The Journal Nature Weighs In On Lab Accidents & Biosafety

 

 

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In the wake of revelations regarding laboratory safety lapses both at the FDA and the CDC involving `select agents’ including anthrax, smallpox, and H5N1 avian influenza, and the ongoing Debate Over Gain Of Function research, we are seeing agencies, scientific journals, universities, politicians, consultants, newspaper editorial boards, scientific working groups, and individual scientists all publicly staking out their positions on these issues.

 

A little over two weeks ago, the Cambridge Working Group produced a consensus statement, which urges caution, and better regulation and oversight of laboratory research seeking to enhance the virulence, transmissibility, or host range of pathogens with pandemic potential (PPPs).

 

While just yesterday, the newly formed coalition Scientists for Science, posted a statement of their own, that called their work `essential’ and dismissed many of the concerns being raised over GOF research as being overstated.

 

Not everyone is convinced, however, as evidenced by last week’s ECDC Comment On Gain Of Function Research, which acknowledged the potential public health risks that these types of experiments can pose, and proposed that the overriding concern of researchers should be first, and foremost  `to do no harm.’

 

Today the Journal Nature has two articles on Laboratory safety standards (or the lack thereof).  First an article by Declan Butler, on the lack of universal, and consistent standards for laboratories conducting work on potentially dangerous pathogens.

 

Biosafety controls come under fire

Experts call for a stronger safety culture at secure sites after incidents involving anthrax and flu in a US laboratory.

Declan Butler

29 July 2014

Recent accidents involving deadly pathogens at a leading laboratory in the United States highlight the need for a major global rethink of biosafety controls, experts say.

The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, reported two accidents involving anthrax and the deadly H5N1 influenza virus. Biosafety professionals argue that such incidents show that without a strong culture of biosafety, even highly secure facilities are susceptible to errors that could place workers and the public at risk.

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A second report, this time an editorial, suggests that lab accidents such as the ones making headlines this summer happen far more often than are ever reported, and calls for full transparency.

 

Safety doesn’t happen by accident

To create a strong biosafety culture, information on mishaps involving deadly pathogens must be reported and shared fully and transparently.

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Vietnam Girds Against H7N9 As H5N1 Spreads

Photo Credit – FAO

 

 

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Vietnam has dealt with the deadly H5N1 avian flu virus for more than a decade, winning temporary battles, but never the war. In recent weeks we’ve seen a steady resurgence in the number of  provinces reporting infected poultry, which I last blogged about on the Feb. 15th (see Vietnam: H5N1 Poultry Outbreaks Spread To 8 Provinces).

Although media sources are reporting a range of figures, today the Bernama news agency is reporting that the avian virus has spread to 21 provinces:

 

Bird Flu Hits 21 Provinces In Vietnam

HANOI, Feb 26 (Bernama) - Bird flu has hit 21 provinces and cities across Vietnam with around 64,000 infected chickens culled, according to latest statistics from the Animal Health Department.

The number of birds killed in the central province of Khanh Hoa and the northwestern province of Lao Cai has reached almost 20,000, members of the National Steering Committee for Bird Flu Prevention and Control heard at a meeting here on Wednesday.

Vietnam News Agency (VNA) reports the outbreak was attributed to the complicated weather in the first two months of the year, and the increase in shipping and trading of poultry during the recently-ended Lunar New Year (Tet) festival.

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Complicating matters, less than a month ago we learned that the H7N9 virus had shown up in Guangxi Province, expanding its range southward, and moving it closer to Northern Vietnam (see  Guangxi Province Reports Their First H7N9 Case). 

 

This prompted the FAO earlier this month to issue a statement on H7N9’s Cross Border Threat advising neighboring countries to act now to prepare for possible outbreaks

 

Today, veteran science writer Declan Butler has a cautionary piece appearing in Nature News on Vietnam’s vulnerability to this new avian threat, and the steps they are taking to combat it.  Follow the link below to read:

 

 

Vietnam on high alert over flu risk

H7N9 avian influenza may spread from China for first time.

• Declan Butler

26 February 2014

The H7N9 avian-influenza virus that has killed more than 100 people in China in the past year has for the first time been detected in a province bordering Vietnam, raising the prospect that the disease may take hold across Asia and beyond. It was found in poultry in the live-bird markets of southern China’s Guangxi province in late January, and has caused three known human cases in the region.

