I am often struck in reading Dr. Henry Niman’s postings how certain he is of his conclusions. Yet they fly in the face of most other news sources. I think we would all like to know if he is correct. Here is a link to his most recent post on his site concerning an IRAQI case:
http://www.recombinomics.com/News/01280601/H5N1_Iraq_2.html
This is what he seems to be saying overall taking into account many of his recent postings:
1. Initial H5N1 testing are mostly unreliable.
2. WHO is being either DELIBERATEELY DECEPTIVE or grossly negligent in regards to H5N1 H2H reporting both in terms of numbers and method of transmission..
3. There are continuing new H5N1 human cases in Turkey and elsewhere which are DELIBERATELY NOT being reported as such.
I compare this with recent news reports which state “all is calm on the western front”. It is easy to dismiss Dr. Niman as simpy wrong. But a little voice in the back of my head says “Maybe he is correct”. I don’t know of any way to tell for sure at this point. Time will tell as they say. But if he is correct, what governments and WHO are doing is beyond “scandalous”, as he often puts it. It would be criminal.
One more set of questions occur to me: Why is he the only expert out there willing to make these types of statements? Why aren’t others with his credentials and background joining in to demand factual reporting from governments and agencies? And finally, is he saying the a pandemic has actually begun?
“The clinical presentation of cases is much more reliable, and such presentations would indicate Iraq has a familial cluster of H2H transmission, as reported in Turkey. Turkey continues to report H5N1 outbreaks on farms, although they have halted reports of new H5N1 cases in humans. Cases are being admitted and treated as H5N1 cases, but not reported as confirmed cases. Neighbors of Turkey are taking the same approach for suspected H5N1 in birds, The birds are culled, but no H5N1 reports are made.”
This would have been shocking a month ago, but now it’s not.
It would be good for Niman to present specific evidence of these charges. I suppose he can and will.
I think Niman is the best. He predicted the S227N polymorphism in Turkey months before it was confirmed by lab testing. He serves a much-needed purpose; he’s “out there” when the normal tendency (WHO, et. alia) is to much more quiet and reserved. If that normal tendency is the keel of this boat, Niman is like a breeze that fills its sails.
NW: I don’t agree with Dr. Niman on everything. I think he suggested higher phase levels (5 or 6) prematurely in the past. However, I think he is right that the WHO is manipulating data in order to understate the frequency, and now the size, of clusters. I base this on having followed the public pronouncements for over a year and reading every single one of their situation updates. He is absolutely correct when he says that the initial H5N1 cases are often falsely called negative until family members become ill with the same symptoms. Better testing then confirms that 1 or more family members were in fact infected with H5N1.
I believe that, in terms of science, we have been at phase 4 since 2003. I am waiting, not so patiently, for the final analysis of the Turkish cases. If the pattern of infection there are as Dr. Niman suggests, then I think we are phase 5.
I am very grateful for Dr. Niman’s reports. Although he has jumped the gun in the past, I would not be anywhere near as ready as I am for a pandemic without his tireless work.
Monotreme, my sentiments exactly.
NW, I think Dr Niman has a strong attachment to a theory; he also has a business interest. That said, I admire his tireless efforts in keeping track of a very complex and often confusing situation. Like a lot of people, I have had my doubts about him, particularly as his pronoucements are often short and explanations brief or non-existence, so that it is quite easy to say that his words are unsubstantiated. Until you try to re-trace what he has been doing, which I have tried and believe me it is a lot of work, then you begin to see the same picture that he has been painting all along.
I would not take his or anyone’s word for granted, and I certainly am not convinced that it is of major practical concern whether the virus is changing part or all of a gene or a gene segment at any moment. Nevertheless, he has been right enough times for me to take what he says seriously.
Henry relies on machine translations of foreign news sources. If you’ve ever used one of them, you would know that this is problematic.
IMO, Dr. Niman’ formulation is coherent - analyzed trough mathematical logic and genetic algorithm rules.
On the other side - dead birds do not fly; retesting positives NOT negatives; virus will reduce kill ratio in order to be more infectious; etc. …
People believe what the want to believe, but in order to ask a question knowing a substantial part of the answer is a must.
In cinema, the first brilliant scientist to discover what ever bad crap is about to happen is always treated like a quack. Right up to everyone saying, “Holy Shit, he’s right!!!” I always like these guys for having the quattos to say it despite the unyielding criticism. They are true believers. (They rarely get killed in the movie, either)
Dr. Niman has suggested H2H since 2004. If that’s true, what haven’t we seen more cases especially in health care workers? One explaination might be that the many/most infections are going unnoticed.
In real time they die broken men. A few make out big time in their time, and then get debunked after it doesn’t matter to them. I think anyone who lives up to their principles can expect to be in for a hard time. And many a charletan is honored. I always warned my children that becoming celebrated for any reason is a double edged sword, and especially dangerous for any young person.
I have always thought that if you want to know where someone’s heart is- look at what they spend their money on- not what they say. Watch the price of gold to find out where peoples collective hearts are. TPTB are terrified of spooking tourism and economies- so everything said is guarded. When the price of gold starts coming down- we can all start relaxing.
I like Henry Niman- he is passionate. He is not afraid of being wrong. He has been rubbished alot by anonymous posters- but he persists. Good on him!!
Hey milo, how can we use the price of gold to assume anything? If a pandemic were imminent I would assume major stock markets, the price of oil, etc to be heading south.
I love it! The paper in your wallet isn’t backed by anything right now anyway. Our country is in debt up to its collective eyeballs, never mind the folks who are living paycheck to paycheck and only able to pay the interest payments on their credit cards. Wonder why Congress redid the bankruptcy laws all of a sudden…kind of makes you wonder, doesn’t it? Would it really take a pandemic to send stocks into the toilet? Not on your life. China has already said that if the flu broke out epidemically in its region, it would seal the borders. How much of our stuff do you figure is made in China right now? And you wonder why the price of gold is so high? At least gold is gold, can’t make a whole lot more of it to cover debt, etc. It will retain its value, along with silver. Holding gold and silver coins is a no-brainer right now.
De jure at 18:06 The paper in your wallet isnt backed by anything right now anyway.
As long as the dollar was the only acceptable payment for oil, its dominance in the world was assured.
Alexis- re: if we’re at H-H now why no illness in health care workers. Agree with you 100%-that’s my personal red flag. It’s what made everyone stand up and pay attention to SARS.
Alexis and Grace RN: Why no HCW? Prophylactic tamiflu is my guess. 100,000 doses went to Turkey. I bet HCWs were top of the list to receive it.
I’ll bet the politicians got there first….
Gold is nice, but I think people who have not prepared would be willing to trade their glitter for a loaf of bread if push really came to shove. Real value is in what you can eat, what you can use to build, to wear in winter, what allows you to survive.
Alexis at 15:34
there are seroprevalence studies from Hanoi suggesting no health care worker positive serology; other studies argue against low level and mild disease.
But some studies suggest that mild cases and H2H transmission may be quite common
Ron, you are citing the Thorson study, which has no seroprevalence data, and relies on anecdotal history of a flu-like illness. You are right to cite it, but it’s less convincing than the seroprevalence data would be.
DemFromCT and Ron, thanks for the links.
I personnally believe that Niman is a bit over the top when he professes H2H since 2004 without hard proof. In fact he feels that the recent Iraq case is iron clad H2H due to the time delay between a 14-year old girl, who tested negative twice BTW, and her uncle getting it. He believes this even though there nothing to show that he ever even had contact with the girl. Even if he did have contact, there nothing to prove he didn’t get it from the same infected source. Again I’ll believe H2H when health care workers are getting it, and thus far they aren’t. BTW did you notice that of the four Turkish children that got it, their parents never did, again strongly suggesting a lack of H2H.
Alexis,
The fact that “…their parents never did…” might also indicate prior antibodies.
PS. I have a strong suspicion that seroprevalence studies have been done. The question is “Why haven’t they been released”.
viralprotein
“did you notice that of the four Turkish children that got it, their parents never did, again strongly suggesting a lack of H2H.”
also might suggest its virulence in the young.
Is there any connection, to how likely one is to catch the virus,or how seriously one becomes infected, such as direct contact with blood over maybe walking through an infected flocks’ coop? Could it be the four Turkey siblings, became so sick because they were playing with the bloody chicken head. The two little sibling boys, that had milder cases of the bf, were playing with a glove that had been used to handle diseased chickens, but maybe it wasn’t bloody.
I can’t write tonight, too late!
Regarding H-H, forewarning and asceptic technique should prevent healthcare workers from getting the infection. SARS increased awareness, pointed out shortcomings. As will be demonstrated in the future, health care workers have a completely understandable first priority for self-preservation.
With respect to a pandemic, evolutionary pressure on the virus will eventually produce the required changes. Nothing at this late stage can prevent this from happening…once again too little to late. The WHO is powerless and is ‘blowing smoke’.
TomDVM the HCWs in the Turkey cases had no forewarning yet they were not infected. Additionally, all of those infected were reported to have had some contact with infected birds. Based on what we know, there’s no way to state with 100% certainty that h2h happened. If there’s more to the story that I’m missing please share it with us.
Alexis…You raise an important point…I will try to explain further. First, I am not an expert but a farm animal veterinarian with twenty years field experience. Farm animal veterinarians diagnose complex disease issues with only a stethoscope, thermometer and I guess rectal glove. We do everything by intuition. If you know of a farm animal veterinarian, ask his or her opinion. You might be surprised with the response in comparison to human health practitioners.
One point I was trying to make is that you should not rely on disease in healthcare workers to confirm h-h because they are specifically trained to avoid it. There were I believe at least two cases in healthcare workers in Vietnam in 2003. Henry Niman is correct in the sense that there has obviously been h-h but there is not as yet sustained h-h.
There was an outbreak of Legionnares in Canada late last fall. A month after the outbreak, it was reported that half of the healthcare workers refused to report to the affected hospital during the outbreak. The Ontario Government is now drafting legislation to make it illegal for certain essential workers (healthcare workers) to refuse to report in the face of an outbreak with jail terms if they refuse.
In Feb. 2005, the Chief Canadian Medical Officer of Health stated that ‘50,000 persons will die from a pandemic and we lose the same number to smoking in Canada each year anyway’. In response, I wrote that my estimate was 1 million in Canada and the outbreak would start in the fall of 2006. My intuition brought me to the same conclusion as Henry Niman before I became aware of any blogs regarding H5N1.
We have had h-h since 2003, we do not have as yet sustained h-h ie. a highly infectious disease with extreme morbidity (sickness) and extreme mortality (death rates). One other thing to consider is the long-term chronic health problems that will curse many who survive this infection. Mortality should never be the only thing considered. There are many persons in the world still largely incapacitated by the sequelae of SARS.
I think we are debating timing but timing is not important. Henry Niman stated the pandemic has already started. One year or one month one way or another won’t matter in a hundred years. I have not prepared yet and have no intention of ordering Tamiflu, or getting a flu shot when they become avaliable because the evidence, in my opinion, clearly indicates that Tamiflu and existing egg based flu vaccines do not work.
Lastly, mutations are in most cases random events. The larger the template avaliable the greater the chance. Those who say that it hasn’t occured in 9 years so it won’t occur now are misguided because the template avaliable to the virus is increasing exponentially. In each emerging disease, there is a tipping point. I believe the final of a series of tipping points occured at the lake in China this spring. Once, a virus can maintain 50 % mortality in humans while at the same time traveling wide distances in other animal species without killing them (subclinically)…the human race is in big trouble.
