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Alarm as Dutch lab mutates killer bird flu virus

From correspondents in Paris, from AFP
December 10, 2011 6:27AM

WORLD health ministers say they are being vigilant after a Dutch laboratory developed a mutant version of the deadly bird flu virus that is for the first time contagious among humans.
"We need to be very vigilant. This is something that we talked about a lot this morning," French Health Minister Xavier Bertrand said overnight on the sidelines of a meeting of the Global Health Security Initiative (GHSI) in Paris.

The GHSI comprises the G7 group of industrialised nations along with Mexico, the European Union's Commission and the World Health Organisation (WHO).

A research team led by Ron Fouchier at Rotterdam's Erasmus Medical Centre said in September it had created a mutant version of the H5N1 bird flu virus that could for the first time be spread among mammals.

The H5N1 strain of bird flu is fatal in 60 per cent of human cases but only 350 people have so far died from the disease largely because it cannot, yet, be transmitted between humans.

The announcement led to fears the mutant virus could find its way into nature or that the publication of the research on how the virus was mutated could be used by terrorists.

EU Health Commissioner John Dalli told journalists he had received assurances from Dutch authorities that the virus was secure.

"The Dutch authorities confirmed that the virus itself is stored in a very secured way and that the necessary permits were given and that the researchers are bound by a code of conduct," Mr Dalli said.

"One of the issues ... is to ensure that any information coming from this research is well controlled and without sensitive details about mutation being given," he said.

Mr Fouchier said in a statement his team had discovered that transmission of the virus was possible between humans "and can be carried out more easily than we thought."

"In a laboratory, it was possible to change the H5N1 into a virus ... that can easily be spread through the air. This process (mutation) could also happen naturally," Mr Fouchier said.

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Malaysia brushes off bird flu warning
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Adelaide Now, 31 Aug 2011
http://www.adelaidenow.com.au/ipad/virulent-bird-flu-on-the-way-back/story-fn6bqphm-1226125897426

Aussies urged to avoid chickens in Asia
Herald Sun, 31 Aug 2011
http://www.heraldsun.com.au/ipad/aussies-urged-to-avoid-chickens-in-asia/story-fn6bfmgc-1226125782963

Deadly flu viruses spreading, UN warns
The Australian, 30 Aug 2011
http://www.theaustralian.com.au/news/world/bird-flu-and-deadly-h5n1-flu-could-be-in-asia-un-warns/story-e6frg6so-1226125185262

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© Herald and Weekly Times

http://www.heraldsun.com.au/news/breaking-news/alarm-as-dutch-lab-mutates-killer-bird-flu-virus/story-e6frf7jx-1226218721424


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H5N1 transmission experiment stirs concern

Robert Roos News Editor
Center for Infectious Disease Research & Policy
Nov 17, 2011

(CIDRAP News) – A national biosecurity board that monitors "dual use" research is apparently worried about an as-yet-published study in which a mutant form of H5N1 avian influenza virus was found to be easily transmissible in ferrets, which are considered good models for flu in humans.

A National Public Radio (NPR) report today said the National Science Advisory Board for Biosecurity (NSABB) is scrutinizing the research by Dr. Ron Fouchier of Erasmus University Medical Center in the Netherlands. The board provides guidance on biological research that has a legitimate purpose but could be misused to endanger public health.

Dr. Paul S. Keim, acting chair of the NSABB, said today that the board is conducting a review of H5N1 virus transmission in mammals, but because of the board's confidentiality rules, he could not give any details. Keim is director of pathogen genomics in the Translational Genomics Research Institute at Northern Arizona University.

Referring to the Office of Biotechnology Activities in the National Institutes of Health's Office of Science Policy, Keim told CIDRAP News, "We have now been directed by OBA staff that we can acknowledge that a review process on the H5N1 transmissibility in mammals is under way. We are not allowed to provide additional details."

The H5N1 virus causes human illness relatively rarely, but it is often deadly when it does, with a case-fatality rate of about 60% among cases confirmed by the World Health Organization. Though the virus has circulated in poultry in many countries since 2003, it has not gained the ability to spread easily in humans. Scientists worry that if it did gain that ability, it could spark a fearsome pandemic.

With the goal of identifying genetic changes that could lead to greater person-to-person transmissibility, a number of researchers have introduced mutations in the virus and studied how the mutant strains behaved in animals.

Fouchier gave a general description of his experiments at a European meeting in September, according to a news story published in Scientific American after the meeting. He and his team introduced various mutations into the virus and watched their effects on its ability to attach to human respiratory tract cells. They found that with as few as five single mutations, the virus could bind to nasal and tracheal cells, according to the story.

