H5N1

US: A meeting I wish I could attend (updated)

Thanks to Greg Folkers for sending me the link to this page on the website of 113th general meeting of the American Society for Microbiology, which lists the sessions for Tuesday, May 21:

Session Number: LBS001 

Session Title: Pandemic Threats from Emerging Avian Influenza Viruses (H7N9 and H5N1): Challenges for Public Health, Research, Surveillance and Countermeasures 

Session Type: Symposium 

Session Start/End Time: Tuesday, May 21, 2013, 11:00 AM - 1:30 PM 

Location: Mile High Ballroom 3 

Presentations: 

The Continuing Influenza Threat: H5N1, H7N9 or More? 5/21/2013 11:00:00 AM Robert G. Webster; St. Jude's Res. Hosp., Memphis, TN. 

H5N1 and H7N9: From Zoonosis to Pandemic? 5/21/2013 11:30:00 AM Albert D. Osterhaus; Erasmus MC, Rotterdam, Netherlands. 

The Challenge of Avian Influenza Viruses: From Basic Research to Practical Public Health Strategies 5/21/2013 12:00:00 PM Carole A. Heilman; NIH, NIAD, Bethesda, MD. 

Responding to the Emerging Avian Influenza Threat: Preventing a Pandemic 5/21/2013 12:30:00 PM Stephen C. Redd; Influenza Team Lead, CDC/CCID, Atlanta, GA.

I will be delighted and grateful to post any reports that come out of these sessions.

Update: And Greg Folkers has promptly sent the link to the ASM live video feed, which will include the Tuesday session. I'll repost the link on Monday night or Tuesday morning. You can also follow events at #asm2013.

Synthetic generation of influenza vaccine viruses for rapid response to pandemics

Thanks to Greg Folkers for sending the link to this just-published article in Science Translational Medicine: Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics. The abstract:

During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. 

Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. 

Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. 

Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.

If nothing else, these stupid viruses are provoking some remarkable technological progress.

US: An economic cure for pandemics

Via The New York Times, a May 4 article: An Economic Cure for Pandemics. Excerpt:

Protection against communicable diseases is a core example of a public good, as is basic scientific research, which can yield new ideas that may be spread at very low additional cost. 

(In contrast, Medicare, which is publicly financed, has some elements of a public good, but any particular expenditure tends to benefit an individual receiving treatment, rather than being spread over a number of beneficiaries.) 

One obvious step forward would be to exempt biomedical research from cuts of the current federal budget sequestration. Research and development grants are a way to pay potential innovators up front — an important move, as an innovator can’t always charge high-enough prices for the value of its remedies when they’re actually needed. 

If a pandemic became a major issue in the United States, demand for remedies would surge far beyond the level associated with a typical seasonal flu outbreak, and permitting high prices would be unpopular — and perhaps unfair. The threat of contagion also makes it crucial to spread the net of protection as widely as possible, which again suggests low prices. 

Yet it is crucial to have some reward system in place for medical innovators. Well in advance of a pandemic, research needs to be done, and vaccine capacity and drug distribution facilities need to be built up. In the H.I.V./AIDS crisis, for instance, the United States was caught flat-footed — and an appropriate response has taken decades, in part because we were not prepared. 

Without government financing for such public goods, the capacity wouldn’t be there if a new pandemic produced a surge in demand. This would amount to an institutional failure.

H7N9: FluTrackers debate the paper

When the virologists and epidemiologists respond to the paper discussed in the post below, they may tell us all to wipe our noses, go to bed and stop worrying about H7N9. Until then, I recommend this FluTrackers thread: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic.

H7N9: Are we in for the duration?

Mike Coston at Avian Flu Diary has posted Chinese Science Bulletin: Early H7N9 Risk Analysis. I downloaded the PDF, opened it up, and started reading. Get over there and download it for yourself, because you need to. I promise it will be on the final exam.

After a page, I printed out all four pages and started reading again with a highlighter in my hand. Before I was done, I was remembering Sergeant Williams, calling us trainees together on the firing range the morning of November 22, 1963 to tell us the president had been shot.

"Any of you draftees think you're in for your two years and out again—if anything comes out of this, you're in for the duration," he said.

If this paper is accurate, we are all in for the duration. The authors, who appear to be major influenza experts, have drawn on the first 91 cases of H7N9 to project where it might go. Maybe other experts will demolish their conclusions; I certainly hope so.

The paper was submitted to Chinese Science Bulletin on April 11 and accepted on April 23. Less than two months after the first Mr. Li fell ill in Shanghai, the team assessed the cases so far. They offered a formula for judging the severity of outbreaks, and defined the outbreak as Grade III (severe).

Here's what clinched it for me: They predicted that it would become a Grade IV (very severe) outbreak by the end of April, when the case numbers would exceed 100. And so they have.

So I'm prepared to accept their eight-point argument, despite its occasionally incorrect English, that H7N9 "is of enormous risk," and some of those points seem irrefutable: it will be "extremely tough" to eliminate it from China's vast bird and pig populations, so it will spread rapidly. One wild bird with H7N9, found in Jiangsu province, indicates it will spread beyond China.