What will work? N95 masks and teaching yourself and your children the basics of sterile technique. Public washroom doors without handles and automatic disenfection of escalator hand-holds would also help. Have avaliable a place where water and heat are not dependent on electricity. Do not store frozen food but dry foods that do not require refridgeration…but we cannot store enough food to last through an epidemic that will last at least eighteen months. We will have to live with and at the same time avoid the disease.
I have not prepared or stored any supplies yet because the virus has not mutated far enough but I expect that this will occur within months.
Sorry for the length.
I have thought about removing all the door knobs inside my house, so my chicks can just push the doors open.
Alexis I forgot one last piece of circumstancial evidence. The flu is an unstable virus prone to mutation. In the recent past many stable animal viruses (over hundreds of years) have mutated to infect other species or change their infective characteristics. This has also included bacteria like Strep. suis, a disease of pigs, killing many Chinese Citizens this summer… same goes for West Nile and Dengue Fever. The Flu that has jumped from horses to dogs in North America recently has no historical precedent. I believe global warming is responsible for the increased mutation rate, in all pathogens, in distinct locations around the world. I believe it will continue to push and accelerate h5n1 mutations.
“We have had h-h since 2003, we do not have as yet sustained h-h ie. a highly infectious disease with extreme morbidity (sickness) and extreme mortality (death rates).”
Niman suggests more H2H than the Vietnam health care workers you’ve referenced. If you agree, then you are in the micro minority of all experts on this subject. Niman has suggested proof positive that the recent Iraqi case is H2H due to a timeline and nothing else. We don’t even have any evidence that the Uncle and Niece ever had contact. Furthermore subsequent testing shows the girl didn’t have it and tests havn’t confirmed that the Uncle had it. Niman assumes much and extrapolates that to H2H while ignoring any possible evidence of a common source.
Of virutally all known cases, there is evidence of sick or dead birds. The overwhelming evidence suggest that any H2H that might have occured was very weak and only happened in rare instance if ever.
Sorry for the rant…LOL.
Alexis..You are right. I didn’t say I agree with everything Dr. Niman has said but I agree with the trend. Let me put it this way. If a chicken gets H5N1 they are infectious. If a cat gets H5N1 they are infectious. I ask the following philisophical question that I think is lost to human specialists and obvious to animal generalists. Why is it that if a human being gets H5N1 they will be the only animal species that is not infectious.
Different receptors. At least, that’s been the story so far.
If humans can be infectious, we’d be seeing a lot more cases that we’ve seen thus far especially in HCW.
Tom DVM at 13:59
“One other thing to consider is the long-term chronic health problems that will curse many who survive this infection. Mortality should never be the only thing considered. There are many persons in the world still largely incapacitated by the sequelae of SARS.”
Do we have any quantitative sense of the enduring incapacitations of SARS and recovered H5N1 cases? Some here, myself included, have speculated that newly recovered / immune patients might have opportunities to take high exposure jobs in situations where their skills and experience or even just their persons could be useful. If most would be incapacitated for long periods of time, that assumption would seem to be wrong.
One imagines the post-trauma conditions of recovered H5N1 cases should be known (by someone).
Dubina. I believe that the sequelae of the 1918 outbreak are documented including a latent neurological syndrome. I believe I treated the same disease in cattle for many years that became SARS. I base my conclusions on the chronic sequelae I observed in cattle.
I guess from my perspective the human health community has remained quite silent on the long-term effects of SARS. I live a two hour drive from Toronto. The epicenter of SARS in 2003.
Tom DVM- my hat is off to you. Beautiful summary of the situation (IMO). Also, your point about the morbidity of H1N5 is an issue that I have never seen discussed before. Please keep contributing! I am enjoying listening.
Long-term Effects of In Utero Influenza Exposure in the Post-1940 U.S. Population Douglas Almond Columbia University and NBER July 2005
Abstract
This paper studies the long-term impact of the fall 1918 Influenza Pandemic. In the 1960–1980 Decennial U.S. Census data, cohorts in utero during the height of the Pandemic typically display reduced educational attainment, increased rates of physical disability, lower income, lower socioeconomic status, as well as accelerated adult mortality compared with other birth cohorts. In addition, persons born in states with more severe exposure to the Pandemic experienced worse outcomes than those born in states with less severe Pandemic exposures. These results demonstrate that investments aimed at improving fetal health can have substantial long-term effects on subsequent health and economic outcomes.
Tom,
If they’ve remained quite silent, should we infer their silence is because they don’t know, haven’t bothered to keep track, or somehow don’t want that knowledge made public?
The latter possibility seems farfetched. Why should anyone want to keep such an arcane secret?
I saw a television news program which featured a young man in Viet Nam who was recovering from BF; his doctor was describing the struggle. I’m sorry I cannot remember which program, therefore can’t provide a link. It was around the time of Sanjay Gupta’s special on CNN, I believe. I will search and provide a link if possible.
Eyewitness: Surviving bird flu
Alexis (to Tom DVM) at 14:15
We have had h-h since 2003, we do not have as yet sustained h-h ie. a highly infectious disease with extreme morbidity (sickness) and extreme mortality (death rates).
“Niman suggests more H2H than the Vietnam health care workers youve referenced. If you agree, then you are in the micro minority of all experts on this subject. Niman has suggested proof positive that the recent Iraqi case is H2H due to a timeline and nothing else. We dont even have any evidence that the Uncle and Niece ever had contact. Furthermore subsequent testing shows the girl didnt have it and tests havnt confirmed that the Uncle had it. Niman assumes much and extrapolates that to H2H while ignoring any possible evidence of a common source.”
If you read Nimans analyses of Turkey cases, youll find his ample references to bimodal infection. The Iraqi case(s) are sequel to his ongoing analysis of the Dogubeyazit Cluster.
Have a look at the two sets of charts made of Nimans case timelines. Extremely provocative if not conclusive.
http://www.fluwikie.com/index.php?n=Forum.DogubeyazitCluster
Furthermore:
23 January 2006
niman at 13:49
WHO is palnning on collecting 10,000 serum samples. Antibodies in contacts would be a good indication of H2H.
However, the data are already pretty overwhelming. Heres another Ozcan added
http://www.recombinomics.com/News/01230601/H5N1_Kocyigit_Ozcan_Grows.html
niman at 18:09
The level of detail is clear from the clusters. There are now 6 families that are related, live in Dogubeyazit, and have been hospitalized with bird flu symtoms. This chain has been going on for over a month.
Dubina. I don’t know why they have been silent…your guess is as good or better than mine. Let me explain a little further. Cattle are very prone to viral pneumonia. Humans are not. One statement that is incorrect, in my opinion, is that we are any better off than those in 1918. Viral pneumonias have the ability to create permanent lung damage within 24–48 hours of clinical infection. The subcutaneous gas described in 1918 is something I have observed in cattle many times and is an indication of direct viral damage. Antibiotics do not treat viruses but treat bacteria that invade after the fact. The problem is the damage is done before the secondary bacteria come in. The cytokine storm causes some of the direct viral damage, is common in cattle and can in many cases be avoided through aggressive treatment regimes. Regarding the chronic sequelae from SARS or H5N1, lungs are not very good at regenerating themselves. The damage is in many cases permanent…emphysema.
from informatic’s link…one who got away.
Now back to his normal life, Hung has decided to take a long leave of absence from his work.
“They were only too happy to release me. Not everybody believes that I don’t have the virus anymore and that it is not easy to contract bird flu virus.
“It is like having a stigma, some people look at you with suspicion and fear. So I think it’s best to avoid having too much contact with other people.
“I also look out for any slightest symptoms of bird flu in my family. I’m watching like a hawk,” he said.
When it comes to his food, Hung admits he no longer eats those “tricky delicacies” he used to love.
“We have also stopped eating chicken, duck, and poultry in general. Maybe it is too cautious but we cannot risk our health.
“We have to stay alert, very alert,” Hung said, adding with a chuckle: “I now know everything about preventing bird flu. I should be employed by the Health Ministry to do their awareness campaign”.
Fully recovered, they say.
Now he sounds like a FluWiki regular.
Alexis. They hope that serological studies will indicate that H5N1 is widespread in the general population with 100′s of mild subclinical cases for each identified case. I don’t believe this will be the case and I have to ask why this wasn’t done in 2003 or 1997. I am quite perplexed by the regulatory actions that have occurred. They don’t make a lot of sense.
It makes me think of the “Roswell” conspiracy. I was born there on the air base that the 59th Bomb Wing was attached to. If the Air Force and US Government did really cover up an alien landing, they really botched the cover up. So much information was leaked that the stories began to be exaggerated. The possible truth then, seemed unbelievable. Sightings were attributed to other phenomenon, with the exception of those they let grow into the suburban legends. Area 51 stories about alien craft were probably promoted to make it an ongoing mystery. Making it more believable makes it more unbelievable. Maybe WHO has got something there.
Tom, please note the following comments from Niman in June 2005. This would suggest that he believes the probabiliy of H5N1 being more widespread and milder, at least as indicated in Vietnam. Do you disagree with Niman on this and what make you think that a seroprevalence study will show him to be wrong?
“Although the positive western blot data has not been confirmed, positive data would be consistent with more clusters in the north which are large and extend over a longer time period. The alarming increase in admission is further cause for concern because the admitted cases have mild disease, suggesting an even larger number of unreported cases with slightly milder disease.
This H5N1 is silently spreading mild disease in human and asymptomatic infections in poultry, which would move the pandemic to phase 6. The seeding of the human population with H5N1 sets the stage for further recombination in the fall when migratory birds bring in new sequences, which will cause new problems.”
http://www.recombinomics.com/News/06260502/H5N1_Silent_Spread_Vietnam.html
regarding the idea that there’s sequelae from a flu pandemic: i believe that might be a legitimate concern.
i had the 1968 hong kong flu; my temp went up to 104. i was 10.
within a couple of years, puberty (and all its hormonal changes) hit.
looking back over all the different chronic health care problems i had through my teens and 20s, and some very minor complaints i still have, it’s possible that i have Hashimoto’s thyroiditis.
In my patient base, i’ve noted a few other patients who had the onset of later diagnosed autoimmune diseases after an illness where they had a high fever.
granted, autoimmune diseases aren’t usually profoundly limiting or fatal (a few can be), but they definitely impede on the quality of life for adults, their ability to participate in the economy, etc.
i also stayed home for the 2 weeks when i had the flu; i was a latch key kid, my mom worked, i called her every day. now we live in a culture where kids can’t miss school without failing….isolation is definitely part of the strategy of any pandemic. and being cognizant that there may be chronic health concerns down the road after infection is probably warranted as well.
Alexis I think if seroprevalence data was avaliable to indicate mild subclinical infections, it would have been presented to the public by now as reassurance by the WHO or other agencies. This may sound a little funny but put yourself in the place of the virus. The H5N1 virus has one goal…to survive. It does this by decreasing virulence to increase infectivity. However, in this case, H5N1 has done essentially the same thing by becoming asymptomatic in other species including migratory birds. It doesn’t have to decrease virulence to survive. This may be the difference between a low virulence avian strain(1918) and high virulence H5N1……….and I could be completely wrong.
Alexis. Sorry, I disagree with Dr. Niman on this. My conclusion is based on intuition and for lack of a better word regulatory strategies observed since 1999 in respect to many issues.
Tom DVM: I wish you would be completley wrong…but I doubt it…
Tom, you give the UN more credit than I do.
