H7 isolates caused eye disease in humans and the two animal models, and are not as concerning because the eye disease is mild, although tests for H7 antibodies in contacts indicate the H7 is easily transmitted.

The validity of the lab data has come under question because the sequences from the New York isolate were deposited at Genbank three days after the acceptance of the PNAS paper, but then removed shortly thereafter. The deposited sequences represented 3 avian (H7, N2, NP) and four human gene segments (PB1, PA, NS, MP). The sequence of PB2 was not included. It remains unclear why the sequences were removed from the database. The sequences can be accessed, but have a red banner stating, “This record was removed at the submitter's request because the source organism cannot be confirmed.” This has led to confusion regarding the virus used in the published papers. If the virus was a lab artifact which had picked up human genes, then the papers would not be characterizing H7N2 from the patient, but rather a theoretical H7N2 that could form at some future date. However, the human sequences were H3N2 circa 2003 from New York, so they may in fact be real, raising questions on why the sequences were removed. The PNAS paper makes no reference to the deposited sequences, which is also confusing since the sequences were discussed in the manuscript and therefore should have been made public.

If the sequences are real, then this is the first H7N2 human / avian reassortant, which raises teh question of what the level of such infections exist in the general population. H7N2 infections are difficult to confirm as was seen in the H7N2 outbreak in England, where there were more suspect human cases than bird cases. Although these patients did not develop pneumonia, several were hospitalized for extended stays, and the large number of suspect cases raises concerns that the H7N2 was easily transmitted. Unlike earlier H7N7 and H7N3 infections, the infections in England, like the New York case, caused respiratory diseases. This outbreak was presented at the Options VI meeting in Toronto at the “breaker” session in June. The report raised concerns that the number of people and sites involved were larger than initial media reports and promised quick answers. However, quick answers were not forthcoming, and the final report described a minimal number of confirmed cases and did not answer questions about the suspect cases who had contact with the infected birds and developed flu symptoms in late May, early June where there were few seasonal flu cases in England.

Thus, there are still many unanswered questions. The removal of the H7N2 sequences from Genbank raises questions about the published research. If the removed sequences are real, then infections by human / avian isolates raise serious pandemic concerns, due in part to the ease of transmission. Moreover, the removed H7N2 sequences also raise questions about the relationship to H7N2 sequences in England, which also have not been made public.

The confusion regarding these sequences and England’s failure to release the H7N2 sequences from the late spring 2007 outbreak remain causes for concern.
 

JPD

Inactive
Tamiflu Vaccine Linked With Convulsions, Delirium and Bizarre Deaths

http://www.naturalnews.com/023324.html

(NaturalNews) An FDA advisory panel has recommended stronger warnings on two influenza drugs after reviewing evidence linking them to neurological and psychiatric problems that have led to deaths in some cases.

The current warning on Roche Laboratories' Tamiflu (generic name oseltamivir) urges close monitoring of flu patients, particularly children, for "increased risk of self injury and confusion shortly after taking Tamiflu." The panel recommended that this warning be strengthened to say that "in some cases, these behaviors resulted in serious injuries, including death, in adult and pediatric patients."

The label of Glaxo SmithKline's Relenza (generic name zanamivir), the panel said, should be strengthened to mention "reports of hallucinations, delirium and abnormal behavior." The panel said that both labels should mention that some flu patients not taking the drugs have also experienced such symptoms.

There have been no reported deaths from Tamiflu in the United States, but in Japan, where the drug is much more widely used, at least 14 deaths have been reported. Five children under the age of 17 died after "falling from windows or balconies or running into traffic," according to the FDA. According to Roche, two people under the age of 21 died from a brain infection, and seven deaths from neuropsychiatric symptoms have also been attributed to use of the drug by adults.

Since Tamiflu's introduction in 1999, a total of 48 million prescriptions have been written, 75 percent of them in Japan. According to Roche, 1,745 of 1,808 reports of side effects came from Japan.

The FDA has noted that people in Japan appear to be more likely to report side effects than people in the United States.

In March, Japan issued a warning against prescribing Tamiflu to people between the ages of 10 and 19, and South Korea followed suit a month later with a warning against use by teenagers.
 

