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Avian Influenza Daily Digest
October 28, 2008 14:00 GMT
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Regional Reporting and Surveillance
Africa bird flu risks remain
10/28/08 tvnz--West Africa, viewed as a potentially vulnerable bird flu hot spot, has moved quickly to reduce the risk of a widespread outbreak, but porous borders remain an obstacle to wiping out the virus.
Regional Reporting and Surveillance
Science and Technology
Genetic evidence of intercontinental movement of avian influenza in a migratory bird: the northern pintail
Molecular Ecology
AI Research
Nasty jab against bird flu research
10/28/08 Bangkok Post--Health ministers from most of the world gathered this past weekend in Egypt to plan against bird flu, with the United Nations saying the threat of a deadly global pandemic is as high as ever and a future vaccine as important as ever.
AI Research
Migratory Ducks Carry Bird Flu From Asia to Alaska
10/28/08 ENS Newswire--Wild migratory birds appear to be important carriers of avian influenza viruses from continent to continent, according to new research that scientists say has important implications for highly pathogenic avian influenza virus surveillance in North America.
AI Research
Vaxart reports positive data from preclinical studies of oral avian flu vaccine
10/28/08 Pharmaceutical Business--Vaxart, a biotechnology company focused on the development of oral vaccines, has announced positive efficacy results from preclinical studies of the company's oral avian flu vaccine.
Vaccines
Full Text of Articles follow ...
AI Research
Genetic evidence of intercontinental movement of avian influenza in a migratory bird: the northern pintail
10/28/08 Molecular Ecology--[full text available, send email with request]--Alaska Science Center, US Geological Survey, 4210 University Drive, Anchorage, Alaska 99508, USA, ?National Wildlife Health
Center, US Geological Survey, 6006 Schroeder Road, Madison, Wisconsin 53711, USA
Abstract
The role of migratory birds in the movement of the highly pathogenic (HP) avian influenza
H5N1 remains a subject of debate. Testing hypotheses regarding intercontinental movement
of low pathogenic avian influenza (LPAI) viruses will help evaluate the potential that
wild birds could carry Asian-origin strains of HP avian influenza to North America during
migration. Previous North American assessments of LPAI genetic variation have found few
Asian reassortment events. Here, we present results from whole-genome analyses of LPAI
isolates collected in Alaska from the northern pintail (Anas acuta), a species that migrates
between North America and Asia. Phylogenetic analyses confirmed the genetic divergence
between Asian and North American strains of LPAI, but also suggested inter-continental
virus exchange and at a higher frequency than previously documented. In 38 isolates from
Alaska, nearly half (44.7%) had at least one gene segment more closely related to Asian than
to North American strains of LPAI. Additionally, sequences of several Asian LPAI isolates
from GenBank clustered more closely with North American northern pintail isolates than
with other Asian origin viruses. Our data support the role of wild birds in the intercontinental
transfer of influenza viruses, and reveal a higher degree of transfer in Alaska than elsewhere
in North America.
Conferences and Training
Nations at Avian Flu Conference Urged to Step Up Fight Against Emerging Viruses
10/28/08 World Bank--The five-year fight against a deadly strain of avian influenza may be at a turning point. The often-fatal H5N1 virus that mainly affects birds has spread to 61 countries and claimed 245 human lives since it emerged in Hong Kong in 2003. But now the virus has been brought under control in 50 countries. No new countries were infected from January to September this year, according to a new World Bank and United Nations report.
Experts at the Sixth International Ministerial Conference on Avian and Pandemic Influenza in Sharm El Sheikh, Egypt, October 24-26, welcomed this news, but said the apparent halt in the spread of the virus may be due to luck as much as the global effort to detect, prevent and respond to it.
?We are at a watershed moment in the global fight against infectious diseases,? says Piers E. Merrick, who helps coordinate the World Bank?s avian flu response in the East Asia and Pacific region.
Avian flu itself is still a pandemic threat, but it also ?harbingers a more persistent global threat because it represents just one in a steady stream of diseases? that could emerge in future and jump from animals or birds to humans, he says.
?Although we have done well with avian and human influenza, addressing many of these infections will require a more sophisticated and comprehensive long-term action plan,? Merrick says.
Stakes Are High
The virus is entrenched and ?still circulating? in a number of hotspots, including Indonesia, Pakistan, parts of China, Bangladesh and from time to time in India (West Bengal), Thailand, Lao PDR, and Vietnam. Nigeria and Togo both recently experienced outbreaks.