Tom DVM: Excellent posts that you have made here. Please stay with us for the long term. And keep your ideas and observations coming.
Sunday, January 29, 2006
“It is maybe even more important to concentrate on the essentials of life for those who are living than it is to focus on the treatment of those who are sick,” he said.
“We learned a lot.”
UN’s World Health Organisation (WHO) in Geneva, a David Nabarro, is the UN’s top influenza coordinator.
http://www.abc.net.au/news/newsitems/200601/s1557327.htm
U.N. agency tests dead Iraqi man for bird flu
GENEVA, Jan 28 (Reuters) - Tests for bird flu will be carried out on a dead Iraqi man, whose niece also died 10 days ago and first raised fears that the deadly virus had reached the country, the World Health Organisation said on Saturday.
Although tests made in Iraq on samples from the girl, who died on Jan. 17 near Sulaimaniyah, not far from the country’s border with Turkey, were negative, both had suffered breathing difficulties, WHO spokeswoman Maria Cheng told Reuters.
“Given that both these people had severe respiratory problems and that it is near the border with Turkey, we need to check,” she told Reuters.
Cheng said that samples from the man, who died on Friday, would be sent to a WHO-affiliated laboratory in Britain, the same one that was used to verify cases in the Turkish outbreak.
Turkey reported more than 20 human cases of the avian virus this month, several months after it first detected the virus in poultry.
So far there have been no confirmed cases amongst poultry in Iraq. However, some birds died recently in the area from which the girl and her uncle came, but it was not yet known whether the deaths were due to bird flu, Cheng said.
“Birds often die of many things,” she said.
http://www.alertnet.org/thenews/newsdesk/B316006.htm
(Occam’s razor is a logical principle attributed to the mediaeval philosopher William of Occam . The principle states that one should not make more assumptions than the minimum needed).
“I guess news of human bird flu in the midst of 160,000 US troops might have a wee tendency to step on the Bush Administration’s “don’t worry, be happy” Iraq message.”
TomDVM see the post DemFromCT at 20:06 with the seroprevalence? link. Studies were done in 1997–2005 and are on that page, published and unpublished.
Tom DVM,
I think that there are many seroprevalence studies going on in different parts of the world. The Chinese probably have several studies of their own but we have a better chance of getting samples of a live H5N1 virus from them than we do the details of those studies.
Second WHO probably has a study in Vietnam or Thailand and certainly in Turkey.
And I doubt if the CDC would rely on the WHO’s numbers or risk estimation so they are probably collecting samples themselves if for no other reason than so our scientists can track the mutations.
And last but not least, Roche probably has a team taking samples in Turkey to track the effectiveness of the 100,000 doses of Tamiflu they supplied… especially because they need to counter the Vietnamese rumor of a lack of efficacy in their upcoming marketing collateral.
The question is “Why hasn’t they been released”.
Politics… both political and commercial.
Frankly anything, that has this kind of potential to close national borders and impact global economics on this scale, is a National Security issue.
viralprotein
DemfromCT. I am not an experienced blogger. I couldn’t bring it up. Not having read it, I would be very surprised if they found any. You would expect that blood samples were taken from close contacts in 2003 and after. If they were positive, they would have been reported.
“…I think if seroprevalence data was avaliable to indicate mild subclinical infections, it would have been presented to the public by now as reassurance by the WHO or other agencies.”
To reassure the public? WHO’s own stats suggest 50% mortality which Turkeish evidence has pretty much blown that out of the water. If seroprevalence data shows 50%+, what does the WHO have to lose, it simply validates their own stats. There was a recent study published in the Archives of Internal Medicine that supports the “more widespread and mild symptom theory”. This supports Dr. Niman and is one of the best and most recent studies we’ve got in the absence of seroprevalence data. You can attack the results, but at least it’s been published as opposed to much of the data thrown around here.
The Thorson study has been discussed at length here. It relies on reports of being ill, not seroprevalence data. It’s important to understand that.
As for long-term effects of SARS, how many cases were finally diagnosed in Canada? There may not be enough of a time-lapse, or not all those who recovered have any symptoms. The greater numbers were in China, correct? In that case, we’re not likely to hear. Also, if there are less-than-visible effects, hard to craft a health news story about it.
In another area, look at the number of brain-injured soldiers returning from Iraq and Afghanistan: there are significant numbers, but the coverage of this problem has been poor.
“The Thorson study has been discussed at length here. It relies on reports of being ill, not seroprevalence data. Its important to understand that.”
If you reread my post you’ll see that I clearly pointed that out: “This supports Dr. Niman and is one of the best and most recent studies weve got in the absence of seroprevalence data. You can attack the results, but at least its been published as opposed to much of the data thrown around here.”
It has indeed been published. So has this, here. The unpublished data simply supports and adds to the published data. I only add the links because the concept of publishing has been brought up.
What’s interesting is the idea that the web can supply peer review of a certain sort as well. The Thorson study, published, is certainly getting its share of that. ;-)
By the way, to all concerned, thak you for the discussion. We continue to work hard to find more, any, seroprevalence data. We continue to press those who have any to publish it, or present it to peers at conferences, or put it on line. We continue to urge anyone who is in aposition to run those studies to do so. Much of the above discussion is happening in an absence of data.
DemFrom CT One last thought. Lets say hypothetically, as I do not have any or have heard of any data, that some studies indicate that close contacts have contacted the virus and produced an immune response; they may or may not have had mild clinical infections due to virus load. As I stated before the current virus is operating under a widening template and will mutate many more times before it develops the ability for efficient h-h transfer. If there are 200,000 chickens in one barn then the virus has the equivalent of 200,000 humans to develop the required mutations (humans are not required). H5N1 is reported to have a wide incubation periods and persons are sick for several days before they are identified and taken to hospital. In my opinion, current seroprevalence data will not affect the final form the virus takes and as current circulating human flu strains demonstrate, flu viruses have extreme mutability, and immunity from this years virus doesn’t ensure immunity next year. Unfortunately, I think we are faced with a difficult adversary…from my veterinary perspective, the perfect storm.
Tom DVM at 21:11 appreciate the comments… you’re quite right that past performance is no guarantee of future results. reassuring data, if that’s what it truly is, is only a snapshot of the here and now.
> If there are 200,000 chickens in one barn then the virus has > the equivalent of 200,000 humans to develop the required mutations > (humans are not required).
but when in these chickens a mutant evolves which is capable for h2h, then it will die because either that mutant is less capable of chicken2chicken or because no human happens to contact it. When on the other hand that mutant evolves in man, it has good chances to spread to other people. I assume c2c is different from h2h and not through coughing,sneezing. However the Turkey mutations seem also to have a “positive” effect on improved c2c and/or b2c and/or b2b else they wouldn’t have evolved.
Alexis at 21:45 “I personnally believe that Niman is a bit over the top when he professes H2H since 2004 without hard proof. In fact he feels that the recent Iraq case is iron clad H2H due to the time delay between a 14-year old girl, who tested negative twice BTW, and her uncle getting it. “
Her 2 negative tests were wrong - as Niman suggested:
Nice catch, NW.
If true, this puts in doubt every `negative’ test we hear about.
Negative tests have been discussed at length here (corrected link).
“Nice catch, NW.
If true, this puts in doubt every `negative test we hear about. “
It looks like the typical pattern that has emerged whenever there is a human case in a “new” country is”
1: We have never found bird flu in any of our chickens or wild birds.
2: This person died of pneumonia, not bird flu.
3: Oops.
“In fact he feels that the recent Iraq case is iron clad H2H due to the time delay between a 14-year old girl, who tested negative twice BTW, and her uncle getting it. “
the indications become more and more. Although there are other possible explanations like birdpoo in the house at a place only rarely touched. Or eggs not properly cooked. Or.. we should ask them. Oops, they are dead. The uncle died 2 weeks after the girl, this is a bit long for h2h
“The uncle died 2 weeks after the girl, this is a bit long for h2h” gs- not if the pre-symptom period can be as long as 17 days as suspected. The uncle could have been infected late in her pre-symptom period. Still, if H2H were efficient at this point there would be many more case. Personally any H2H makes me very worried … And there’s more interesting news… “Another suspected case is 54-year-old Mariam Qadar, who hails from the same region as the two fatalities and was taken to hospital in Sulaimaniyah by her family on Wednesday. “The analysis so far has not confirmed if she has the disease, but there is a suspicion,” hospital director Shirku Abdallah told AFP.” …http://www.channelnewsasia.com/stories/afp_world/view/190794/1/.html
Since H2H keeps coming up, it is worth briefly reviweing the evidence. When there are clusters of cases they are generally due to a common source or H2H. The most inportant data point for distinguishing the two possibilities is the disease onset date. If the infection is a common source, the disease onset date of the index case and other family members (for familial clusters) will be close in time (within a few days). If it is H2H, there will be a larger gap (in the range of 5–10 days).
Thus, if there is a 5–10 day gap, chances are pretty good that the index case infected the other family members. The gap can be explained via common source, but the liklihood that it is H2H is much higher. If there are two clusters and both have the gap, then the H2H case is much stronger. If there are 10 clusters and most or all have the gap, then thre is little doubt that almost all clusters with the gap are H2H.
For H5N1 there are now something like 30–40 such clusters and virtually ALL have the 5–10 day gap, indicating that virtually ALL are H2H. These clusters have been seen in Vietnam, Thailand, Cambodia, Indonesia, China, Turkey, and Iraq. If fact the iniial confirmed case in all countries since Cambodia has been a member of a familial cluster with a 5–10 day disease onset date gap.
When pressed, WHO will admit that H2H can’t be ruled out. However, the data is grossly distorted. Just yesterday Julie Gerberding told the Senate appropriations committee that there was evidence for TWO H2H clusters. This analysis is absurd. WHO and CDC use any report of chickens or chicken meals to excluded the obvious H2H (and they also exclude cases from the “confirmed” column because of poor sample collection on cases that are clinically H5N1 and are family members of confirmed H5N1 cases).
This denial of most H2H clusters has been persistant, relentless, and based on NO data. In Turkey, the clusters were so long and so large that the disease onset dates and relationships with glaringly withheld from WHO situation updates.
For the most part, WHO has bene given a free reign to distort the data by journalists who have little training and who merely spit back the spoon fed propaganda that the public and politicians willingly swallow.
Dr. Niman, do you still stand be these statements from June 2005? If so, what are your thoughts on the true mortality rate of H5N1?
Although the positive western blot data has not been confirmed, positive data would be consistent with more clusters in the north which are large and extend over a longer time period. The alarming increase in admission is further cause for concern because the admitted cases have mild disease, suggesting an even larger number of unreported cases with slightly milder disease.
This H5N1 is silently spreading mild disease in human and asymptomatic infections in poultry, which would move the pandemic to phase 6. The seeding of the human population with H5N1 sets the stage for further recombination in the fall when migratory birds bring in new sequences, which will cause new problems.
http://www.recombinomics.com/News/06260502/H5N1_Silent_Spread_Vietnam.html
Perhaps someone, perhaps Nieman himself, should post his posting and a chart of all 30 clusters with onset dates for the world to see. Sending it to news outlets would also be a good idea. Then let WHO respond.
Let me try that again: Niman has a good point that can be diminished by the idea that a single study or case is not sufficient for generalization purposes. He suggests 30+ instances of clusters and WHOs misrepresentation of the facts. Niman has made his point about Goldilocks cases in the past and the use of clinical data (This too can be substantiated. What is needed is a presentation of the data in a format that would be palatable to journalists and others in order to get WHO to defend and or refine its policies.
