Increasing genetic diversity in H5N1

WHO has taken note (.pdf) of the increasing genetic diversity of the H5N1 influenza/A viral isolates as the disease spreads geographically. Clades are genetically related viruses with common ancestors. Since 2003, two such clades have appeared (clades 1 and 2), distinct from the original H5N1 viruses from the 1997 Hong Kong outbreak (now called clade 3). Clade 1 viruses have been isolated in southeast asia (Vietnam, Cambodia, Thailand, Laos), sandwiched between clade 2 viruses from southern China and Indonesia and Malaysia.

Until now, the experimental human vaccines have been made with seed strains reverse engineered using clade 1 (southeast asian) viruses, but since late 2005 human and poultry cases have occurred in Indonesia's clade 2 strains, of which three sub-clades (1, 2 and 3) have been involved in human cases. The extent to which there is immune protective cross-reactivity between vaccines made from clade 1 against clade 2 viruses is now under investigation. Studies in ferrets showed cross-reactivity (but much variation; cf. Table 2 in this paper) within and between clades for representative viruses, with the exception of the virus from the Karo, Indonesia cluster, which appeared to be antigenically distinct from most of the other human isolates from Indonesia. However, WHO is recommending that vaccines be made from seed strains prepared from clade 2 viruses in addition to the current clade 1 vaccine prototypes.

The vaccine strategy aside, what do we make of the increasing genetic variation seen in this virus, with distinct geographic distributions of the clades and subclades? WHO is low key:

"I don't think it's possible to interpret these kinds of changes in terms of whether the virus is moving closer to developing greater transmissibility properties among people," said Dr. Keiji Fukuda, co-ordinator of the WHO's global influenza program.

"I think what it simply reflects is that influenza viruses have evolutionary pressures on them and they evolve. They change. And that's what we're seeing."

Experts who have studied numerous samples of the virus have suggested nothing in them points to the development of mutations that would increase H5N1's ability to infect people and spread among them. (Helen Branswell, Canadian Press)

It is true that nothing about the changes specifically suggests there is a change to greater transmissibility. The problem is, however, we don't know what to look for, a point made by Dr. Michael Osterholm:

"What does it mean for an influenza strain today to be more adapted towards human-to-human transmission?" Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy, wondered.

He said he was not suggesting the virus is becoming more transmissible, only that the patterns that would lead to that end aren't defined.

Exactly right. Unfortunately.

More like this

The World Health Organization = spin, spin and more spin.

You would need the enigma machines to figure out the truth but then again, you would have to speak the truth before you encoded it...and they don't.

Tom DVM,
The World Health Organization is actually a death machine, and what they are selling you are lies.

Extract of above Xinhua links' text:
"According to the newspaper, the disease, which was first detected in dogs and chicken in the last week of June, had started spreading to humans in Netini, a far eastern village of Nuwakot district, some 50 km northwest of Kathmandu.
Major symptoms of the disease are high fever together with bleeding from nose and mouth at the time of death."

The new clade in Indonesia appears to be extremely lethal.

A bit off topic (tho, maybe not). . .

These 3 or 4 diffenet clades or strains are out there circulating. . . if / when the reach H2H capability (perhaps within weeks or months of each other), could this in fact be the cause of the different "waves" ??? Or could one assume that only ony strain will mutate to H2H and further mutations to that first strain will be the "wavemaker"???

Gilmore: A clade is a family with a common ancestor. Different members of the same clade could become more easily transmissible or it could happen indpendently or via some kind of genetic interaction between different clades. It is not uncommon for strains of the same subtype to circulate simultaneously, as happened in the especially serious seasonal outbreak of H1N1 in 1951. Thus they could produce different outbreaks in different parts of the world more or less at the same time or do so asynchronously as well. Much would depend on the extent of immune cross reactivity, so asynchronous waves is less likely IMO.

