Saturday, June 23, 2012

H5N1 Mutation Guide Goes Online

by David Malakoff on 22 June 2012, 4:01 PM

As a controversial study of the H5N1 avian influenza virus published online today in Science shows, researchers are keenly interested in how mutations in the virus' genes might enable it to become transmissible in humans. Now, a new H5N1 Genetic Changes Inventory is available online to help scientists keep tabs on how the virus is evolving and spot mutations that might spell trouble.

"We thought it would be useful for people to know what changes they should be looking for," says Nancy Cox, an influenza researcher at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, who helped assemble the inventory with researchers from around the world. "It's not so much that we want people to focus on one mutation or another, but to know if there are combinations that confer certain properties" that might threaten humans, such the ability to move through the air from person to person.

The ability to quickly recognize emerging genetic changes is "essential" for robust public health surveillance, notes a statement from the World Health Organization Collaborating Center for Influenza Reference and Research at CDC, which will maintain and update the inventory. The color-coded list identifies documented mutations in key viral genes, along with literature citations and a description of how the mutation is believed to change biological function. For instance, notations next to the mutations described in today's Science paper, from a laboratory led by Ron Fouchier of Erasmus MC in the Netherlands, notes that they make the "H5 virus transmissible among ferrets."

Cox says discussion of creating and publishing the inventory began before controversy emerged late last year over publishing Fouchier's paper. "
We wanted to be more organized," she says, "about how we provided critical information to our surveillance partners as to what changes they should be looking for."

CDC: H5N1 Genetic Changes Inventory: A Tool for Influenza Surveillance and Preparedness

Since highly pathogenic avian influenza (HPAI) H5N1 viruses were first identified in humans in 1997, they
have evolved rapidly and have formed multiple distinct genetic clades. During this time HPAI viruses have
caused millions of deaths among birds and over six hundred deaths in humans.
Laboratory studies have implicated convergent evolution of certain molecular determinants for
pathogenicity and host specificity for influenza viruses in nature; however, our understanding of the precise
molecular determinants required for transmissibility and severe disease in mammals remains incomplete.
It is believed that there are likely to be multiple evolutionary pathways that would increase mammalian
transmissibility of avian influenza viruses, including HPAI H5N1 viruses.
In light of the expanding host range, geographic spread, and the effect of co-circulation of heterogeneous
viruses on interspecies transmission of H5N1 viruses, it is critical that enhanced approaches to influenza
surveillance are maintained. Early detection of the natural emergence of genetic changes that may enhance
adaptation of HPAI H5N1 viruses for humans and/or other mammals or may impair antiviral interventions
is an essential component of this effort. The WHO Collaborating Center for Influenza Reference and
Research at the Centers for Disease Control and Prevention in Atlanta, with input from many influenza
subject matter experts from around the world, has developed an inventory of amino acid mutations in
H5N1 viruses that is intended to be used by the influenza surveillance and research community as a tool to
inform the influenza knowledge base for surveillance and public health preparedness.

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Friday, June 22, 2012

Science Magazine Special Issue #H5N1

This special issue is available to AAAS members and institutional subscribers. As a service to the community, AAAS is also making these articles free to the public.


The publication in this issue of these research papers on the airborne tranimssion of H5N1 marks the end of 8 months of controversy over whether some of the data, now freely accessible, should be withheld in the public interest.


Benefits and Risks of Influenza Research: Lessons Learned

Public concern over two H5N1 influenza manuscripts has triggered intense discussion on dual use research and the way forward.


Airborne Transmission of Avian Influenza a/H5N1 Virus Between Ferrets

Avian flu can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host.


The Potential for Respiratory Droplet Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host

Some natural influenza viruses need only three amino acid substitutions to acquire airborne transmissibility between mammals.


Regulating the Boundaries of Dual-Use Research

Government must balance many competing interests in its regulation of science.


Implementing the New U.S. Dual-Use Policy

Recent dual use provisions from the federal government may provide more questions than answers.


Securing Medical Research: A Cybersecurity Point of View

Lessons from cryptography illustrate that neither secrecy measures, such as deleting technicaldetails, nor national solutions, such as export controls, will work for biological research data.


Evolution, Safety, and Highly Pathogenic Influenza Viruses

Future experiments with virulent pathogens whose accidental or deliberate release could lead to extensive spread in human populations should be limited by explicit risk-benefit considerations.


Influenza: Options to Improve Pandemic Preparation

While we wait for the development of a universal influenza vaccine, we have practical options to reduce the risk of massglobal mortality from the next influenza pandemic.

Report Abstract: Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets

Science 22 June 2012:
Vol. 336 no. 6088 pp. 1534-1541
DOI: 10.1126/science.1213362

Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets
Sander Herfst1, Eefje J. A. Schrauwen1, Martin Linster1, Salin Chutinimitkul1, Emmie de Wit1,*, Vincent J. Munster1,*, Erin M. Sorrell1, Theo M. Bestebroer1, David F. Burke2, Derek J. Smith1,2,3, Guus F. Rimmelzwaan1, Albert D. M. E. Osterhaus1, Ron A. M. Fouchier1,†

Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet (“airborne transmission”) between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.

Influenza: Five questions on H5N1

21 June 2012

Scientists now know that the deadly bird flu virus is capable of causing a human pandemic. That makes tackling the remaining unknowns all the more urgent.

The biology of the H5N1 avian influenza virus is rife with paradoxes. The virus is widespread, but hard to detect. It kills more than half of the people known to be infected, but thousands of those exposed have no apparent problems. It seems to be just a few mutations away from gaining the ability to spread from person to person, but despite more than 16 years of fast-paced evolution, it has failed to do so.