The news comes as a surge in human H7N9 flu cases in China since the start of the year shows signs of abating, possibly because of the re­introduction of control measures. Vietnam, which had already prepared response plans for such an H7N9 outbreak, has placed itself on high alert. “There is a very high likelihood of H7N9 entering the poultry sector in Vietnam,” says Peter Horby, a researcher at the Oxford University Clinical Research Unit in Hanoi.

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In a related story, Thanh Nien News is reporting:

 

Vietnam fears lack of equipment to cope with H7N9

Wednesday, February 26, 2014 10:24

Vietnamese health authorities have expressed concerns over the lack of equipment to cope with the possible outbreak of the new virulent H7N9 strain of bird flu.

Health Minister Nguyen Thi Kim Tien told an online conference Sunday that nine of the 28 thermometers at border gates across the country used for anti-bird flu work are currently out of order.

Meanwhile, H7N9 can enter the country at any time, she said.

According to a representative from the US Food and Agriculture Organization (FAO), the shut-down of poultry markets in China has led to poultry being sold to other countries at low prices, while it is difficult for Vietnam to control the imports of poultry via the border with China.

Takeshi Kasai, World Health Organization (WHO) representative to Vietnam, said H7N9 can enter Vietnam via smuggled poultry or humans.

Authorities in Lang Son Province, which borders China, said they are maintaining 14 checkpoints to control the import of poultry around-the-clock at border areas.

Currently, 17 provinces around Vietnam have reported outbreaks of the H5N1 strain of bird flu.

 

 

Given the history of a porous border with China, considerable illicit poultry trade, and the devastating effects from the introduction of the H5N1 virus more than a decade ago,  Vietnamese officials are understandably on guard against this new virus.

 

The history with avian flu viruses has been, that once they become entrenched in a region’s poultry population, they can be extraordinarily difficult to eradicate.

 

And while H5N1 and H7N9 are currently the two viruses that are viewed with the most concern, we’ve seen evidence of other novel reassortants appearing in Chinese poultry (H10N8, H5N5, even a new version of H7N7, etc) which conceivably could eventually spread beyond their borders as well.

Declan Butler On The Lull In H7N9 Cases

 

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Declan Butler, writing for Nature News, has an update (and Google Earth Maps) on China’s H7N9 outbreak, and the apparent lull in cases over the past couple of weeks.

 

Follow the link to read:

 

Avian flu update: lull in new H7N9 cases

Epidemic has spread to three more Chinese provinces, but no new cases reported since 7 May.

Declan Butler

Nature  doi:10.1038/nature.2013.12910

14 May 2013

 

An update to Nature's exclusive map of the H7N9 avian influenza shows how the virus expanded its geographical range in mainland China in late April. Since then, however, the epidemic has gone into a lull, with just one person falling ill with H7N9 since the start of May. The drop might reflect that authorities's control measures, such as the closure of live bird markets, are working, but it is also possible that the epidemic will rear its head again later.

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Nature: The Row Over H7N9 Sequencing Data

Photo Credit – CDC 

 

 

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There is an old adage of uncertain parentage – but most often attributed to political scientist Wallace Sayre – that (paraphrased) states, `Academic infighting is so bitter, because the stakes are so small’.

 

Of course, that isn’t nearly as true as it once was.

 

The stakes in academia now extend far beyond the publish or perish incentive in order to achieve tenure.  In addition to prestige, the fruits of research today can be worth millions in terms of government and private grants, patents, or licensing agreements to individuals, universities, organizations, and even governments.

 

These incentives have often led to research being closely held until papers can be published and proper credit bestowed to the originators.

 

In the fast moving world of virology, where – as we’ve recently witnessed – new, and potentially dangerous viruses can pop up and begin to spread quickly, delays in releasing data can have serious consequences for public health.

 

To overcome this hoarding of data - which can impede other researcher's progress for months or even years - GISAID was set up in 2008 to allow researchers to deposit, and get credit for, genetic sequences they have worked out.

 

But as the following  Nature article from Declan Butler & David Cyranoski explains, once sequences are deposited, the process gets complicated and things don’t always go as well as planned. 