Access to the data that Niman references is needed.
The access to the data is pretty easy to get (except the withheld data on Turkey). WHO does an situation update when new H5N1 positives are confirmed
http://www.who.int/csr/disease/avian_influenza/updates/en/index.html
The data ondisease onset dates or relationships has been withheld for the cases in Turkey because the cluster are so huge and the chain is so long
http://www.recombinomics.com/News/01230601/H5N1_Kocyigit_Ozcan_Grows.html
http://www.recombinomics.com/News/01220601/H5N1_Kocyigit_Ozcan_Timeline.html
http://www.recombinomics.com/News/01210603/H5N1_Turkey_Ozcan_6.html
I have given data on earlier clusters in Vietnam
http://www.recombinomics.com/News/02050503/Human_Transmission_One_Third.html
http://www.recombinomics.com/News/02050501/Clusters_Human_Transmission.html
and here is more on clusters in Indonesia
http://www.recombinomics.com/News/12060501/H2H_H5N1_Efficient_Indonesia.html
For those of us with no medical education, can someone please translate this into layman’s terms and conclusions?
Niman, how about it?
Is there any conclusive test for H5N1? Are disease onset dates / contact relationships sufficient to conclude H5N1? By virtue of various opinions and comments here and there, it sounds as though h2h can only be ascertained asymtotically: one can get ever closer to confirmation, but never quite say for sure.
That’s nonsense of course. Why test or do case history interviews if definitive conclusions can’t be made at some point? And if definitive conclusions can be made, what are their bases?
Another way of asking this question is pose it as tea leaves or entrails: only the utmost shaman can read them correctly?
Dr. Niman, would it stand to reason that as the virus mutates, the assay is less sensative or reliable?
OK, I for one will look into it. I am a psychologist (teaching stat and methods) by training and would like to know what others with training in virology or related areas think. Can a reasonable case be made here? What do the journalists think?
Dr. Niman, do you still stand be these statements from June 2005? If so, what are your thoughts on the true mortality rate of H5N1?
Although the positive western blot data has not been confirmed, positive data would be consistent with more clusters in the north which are large and extend over a longer time period. The alarming increase in admission is further cause for concern because the admitted cases have mild disease, suggesting an even larger number of unreported cases with slightly milder disease.
This H5N1 is silently spreading mild disease in human and asymptomatic infections in poultry, which would move the pandemic to phase 6. The seeding of the human population with H5N1 sets the stage for further recombination in the fall when migratory birds bring in new sequences, which will cause new problems.
http://www.recombinomics.com/News/06260502/H5N1_Silent_Spread_Vietnam.html
The are many ways to generate false negatives, but the most common and efficient way for H5N1 is to do Goldilocks testing. H5N1 is an infectious disease and in comes and goes. It is there fore fairly easy to miss if the wrong sample is collected or it is collected at teh wrong time. For mild cases, H5N1 will be around for a short time. For severe cases it will migrate from the nose and throat to the lungs.
Goldilocks testing is done about a week after symptoms. By then there is little H5N1 in the nose and throat. Mild cases have cleared the virus and severe cases have the virus in their lungs. Antibodies don’t reeach detectable or peak levels in the blood until 2–4 weeks after symptoms.
Testing at 1 week is too late for PCR of nasal or throat swabs, and too early for antibody in the blood. However, it is just right for false negatives.
Dr. Niman Is infection related to virus load…ie presence of virus in small enough concentrations to illicit immune response without being high enough to cause systemic infection. Is it possible that serological testing will indicate that high virulence flu (H5N1) is not widespread in the population and is not causing mild systemic cases? Possibly, a difference between our first high virulence infective agent and the low virulence flu’s we have experienced in the past.
Is it possible that serological testing will indicate that high virulence flu (H5N1) is not widespread in the population and is not causing mild systemic cases?
So far from what we have collected and seen, that seems to be the case (no widespread positive seroprevalence). But we have nothing yet from Turkey (it is too early to expect that we would, but it’s not too early to start asking and within the next few weeks, data should theoretically be available).
I’m a journalist. To get a story printed or aired, you not only have to convince the frontline reporter, but the reporter has to be able to persuade his editor/producer. And reporters — at least reporters for legit news sources — aren’t allowed to draw conclusions. They have to quote an expert, an authority figure, someone whose credentials justify their opinions. So, directing a reporter to the data isn’t enough. Some live person has to be willing to interpret the data on the record.
I’m not saying that planting the suggestion wouldn’t work. Just that some follow-up would need to be done, too.
Sadly, I don’t cover this beat, so I’m not in a position to raise the red flag.
“…WHO has consistently try to find data to support its preconceived notions on H5N1 transmission. Iraq, like Turkey, China, Indonesia, and Cambodia was not considered to have a human case until there was a familial cluster that almost certainly involved human-to-human transmission. WHO continues to misrepresent the frequency of human-to-human transmission and withheld disease onset dates and familial relationships in its updates on Turkey. These commissions by omission deserve a third party investigation.”
http://www.recombinomics.com/News/02010602/H5N1_Iraq_Cluster_Concerns.html
Henry, I’m with you. I couldn’t more agree that someone needs to investigate either at best the WHO’s gross incompetence or at worst their intentional ‘negligence’ in releasing onset dates and relationships of the victims. No surprise that the WHO has failed the world again. Time after time after time. Blunder after blunder and we still believe that they are going to eventually get it right. What a farce. Why does ANYONE even listen to them and what they have to say like they are the preminent authority on right, wrong, good, bad, sick or healthy. It makes me so mad I could spit. Patooey. There, they went and made me do it. It’s time to start forwarding this information to the people in power. Someone needs to know what’s going on. Thank God for Dr. Niman, I say.
Cheerio! 007
DemFromCT, there was a recent article I read (and I now can’t find) that essentially stated widespread exposure has not been found per seroprevalence data. They referenced a recent unpublished study from Vietnam(?) I believe as an example. It stated that out of 800 samples, slightly less than 1% tested positive for H5N1 antibodies. While this confirms no widespread exposure it certainly suggests enough exposure to significantly lower the reported ~50% mortality rate. For instance China 1.2 billion people at 1% infection rate would be 12 million….
DemFromCT, forget it I found it:
Dr. Kumnuan Ungchusak, Director of the Bureau of Epidemiology of the Thai Ministry of Health has reported (personal communication) that a study of 800 contacts of H5N1 victims has shown a seropositivity rate of less than 1%.
Alexis: Less than 1% is not 1%. 1 in a billion is less than 1%. Also important is what population were they testing. Was it a random sampling of the population at large or people with flu-like symptoms or poultry cullers? The rules used for collecting samples will affect whether you can extropulate to the general population.
I’m a journalist by training as well and would second Worried Well’s advice. I’m not a scientist but I’m guessing that the point being argued here — i.e. that available data points to limited H2H, which WHO is downplaying in its interpretations — is a question of epidemiology(?) rather than virology. I think Dr Niman is a virologist. If I’m correct, then he’d need the support of an epidemiologist to make a credible case. And if he’s taking on the collective might of the establishment, he’d have to have a very solid case to stand up to those who are bound to challenge his conclusions.
It would be a good thing to do, though. Rather than having these discussions in circles on Internet chat forums, it’s time Dr Niman put his case out formally in the public spotlight so that we can hear how WHO etc respond.
Alexis. I think the question is whether the indication of contact with the virus is defined as a clinical case. The standard used to be repeated blood tests 2–3 wks apart demonstrating statistically significant increases in titer.
Okay Monotreme let’s use 1 in 800 as a worst case scenerio since there were only 800 tested (roughly 0.1%)…happy??? As far as who they tested, I have no idea. It was on the link that DemFromCT keeps posting, so I assume it’s relavent!
1.2 Billion people x 0.1% = 1.2 million people! It would still make the apparent mortality rate MUCH SMALLER.
I said it the day after the girl in Iraq died, and I’ll say it again; the clinical picture is going to offer the first line conclusive evidence of incidence of diseaase and H-H spread. I am blown away by the lack of information about the 12 in isolation in Iraq and the 5 mobile medical hospitals. Me thinks they tell us not for fear we might know!
PS: Dr. Niman - your interpretations are invaluable to me and I have found you always to be ahead of the curve. Bless you and thank you for your work!
WHO is well aware of Recombinomics’ commentaries. The Recombinomics website is well attended by all of the major players. The concept of the time gap is about as basic as it gets. Even the general public knows that if someone in their family gets a VERY rare disease and then 5–10 days later more in the family get the same RARE disease, it isn’t due to something they ate at a friend’s house a few weeks ago.
WHO is well aware of the H2H, which is why all of the relevant data was excluded from the Turkey updates. WHO’s Klaus Stohr acknowledged that there were investigating two large family clusters when he made comments to the media. However, when these cases were described in the WHO updates, the fact that the two large families were in fact related to each other and the fact that many were hospitalized at the same time in the same hospital with each other was deliberately excluded.
http://www.recombinomics.com/News/01220601/H5N1_Kocyigit_Ozcan_Timeline.html
The omissions are EXTREMELY gross and quite obvious to anyone paying attention. WHO has clearly made the flu pandemic VERY political. There press releases and public comments have little to do with science.
The latest comments on Iraq deserve a thrid party investigation. The paper and electronic trails are quite evident.
http://www.recombinomics.com/News/02010602/H5N1_Iraq_Cluster_Concerns.html
NP Mom-I think we share the same sense of what is really cooking in Iraq. Hope I’m wrong, but I think it could be fast h-h-h. If the US military is there, which I think it is, I’m actually relieved-the WHO can’t move that decisively, and they could contain it and hopefully buy some time.
Alexis. I have reviewed the seroprevalence data from DemfromCT from the other night and I would not want to have the task to convince anyone that there are asymptomatic or mild symptomatic cases on the basis of the evidence provided. I think it proves the exact opposite. The hard truth is that the virulence of the virus is not decreasing as predicted.
Tom, I’m not asking for your help in convincing anyone of anything. I’ve simply made a calculation based on the information provided. Can you show me where my arithmatic has failed? Again, I’m only using the data provided by DemFromCT. I ignored some of the other data as it was mostly heathcare workers and not necesarily representive of an entire population.
One more time.
Dr. Niman, do you still stand be these statements from June 2005? If so, what are your thoughts on the true mortality rate of H5N1?
Although the positive western blot data has not been confirmed, positive data would be consistent with more clusters in the north which are large and extend over a longer time period. The alarming increase in admission is further cause for concern because the admitted cases have mild disease, suggesting an even larger number of unreported cases with slightly milder disease.
This H5N1 is silently spreading mild disease in human and asymptomatic infections in poultry, which would move the pandemic to phase 6. The seeding of the human population with H5N1 sets the stage for further recombination in the fall when migratory birds bring in new sequences, which will cause new problems.
http://www.recombinomics.com/News/06260502/H5N1_Silent_Spread_Vietnam.html
Alexis. Sorry. The calculation is 8 of 800 (less than 1% usually means unmeasurable). These are I guess 800 close contacts of infected persons but I don’t think you can extrapolate the rates through the general population that would not be in close contact….but you raise a very interesting point.
Alexis: You missed my point about sampling. Since most cases of H5N1 influenza came from birds, poultry workers are much more likely to be exposed than the general population. Thus, extrapulating from this group to the general population is not valid. Please check out this WHO table?, published in the New England Journal of Medicine. Note the difference between the 1997 results and the 2004 results. I outline my interpretation of this table and animal studies here?.