The eighth argument arrives like a conviction for a capital offence:

Eighthly, the probable long existence of the H7N9 virus in humans will provide the driving force to the virus to adapt to humans through mutations. The virus may thus obtain human-to-human transmission, and may spark a pandemic influenza thereafter. The possible pandemic should likely be very dangerous with the consideration that the virus has showed highly pathogenicity in the first 91 cases.

The paper goes on to call for "forceful scientific measures," ranging from vaccine production to replacement of much of China's food distribution system: Never mind those stupid high-speed trains to Lhasa and Guangzhou, ditch the wet markets!

And while the authors point to the successful suppression of Nipah virus in Malaysia in 1998 and of SARS in 2003, they pin our real hopes on the virus itself: It may be structurally incapable of making itself capable of human-to-human transmission because the mutations that would enable it to do so would also kill it. Failing that, eradicating H7N9 in poultry markets may keep it from getting into poultry farms, and thereby push it toward oblivion.

No doubt more implications of this paper will emerge in coming days, but a few spring to mind at once:

If China really is suppressing some H7N9 news, it has just lost that option. Its own experts have painted it into a corner.

The political and economic consequences will be seismic as 1.4 billion people adjust to a new food-security regime. The same is true of trade and travel.

China will also have to deal with the irony of being a communist country without a real health insurance system. Without such a system, the country can expect that the 2020s will look like the 1920s, when warlords ruled.

I really hope I'm overreacting to this paper, and I will be hugely relieved if other experts can refute it and reassure the world that H7N9 is just another scare, soon to be forgotten. But I'm not holding my breath until they do.

Pandemic preparedness: Coming, ready or not

Via The Economist: Pandemic preparedness: Coming, ready or not. Excerpt:

The threat of a global pandemic is rising again. In China an influenza virus never before seen in people had, as The Economist went to press, infected at least 82 and killed 17. Meanwhile a new type of coronavirus, the family that brought severe acute respiratory syndrome (SARS), is festering in the Middle East. 

The risk of such an outbreak turning into a pandemic is low, but the danger, if it does, is huge: in 1918 50m-100m people were killed by Spanish flu, compared with 16m in the first world war and 30m so far from AIDS. 

Fortunately, the world is better prepared for an outbreak than ever before (see article). SARS in 2003, the H5N1 bird flu of 2005 and the H1N1 swine flu of 2009 have prompted action. By 2011, 158 countries had pandemic-preparedness plans. America has poured money into the development of new vaccines and antiviral drugs. Researchers have a better understanding of influenza and other risky pathogens. Rapid amplification of DNA segments helps scientists identify viruses quickly. Full genomic sequencing allows them to explore worrying strains. Mathematical models predict where a new disease might emerge and how it might spread. 

Going viral 

Yet all this may not be enough. No one has yet managed to predict an influenza outbreak. H1N1 exposed many problems, from the slow deployment of vaccines to simple breakdowns in communication. Thankfully that virus was not especially deadly. 

But an independent commission, charged with reviewing the response of the World Health Organisation (WHO), issued a bleak assessment: “The unavoidable reality is that tens of millions of people would be at risk of dying in a severe pandemic.” 

Reducing that risk means, among other things, more government spending—an unwelcome prescription at a time of austerity, but a necessary one, for protection against pandemics is a valuable public good.

Click through to see the magazine's recommendations on how the money should be spent.

Hong Kong expert warns new H7N9 virus could become a pandemic

Via the South China Morning Post, an April 16 report: Hong Kong expert warns new bird flu virus could become a pandemic. Excerpt:

The deadly new bird flu may pose a bigger threat to humans than the H5N1 bird virus that has killed hundreds of people worldwide, a University of Hong Kong microbiologist warned yesterday. 

Ho Pak-leung became the first expert to publicly express fears it could become a pandemic. 

The H7N9 strain emerged in humans only last month and is so far contained to the mainland. 

But it has already infected more people than the H5N1 virus has infected in the past 10 years. 

Ho said the new virus showed a higher ability to be transmitted rapidly from birds to humans and to spread geographically. 

And because infected birds appeared healthy, it was also harder to detect. 

Ho said: "The pathology pattern of H7N9 so far is very special and quite different from H5N1. "But the pattern points to one alarming conclusion - it may be a bigger health threat than H5N1." 

He said news that a four-year-old Beijing boy was found to have the virus despite not showing any flu symptoms was a "warning sign" for a pandemic. 

"It is possible for the virus to grow more adaptable to the human body … and eventually becoming transmittable among humans," he said. 

The number of confirmed H7N9 cases has reached 63 - and 14 have died, according to the national health commission. 

A boy who is now under medical observation in hospital was screened for the virus after coming into close contact with the capital's first H7N9 case, a seven-year-old girl. So far, H7N9 has emerged in Shanghai and the provinces of Zhejiang , Jiangsu , Henan and Anhui , as well as in Beijing. 