It?s also constantly mutating and could change to a form that spreads among humans, says Olga Jonas, the World Bank?s Avian and Human Influenza Global Program Coordinator.
?Human to human transmission would be a catastrophic event,? she says. ?In six months, the virus would hit people in every part of the world.?
A severe global flu epidemic could claim more than 71 million lives and cost the world economy $3 trillion, estimates a World Bank paper, Evaluating the Economic Consequences of Avian Influenza.
With those stakes in mind, representatives from more than 120 nations went to Egypt to take stock of efforts to contain the virus. Also high on the agenda was the need for comprehensive pandemic plans around the globe.
Egypt is one of several nations that have mounted vigorous responses to the virus. The country has had 50 human cases of avian flu since 2006, about half of them fatal. The government is now waging a public information campaign to encourage safe practices in the handling of poultry.
But many developing countries lack adequate prevention, response and pandemic plans, says the World Bank-UN report.
?We have to look at the fragility and susceptibility of the whole world,? David Nabarro, Senior UN System Influenza Coordinator, said in a recent interview. Countries are not relevant when it comes to a virus of this kind. The whole world is at risk.?
$2.7 Billion Pledged Since First Outbreak
Countries have pledged some $2.7 billion to combat avian flu since the 2003 H5N1 outbreak. About $1.5 billion, mostly in grants, was disbursed during virus outbreaks and used for animal health, pandemic preparedness, and compensation for farmers forced to destroy poultry stocks. Some 600 million chickens have died or been culled in the last five years.
World Bank financing has been used to complement bilateral assistance, which is often in the form of in-kind aid. The Bank has disbursed $100 million of $400 million in commitments for 55 avian flu response and preparedness operations (mainly culling) in more than 50 countries, says Jonas.
Alt Text
Egypt has reported more than 1000 outbreaks
of bird flu in poultry, mostly in the Nile
Delta region
About a quarter of this financing is from the Bank-administered Avian and Human Influenza Facility, which has received important contributions from the European Commission and eight other donors. The Asian Development Bank has committed another $40 million in loans.
Countries had an opportunity to offer additional financial support at the Egypt conference (the United States pledged $320 million), but ?at this point political commitment on response and preparedness is as important as funding,? Jonas says.
Merrick says all countries need to develop pandemic preparedness plans that are part of an ?overarching multihazard architecture.?
These plans need to cover more than just the health sector. Banks, government agencies, grocery stores, utilities, and police all need business continuity plans to allow them to keep functioning even if, as expected, a third of the workforce is ill during a pandemic.
Merrick says the ?largely effective? global response so far to the avian flu threat should stand as an example of what can be achieved through ?sustained investment and focus on public and veterinary health systems.?
AI Research
Nasty jab against bird flu research
10/28/08 Bangkok Post--Health ministers from most of the world gathered this past weekend in Egypt to plan against bird flu, with the United Nations saying the threat of a deadly global pandemic is as high as ever and a future vaccine as important as ever.
Science is usually the biggest hurdle in vaccine development but this time it's politics, with samples being held hostage by Indonesia.
The 1918-1919 influenza pandemic killed between 20 and 40 million people around the world - more than the fatalities of the First World War.
The World Bank estimates a new pandemic could kill up to 71 million people and cost US$3 trillion. Researchers must therefore get hold of every weapon in the arsenal if they are to prevent it.
Indonesia is vital to this research.
The World Health Organisation says at least 53 types of H5N1 bird flu viruses have appeared in humans and chickens in the country, meaning that any global pandemic is most likely to start there.
Vaccine development companies are therefore keen to get their hands on samples of viruses, which are the key to a vaccine that could save millions of lives.
The Indonesian government knows this and can smell an opportunity.
During negotiations at the WHO, Indonesian Health Minister Siti Fadilah Supari insisted that, in return for sharing virus samples, foreign vaccine companies should subsidise manufacturing capacity in Indonesia; guarantee stockpiles for Indonesians; pay significant royalties to Indonesia and transfer to local Indonesian producers their cutting-edge technologies.
Although anti-corporate activists will applaud her demands, everyone else should be very scared.
While Indonesia legitimately worries about the availability of vaccines in the event of a pandemic, the current generation of vaccines is unlikely to deal with a future virus that causes a pandemic.
