H7N9 Flies from China to Canada – On a Plane

From SCMP, January 27, 2015

North America’s first case of bird flu in humans has been identified in a Vancouver-area woman who returned to the city on a flight from Hong Kong this month.

Canadian health authorities said the patient, who tested positive to the H7N9 strain of avian flu on Monday morning, is not gravely ill.


The Globe and Mail newspaper reported that the patient and her husband, both aged in their 50s, had travelled together and both were now sick at home. Tests have not yet confirmed the man’s suspected H7N9 infection.

The newspaper quoted Bonnie Henry, BC’s deputy provincial health officer, as saying the couple “did some touring of areas and villages in China where poultry are seen throughout the village, but there was not a particularly high-risk exposure that we were able to identify.


H5N1 in the US

From NBC News, January 22, 2015:

A green-winged teal shot by a hunter in northern Washington state has tested positive for H5N1 bird flu — a relative of the virus that’s infected nearly 700 people globally and killed 400 of them.


To make matters more complicated, this strain of H5N1 found in the teal appears to be a mix of H5N1 and the H5N8 found in Washington state and elsewhere in the U.S. as well as in Europe, South Korea, Japan and Taiwan.

The pandemic potential of this version of H5N1 is unknown.

The Kawaoka droplet transmission H5N1/pH1N1 study

Nature has just published the long-awaited paper by Kawaoka and colleagues describing the creation of a hybrid H5N1/pH1N1 virus which can be transmitted by respiratory droplets between ferrets:

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets, Nature, May 2, 2012

There are many interesting facets to this study, but this blog will focus on a few key issues of interest to the flu preparedness community.

1. This was a hybrid virus. Only one of the eight genomic segments, haemagglutinin (HA), was derived from H5N1. The other 7 came from the pandemic H1N1 virus (pH1N1).

2. Four mutations in the H5N1 HA genomic segment were sufficient to allow the hybrid virus to spread from ferret to ferret.

3. None of the ferrets died during the course of the experiments. However, one virus was recovered from the brain of one of the ferrets. Since only a small number of ferrets were used, little can be concluded about the potential case fatality rate (CFR) of this virus if it were to occur in the human population except that it would not be rapidly lethal in 100% of the affected individuals. A much larger number of individuals would need to be tested to detect a fatality rate of 2%, the CFR of the 1918 flu virus.

4. A hybrid virus with its HA from H5N1 but the other genomic segments from pH1N1 would not necessarily be expected to be any more lethal than pH1N1. This is because HA is primarily involved in transmission of flu viruses. Although it plays a role in virulence, other genomic segments, for example, PB1, PB2, NA and NS, have been strongly implicated in the pathogenicity of flu viruses. Since these genomic segments were derived from pH1N1, it would not be surprising if the hybrid virus was about as lethal as pH1N1.

5. H5N1 and pH1N1 are genetically compatible. One type of hybrid was produced in these experiments, but others are possible. A hybrid which contained the PB1 or NS from H5N1 with other genomic segments from pH1N1 might have a very different CFR than the virus described in the current work.

6. The mutations which can cause H5N1 HA to permit mammal to mammal transmission are limited. The authors describe a range of mutations in H5N1 HA which did *not* result in increased transmissibility of the virus. Thus, we now know better which variants of H5N1 in the wild are likely to be most dangerous. This also sets the stage for the possibility of developing pre-emptive pandemic vaccines.

Publication of this work is long overdue. The fear that terrorists living in caves could use this information to produce a weapon seems quite ridiculous when reading this paper. The techniques and sophisticated analyses involved in this work are way beyond the limited intellects, knowledge base, and resources available to these groups. Nation-states run by dictators could develop biological weapons using the approaches described here. But if this was their intent, they likely have already pursued experiments to accomplish this without the many constraints researchers in free countries are subject to.

We now know that H5N1 could become easily transmittable between mammals. That knowledge alone will make us safer.

The National Science Advisory Board for Biosecurity and the slippery slope of censorship – Part 1 – The wrong focus

The National Science Advisory Board for Biosecurity (NSABB) has been in the news recently because it has advocated, strongly, the censorship of flu research which has created an H5N1 virus which is highly lethal and highly infectious among ferrets.