But when tested in ferrets, this mutant virus still didn't spread very easily through close contact. Fouchier and his team then undertook to let the virus evolve naturally—a project that he described as "really, really stupid," according to the story. They inoculated one ferret with the mutant virus, and after it got sick, they exposed a second ferret to infectious material from the first one.

After they repeated this process 10 times, "H5N1 became as easily transmissible as seasonal flu," the story said. Fouchier said he concluded from this that H5N1 viruses "can become airborne" and do not need to reassort with other mammalian flu viruses to do so.

The report quoted another expert, Albert Osterhaus, also of Erasmus University, as saying the individual mutations that Fouchier introduced have already occurred naturally in animals, but not together.

Further details about Fouchier's study have been hard to come by. In response to a CIDRAP News query last week, Fouchier said he couldn't comment on the study until it is published. Other flu experts, including those at the Centers for Disease Control and Prevention (CDC), also declined to discuss the study or didn't reply to queries last week.

The NPR report said the Fouchier study is the subject of a "fierce debate" among disease experts and is being reviewed by the NSABB. The experiment was criticized by some experts quoted in the NPR report.

"It's just a bad idea for scientists to turn a lethal virus into a lethal and highly contagious virus, and it's a second bad idea to publish how they did it so others can copy it," said Thomas V. Inglesby, MD, director of the Center for Biosecurity at the University of Pittsburgh Medical Center, who is not a member of the NSABB.

While biology has a culture of openness and relies on the full sharing of findings, occasional exceptions to this policy are warranted, and Fouchier's study calls for an exception, he told NPR.

It was not immediately clear just how the NSABB might influence whether and in what form Fouchier's findings would be published. The board makes recommendations on policies governing publication, public communication, and dissemination of dual use research methods and results, according to information on the OBA Web site. It is up to the federal government to convene relevant agencies to determine how to respond to the recommendations.

One previous case in which the NSABB influenced a research publication pertained to reports on the reconstruction of the 1918 pandemic flu virus using material from preserved tissue samples, according to Keim.

"In this case NSABB recommended that the papers be modified to better represent the biosafety aspects of the research and also to explain the positive benefits of the work to public health," he told CIDRAP News. "There were no restrictions recommended by NSABB on the actual data or limitations to the results distribution."

Some other recent studies have tested the ability of mutant or reassortant strains of H5N1 to replicate and spread in animals, but the findings were less dramatic than Fouchier's.

For example, the December issue of the Journal of Virology includes a study in which researchers at St. Jude Children's Research Hospital in Memphis inserted the hemagglutinin gene from a 1997 Hong Kong strain of H5N1 virus into a pandemic 2009 H1N1 virus. When this hybrid was grown serially in human lung epithelial cells, it became more pathogenic in mice, "suggesting that these viruses may easily adapt to humans and become more virulent," the report says. The authors concluded that natural reassortment between circulating 2009 H1N1 and H5N1 viruses could lead to viruses with increased pathogenicity in mammals.

Dr. Lynn Enquist, the Journal of Virology's editor-in-chief and a member of the NSABB, told NPR that the journal's staff carefully considered whether to publish the paper. He observed that the type of reassortant the scientists created could occur in nature.

Another recent study, by researchers from the CDC and Scripps Research Institute, suggested that it would take a series of complex changes for H5N1 viruses to achieve airborne transmissibility in ferrets.

They determined that a particular strain of H5N1, when modified with certain mutations from previous pandemic viruses, could spread in ferrets by direct contact but not by airborne respiratory droplets, according to their report in Virology. Only when they inserted a neuraminidase gene from a human flu virus did this virus achieve a modest ability to spread via respiratory droplets.

"The complex genetic changes required by a clade 2.2 H5N1 virus to reach a low level of transmissibility in ferrets would indicate that considerable functional evolution is still required for acquisition of transmissibility in humans," the report concludes.

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See also:

Information about the NSABB
http://oba.od.nih.gov/biosecurity/about_nsabb.html

Nov 17 NPR report
http://www.npr.org/player/v2/mediaPlayer.html?action=1&t=1&islist=false&id=142435910&m=142437667

Scientific American story describing Fouchier's study
http://www.scientificamerican.com/article.cfm?id=next-influenza-pandemic

Journal of Virology study abstract
http://jvi.asm.org/content/85/23/12262.abstract

Virology study abstract
http://www.sciencedirect.com/science/article/pii/S0042682211004752

October 2005 CIDRAP News report on re-creation of 1918 flu virus
http://search.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/oct0505studies.html

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Copyright © 2011 Regents of the University of Minnesota

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/nov1711board.html


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ECDC warns of rising antibiotic-resistance threat

Lisa Schnirring Staff Writer
Center for Infectious Disease Research & Policy
Nov 17, 2011

(CIDRAP News) – New surveillance data in Europe show a steep rise in the percentage of carbapenem-resistant Klebsiella pneumonia, a drug-resistant issue seen as a growing threat in the United States as well.