Alexis. I will go back to the data and try to come up with an interpretation. The point you raise is the real point in all of this. What is the mortality rate and more importantly what will the mortality rate be when the virus accomplishes efficient human to human transmission. I think we would all agree that the tone of the WHO has changed. I believe it is because they are now considering the worldwide effects of a pandemic with 10–15% mortality rather than 1–5%.
Monomtreme, I understand your point however I’m using available data, data that’s on this site. Since it’s constantly being thrown around here, I assume it’s statistically signficant. If not, then we shouldn’t be using it! Assuming it is statistically significant, then my calculations should at least suggest a much higher infection rate that what’s been shown. For example in China alone what is the total reported cases, less than 10? Assuming a seroprevalence rate range of 0.1% (worst case scenero per the 800 contacts) to 0.99% that would suggest 1000 - 10,000 contacts with sick birds which I think we can all agree is highly unlikely in a third world country with 1.2 billion people (and lots more chickens)and that has had the virus perculating for at least 9 years.
If you are correct and there are not undiagnosed mild cases then we must assume transparency regarding infections among the cabal of China, WHO, Indonesia, etc…
“I think we would all agree that the tone of the WHO has changed. I believe it is because they are now considering the worldwide effects of a pandemic with 1015% mortality rather than 15%.”
Wow Tom that would be quite presumptuous of you. How in the world could you intrepret a change in tone and come to that conclusion, especially come up with a specific mortality range?
Alexis. Intuition and again I could be completely wrong.
Alexis,
“Perculating”??… or pressure cooking.
Dr. Niman,
There seem to be many who feel that the massive cull of poultry in Hong Kong in 1997 may have stopped a pandemic from starting. Do you agree? If we stopped it then, would the virus ‘regroup’ and come back more virulent and better adapted? Is that potentially why we are seeing the higher mortality rates?
Effect Measure recently had a post that mentioned the Turkey virus isolates were displaying three mutations (receptor site, antibody site and low temperature) that have not been seen at once in the same virus until now, which is what made me wonder about the 1997 situation. Of course we will not know until the pandemic strain emerges [and is published ;)], but is it possible that the efforts in 1997 will ultimately end us up with a true “Superflu”?
Where is WHO considering a pandemic with 10 - 15% mortality?
Alexis, my understanding of the seroprevalence studies supports what Monotreme says — the 1% seropositive result wasn’t based on a random population sample and therefore we can’t extrapolate in terms of concluding anything about seroprevalence in the wider population. You could however add those eight cases or whatever to your total case count denominator for that country, which would slightly lower their average mortality rate.
In terms of an eventualy pandemic, it’s still all guesstimation and speculation in any case, as so much could change — the lack of antivirals and hospital capacity in a real pandemic could send any assumed mortality rate way back up, for example.
Isn’t intuition what buried Dr. Gary Butcher on this message board? He couldn’t back up his opinions.
Alexis. My main argument isn’t conflict of interest.
Alexis, another thought is that if various strains of this virus have been floating around and mutating in different directions since before 1997, then what was true in terms of seroprevalence or mortality for one time and place (Say, one province in China in 2002) could be very different in another (Southern Vietnam - 2005).
Alexis: I do not believe it would be possible for any cabal to hide sustained transmission of H5N1 for more than a few weeks. However, hiding small clusters of family cases, even with a high fatality rate, would be quite easy in countries run by dictators. This is almost certainly happening in China. I don’t think the WHO is hiding cases, I think they are omitting data concerning onset dates of symptoms and the relationships between patients to obscure the H2H cases. Just to be clear, I think the available data still indicates that H5N1 is NOT being efficiently transmitted between people. Close contact is required. Of course, this could change at any time.
Monotreme, the available data speaks for itself as my calculations demonstrate. Also it’s a helluva lot harder to hide bodies that merely hiding infections. The available data would suggest that hiding cases wouldn’t even be necessary if the symptoms were mild and unnoticed. What happened to all the cases that were deemed strongly suspect in Turkey? They’ve suddenly been determined H5N1 (-). Even using the WHO’s rediculously narrow interpretation of a positive H5N1 Turkey still hasn’t reached 35% mortality. This would validate Niman’s theory of more asymptomatic or mild cases….
I’m not using “intuition” here, I’m basing my points on available data and simple mathematics. Takes hiden biases and predispositions out of the equation. The bottom line is the stated mortality rate of 50% means nothing and should be strongly questioned until more seroprevalence data is published.
You can’t ‘validate’ Niman by using the ‘ridiculously narrow’ (an unbiased term, eh?) WHO data. In fact, the mortality in Hong Kong in 1997 was an official 33%.
What’s more important is your last statement. The case fatality numbers are so small in each SE Asian cuontry (and for Turkey) that we really need more data to know. WHO acknowledges this, as do the authors of the WHO summary paper when they state “The fatality rate among hospitalized patients has been high (Table 3), although the overall rate is probably much lower”.
This is from the WHO summary, in May 2005:
The likelihood of asymptomatic infection is there. It happens. We don’t know how often it happens, but so far it hasn’t happened often. It is likely that if you’re a SE Asian poultry worker, you have a higher chance of an asymptomatic infection. Maybe you’ve had H5 in the past. But this is speculation because we don’t have enough data.
That’s why I would shy away from terms like ‘validation’ and ‘proof’.
Dem—what do you think of his new claims of 162 people infected in Iraq?
Sorry—162 suspected cases.
The above WHO summaries, btw, make me think we agree more than we disagree. For that reason, and maybe just from temperment, I also prefer to avoid terms like ‘scandalous’ and ‘criminal’ when I try to put the data together and find information missing that I’d dearly like to have. ;-)
flewbie at 07:42
Bottom line is that a suspected case is not a proven case. Most suspecteds in the past turned out to be negative. So, worry but verify. And it sounds form the sketchy reports that quarantine and other measures are being taken.
The thing that is disturbing, of course, and should not be forgotten, is that this is a war zone. Let’s hope everyone working for the greater good of humanity stays safe. That hasn’t been the case in Iraq up until now. And no politics, please, I’m just worried about the health and safety of the public health folks, who are, in the end, trying to do their job.
I wonder if the reports of no Tamiflu are propaganda. You would think the military would blanket the area considering that BF in soldiers would significantly decrease support for the war. (or is that too logical?)
Alexis, “Also its a helluva lot harder to hide bodies that merely hiding infections.”
I am not going to get into the myriad arguments/discussions on this thread at this point. I just wanted to point out that the above statements may need to be re-considered. And this is not just directed to your post Alexis but just as a general remark.
I am thinking of the various times when confirmed cases had family members who had died previously with undiagnosed disease and never been tested or autopsy carried out. Like one of the first cases in Jakarta, where a girl died and was cremated, then her father and sibling developed symptoms and both died. Of these, one tested positive for H5N1, the other tested positive for antibodies but because he/she did not survive the 14 days necessary for a second test needed (to show rising antibody levels) was not counted as a confirmed case. So here we have 3 bodies but only 1 counted in WHO data.
And then there was the famous case in Thailand that even WHO agreed was probably h2h. A girl came down with symptoms and was diagnosed to have dengue fever. Her mother who was working in Bangkok flew home to care for her just before she died. The mother developed symptoms a week or so later and died. The aunt with whom the girl lived also got sick but survived. The 2 adults were diagnosed to have H5N1 but if it hadn’t been for these subsequent infections, the index case would not have been brought to the world’s attention and would always be thought to have died from dengue fever.
Another was a later cluster in Indonesia where a teenage confirmed case gave a history of 2 brothers having died within the prior 2 weeks with febrile illness. They were diagnosed by the village doctors to have ‘typhoid’ but never tested for anything and again no autopsies.
In developing countries it is quite common to lose children to infectious diseases which are never diagnosed properly. Apart from cost considerations, cultural barriers to autopsies are high. Therefore, it is a lot easier to hide ‘bodies’ than we living in the West would think.
The 162 suspected cases in Iraq are from media reports. Not all will test positive, but many that test negatove will be positive. News on infected people in Turkey has pretty much halted, but H5N1 outbreaks in birds continue to be reported, and new cases are admitted, put in isolation, and treated with Tamiflu throughout Turkey (and soon in many countries in the Middle East).
The H5N1 there has recombined with H9N2 to create HA S227N, which makes infections of humans by H5N1 more efficient (as predicted in October)
http://www.recombinomics.com/News/10220501/H5N1_H9N2_Recombination.html
Dr. Niman You Stated “News on infected people in Turkey has pretty much halted, but H5N1 outbreaks in birds continue to be reported, and new cases are admitted, put in isolation, and treated with Tamiflu throughout Turkey.”
From where did you get this information?
Turkish media reports new admissions (as well as isolation and Tamiflu treatment).
How appropriate if the big one comes out of Babylon.
DemFromCT/anon_22, you can try to explain away the theory of lower mortality all you want. My demonstration of it, however, is based on data that DemFromCT continues to reference. Even using the worst case scenerio of (1 positive for 800 contacts) I’ve demonstrated that the number of cases has been significantly underreported, which is what convention wisdom would lead one to believe (mild/moderately sick people in the third world don’t go to hosipitals). Don’t attack me, as I’m only as accurate at the data allows. More published seroprevalence data will be needed. Until then, we need to strongly question the WHO’s numbers suggest ~50% mortality rate.
PS - I use terms such as “rediculously narrow” to define the WHO’s number because they’ve refused to use clinical signs in making a diagnosis even in cases where it’s painfully obvious to everyone but them. They’ve also tested during the “Goldilocks” period to generate false positives. What makes you sure they won’t generate the same false positives during testing of blood serum if Turkish and Iraqi seroprelance studies are proceding? The recent case (15 yr old girl in Iraq)was originally deemed H5N1(-) and probably would have remained so if she hadn’t died and more tests run. How many more cases like her’s are out there? I would suggest it’s possibly a very large number.
Here’s one of the clusters from Turkey reported today:
KU GRB: HAMUR’DA AYNI ALEDEN 10 K HASTANEYE SEVK EDLD ANKARA - Ar’nn Hamur lesi’nde, ayn aileden 10 kii, ku gribi phesiyle Erzurum Atatrk niversitesi Aziziye Aratrma Hastanesi’ne sevk edildi. 2 ubat 2006 Perembe — 17:45:00
Translation: BF: 10 people from the same family admitted to hospital from Hamur
10 people from the same family have been admitted to Erzurum Ataturk University Aziziye Research Hospital with bf suspicion. They’re from Agri’s Hamur village
Here are more Ozcans
http://www.recombinomics.com/News/01210603/H5N1_Turkey_Ozcan_6.html
Here’s another from a few days ago:
Update : New suspect cases in Sivas and Batman
2 suspect cases from Kangal Sivas and 4 people from Kozluk, Batman have been brought to hospitals of Sivas and Diyarbakir.
Sivas/Diyarbakr - Sivas’n Kangal lesi’nde 2, Batman’n Kozluk lesi’nde 4 kii ku gribi phesiyle hastaneye kaldrld.
The Diyarbakir hospital administration made a press announcement that so far they have recieved 92 suspect cases, one of them was confirmed (+) and was cured, and there are still 10 suspect cases (2 adults, 8 children) in their hospital waiting for test results ..