JPD

Inactive
Vietnamese agency to test bird flu vaccine among humans

http://news.xinhuanet.com/english/2008-05/30/content_8284664.htm

HANOI, May 30 (Xinhua) -- A Vietnamese health institute has asked for permission from the Health Ministry to test its bird flu vaccine among humans, after it worked successfully on animals.

The Nha Trang Institute of Vaccines and Medical Biological (IVAC) in central Khanh Hoa province said on Friday the first 5,000 doses of its vaccine were tested successfully on rats and chickens.

Last year, the World Health Organization (WHO) funded the institute to the tune of 2.7 million U.S. dollars, helping it build a vaccine factory with annual capacity of 500,000-1,000,000 doses. The factory, still under construction, is expected to become operational next year.

Vietnam's National Hygiene and Epidemiology Institute is testing its bird flu vaccine on 30 volunteers. The locally made vaccine has initially shown its effectiveness and safety.

The World Health Organization has confirmed a total of 106 human cases of bird flu infection, including 52 deaths in Vietnam since the disease started hitting the country in late 2003.
 

JPD

Inactive
H7N2 New York Case Due to Human Transmission?

http://www.recombinomics.com/News/05290802/H7N2_H2H.html

Recombinomics Commentary 20:41
May 29, 2008

Researchers have found that some North American strains of influenza have increased their affinity for human cell surface molecules. These findings suggest that the viruses are coming closer to attaining the characteristics needed to cause a human pandemic and that surveillance of avian flu viruses, and preparations for a possible pandemic, should continue.

They show that one strain of the H7N2 virus, isolated from a man in New York in 2003, replicated in the ferret respiratory tract and was capable of transmission through direct contact with other ferrets. Belser et al. suggest that these viruses could be evolving toward the same strong, sugar-binding properties that characterized the three pandemic viruses of the 20th century. If this evolution continues, avian flu viruses could potentially travel easily between animals and humans, according to the authors.

The above description from the PNAS commentary highlights the importance of the H7N2 isolate, A/New York/107/2003(H7N2). However, interpretation of the experimental results is muddied with the removal of the sequences from the public database shortly after they became public in late April. The deposited sequences clearly represented reassortment data since three of the sequences (H7, N2, NP) were avian, and the other four sequences were human (PB1, PA, MP, NS). The sequence of the eighth gene segment (PB2) was not made publc. The removal of the sequences by the submitter, because the origin of the sequences could not be determined, raises concerns that the sequences are due to lab artifact or a dual infection.

However, there is significant support for reassortment. The human sequences are closely related to H3N2 isolates from New York isolated in 2003, which is the expected result if the H7N2 was an early lab artifact, or was due to a dual infection. The patient was initially thought to be H1N1 infected, strongly suggesting that he tested negative for H3N2. If the original infection was a dual infection, the patient should have been positive for H3N2. If the virus was a reassortant, the patient would not have tested positive for either seasonal flu serotype, because both HA and NA were avian.

If the H7N2 in the patient matched the removed sequences, then the isolate would be a major discovery, because a reassortant between human and avian H5N1 or H7N2 genes has not been reported previously. Experiments which created reassortants with human H3N2 and H5N1 were viable, but generally did not replicate or transmit as efficiently as viruses with only avian genes. In this case however, the reassortant was transmitted more efficiently from ferret to ferret and had increase binding for human receptors, and decreased binding for avian receptors. Moreover, the infection in 2002 was not linked to any poultry exposure.

If the virus was a human / avian reassortant and the patient was not co-infected with H3N2, then it is likely that he was infected by another human, since the H7N2 had human genes. These data would raise concerns of undetected H7N2 transmissions.

Thus, the delay and/or hoarding of sequence data has clouded the interpretation of the animal experiments, as well as considerations of human to human transmissions. This delay in the human case in New York is compounded by delays in release of sequence data from human cases in England linked to the H7N2 outbreak there a year ago. These sequences are being hoarded by another WHO regional center.

The continued widespread hoarding of sequence data by WHO regional labs continues to be hazardous to the world’s health.
 
Top