The European Centre for Disease Prevention and Control (ECDC) released the data on antibiotic resistance today, along with new risk assessments on carbapenamase-producing Enterobacteriaceae (CPE) and New Delhi metallo-beta-lactamase 1 (NDM-1).

The release coincides with European Antibiotic Awareness Day and the launch of a new European Union strategy to battle antibiotic resistance, according to an ECDC press release. Other countries such as the United States and Canada are also conducting public awareness campaigns this week focusing on antibiotic resistance.

Klebsiella pneumoniae carbapenemase (KPC) is an enzyme that can make bacteria resistant to carbapenem and most other antibiotics. It was first found in K pneumoniae but has spread to other species of the Enterobacteriaceae family. NDM-1 is another resistance enzyme that has been recognized as a growing public health threat.

Some US-based health experts have said that, of the two resistance enzymes, KPC is the bigger concern, having spread to Southern and Western locations after first appearing on the East Coast 6 years ago. However, they warn that NDM-1 bears watching as well.

EU member states are reporting that 15% to nearly 50% of K pneumonia from bloodstream infections are resistant to carbapenems, the major category of last-line antibiotics to treat multi-drug resistant Gram-negative bacterial infections, which are often linked to pneumonia and urinary tract infections in hospitals.

Dr Marc Sprenger, the ECDC's director, said in a press release that the need to curb antibiotic resistance is critical. "Failure to act will mean that treatment options for patients with bloodstream infections, pneumonia, and urinary tract infections in hospitals will be severely limited," he said.

In a report on antibiotic use patterns, the ECDC said most use of antibiotics occurs in the community, but not all resistance to drugs such as carbapenems is linked to use outside hospitals. It noted that up to 50% of all antibiotic use in hospitals is inappropriate.

The ECDC said a risk assessment for CPE released in September follows an increasing number of healthcare facility outbreaks across the EU involving the highly drug-resistant pathogen. The report said transferring patients between hospitals, and especially between countries, boosts the risk of spreading CPE.

It said lowering the risk will require early rectal screening, added precautions such as disposable gloves and gowns, cohort nursing, and more intensive monitoring of cross-border patients.

In its updated risk assessment for NDM-1, the ECDC said though carbapenemases such as KPC and Verona integron-encoded metallo-beta-lactamase (VIM) are more common in Europe, others such as NDM and OXA-48 are increasing in prevalence.

It said patient mobility is also a risk factor for the transmission of NDM-producing Enterobacteriaceae. It urged better surveillance across the EU and the development of national guidelines on preventing the spread of the resistant organisms.

The ECDC said 13 EU countries have reported 106 NDM-producing Enterobacteriaceae cases through the end of March, an increase of 77 since October 2010.

In other drug-resistance findings, it said that some European countries are reporting a decrease in methicillin-resistant Staphylococcus aureus (MRSA) cases, though one-fourth are reporting that 25% of invasive S aureus infections are MRSA.

"This brings hope that national efforts on infection control and containment of resistance may in some cases slow down the development of resistance," the ECDC said in its report. "Nevertheless, MRSA remains a public health priority, since significantly increasing trend of MRSA was observed in four countries (Italy, Hungary, Germany, and Slovenia)."

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See also:

Nov 17 ECDC press release
http://ecdc.europa.eu/en/press/Press%20Releases/1111-EAAD-2011.pdf

Sep 13 ECDC CPE risk assessment
http://ecdc.europa.eu/en/publications/Publications/110913_Risk_assessment_resistant_CPE.pdf

Nov 17 ECDC NDM-1 risk assessment
http://ecdc.europa.eu/en/publications/Publications/1111_TER_Risk-assessment-NDM.pdf

Aug 20, 2010, CIDRAP News story "Experts offer perspective on NDM-1 resistance threat"
http://www.cidrap.umn.edu/cidrap/content/other/news/aug2010resistance_ms.html

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Copyright © 2011 Regents of the University of Minnesota

http://www.cidrap.umn.edu/cidrap/content/other/news/nov1711antibiotic.html


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