Alnan bilgiye gre, Sivas’ta ku gribi phesiyle Kangal Sabanc Devlet Hastanesi’ne bavuran Emine T. (61) ile olu Kazm T. (38), muayenenin ardndan Cumhuriyet niversitesi Tp Fakltesi Aratrma ve Uygulama Hastanesi’ne sevk edildi.
Anne ile olunun Enfeksiyon Hastalklar Servisi’nde tedavi altna alnd bildirildi.
Dicle niversitesi Tp Fakltesi Aratrma Hastanesi Bahekimi Prof. Dr. Birsel Ba ise Diyarbakr merkez ve ileleri ile Batman, anlurfa, Siirt ve Mu’tan ku gribi phesiyle bugne kadar hastanelerine toplam 92 kiinin getirildiini syledi.
Bunlardan sadece birinin tahlil sonucunun pozitif ktn bildiren Ba, “O da yaplan tedavinin ardndan iyileti. En son Kozluk lesi’nden 4 hasta geldi. 92 hastadan 82′sini taburca etmitik. Hastanede tedavi grenlerin says 10′dur. Bunlardan 2′si yetikin 8′i de ocuktur. Hepsinin de genel durumu iyi. Tahlil sonularn bekliyoruz” dedi.
I looked at Nimans referenced URLs and found that this will take some doing. Some of the info is buried four to five screens deep and the data source is not sited other than it appears to be a machine translation of a news report. (There is no reason to suspect his sources). I did a timeline on the Turkish data about a week ago just to trying to confirm his hypothesis for myself he is right, given the assumption that a 4–5 day disparity is indicative of H2H
Tabular presentation might look something like this for the headers:
Case#, Symptom Date, Outcome, relative case#, Disparity in days from symptom onset.
Rows would be the case numbers and the raw data file would contain names and sources of the data. Blank rows would separate clusters.
Obviously this is a fuzzy data set, and that is an understatement. Some instances list admission dates, some list death, some list symptom dates. In this data set we have mixed type of dates reported within clusters. None-the-less a brief review of the data supports Nimans position as I read the sources. Of course it would be better if data sources independent of Niman could be used. A look at the WHO data (referenced by Niman) is not helpful but that is the point. Apparently, to conduct this study it would be necessary to have independent access to the news reports and then limit the study to operationally defined terms such as using symptom dates only. Of course the richness of the data is lost.
Anyone have any ideas ???
Alexis, I’m not attacking you or Niman or your hypothesis on case fatality or his. I am suggesting the available data is not the complete data and that the available data is subject to interpretation. You and Henry might well be right. Case fatality ranges from 33% to 80% depending on which country and what year, but ought to be referred to as ‘hospital fatality rate’, bewcause the denominator is known. Turkey is in the same range as Hong Kong.
Everyone who reviews this suggests the true faatality rate is probably lower, but we don’t know the number. OTOH, the current data suggests the inapparent infection rate is low. It needs to be added to; it’s not proof. We don’t know how ‘low’ low is.
Suggesting I’m trying to ‘explain away’ anything is completely missing the point of everything I’ve posted.
“the current data suggests the inapparent infection rate is low.”
DemFromCT, my calculations use the available current data, which by the way you directed me to. Why do you continue to suggest that the inapparent infection is low? The only thing that validates that the inapparent infection is “low” are the WHO’s “official” stats. I’ll say it once again, even using the very narrow interpretation (clinical signs ignored, goldilocks false positives, persons sent home from hospitals without tests) the numbers in Turkey are still in the 30% mortality range, which is roughly half the rate the WHO keeps touting. Even half the mortality rate is significant (for example it could mean 1 millions deaths vs 2 million).
Please don’t mistake my debating you for being confrontational, it’s certainly not my intent. The available data, whether observational or sero based, seems to suggest a much lower mortality rate than 50%. Not that I often agree with Niman, but his recent statements certainly support this observation as well.
Do we know as of yet whether any hospital workers have been infected? Anywhere? To me this would still be the primary reason for concern.
Health Care Workers in Vietnam and Indonesia have become infected with H5N1.
Recent post from Dr. Michael McDonald:
H2H: Essential Mutations I Submitted by MDMcDonald on Thu, 2006–02–02 15:52.
I was in a meeting last night with Jeff Taubenberger, the virologist that sequenced the 1918 flu. He gave a talk over dinner at the Academy of Medicine. His talk is relatively stable, meaning that it isn’t substantially different than the key points he made at Georgetown in September. He believes that there will need to be two mutuations in H5N1 to make it “1918″ like in its transmissibility. How probably is it that the virus will stabilize in this mutation? A truthful answer is we do not know.
We do know that the human infections that have been found so far, seem to be in the GI tract and the deep lungs. If we see infections in the upper respiratory system, that would potentially indicate a change in the molecular biology of the H5N1 virus, which would make it far more dangerous in terms of rapid transmission. To date, we have not observed clinical manifestations like this. The result is that we will continue to see zoonotic disease in humans from contact with domestic birds, like chickens.
We may see other cross-species infections including from wild animals to humans. We will probably see care givers, mothers (for example) taking care of sick children infected with H5N1 from a chicken getting infected when they are intimately exposed to the virus in the process of caring for the child. However, without a sustainable mutation in the receptor site of the H5N1 virus, we will not see rapid, sustained community outbreaks from human to human transmission of H5N1.
There already has been a change that affects HA receptor binding (S227N, aka S223N), which is what produced the explosion of clusters in Turkey.
Hey doc, how do you feel about those three mutations that have never been seen all in the same virus until now?
The tabulation of familial clusters has already been done (although the list now is probably about twice as long). There is no doubt that the 5–10 gap exists in almost all clusters (but only 1 or 2 clusters are required to show likely H2H - 30 is WAY over the top - almost all familial clusters are H2H and the biggest and most extended clusters were in Turkey - but the data on diseae onset dates and relatiopnships between clusters was withheld).
Here are the earlier cases (which were posted at Recombinomics long before the paper, which includes authors from CDC)
Two of the three are well characterized (PB2 E627K and HA S227N). They are a problem, which I predicted in October
http://www.recombinomics.com/News/10220501/H5N1_H9N2_Recombination.html
Actually, I predicted HA S227N in October. I discussed PB2 E627K in July
http://www.recombinomics.com/News/07060502/H5N1_Qinghai_Catastrophe.html
niman,
“…but only 1 or 2 clusters are required to show likely H2H - 30 is WAY over the top - almost all familial clusters are H2H and the biggest and most extended clusters were in Turkey….”
I’ve missed something: what is “likely H2H - 30 is WAY over the top”? What’s “H2H - 30″?
Many believe a pandemic was prevented in 1997 in HK by the massive cull of poultry, do you agree in theory? If so, will the virus be stronger as it comes back? I am curious if there is such a thing as ‘pandemic pressure’? IE. Pandemics happen every 30 years or so, if we go 40–50 years, does the necessarily mean the pandemic strain will then be that much more virulent?
Thanks jenny uk for the info. Dr. Taubenberger is one of the world’s authorities on the subject and his opinions should be taken seriously.
Also Doctor Niman, I am curious, since all of the authorities on the subject agree a pandemic is inevitable at some point, can we draw the conclusion that our efforts to stop its spread are going to make it worse in the long run? Could we potentially drag the pandemic out longer than if we “just let it happen”? Again, just curious as to your opinion; I understand we are also a self-preserving organism that will do anything it takes to prevent our demise.
This is a complex issue, No one will be apsolutely correct in predicting future events. The best anyone can do is to think in terms of possible generalities. Personaly i think Dr. Niman has been correct enough of the time to warrent thanks. To put yourself on the line against the prevailing line of thought or convention requires strenght of character, Which i am glad Dr. Niman possess. What this potienal disease intails to humanity should be enough to obligate others to risk as much to public criticism. So i again offer my thanks to Dr. Niman, And wish to express specificly my admiration for his work in this reguard. Thank you.
Here’s a little more detail on the 5–10 day gap in the familial clusters. If there was just one cluster and it had a 5–10 day gap between the disease onset date of the index case and the other family members, the chances would be veru high that the family members were infected by the index case. There coudl be special circumstances that would lead to two seperate infections by the same (poultry) source, but infections of humans by poultry is quite rare, so two seperate infections by the same source would be unlikely.
If there were two clusters and both cluster had the 5–10 day gap, it would be a virtualy certainty that one or both clusters involved H2H because have two serparate infections from the same source is unliely and having it happen two out of two times would be EXTREMELY unlikely.
That is why tablating all 30–40 familial clusters is not necessary. Just do a few would quickly show that H2H is common in families. The paper I linked had 15 such clusters abd almost all had the 5–10 day gap, indicating almost all familial clusters in Vietnam, Thailand, Cambodia, and Indonesia were H2H.
Now the list has become much larger which additional clusters in the aboev countries as well as China, Turkey, and Iraq. The newer clusters are the same as the earlier cluster. Virtually all have the 5–10 day gap. Thus, there is no doubt that H2H is common in familial clusters,a nd such clusters make up an ever increasing percentage of the total. In fact every new country to report H5N1 in humans since 2005 (Cambodia, Indonesia, China, Turkeym Iraq) has involved a familial cluster with a 5–10 day gap between the disease onset date of the index case and other family members.
Thus, when Julie Gerberding testified in front of the Senate appropriations committee yesterday and said that there were only two conclusive examples of H2H, she either doesn’t know how to interpret VERY straightforward data, was unaware of the familial cluster data, or was misleading.
Per Dr. Jeff Taubenberger (2/1/06), the virologist that sequenced the 1918 flu:
We may see other cross-species infections including from wild animals to humans. We will probably see care givers, mothers (for example) taking care of sick children infected with H5N1 from a chicken getting infected when they are intimately exposed to the virus in the process of caring for the child. However, without a sustainable mutation in the receptor site of the H5N1 virus, we will not see rapid, sustained community outbreaks from human to human transmission of H5N1.
So what constitutes Phase 4 conditions: an H2H common in familial clusters (due to “intimate exposure”) or some other H2H somehow short of “rapid, sustained community outbreaks” (which we all now recognizise as Phase 6, the onset of Pandemic conditions)?
It seems WHO is gradually pushing its Phase 4 definition towards its Phase 5 definition (which still has semantic play) and its Phase 6 definition, which has no play at all.
Why won’t WHO clarify what it needs to see and how they need to see it?
I wonder if all influenza A virii mutate at the same rate, or if this one is mutating faster?
H5N1 evolves incrementally via recombination. It has already recombined with H9N2 in the Middle East to acquire HA S227N which increases the H5N1 affinity for human receptors. Acquisition of PB2 E627K allows efficient replication at cold temperatures.
These two chnages will increase the number of huamns infected with H5N1 in the winter, which is when many humans are also infected with H3N2. A dual infection will increase the liklihhod of another recombination to acquite the polymorphisms that will lead to efficient sustaned human to huamn transmission.
H5N1 knows exactly what it is doing, even if WHO and consultants do not.
H5N1 is recombining. No mutation required.
Article from New Scientist that’s instructive regarding “changes” in H5N1:
The first sequences of H5N1 bird flu from Turkey have mutations that scientists fear might help the virus adapt to humans. But New Scientist can reveal that these fears might be misplaced: as cases multiply in Turkey, the virus is showing none of the mutations expected effects.
Mehmet Ali Kocyigit, 14, and his sister Fatma, 15, died of bird flu in January after handling sick chickens. Sequencing of viral genes now reveals their virus is most closely related to the distinctive H5N1 found in wild birds at Qinghai Lake in China in May 2005, according to scientists at the National Institute for Medical Research in London, UK.