For a scientist, censorship is considered a violation of our fundamental mission: free enquiry and dissemination of the results of that enquiry. The story of the persecution of Galileo for stating the simple truth is strongly impressed on our consciousness. The vast majority of us are outraged by and fight against attempts to suppress the teaching of evolution in schools. For us, sharing what we learn about the natural world with others is a core part of our mission. People who try to stop this are our natural enemies.

Thus, I find myself in a strange position. The people who are censoring this flu research include my fellow scientists, some of them quite well-known and respected. What has caused them to turn their backs on their core responsibility as scientists? For many of them, I believe it is fear. Perhaps blind, unreasoning fear.

When I first realised the consequences of a high CFR flu pandemic (years ago), my initial reaction was shock followed by strong fear. This, in itself, is not an irrational response. As has been discussed in Flublogia for many years, a high CFR flu pandemic would be devastating to the world’s population. It is difficult to estimate the losses, but it would surely rank among the greatest disasters to befall mankind.

After the initial shock, fear motivated me to prepare for such an event. At first, I assumed that the government would have a well-thought out response to a high CFR pandemic. I was certain that this would involve movement restrictions until an effective vaccine could be produced. Although I imagined that plans were in place for the distribution of food and other necessities, I still thought it prudent to prepare to stay in my house for the time that a local outbreak typically lasts – 6 to 12 weeks. I knew other scientists who were making similar preparations, so I was unconcerned about the scorn such preparations received in the mainstream media. But I was puzzled by it. Why weren’t leaders in public health strongly pushing for these preparations? Surely they understood the risks as I and other scientists did.

Recent work by Dr. Fouchier and his colleagues have shown that H5N1 could become a high CFR pandemic strain. This is not inevitable, as Dr. Kawaoka’s work apparently shows that H5N1 could go pandemic with a lower kill rate. But clearly, a high CFR, highly infectious virus is in the realm of possibilities. Given this finding, one would naturally assume that the predominant response would be gratitude that we know this before a pandemic has started so that the public could be alerted to start preparing.

This has not happened.

Instead, almost all media attention has focused NSABB’s censorship of the results. Although the Chair of NSABB, Dr. Paul Keim, correctly notes that the world is not prepared for a high CFR pandemic, he gives no indication of what the public should do to prepare for such an event. Indeed, he gives the false impression that terrorists’ use of this knowledge is the main threat. He ignores the fact that the virus could go pandemic naturally. He also fails to discuss the possibility of strategic use of such a virus by a nation-state. He further suggests that by censoring this research, governments will use the time to prepare for a high CFR pandemic. I’m afraid this assumption is also likely to be false.

Governments have known for over 9 years that a high CFR pandemic is a possibility. Although there has been some progress in basic vaccine research, this has not yet been translated to a plan for rapid vaccination. Instead, the only way to survive the first wave of a high CFR pandemic will be to avoid being infected. And this means movement restrictions, either imposed by the others or self-imposed.

DoD plans for a smallpox outbreak include draconian movement restrictions. These can be justified because it is at least theoretically possible to supply a single city while stockpiles of vaccine are distributed. However, such a plan is certain to fail in confusion and terror should multiple cities be afflicted with a high CFR, highly infectious virus for which there is no immediate vaccine. This is because, currently, the vast majority of the US population has made no plans for such an event and the government has no serious plans for providing supplies for mulitple large cities.

Given that we know that current government plans will fail in a high CFR flu pandemic, why isn’t the public being warned to prepare? Why is there no discussion of movement restrictions?

Is this also censored? If so, why?

Mutation in Shenzhen H5N1 virus

Reports in Chinese language news sources indicate that Shenzhen health authorities have discovered a mutation in the H5N1 virus that recently killed a bus driver in that city. The nature of the mutation or its effects are unclear, but may make the virus more pathogenic and difficult to treat. The Chinese public is being reassured that the virus cannot transmit human to human, easily.

Immediate deposit of sequences in GenBank is necessary for evaluation of this virus.

The bird flu death man virus has the sudden change (Sina.com)

Shenzhen bird flu death man virus gene mutation (881903.com)


Bus driver dies of H5N1 in Shenzhen China

Chen Xing, a 39 year old bus driver in the city of Shenzhen, Guandong Province, China, became ill on December 21, 2011. He was treated but did not improve (NDTV). On December 25, 2011 he was hospitalised. On December 26, 2011 he was diagnosed with pneumonia. He died of multiple organ failure on December 31, 2011 (Chinese Today). H5N1 infection was confirmed (New York Times). He had no known contact with birds prior to his infection. He also had not recently traveled.