 

Follow the link to read:

 

 

Nature | News

Flu papers spark row over credit for data

Rush to publish on H7N9 avian flu upsets Chinese scientists.

• Declan Butler
• & David Cyranoski

01 May 2013

On 31 March, China reported the first human cases of infection with a new H7N9 avian flu virus. The same day, a team at the Chinese National Influenza Center (CNIC) in Beijing uploaded to a research database the genetic sequences of viruses isolated from the first three human cases. But Nature has learned that in the days that followed, Chinese scientists and officials grew increasingly concerned that China might lose credit for its work in isolating and sequencing the virus.

 

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China: Currently No Positive H7N9 Tests In Pigs

Credit Wikipedia

 

 

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Determining the reservoir host (or hosts) for the emerging H7N9 virus remains a a top priority (see Declan Butler’s Urgent search for flu source) if this bird flu outbreak in China is to be quickly quashed. 

 

While traces of the virus have been found in a small number of birds (see Shanghai: Testing Reveals No Widespread H7N9 In Market Poultry) sold in live markets, another focus of the investigation has been on pigs.

 

The deaths, and illegal dumping, of thousands of pigs into the Huangpu river that flows into Shanghai last month has raised suspicions, but so far none of the limited samples tested have yielded a cause of death.

 

Today we get a story reassuring that thus far, no pigs in China have tested positive for the H7N9 virus. 

 

Missing from this report are such useful details as:

 

• how many pigs have been tested
• when and where these samples were collected
• the type (and sensitivity) of the tests used

 

These are still early days in the epidemiological investigation into this outbreak, and so it is probably safe to say that pigs have not yet been completely eliminated from the suspect list.

 

This from Xinhua News.

 

 

Currently no positive samples of H7N9 found in pigs: WHO

English.news.cn   2013-04-09 23:09:35
 

GENEVA, April 9 (Xinhua) -- No positive samples of the H7N9 virus have been found in pigs or farms in China so far, the World Health Organization (WHO) announced on Tuesday.

 

WHO spokesperson Gregory Hartl said animal samples that tested positive were from poultry markets, including live bird markets.

 

"So the focus at this point is on poultry markets," said Hartl.

 

However, Hartl told reporters that for the moment, "we don't have 100 percent surety on what the source of infection is. That might not be the correct source or the only source.

 

"He added close contacts of confirmed cases of the deadly disease had been closely monitored with none so far testing positive for H7N9.

 

"At this point, there is no evidence of sustained human to human transmission," he said, adding that there are some "suspected but not yet confirmed cases of perhaps very limited transmission between close family members."

 

"They are still being investigated," he said.

 

Hartl told Xinhua one of the suspected family clusters was in Shanghai, with three family members having similar symptoms and one of them being confirmed of H7N9.

 

The confirmed case died, so has another suspected family member, according to Hartl.

 

The other suspected family cluster, which included two family members with one of them being confirmed, was in Jiangsu Province, he said.

 

Hartl said that even if the infection of H7N9 is confirmed in other family member, further investigations are still needed to make sure whether that's a human to human transmission between constant and close contacts or an infection with virus from the same environmental source.

 

He said Chinese health authorities had been working openly and closely with WHO.

 

Nature: Declan Butler On The H7N9 Virus Sequences

 

Site of recent H7N9 infections

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Declan Butler, writing for the Journal Nature, has commentary and opinions on the H7N9 virus from a pair of heavy hitters in the world of virology; Malik Peiris & Masato Tashiro.

 

Too good to synopsize, so I’ll just step aside and invite you to read:

 

 

Nature | Breaking News

Novel deadly bird flu virus kills two in China.

Declan Butler

02 April 2013

 

Scientists worldwide are racing to assess the pandemic potential of an H7N9 flu virus that has killed at least two people in China.

 

Scientists and public health officials worldwide are on alert after China announced on Easter Sunday that two people had died and a third had been seriously sickened from infections with a new avian flu virus, H7N9, that has never been seen before in humans.

 

The emerging, if preliminary, analyses of the viruses' genomes point to the possible spectre of a pathogen that might spread silently in poultry without causing serious disease. That would make the virus difficult to monitor even as it causes serious disease in humans.