How can we obtain unbiased information regarding the new clade in Indonesia, when we have to depend on the biased reports of Indonesian officials and WHO representatives?
In in update on the Cikelet cluster today the stonewall of information continues. It says:
"Indonesian officials said at present they believed no human-to-human transmission has occurred."
"The disease appears to be spread by sick poultry."
Please note it is very probable WHO, after several days of investigation of human H5N1 victims in Cikelet, will conclude: no human-to-human transmission has occurred."
Indonesian officials and WHO cannot be trusted to tell the truth. Those in power in Indonesia do not want it known there may be human-to-human transmission; because it would devastate the economy, especially the tourism industry.
Because of information regarding a more harmless strain of bird flu in chickens in the US, Mexico has annnounced it will not buy US poultry. How much money will poultry producers in the US loose as a result of this decision?
Indonesian officials also read the newspapers, and they know about this decision of the Mexican government. They know how much damage this type of information can do to their economy.
Therefore, can you believe what these officials and WHO reports? The answer is no.
And the possibility of a mammalian reservoir of H5N1 also continues to be ignored. Dogs ate sick chickens in Cikelet. Dogs, cats, and other mammals should be investigated in Cikelet to determine if a mammal may be the source of human H5N1 infections there.
To stonewall this information demonstrates the putrid corruption that exists in Indonesia, that may allow a pandemic to explode, and perhaps kill you and me.

william: This virus either can go H2H or it can't, for biological reasons. If the biology allows it, there is no way to stop it, no matter where it breaks out, in the US or in Indon. I think your incessant clamor to asign blame for something which can't be helped is itself very unhelpful. We should be working on getting our public health and social service systems ready for serious sickness in our communities. Blaming the Indonesians, WHO or corporate interests just doesn't help and is misplaced and not constructive. Turn down the volume, roll up your sleeves and get to work making your community a place better able to withstand emerging infectious diseases, this one or another one.

Revere:

I understand william's frustration completely. No one knows what the true bird flu situation is except the individual laboratories worldwide that are testing for bird flu.

Whether these laboratories are WHO laboratories or government controlled laboratories or veterinary laboratories--they hold on to the information and mainly keep it a secret.

The authorities in charge of these laboratories have not told the public what is happening. There are reports of negative, then positive, then negative, on an individual case. There are reports that test results will be available soon---but then are never reported.

We can do almost NOTHING to get people to take action in our individual communities until they BELIEVE there is a true and imminent threat----a SEVERE threat.

With the paucity of truthful and reliable imformation and the ridiculous media assurances about vaccines and drugs in the pipeline---the majority of the general public cares nothing about bird flu. Community preparation will remain at a standstill as long as the complete bird flu laboratory test results are kept hidden.

I have to agree with Earl E. I have tried to get the school board of my little public charter school to take an interest in making plans for a possible pandemic, and they quite literally laughed at me, telling me our time would be better spent planning what to do on rainy days when the bus can't get through, that was more realistic. I have sent articles and warnings to my adult children in California that they delete without even reading. I am chicken little, the mom who cried wolf. The vast majority of the public will not do anything or believe they need to until the pandemic is upon us. I would love to have some suggestions about how to mobilize them to be proactive, to at least have a plan in place. I am open to any realistic suggestions. But I think that WHO needs to create more levels of alert as this flu evolves, and needs to be less afraid to post them for the public. Their assessment of risk seems flawed, and they err on the side of caution to a dangerous extreme. We currently should be at least one level up from 3: that might get some attention.