"The previous H5N1 pandemic never affected so many provinces at the same time," Ho said. 

H5N1 has infected 45 people on the mainland since 2003, killing 30.

China, Egypt could be new-flu hot spots

Via The Los Angeles Times: UCLA-led team predicts China, Egypt could be new-flu hot spots. Excerpt:

No one knows where the next deadly pandemic flu is likely to emerge. But a new analysis of flu surveillance and other data from a UCLA-led team suggests that coastal and central China and Egypt's Nile Delta might be areas worth watching. 

UCLA postdoctoral researcher Trevon Fuller and colleagues published their work online on March 13 in the U.S. Centers for Disease Control and Prevention journal Emerging Infectious Diseases. The thinking behind their research goes something like this: 

Dangerous influenza outbreaks, including pandemics in 1957 and 1968 that killed around a million people apiece, arise when new, aggressive flu strains arise through a process known as reassortment. A single animal is infected with several flu viruses at the same time -- which then swap genetic bits to create new and sometimes deadly strains.  

Fuller and his colleagues used new techniques to assess conditions in a number of places to see how likely a reassortment event might be. While a new pandemic could possibly emerge from a number of combinations of flu strains, the team focused on reassortment between human H3N2, a version of which was prevalent in the U.S. this flu season; and avian H5N1, a widespread bird fluthat has been rare in humans so far but has proven deadly among the hundreds of people it has infected. 

CIDRAP: News scan for March 28

Via CIDRAP: NEWS SCAN: Injection-related anthrax, drug-resistant gonorrhea, post-pandemic illness, imported rubella, polio vaccine deal. Excerpt:

A German analysis of patients hospitalized with 2009 H1N1 (pH1N1) flu during the pandemic year and the first post-pandemic year found that severe illnesses and deaths jumped dramatically the year after the pandemic. 

Researchers who conducted a retrospective study on patients hospitalized with lab-confirmed flu at University Hospital Heidelberg during the two seasons published their findings yesterday in Emerging Infectious Diseases. 

They identified 102 patients with pH1N1 infections during the 2009-10 season and 76 in the first post-pandemic season. The proportion of severe illnesses rose from 14% the first year to 46% the second year, and the mortality rate rose from 5% to 12%. Patients hospitalized during the post-pandemic season were older, at an average age of 38 compared with age 18 during the pandemic year. Those hospitalized during the second year were also more likely to have an underlying medical condition. 

Researchers noted that there weren't any virus changes that were known to account for the change in clinical pattern and that it's not unusual for trends to change from a pandemic season to the following one. They suggested that the increase in severity could reflect the effects of pH1N1 on remaining susceptible adults and risk groups.

NCoV appears deadlier than SARS, says HKU

When the University of Hong Kong talks about this, we should listen. Via the South China Morning Post: New coronavirus appears deadlier than Sars, says HKU. Excerpt:

The mysterious new coronavirus that emerged in the Middle East and has killed 11 people is potentially more deadly than Sars and also more "promiscuous" - able to infect many different species - University of Hong Kong research has found. 

Unlike Sars (severe acute respiratory syndrome), the new coronavirus can affect many different organs in the body and kills cells rapidly, the researchers say. 

The source of the new infection is still unknown, but the virus appears to have originated in bats, a team of European experts wrote in the journal mBio. 

The HKU research listed animals including monkeys, pigs, civet cats and even rabbits that could be hosts of the virus before it found its way to humans. Lead researcher Yuen Kwok-yung, a microbiologist, said this meant the source of human infection would be difficult to trace. 

The World Health Organisation announced yesterday that the disease had killed two more people - a 73-year-old from the United Arab Emirates and a Briton who had visited Saudi Arabia and Pakistan - bringing the death toll to 11. The WHO has confirmed 17 cases to date. 

Yuen told the South China Morning Post that the virus could cause a deadly pandemic if it mutated further. "It could be more virulent [than Sars]", he said. "The Sars coronavirus infects very few human cell lines. But this new virus can infect many types of human cell lines, and kill cells rapidly." 

The findings, tested in human cell lines, suggest the virus could cause widespread organ infection. It could attack the lower airway, liver, kidneys and intestines as well as tissue macrophages - cell clusters that "eat" bodily debris such as dead cells. 

The report, published by the Journal of Infectious Diseases this week, says the new virus "is markedly different" from the other non-Sars human coronaviruses that usually have little ability to move among different cells, and cause self-limiting upper respiratory tract infections. 

This may explain why patients with the new coronavirus can suffer multiple organ failure, resulting in a high mortality rate of 56 per cent - in contrast to 11 per cent for Sars. 

Yuen said: "The Sars coronavirus infected very few animal cell lines. It was finally traced to bats and civets. But we may have a very hard time, as this new virus seems to be much more promiscuous." 

Yuen said, however, that the new virus did not appear to be very infectious, as it tended to infect lower respiratory cells instead of upper respiratory ones like Sars, but this pattern might change as the virus mutated.