Stockpiling current vaccines would therefore be futile.
According to UN influenza coordinator David Nabarro, most of the focus has to date been on the H5N1 virus, but any influenza virus could cause a pandemic. It is therefore vital that the private sector engages is as much research and development as possible before any outbreak.
Vaccine research is a risky business, with an extremely high failure rate: even if a company does get access to the virus samples, it is unlikely that anything marketable will emerge for ages.
For a drug to make it to market, drug approval bodies (such as the FDA in the US) require it to pass through at least four phases of trials.
Less than one in a thousand molecules make it past the first, pre-clinical stage. The chances of a drug making it all the way to approval are less than 0.03%. It therefore costs on average $1 billion to bring a new vaccine to market - a huge amount for even the biggest company to risk.
Another issue in pandemic control is the need to produce huge quantities of vaccines rapidly.
It takes several months to mass-produce seasonal flu vaccines via the traditional, egg-based method. This won't be quick enough in times of emergency. Therefore millions need to be spent on researching new, speedier cell-based methods of vaccine production.
If the Indonesian government demands that the private sector hand over too much in the way of intellectual property and technology in return for samples of body fluid in which viruses reside, companies will be deterred from researching an avian flu vaccine. And without a preventative vaccine, the chances increase of a 1918-style pandemic.
Indonesia may have already pushed too far on this: at the World Health Assembly in May, WHO member states rubber-stamped many of Indonesia's proposals relating to mandatory private-sector technology transfer in return for virus sharing.
These kinds of provisions make it too risky for companies to invest in vaccine research, so they render a vaccine less likely. (While governments can be good at early stage research, the vast majority of medicines available today were developed by the private sector.)
The WHO will discuss this matter again in Geneva this December. Indonesia's health minister has already stated that her plan will win global support.
Kartono Mohamad, former head of Indonesia's Doctors Association, has said: "She is not only gambling with the virus, but with the safety and security of the Indonesian people as well."
This gamble could leave Indonesia and vaccine companies with nothing.
The losers will be the ordinary people of the world, who will be left defenceless against an avian flu pandemic.
AI Research
Migratory Ducks Carry Bird Flu From Asia to Alaska
10/28/08 ENS Newswire--Wild migratory birds appear to be important carriers of avian influenza viruses from continent to continent, according to new research that scientists say has important implications for highly pathogenic avian influenza virus surveillance in North America.
Migratory bird species, including many waterfowl and shorebirds, that frequently carry low pathogenic avian influenza and migrate between continents may carry Asian strains of the virus along their migratory pathways to North America.
Scientists with the U.S. Geological Survey, in collaboration with the U.S. Fish and Wildlife Service in Alaska and the University of Tokyo, have found genetic evidence that northern pintail ducks carried Asian forms of avian influenza to Alaska.
"Although some previous research has led to speculation that intercontinental transfer of avian influenza viruses from Asia to North America via wild birds is rare, this study challenges that," said Chris Franson, a research wildlife biologist with the USGS National Wildlife Health Center and co-author of the study.
Most previous studies examined bird species that are not transcontinental migrants or were from mid-latitude locales in North America, regions far removed from sources of Asian strains of avian influenza, Franson said.
For this study, scientists with the USGS, in collaboration with the U.S. Fish and Wildlife Service, state agencies, and Alaska native communities, obtained samples from more than 1,400 northern pintails from locations throughout Alaska.
Samples containing viruses were analyzed and compared to virus samples taken from other birds in North America and Eastern Asia where northern pintails are known to winter.
Researchers capture northern pintail ducks at Lake Izunuma-Uchinuma, Japan. (Photo courtesy USGS Alaska Science Center)
The scientists observed that nearly half of the low pathogenic avian influenza viruses found in wild northern pintail ducks in Alaska contained at least one of eight gene segments that were more closely related to Asian than to North American strains of bird flu.
None of the samples were found to contain completely Asian-origin viruses and none were highly pathogenic.
The low pathogenic form of the disease commonly causes only mild symptoms such as ruffled feathers and a drop in egg production, and may easily go undetected.
The highly pathogenic form is far more dramatic. It spreads very rapidly through poultry flocks, causes disease affecting multiple internal organs, and has a mortality that can approach 100 percent, often within 48 hours.
Under the crowded conditions of intensive poultry farming, some variants of the H5 and H7 viral subtypes derived from wild birds can evolve into highly pathogenic avian influenza viruses.