This makes it almost certain that the virus reached Turkey via wild birds, underscoring the risk to other countries on the migratory flyway.
Some of the virus from Mehmet had a mutation in a surface protein called haemagglutinin. Here, an amino acid the building blocks of proteins - called serine, was replaced another called asparagine at a crucial position.
This mutation, research has shown, allows the H5N1 virus to bind a bit more strongly to a complex sugar found on cells in the human respiratory tract, which is different from the sugar the virus normally binds to in birds, says Jeff Taubenberger of the Armed Forces Institute of Pathology in Rockville, Maryland, US. He found that a much stronger increase in binding helped the 1918 human pandemic flu virus evolve from a bird flu strain.
Respiratory tract But how much the mutation really helps the virus is currently unknown, Taubenberger told New Scientist.
Moreover, says Alan Hay at NIMR, only some of the boys viruses had the mutation. Such mixtures can arise during an infection, as the virus mutates and strains that bind human receptors better emerge, says Mike Perdue at the World Health Organization. But he says well only know it means something if we see it in a cluster of human cases, where it has been selected for because it eases spread among humans.
But this has not happened so far Fatmas virus did not carry the mutation, says Hay, meaning she did not get it from her brother. And all human cases in Turkey can be traced to sick birds, says the WHO.
The mutation has been seen twice before in H5N1, in a family cluster in Hong Kong in 2003, and in a fatal case in Vietnam in 2005. Then, too, it did not get passed on further.
The Turkish virus also has a mutation in another gene called PB2, which has also cropped up at Qinghai, and in human and cat H5N1 cases in Thailand and Vietnam. It allows the virus to grow at the temperature of a mammals respiratory tract, which is cooler than a birds. It also increases the deadliness of H5N1 in mice.
But, notes Hay, most recent H5N1 cases in Turkey have been notable for their mildness.
I wish I knew more about the morphology of this virus. The recombination part is down-right chilling. But why haven’t the other virii such as H7N7, or any of the H7N? virii recombined with H3N2? What makes this H5N1 so likely to recombine? By the way, thank you very much for your insightful commentary on your website, Dr. Niman. It takes a special skill to communicate highly technical information to where a layman can understand it. Your commentary is much appreciated.
The differences in the H5N1 in Turkey is almost certainly influence by lab selection (eggs vs MDCK cells). This selection was not addressed in the New Scientist piece.
H5N1 knows exactly what it is doing, even if WHO and consultants do not.
Dr. Niman, I respect your opinion, but disagree. The virus doesn’t “know” anything. It is simply trying to replicate. It has no intelligence, but will hit the magic combination by random recombination or mutatation. I might win the lottery too, but in all honestly, I don’t know which numbers to pick. The virus doesn’t “know” what it needs either.
I understand that you may not have meant that literally, but it is important to distinguish the difference, I think.
I have one question. You usually refer to recombination, verses mutation. Assuming a recombination, rather than a mutation, is it correct to say that it will likely not have the same virulance if recombined into a new virus? Which would mean we have no idea if it will be HPAI or LPAI? Where as a mutation of an existing HPAI would lean toward a continued HPAI?
Why wont WHO clarify what it needs to see and how they need to see it?
[Dr. Jeff Taubenberger (2/1/06)]
“We may see other cross-species infections including from wild animals to humans. We will probably see care givers, mothers (for example) taking care of sick children infected with H5N1 from a chicken getting infected when they are intimately exposed to the virus in the process of caring for the child. However, without a sustainable mutation in the receptor site of the H5N1 virus, we will not see rapid, sustained community outbreaks from human to human transmission of H5N1.”
Thus, given the implications of going to Phase 4 or staying at Phase 3, Taubenberger, Gerberding and others conclude there may be ample time from now to the onset of Phase 4 conditions (whatever they eventually prove to be) and beyond to the onset of Phase 6 pandemic conditions to accomplish such preparation as pandemic conditions require. In effect, even though the circulating virus might be only one slot machine mutation / recombination away from a much feared pandemic strain, and even though nobody can say for sure when that fateful tumbler might fall, a bet has been made to delay the global economic dislocations of Phase 4 a bit longer.
Meanwhile, that obvious, but so far unspeakable bet is being hedged behind the scenes in plans to be executed under Emergency Authority if need be.
“PS: Dr. Niman - your interpretations are invaluable to me and I have found you always to be ahead of the curve.”
Do you find if curious that Dr. Niman is the only bird flu expert with enough spare time to devote countless hours posting on this and other message boards?
Occasionally, these threads sound like arguing whether the Montana sized asteroid is going to hit in Texas or Wisconsin.
teacher,
My thoughts exactly while reading the highway threads. And there in the distance, it was.
The viral genome is still two critical mutations away from efficient H2H.
There are other scientists commenting on these boards, they don’t use their real names.
Luke wondered earlier: “I am curious if there is such a thing as pandemic pressure? IE. Pandemics happen every 30 years or so, if we go 4050 years, does the necessarily mean the pandemic strain will then be that much more virulent?”
The Journal of Infectious Diseases 1997:176 Suppl 1 has an article by Alan Hampson which documents Patterson’s and Beveridge’s lists of “known” pandemics since 1729.
Note that the pandemic preceding the 1918 pandemic was 29 years earlier. There is no “every 30 years” type periodicity.
Pandemic Years between pandemics
1729 3
1732 49
1781 49
1830 3
1833 56
1889 29
1918 39
1957 11
1968 37+
The Hampson list mentions that Patterson considered an 1899 episode to have been a pandemic but Beveridge did not. The Hampson list also states that Patterson and Beveridge both considered 1977 as a pandemic. I am not listing either 1899 or 1977, because there is not a robust consensus that those were “true” pandemics. Adding them would still not lead to anything that would normally be called a “cycle”, though.
Melanie, “The viral genome is still two critical mutations away from efficient H2H.”
Can you (or anyone) explain how this conclusion is reached and what these two critical mutations might be?
I suspevct he is talking about 2 amino acid changes in the receptor binding domain (like S227N but at two close positions).
Dr Niman, what is the significance of mutation at position 153?
Also, Alan Hays in the Nature article appears to be saying that the S227N mutation favors upper respiratory receptors against lower. Do you agree? Would this be a mechanism for lower mortality while increasing transmissibility?
Good Evening Folks,
Do we have and A list of Mammalian Polymorphisms, such as S227N, that H5N1 can use to improve its transmission efficiency in a human population?
viralprotein
vp, Taubenberger thinks that does not exist. We don’t know enough. We are at best making guesses, and some guesses are easier than others. That’s all. Bottomline, if we want a list that we can check off to see whether a pandemic is round the corner, that doesn’t exist.
anon_22 you are very correct it doesn’t exist. Anyone that pretends to know or thinks they know is either guessing or pulling your leg.
Good information Path. Thanks!
Indeed, the only pattern seems to be three per century.
niman at 14:05 “Health Care Workers in Vietnam and Indonesia have become infected with H5N1.”
HELP — where can I find information on this?
(Not seeing anything at recombinomics)
look it up on line i know a docter in vietnam was infected it was a while ago
anon_22,
Just to be clear, are you saying Taubenberger thinks that (S227N) does not exist?
More to that, I suppose Tram’s remark is that a checklist doesn’t exist…not so surprising…but the possibility that Taubenberger might think S227N doesn’t exist, that structural features are best guesses, not confirmed by observation, that would be surprising. I can almost remember a January post or a link to a lab report that seemed to confirm it.
here is a checklist for 1918-H1N1 vs. 2005-H5N1 http://www.setbb.com/fluwiki2/viewtopic.php?p=37&mforum=fluwiki2#37 (excluding the H-gene)
The H5N1 infected health care workers are pretty well known. One was linked to the longest cluster in Vietnam. The brother of two siblings was hospitalized for something like 85 days. His sister is the case that developed Tamiflu resistance. The nurse of the brother was H5N1 positive. A secomnd nurse also had symptoms, but she tested negative. Grandfather also has H5N1 antibodies.
http://www.recombinomics.com/News/04230501/H5N1_P2HCW.html
http://www.recombinomics.com/News/04170504/H5N1_H2H_Proof.html
http://www.recombinomics.com/News/03130503/H5N1_Nurse_False_Negative.html
Here’s a commentary on a hospital cluster in northern Vietnam that included the death of a 34-year old pysician which I belive led to the April 1, 2005 executive order in the US making bird flu a quarantinable disease
http://www.recombinomics.com/News/04060505/H5N1_Vietnam_Sweden.html
dubina, no Taubenberger thinks that a list of all mammalian polymorphisms that can increase efficiency as viralprotein described does not exist.
Dr Niman,
Thought I should ask again in case you didn’t see it:
what is the significance of mutation at position 153?
Also, Alan Hays in the Nature article appears to be saying that the S227N mutation favors upper respiratory receptors against lower. Do you agree? Would this be a mechanism for lower mortality while increasing transmissibility?
The signifocant of the 153 change isn’t known. That is an antigenic site, but the change hasn’t been given, although I suspect it is H153T based on chnages in otehr isolates.
S227N increases the affinity of H5N1 for human receptors in the upper repiratory tract, which would make it more transmissible to humans. I don’t think it would reduce mortality, which may be a dose function for H5N1.
Dr Niman
What are your opinions on if/when this potential pandemic threat will develop?
anon_22, I again reference the New Scientist article:
This mutation, research has shown, allows the H5N1 virus to bind a bit more strongly to a complex sugar found on cells in the human respiratory tract, which is different from the sugar the virus normally binds to in birds, says Jeff Taubenberger of the Armed Forces Institute of Pathology in Rockville, Maryland, US.
But how much the mutation really helps the virus is currently unknown, Taubenberger told New Scientist.
Moreover, says Alan Hay at NIMR, only some of the boys viruses had the mutation. Such mixtures can arise during an infection, as the virus mutates and strains that bind human receptors better emerge, says Mike Perdue at the World Health Organization. But he says well only know it means something if we see it in a cluster of human cases, where it has been selected for because it eases spread among humans.
But this has not happened so far Fatmas virus did not carry the mutation, says Hay, meaning she did not get it from her brother. And all human cases in Turkey can be traced to sick birds, says the WHO.
The mutation has been seen twice before in H5N1, in a family cluster in Hong Kong in 2003, and in a fatal case in Vietnam in 2005. Then, too, it did not get passed on further.
Tram,
Thanks for the posting. There seems to be some good old fashioned horse sense in there, even if you don’t believe WHO. Horse sense also indicates, that if this has gone H2H, we would be seeing more cases, I think.
I think it would be helpful in this discussion to distinguish between very limited H2H, which seems likely to have occured, and efficient H2H, which would be required for the start of a pandemic. H2H transmission between two individuals with very close contact is very different from what would be required for a flu pandemic. (Example, HIV vs. seasonal flu)
Name,
Perhaps it would be useful for WHO to make that distinction together with other missing distinctions in their Phase Alert definitions.
Re: the HCW in Vietnam who became infected: IMHO a single case is not as much a concern as a large number of HCW’s becoming infected. The doctor may have lived in the same infected poultry environment that gave the disease to the patients.
A SARS-like spread of H5N1 infection to HCW’s, well that would be something to worry about.
The death of the doctor in Vietnam was quickly followed by an executive order (April 1, 2005) in the US making bird flu a quarantinaable disease. The data on H2H are quite clear (no whoda, woulda, shoulda’s required).