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Note: Link repaired.

Nature: Receptor For NCoV Found

Photo Credit NIAID

 

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A fairly technical report appears in the Journal Nature  today - produced by research teams in both Europe and Saudi Arabia - that establishes the mechanism by which the novel Coronavirus NCoV (here called hCoV-EMC) binds to, and infects, mammalian cells.

 

They found this novel coronavirus uses a well known cell surface protein called dipeptidyl peptidase 4 (DPP4) to enter and infect human cells. 

 

This DPP4 cell surface protein (also called CD26) is evolutionarily conserved in other species, including bats (suspected of being potential species), non-human primates, and other animals – all of which suggests that this virus might be able to infect a wide range of hosts.

 

Working in vitro with Vero & COS-7 cells (African Green Monkey kidneys), Huh-7 (human hepato-carcinoma) and kidney cells of the P. pipistrellus bat, researchers found how hCoV-EMC’s receptor-binding domain latched onto cells. 

 

Using protein-specific antibodies, they were able to block specific receptors, systematically narrowing the field of possible attachment sites.

 

When DPP4 proteins were blocked, the virus was no longer able to attach to cells and cause infection. A discovery that could potentially lead to some specific treatment for this virus down the line.

 

These are, of course, early days.  And we still know very little about the origin – and the potential – of this virus.

 

The researchers point out that (in humans) DPP4 is primarily expressed by epithelial cells in the in kidney, small intestine, liver and prostate. They also observed that DPP4 is expressed by non-ciliated bronchial epithelial cells of the respiratory tract.

 

Locations consistent with the clinical picture of infection we’ve seen over the past year, that has often included both pneumonia and renal failure.

 

Declan Butler at Nature has far more on all of this, after which you’ll find a link to the study.

 

Receptor for new coronavirus found

Virus might have many animal reservoirs.

Declan Butler 13 March 2013

 

 

And the study’s abstract can be found at:

 

Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

V. Stalin Raj, Huihui Mou, Saskia L. Smits, Dick H. W. Dekkers, Marcel A. Müller, Ronald Dijkman, Doreen Muth, Jeroen A. A. Demmers, Ali Zaki, Ron A. M. Fouchier, Volker Thiel, Christian Drosten, Peter J. M. Rottier, Albert D. M. E. Osterhaus, Berend Jan Bosch & Bart L. Haagmans

Declan Butler On the CFR Of H5N1

 

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Declan Butler, who is a senior reporter Nature.com, was one of the first journalists to call attention to the H5N1 virus.  He holds a degree in biology from Queen's University, Belfast, has a PhD from the University of Leeds, and writes on a variety of scientific topics.

 

The CFR (Case Fatality Ratio) of the H5N1 virus – which hovers around 60% of known cases - has been the subject of considerable discussion over the years, and is currently front and center in the recent debate over H5N1 research in ferrets.

 

Some scientists maintain that a great many `mild’ cases go undetected, and that the true CFR is far lower (perhaps `orders of magnitude lower’) than the official numbers would indicate (see Vincent Racaniello’s argument Should we fear avian H5N1 influenza?). 

 

As we saw in a CIDRAP article last week by Robert Roos (Undetected H5N1 cases seem few, but questions persist), not everyone buys into that theory.

 

Today Declan Butler talks to a number of experts (including Malik Peiris and Jeremy Farrar), who say they’ve not found much evidence to support a claim that we are missing a lot of `mild’ cases.

 

While the true CFR may be far lower than 59%, many experts believe this virus is fully capable of producing a pandemic that could far exceed what we saw with the 1918 Spanish Flu.

 

Very much worth reading, so follow the link to:

 

 Nature | News

Death-rate row blurs mutant flu debate

Even if a 59% mortality rate for H5N1 is too high, the virus could still cause a flu pandemic more serious than that of 1918.

Declan Butler

13 February 2012

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Declan Butler: Lab flu may not aid vaccines

 

Photo Credit – CDC PHIL

 

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One of the counter arguments offered by researchers when biosecurity experts have warned on the dangers of `dual use’ H5N1 research, is that these experiments put us in a position to create a vaccine faster, should these genetic changes occur in nature.