It was a highly pathogenic form of the H5N1 bird flu virus that spread across Asia to Europe and Africa over the past decade, causing the culling of hundreds of millions of chickens and ducks, and the deaths of 245 people, raising concerns of a possible human pandemic.
Avian influenza viruses do not normally infect humans but there have been instances of certain highly pathogenic strains causing severe respiratory disease in humans. In most cases, the people infected had been in close contact with infected poultry or with objects contaminated by their feces.
Still, there is concern that the virus could mutate to become more easily transmissible between humans, raising the possibility of an influenza pandemic.
In June, the Centers for Disease Control and Prevention in Atlanta released results of a study suggesting that some North American avian influenza A H7 virus strains have properties that might enhance their potential to infect humans and their potential to spread from human to human.
"We know that influenza viruses are constantly changing and that is why it's so important to watch them carefully," explained Dr. Jessica Belser, CDC lead author on the project. "In this study, we discovered that some recently identified avian influenza A H7 viruses have some properties that could enhance their potential to infect people and possibly spread among people."
The role of migratory birds in moving the highly pathogenic virus to other geographic areas has been a subject of disagreement among scientists that focused on how likely it is for H5N1 to disperse across continents via wild birds.
For this study, the researchers chose northern pintails because they are fairly common in North America and Asia, they are frequently infected by low pathogenic avian influenza, and they are known to migrate between North America and Asia.
In addition to the samples from more than 1,400 ducks, the scientists utilized satellite telemetry in their research. In February 2007, biologists from the Alaska Science Center worked with Japanese scientists to mark 27 northern pintail ducks with satellite transmitters at Lakes Izunuma-Uchinuma in the Miyagi Prefecture of Japan. In February 2008, this international research team marked 52 pintails with satellite transmitters. Pintails were again marked at Lake Izunuma-Uchinuma as well as at Gosho Reservoir in the Iwate Prefecture. An additional sample of pintails will be marked in 2009, the final year of the study.
"This kind of genetic analysis - using the low pathogenic strains of avian influenza virus commonly found in wild birds - can answer questions not only about the migratory movements of wild birds, but the degree of virus exchange that takes place between continents, provided the right species and geographic locations are sampled," said John Pearce, a research wildlife biologist with the USGS Alaska Science Center and co-author of the study.
"This research validates our current surveillance sampling process for highly pathogenic avian influenza in Alaska and demonstrates that genetic analysis can be used as an effective tool to further refine surveillance plans across North America, said Pearce.
The study is published this week in the journal "Molecular Ecology."
Regional Reporting and Surveillance
Africa bird flu risks remain
10/28/08 tvnz--West Africa, viewed as a potentially vulnerable bird flu hot spot, has moved quickly to reduce the risk of a widespread outbreak, but porous borders remain an obstacle to wiping out the virus.
Creaking infrastructure and grinding poverty that affects large swathes of the population also complicate efforts to contain the deadly H5N1 bird flu virus, which has killed 245 people since 2003 in Asia, Africa and Europe.
West African governments have found it hard to control the movement of people and animals across borders - necessary to contain the virus - in a region where some countries are only now recovering from years of civil strife, officials say.
"The borders are porous and there are unapproved routes that people use without being seen. It is difficult," said Anna Nyamekye, Ghana's deputy minister for agriculture.
The bird flu virus, having earlier hit Asia, appeared to arrive in West Africa in 2006 and has been detected in a string of countries there including Nigeria, Benin, Cameroon and Ghana.
"Nigeria still has it. Togo, our direct neighbour, still has it, and on our north we are bordered by Burkina Faso which also has it. We are hemmed in," Nyamekye said.
The immediate concern for most governments dealing with bird flu is the loss of food supply, while the bigger global concern is of a possible future pandemic.
Scientists say H5N1 is steadily changing and fear it could mutate and jump between humans, threatening a much more deadly flu pandemic that experts worry could quickly sweep the world, killing tens of millions.
Experts fear poverty, inadequate medical facilities and a large unregulated farming sector in Africa could allow outbreaks to go unnoticed longer, increasing the risk of the virus mutating. But compensation plans for culled birds and strident surveillance have so far limited damage in West Africa.
"The virus in Nigeria is still there, but it is under control," Joseph Domenech, the chief veterinary officer of the Food and Agriculture Organisation (FAO), told Reuters on the sidelines of a bird flu conference in Sharm el-Sheikh.