By mary in hawaii (not verified) on 20 Aug 2006 #permalink

Earl E.,
If those in power, or WHO, in Indonesia or Thailand, know human-to-human infections with H5N1 exit; they should make it public. How many times has Henry Niman said these large clusters imply human-to-human infection; and not infection through birds in many cases.
How can the public have a realistic awareness of the threat, if this information is being concealed? Why get ready for a pandemic, when the human clusters show no or very few human-to-human infections, and when governments insist the only way to catch the disease is through sick birds? Do you know many people that spend a lot of time with sick birds?
What benefit is there for the public, when scientists and governments refuse to release information of H5N1 sequences? Does blocking research into the disease help the public?
What is gained by these announcements that a miracle vaccine is ready to protect the public against bird flu; and medicines exist, or will soon be released, to cure those who are infected?
If there are miracle vaccines and medicines available, why worry about a pandemic?
When governments and WHO announce they can contain a bird flu epidemic in one country, so it won't become a pandemic, then why work to get ready for a pandemic?
When WHO announces we are at stage 3, with rare human-to-human infection with H5N1; then why worry about, or spend energy getting ready?
When the CDC tells nurses a cheap 25 cent mask will protect them from bird flu, does that build confidence in the CDC, especially when there is documented evidence these masks are useless. Will that encourage nurses to report to work during a pandemic?
When doctors and paramedics in Australia announce, if a bird flu pandemic arrives in Australia, they will dissappear; and come back when the pandemic is over; because they do not want to risk their lives and the lives of their families; does that motivate the public to get ready for a pandemic?
When the adminstrators of private hospitals in Thailand refuse to release information on those patients in their hospitals with bird flu, because to do want to produce a panic; does that help build confidence?
When Indonesian government officials admit they were aware of bird flu infections in poultry for 2 years, before they released the information; hoping the problem would go away, does that help get ready for a pandemic?
When a virologist in Hong Kong, upon releasing information regarding bird flu sequences, was informed by Chinese government officials the information was a state secret, and could not be allowed to be released; and when China admits now that human bird flu infections existed in their country since 2003, but they did not release the information, is that also helpful?
When President Bush stated it may be necessary to quarantine cities, and not allow citizens to leave these cities, if human H5N1 infections are discovered there; even though the evidence shows the quarantine of cities is useless. Does that also help? When Bush says it may be necessary to delcare martial law and call out the US Army; does that also help? Would you like to be locked up in a detention center, built by Halliburton on a $325 million dollar contact? The government says these detention centers are for illegal aliens, and would only be used to house US citizens during an emergency. If you violate the quarantine in a city, do you think they will not put you in one of those detention centers? Please remember, with the Patriot Act, your constitutional rights are negated, and you have no right to a defence lawyer, under certain circumstances.
The British government has already announced it may be necessary to use the army to quarantine the cities, to stop the spread of the disease. Do you want to be locked down in London while people are dying all around you with bird flu?
Does this help to build conficence?
When governments refuse to test mammals for bird flu, does that help discover the reservior in mammals?

william:

There is nothing I can say to anyone today that will convince them to run out and buy extra food and water, or lay in medical supplies.

Even Revere, (please correct me if I am wrong, Revere) has not made any special pandemic preparations for his own household.

I wonder if Revere has made any progress with his own community. I report that I have made no progress. I have now given up until there is some event that will convince people to contact ME. Everyone I know is aware that I have a lot of information available for the asking to prepare for a pandemic---no calls yet.

I will suddenly get calls. I will have ready a comprehensivce plan of action that can be accomplished quickly that I can email to those that request it.

I cannot control world governments. I do not know what I would do if I were in their shoes. I would never want to be in their shoes.

My Dad always said, "A little knowledge is a dangerous thing". The trouble is, we have a little knowledge, but not enough to know WHEN the pandemic will come, or how SEVERE it will be.

Until then, I recommend finishing one's own preparations, and then relaxing and enjoying each day as God would wish us all to live---in a spirit of love instead of outrage and fury at the uncontrollable and unknowable.

Speaking as someone who lives a mere 4 hours by plane from the latest clusters, the words "don't panic" spring to mind. The current Java cluster is a good thing if it's H2H because it has given the authorities in Indonesia and Australia a chance to beef up there preparedness being isolated at least in Indo terms. The odds are pretty good that the Indo army has shut down the roads to Cicelet until they can sort it out.

The Australian Foreign Minister, Alexander Downer reiterated the 'high' threat level to travellers to Indonesia on Saturday night TV news, apropos of nothing in particular. All returnees from anywhere in SE Asia are already routinely quizzed at the airport about contacts etc.

I'm not saying that any of this will do any good but I suspect that somebody in ASIO or JIO in Canberra has sat down with Cabinet and told them what to expect and as soon as HTH transmissions confirmed in Indonesia I'm pretty sure plan A will be an immediate no-exceptions closure of the border. This will, of course, strand lots of aussies who will write songs about in years to come.

Not that it will work, of course. Since it will only take a customs officer to catch it off an Indonesian fisherman being into custody at Darwin or Broome.

But it's not going to happen tomorrow, next month, maybe, end of the year probably. Anyhow, I read somewhere yesterday that the wholesale supply of P95 masks has gone from being instant to 3 month wait. So I went and bought one from the hardware store this morning just in case the 40 million that the Oz governemt claims to have in stockpile doesn't make it out of the store room.

By kyangadac (not verified) on 21 Aug 2006 #permalink