 

Today Declan Butler, writing for Nature, explores that argument and finds that while the logic behind it is appealing, the reality may fall a bit short. 

 

Lab flu may not aid vaccines

Game-changing vaccine technologies are needed to strengthen global pandemic defences.

• Declan Butler

08 February 2012

Declan Butler On Growing Mosquito Insecticide Resistance

 

 

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The old adage is true.

 

If you build a better mousetrap, sooner or later nature will come up with a better mouse.

 

Bacteria learn to resist antibiotics, viruses learn to ignore antivirals and drift antigenically to evade vaccines, and eventually your neighbor’s dog learns how to burrow under your fence to get at your prized petunias.

 

Hence the old saying that Nature always bats last.

 

Adaptation is the lynchpin of evolutionary survival, often making victories against bacteria, viruses, and other pests fleeting at best.

 

Today Declan Butler writing for Nature News, brings us details of another battlefront where the pests are making gains against our modern technology; growing insecticide resistance among malarial mosquitoes in Africa.

 

It’s a good article, so I won’t bother excerpting it.  Follow the link to read it in its entirety.

 

 

Mosquitoes score in chemical war

Growing resistance is threatening global malaria-control efforts.

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For more background on this growing problem, the World Health Organization has produced a 46 page report called The Technical Basis for Coordinated Action Against Insecticide Resistance.

 

 

Declan Butler On Haiti’s Cholera Epidemic

 

 

 

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A lot of my readers are no doubt familiar with Nature News senior reporter Declan Butler for, among many accomplishments, his early work in bringing the avian flu story to the public.

 

But Butler is hardly a Johnny one-note. He holds a PhD in marine biology from the University of Leeds, and writes on a variety of scientific issues.

 

Today he brings us background and sobering analysis of the potential impact of the cholera epidemic on Haiti’s population over the next year or so.

 

A hat tip to David Dobbs for retweeting this link.

 

I’ve just posted his lede.

 

Follow the link to read it in its entirety.  As with practically anything Butler writes, this is highly recommended.

 

 

Cholera tightens grip on Haiti

Those tackling the epidemic are struggling to keep pace with an escalating crisis.

Declan Butler

As cholera rampages through Haiti, some epidemiologists are warning that the country could face more than half a million cases over the coming year. Yet tracking and treating the disease is proving increasingly difficult as civil unrest grips the county.

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Experts Weigh In On Allegations Against The WHO

 

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A hat tip to Crof over at Crofsblog for picking up this story while I was away from my computer, penned by Declan Butler of Nature News.

 

Included are responses from such heavy hitters as Michael Osterholm of CIDRAP, Virologist Albert Osterhaus of at Erasmus Medical Centre in Rotterdam, Epidemiologist David Ozonoff of the Boston University School of Public Health, and Marc Lipsitch, an epidemiologist at Harvard School of Public Health.

 

Frankly, there’s so much quotable material in this article, rather than excerpt any of it, I will just direct you to the link so you can read it for yourself.

 

 

Published online 8 June 2010 | Nature | doi:10.1038/465672a

News

Flu experts rebut conflict claims

Reports throw unsubstantiated suspicion on scientific advice given to the World Health Organization.

Declan Butler: Portrait Of A Year Old Pandemic

 

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Declan Butler, senior reporter for Nature and a blogger in his own right,  was one of the first journalists to begin covering the avian flu threat back in 2004, and it was his work that helped inspire me to begin this blog.  

 

But hey, you really shouldn’t blame him . . .

 

But I digress.  Today Butler brings us a portrait of the H1N1 pandemic on its first birthday.  

 

I’ll do the wise thing here, and simply give you the link and step out of the way.

 

 

Portrait of a year-old pandemic

'Swine flu' isn't over yet, but it already holds lessons for the future.

Declan Butler

 

One year ago this month, the world watched with trepidation as a novel influenza A virus, to which the global population had little or no immunity, emerged in Mexico and the United States. In the weeks that followed, the H1N1 'swine flu' virus spread rapidly to countries worldwide, leading the World Health Organization (WHO) on 11 June 2009 to officially declare the first flu pandemic in more than 40 years. Nature looks at the lessons learnt from H1N1, and how they will help scientists and health authorities to handle the next flu pandemic.

 

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