This week saw the publication of the second of two papers identifying mutations that give H5N1 the ability to spread through the air between ferrets. The papers, the latest1 from a group led by Ron Fouchier at the Erasmus Medical Center in Rotterdam, the Netherlands, and the earlier one2 by Yoshihiro Kawaoka at the University of Wisconsin-Madison and his colleagues, have been controversial because they offer what some see as a recipe for disaster — that they increase the risk of accidental or intentional release of a deadly human pathogen. But what is most unsettling about them, say many in the flu community, is the evidence they provide that the wild virus could spark a pandemic on its own. That threat makes the outstanding scientific mysteries about this tiny RNA virus — its genome just 14,000 letters long — even more pressing. Here are five of the biggest puzzles, and what researchers are doing to solve them.

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Bird Flu Paper Is Published After Debate

Published: June 21, 2012

The more controversial of two papers describing how the lethal H5N1 bird flu could be made easier to spread was published Thursday, six months after a scientific advisory board suggested that the papers’ most potentially dangerous data be censored.

The paper, by scientists at Erasmus Medical Center in the Netherlands, identified five mutations apparently necessary to make the bird flu virus spread easily among ferrets, which catch the same flus that humans do.

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Monday, June 18, 2012

Egypt: Production Of The First Egyptian-Made Vaccine For The Treatment Of Bird Flu


Announced Minister of State for Scientific Research, Egyptian Dr. Nadia Zachary for production of the first Egyptian-made vaccine for bird flu .. Confirmed that her country has become a technology for the manufacture of vaccines for avian flu with any strain may appear in Egypt or mutate.

Zachary said in a press conference held today that the vaccine has Pthouderh and manufacturing research team from the Egyptian National Center for Research .. Noting that the bird flu vaccine has passed the assessment tests a degree which makes it 95 percent better than any vaccine imported. She added that this vaccine will be put on the market during the month .. Pointing out that the need for Egypt from bird flu vaccine is estimated at about one billion and 250 million doses to combat this virus, especially as Egypt is one of the first countries in the world in the number of foci of infection with the virus in poultry and human cases of the virus and the number of deaths.

And concluded to say that there is a radical change in strategy of the state after the revolution of January 25 ..Shown that the Egyptian government has become attached particular importance to scientific research by increasing the budget for scientific research for the current fiscal year to 5.3 billion pounds.

Egypt: Veterinary sector: billion doses per year for bird flu

Monday, June 18, 2012 - 14:13

Said Dr. Osama Sulayem, Chairman of the Veterinary Services, Ministry of Agriculture and Land Reclamation, Egypt might need more than one billion per year and 300 thousand doses of resistance to bird flu.

He said a sound that has to be coming together all until we rise with wealth poultry suffered by Egypt in the past few days indicating that the disease may pose a risk to the Egyptian economy as well as on human health and the doses found in Egypt is not enough for the occurrence of any disease comes suddenly and must be vaccine development is located to suit with the disease, which happens to keep poultry.

Indonesia: Bird Flu In Humans Occurs in Bengkulu and NTB

15 June 2012

Jakarta, InfoPublik – During January to May 2012, the number of cases of avian influenza (AI) reported as many as six cases with six deaths. Additionally this year, the province of Bengkulu and NTB reported cases of AI in humans. This was said by the Acting / Deputy Minister of Health Ali Ghufron Mukti in a press release Public Puskom Strathmore on Tuesday (12/6). But the case continues to occur despite Indonesia most people including medical professionals, believe that the Influenza in Indonesia is a mild disease that self-limiting disease. So far, Indonesia has not had a specific influenza immunization program. “Although influenza vaccination to existing ones, but still given the seasonal nature Indonesia is only for people who travel to Saudi Arabia to perform Hajj,” he said. Based on surveillance data Influenza Like Illness (ILI) in 24 health centers and the Severe Acute Respiratory Infection (SARI) in 30 hospitals Indonesia is reported to the National Institute of Health Research and Development (2012), showed an increase of influenza cases from October 2011 until February 2012. Cases of Influenza H5N1 found in poultry in 33 provinces in Indonesia. Since first reported in July 2005, the cumulative number of cases reached 189 with FB 157 deaths. Stated, in Indonesia, mortality and morbidity due to FB is relatively low compared with other infectious diseases such as tuberculosis and malaria. However, FB threats to human security is greater than any other infectious disease, because there is the possibility of mutation and initiate a pandemic influenza. In addition, when the influenza pandemic occurs, the impact will affect all countries in the world. It is estimated there will be deaths in large numbers, drugs, inadequate social and economic disruption. Therefore, each state must prevent that happening and it’s not always anticipate. We remember the pandemic severe acute respiratory syndrome (SARS) in 2002-2003 and Pandemic Influenza H1N1 in 2009. The second pandemic has an impact not only health but also on economic and social aspects, he said. Ali Ghufron stated, the Government of Indonesia has taken several steps influenza pandemic preparedness and response, including the strengthening of 100 bird flu referral hospitals, strengthening epidemiology and virology laboratories, the application of sentinel and routine surveillance, vaccine development, the implementation of the ecology and transmission, clinical spectrum, management of disease and molecular genetics, training, build coordination and distribution logistics arrangements as well. “Indonesia and other developing countries have also succeeded in realizing the fair, transparent, and equitable framework in the WHO system,” he said. He explained that the framework of the fair, transparent, and equitable framework that established the World Health Assembly on the 64th WHA in 2011 in 64th WHA resolution. “This framework guarantees the right of all developing countries to gain equal access to affordable vaccines, antiviral, and diagnostic kit for influenza pandemic, and assisted in their vaccine production capacity,” concludes Ali Ghufron.