He is estimated to have been in contact with over 100 people while infected. According to reports, these people have been identified and are being monitored for signs of infection. Thus far, there have been no additional cases.

Outstanding questions:

1. How was the patient infected? With no connection to birds, the possibility of human to human transmission is obviously a possibility (Voice of Russia).

2. Was the patient treated with Tamiflu? If so, that would suggest that he may have been infected with a resistant strain.

3. When will the sequences be deposited in GenBank? China has the capacity to rapidly sequence, analyse and deposit the relevant sequences. BGI is located in Shenzhen and was especially helpful in sequencing the bacteria that caused the E Coli outbreak in Germany earlier this year. It would be odd if they were not equally speedy in sequencing and depositing data from a lethal virus in their own backyard.

Serial passage of H5N1 can create an airborne virus

H5N1 is an extremely lethal flu virus. However, to become a pandemic virus, it must be transmitted efficiently between humans. Although there have been numerous clusters of human to human spread of H5N1, it has not yet succeeded in sustained transmission. Why not?

Viruses can be transmitted by direct contact on surfaces or in the air. There have been a few documented H5N1 clusters where airborne spread seems a likely explanation, but these did not result in further spread, perhaps due to specific environmental conditions associated with those outbreaks. Because efficient airborne spread of H5N1 among humans has not yet occurred, some suggest that the virus is incapable of acquiring this ability. This has now been proven to be a false assumption.

From Scientific American, September 19, 2011 [hat-tip, Goju]


…researchers wonder: Could the dreaded H5N1 ever morph into a disease that could spread among people, via a cough or sneeze, to attach to nasal or tracheal membranes, as the seasonal flu does every year?

To help answer this question, Ron Fouchier, also of Erasmus Medical Center, and his team “mutated the hell out of H5N1” and looked at how readily it would bind with cells in the respiratory tract. What they found is that with as few as five single mutations it gained the ability to latch onto cells in the nasal and tracheal passageways, which, Fouchier added as understated emphasis, “seemed to be very bad news.”

The variety that they had created, however, when tested in ferrets (the best animal model for influenza research) still did not transmit very easily just through close contact. It wasn’t until “someone finally convinced me to do something really, really stupid,” Fouchier said, that they observed the deadly H5N1 become a viable aerosol virus. In the derided experiment, they let the virus itself evolve to gain that killer capacity. To do that, they put the mutated virus in the nose of one ferret; after that ferret got sick, they put infected material from the first ferret into the nose of a second. After repeating this 10 times, H5N1 became as easily transmissible as the seasonal flu.

The lesson from these admittedly high-risk experiments is that “the H5N1 virus can become airborne,” Fouchier concluded—and that “re-assortment with mammalian viruses is not needed” for it to evolve to spread through the air. And each of these mutations has already been observed in animals. “The mutations are out there, but they have not gotten together yet,” Osterhaus said.


Serial passage has long been known to be an effective way to increase the transmissibility of viruses in a new host. By inoculating one animal, collecting the viruses that survive, and inoculating another animal, investigators are selecting for the viral variants that are best adapted to the new host. In the experiments described above, it took 10 “rounds” of passaging from animal to animal to achieve an H5N1 virus which could spread efficiently in the air.

One of the reasons why human clusters of H5N1 are so dangerous is because each human to human transmission increases the probability that H5N1 will become completely adapted to humans and spread efficiently in the air. In effect, each human to human transmission is one passage of the virus. It now seems clear that concern about pandemic H5N1 is justified. There is now no reason to assume that H5N1 cannot become airborne in humans.

Although the scientists doing this work were interested in modeling natural evolution, it should be noted that they likely created a very dangerous virus in the laboratory. We don’t know how lethal a virus adapted to ferrets would be to humans, but given that we are both mammals and that ferrets accurately model many aspects of human influenza infection, there is a good chance that the virus created is quite dangerous to humans. One interesting aspect of this experiment is that this was achieved with a relatively low tech approach: serial passaging of virus in a new host. Such an approach could be imitated by bad actors with only modest technical skills and equipment.

Are we prepared for a highly lethal, highly contagious virus, whatever its origins? No, we are not, imo.