"When they had the reintroduction one month ago, it was detected and eliminated immediately," he said. "The same in the surrounding countries."
The virus is also present elsewhere in Africa, in Egypt, Sudan and Djibouti. In Egypt, it is considered endemic in the domestic bird population, and has killed 22 people.
Compensation and cooperation
Bird flu, while present in West African poultry, has caused only one known human death there, and analysts say a concerted regional response, with international help, has lowered the risk of large-scale outbreaks despite the difficulties.
Taking early lessons from Asian bird flu outbreaks, countries in the region quickly established compensation as a means to encourage farmers to come forward when their birds fall ill with suspected bird flu. Rural farmers are often reluctant to report an outbreak in their flocks because they fear a loss of revenue from a quarantine and culling programme, essential for stopping further spread of the virus.
Nigeria -- the most populous African country and home to the biggest poultry industry in West Africa -- pays market rates for all birds that die after notification of a confirmed outbreak, whether by government-imposed culling or from the virus itself.
"We won't pay for birds that died before notification. That way they have to report quickly," Nigeria's chief veterinary officer Junaidu Maina said.
Since 2006, the Nigerian government has culled 1.3 million birds and paid $5.4 million in compensation to poultry farms and owners of backyard flocks, Maina said.
Ghana, which also has a compensation programme, has made payouts dependent on adequate biosecurity on private farms.
"If the cause was because the place was not clean enough, then you will pay. We have used that to force them to go by (national standards)," Nyamekye said.
China and Vietnam, two Asian countries where the virus is entrenched, both initiated mass vaccinations that appear to have halted the spread of the virus, but at huge cost that most African nations cannot afford.
North African Egypt says it cannot afford to provide compensation and instead relies on awareness-raising and free vaccinations of backyard birds. It is also seeking to minimise the live bird trade.
Most countries in West Africa now have integrated bird flu plans that involve ministries of health, agriculture, finance and communication. They also pool resources and skills for the shared fight against this looming threat to food security.
In one example, Ghanaian veterinarians travelled to Togo to provide assistance after a recent outbreak there, and samples were sent back to laboratories in Accra.
"We work in collaboration with our neighbours. If you look at the nature of our borders in West Africa, we are so close to one another," Ghana's Nyamekye said.
"We don't joke with the fact we are still at risk."
Vaccines
Vaxart reports positive data from preclinical studies of oral avian flu vaccine
10/28/08 Pharmaceutical Business--Vaxart, a biotechnology company focused on the development of oral vaccines, has announced positive efficacy results from preclinical studies of the company's oral avian flu vaccine.
The data presented are from studies measuring the effectiveness of an orally administered avian flu vaccine designed by Vaxart scientists using the company's proprietary modular platform. The Vaxart vaccine (ND1) comprises a non-replicating chimeric adenovirus-5 vector, or delivery vehicle, engineered to express avian flu hemaggluttinin (HA) and a TLR3 ligand as a vaccine adjuvant.
In the study, Vaxart tested the ND1 vaccine using oral administration to ferrets, widely recognized as the most predictive animal model for influenza research. Researchers administered vaccine at the start of the study and at four weeks. At eight weeks, researchers measured antibody responses, then monitored survival following direct nasal exposure of 10 times the median lethal dose of H5N1 avian influenza virus.
Approximately 75% of oral vaccinated ferrets developed antibody levels of 1:200 or greater, survived the challenge and were healthy as demonstrated by weight gain after challenge, while all 12 control ferrets either died (67%) or became very ill (33%). These results, if confirmed in human immunogenicity studies, compare well to the approved, injectable avian flu vaccine that achieved protective antibody levels in 45% of human subjects.
Based on these results, Vaxart plans to proceed to an investigational new drug application (IND) and begin clinical studies of the avian flu vaccine in 2009. The company is also developing an annual flu vaccine.
Sean Tucker, Vaxart's founder and vice president of research, said: "Injected vector-based vaccines that deliver a target pathogen protein have shown excellent potency in animal models, but their application has been limited in humans because the immune system typically responds to the vector rather than the target.
"By using oral delivery of a non-replicating vector with a potent adjuvant, we achieve a robust immune response that is focused on the targeted pathogen rather than the delivery vehicle. This approach addresses the problems that have plagued vector-based vaccination and also allows us to create different vaccines simply by switching out the antigen."
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