Dr. Niman, can you infer anything by graphing the transmission rate from ‘97 to the present? Is there any mathematical model to show increasing H2H efficiency?
Dr Niman what is the status of the 162 patients in your commentary?
Commentary . 162 Admitted H5N1 Suspect Cases in Northern Iraq
Recombinomics Commentary February 2, 2006
162 people have been admitted to the diagnosis center on suspicion of contracting the virus
On January 17, a 15-year-old villager in Rania died of the deadly flu.
“Two other citizens have died of the infectious virus while two other cases are in intensive care, in addition to four other cases,” Mohammed added.
Al-Hayat reported that a 35-year-old woman identified as Sarya Mirza is being hospitalized in an Erbil hospital on suspicion she has sustained the deadly flu.
Increased H2H efficiency is measure by the size of clusters and the cluster to cluster transmission
http://www.recombinomics.com/News/01220601/H5N1_Kocyigit_Ozcan_Timeline.html
http://www.recombinomics.com/News/01160601/H5N1_Turkey_C2C.html
Dr Niman
Would you give a prediction on if/when you think a pandemic will start (and where you think it is most likely to start)?
Dr. Niman, what do you make of the 2 new deaths in Indonesia (is this more efficient B2H?), and do you think Turkey really has a handle on their situation, as they are now claiming?
I don’t think negatives out of Turkey are reliable. Weybridge can’t confirm 9 of the 21 positives, indicating serious problems in sample collection, storage, and shipments. Most of the cases in Turkey were paired and have been identified, so trying to claim false positives will create some extremely curious explanations.
The situation in Iraq and Turkey are markedly worse than advertised in the popular press or WHO updates.
According to the January 16 WHO update:
“Ducks began dying in the familys household flock on 1 January. On that day, the girl, assisted by her brother, slaughtered a duck for food. Both children developed symptoms on 4 January and both were hospitalized on 11 January.”
This suggests an incubation period for H5N1 similar to what is typically seen in seasonal influenza. Yet other reports suggest a much longer incubation time.
Dr. Niman, Where do you currently stand on this?
http://www.recombinomics.com/News/02040603/H5N1_H2H_Most.html
Don’t know if you all saw this yet or not.
Niman’s signature: to end each of his recombinomics comments with a bit of massive understatement.
Good show.
“These data leave little doubt that human-to-human transmission of H5N1 is quite common and now represent the majority of human cases. Representations to the contrary are cause for concern.”
Chillindame: Thanks for the update. Yes, I believe this is Dr. Niman’s most alarming commentary heretofore. I can honestly say that no one else puts it into proper perspective, with numbers and dates to back up his analyses, like Dr. Niman. If this is the beginning of the pandemic, I will be aware of it due to his insightful commentaries.
There seems to be a thought that if there is a duck or chicken anywhere on the scene,- this encounter explains everything. A meeting/eating a duck equals onset date. It is like listening to a religeous fanatic- one explaination covers all eventualities. I live in New Zealand- there are ducks and chickens everywhere.
If it looks like a duck, quacks like a duck and smells like a duck, it’s infectious like a duck. The presence of a duck isn’t proof of B2H, but presence of infected fowl introduces a plausible explanation other than H2H.
Plausible if you’d rather believe, or, rather say to the press, that people can get sick from the same bird, one right away and the other people 5 to 10 days later…but… it’s only the bird’s fault! No need to panic, everything’s under control, nothing to see here, move along, never mind that the WHO hasn’t updated the alert level since Nov.
The plausible explanations are good once or twice. When you get 3–4 clusters with 5–10 day gaps, the plausibility is close to zero. When the 5–10 day gap is in almost all cluster and the number of clusters is above thirty, the B2H is an anomaly at best, but in reality it is utter nonsense (repeated almost daily by WHO and clueless reporters).
When H5N1 is in an area, there’s more than one duck that could be responsible. And when culling reduces spread, the logic favors B2H. I find your cluster data very worrisome, but it’s not proof. It is, however, the clarion call to investigate.
I am as frustrated as you are that there’s not more transparency to the data. The Turkey clusters really need such an investigation, publicly written up. WHO is the only group in a position to do that. It needs to be forthcoming (so does seroprevalance data and sequence data).
Wow, when you don’t check in for a day or two it’s hard to catch up.
In my viralprotein at 20:41 post I asked for an “A List” of Mammalian Polymorphisms not “THE List”…Like, What are the top 5 reassortments that we should be looking for… since alteration in receptor recognition is important for replication of avian viruses in humans.
EXAMPLE:
S227N binding protein
E627K increases the replicate efficiency
A138S binding protein
Kiyoko Iwatsuki-Horimoto who has been working on chimeric viruses discovered that cells expressing A138S or S227N represent more than a 50% increase of adsorption by human RBCs. J Gen Virol 85 (2004), 1001–1005
Q226L H5 receptor binding
G228S
“simultaneous amino acid exchanges in the receptor binding site of the HA protein of the Asian lineage HPAIV H5N1 (Q226L and G228S) optimises binding to human receptors”
http://pubmedcentral.com/articlerender.fcgi?artid=303389
Now are these the top 5 amino acid exchanges needed for efficient and sustained human-to-human transmission? OR are there others we should be looking for?
viralprotein
The PROOF of H2H is overwhelming. When there were a few clusters back in 2004, the PROOF of H2H was strong because B2H was VERY rare and having two indepent B2H events (even involving TWO ducks) was HIGHLY unlikely. In early 2005 there were about a dozen clusters and almost all had the 5–10 day gap. It was possible that one or two involved 2 or more independent B2H transmission but it was HIGHLY unlikely and irrelevant. The VAST MAJORITY of the clusters with 5–10 gaps (which was almost all) involved H2H.
Now the number of clusters is greater than thirty and almost ALL have the 5–10 day gap so maybe a FEW involve multiple B2H but ALMOST ALL are H2H. The proof just doesn’t get any stronger.
Almost ALL familial clusters involve H2H. That a fact and the PROOF is overwhelming.
Statements to the contrary a GROSSLY misleading, at BEST.
Asking for more PROOF displays a fundamnetal misunderstanding of the data, which could not be clearer.
now, what do we estimate is his estimate of the probability that a H5N1-pandemic will start this year ? He won’t answer that question…. But he often writes “is cause of concern”. So, when we already have 20 causes of concern, one more or less won’t matter a lot ?! Does he think we will have a pandemic this year with >50%, what do you think ? (I think, he’s at ~30%)
(Ma Ma’s Husband actually) I don’t think it is possible to supply a number because too much is strictly speculation. The estimate of intelligent civilizations outside our world is in the millions according to some experts. The chance of life as we know it existing outside our solar system is pretty well zero according to other experts. There are just too many unknowns to assign numbers to. Each error can multiply the wrongness of the answer. Try to estimate the probability of having a set of dice and throwing all sixes. Of course you don’t really know how many dice you have, how many sides each die have and you’re highly suspicious the dice are loaded, you just don’t know how.
H5N1 is VERY predictable
http://www.recombinomics.com/News/10220501/H5N1_H9N2_Recombination.html
“The situation in Iraq and Turkey are markedly worse than advertised in the popular press or WHO updates.” - Niman
So what is the situation based on your “on the ground reports”? I hope you’re using more that the single Thai news report (that initially reported the “162″ suspected cases in Iraq) to make such bold & responsible statements. Can you tell us the status of the “162″?
Dr. Niman, you have already successfully predicted the S227N change. What is the next polymorphism you think might occur with this virus?
I have read much about the effects of denile. A subject with such horrible potential should be viewed as a prime example testing this capactity. The idea of killing the messagenger is not new. Nor is faults in trying to determine what future events are to become. We all have the responsibility to determine what we believe, And more importantly why we hold these beliefs. I am gratefull for Mr. Nimans loyal opposition to the the standard line held up as truth in the press. I choose to believe his view on this issue based on his track record to this point. Of course not fualtless. But who could be?
“I hope youre using more that the single Thai news report (that initially reported the 162″ suspected cases in Iraq) to make such bold & responsible statements.”
Tram- It was asserted yesterday on the forum that this news story originated in Thailand. I did some research and found out that the story was originally released by the Pan-Arab news agency Al-Hayat. The other articles were all rehashes of this article. Most were directly attributing the quotes from the head of the pre-emption comittee in the Kurdistan Province- Najm Eddin Mohammed and Health Minister (Erbil) Jamal Abdel Hamid to Al-Hayat. Incidentally this story has been run by dozens of other reputable news agencies in the world, not one.
MaMa, the “162″ has never been veried. It is nothing more that an unsubstantiated rumor that magically matches the WHO’s total number of infections. Since the “162″ is a number that you feel is worthy of reporting, can you tell me the status of those cases? Also, what “Diagnosis Center” were they taken to?
If we are going to complain about the reporting on bird flu by the media, don’t we owe it to ourselves to ensure the quality of the reports before we validate them?
MaMa - I don’t have a completely CCclear picture of what you are saying. When you say “The other stories were all rehashes of this article,” I interpret it to mean the other stories relied solely on this article for information. Yet in the next sentence you say “Most were directly attributing the quotes form the head of the pre-emption committee …,” which seems to say they did not rely solely on the one article.
MaMa is correct. Some examples:
None of this makes the story true. But, the story was clearly deemed credible by several news organizations.
(MaMa’s husband) Regarding my attempted illustration about probability - it was not about probabilities that are predicted by research - it was about the futility of requesting probabilities that don’t have research - if a probability is based on a sequence of speculations it really isn’t worth anything. Don’t be frustrated by the predictions not available from ‘the experts’ - be thankful for the things they can tell you. My comment was not a critique of Dr. Niman’s work and I’m sorry if I just muddied the water.
I will be updating the “need to know” governmental groups on the next major change. It will be specific for the time, location, source, and genetic change (just like HA S227N in the Middle East in the fall).
“niman - at 00:16″ Does that mean we have had a change “of concern?” Gees, Flu Wiki is the group (grin) with the “need to know.”
mama,I repeat myself:everyone has a probability estimate on any future event. Often it’s just a feeling or subcontious.But you _can_ assign a number to it. All those “experts” who repeatedly deny this are wrong. They can, but don’t want to, so they say they can’t. So we must estimate their estimates from their writings.I made it 30%, what’s your estimate ?
Tram- I was not commenting on the veracity of the news article. I was correcting the original source.
…But since you asked…
I find it very interesting that this particular news article has so many people up in arms. I have not seen this reaction to other news articles regarding BF. The confirmed number of cases according to WHO as of Feb.2 is 161, not 162, and this proves what? Are you saying that because there is some resemblance to the two figures that it logically follows the difference between the two has become confused somehow? If you look at the entire article instead of fixating on the one figure you will see that there is no mention of WHO’s cumulative cases at all in this article, never mind in direct relation to the two Kurdish official’s quotes. The only mention of WHO is that they are testing the samples of two suspected cases. Nothing magical about that.
As to where the suspected cases may have been taken to, could it be here?…
…”Mobile clinics are also being set up in Sulaimaniyah and two other northern provinces, Erbil and Duhuk. Two patients with bird flu-like symptoms are being treated at hospitals in Sulaimaniyah province.”…http://www.krg.org/…
This is an excerpt from a news article posted on the Kurdish Regional Goverment’s site. Maybe that is the source of the ‘rumored’ 5 mobile hospital story, hmmm. If the only suspected cases (2) are in the Sulaimaniyah hospital, then what need could there possibly be for having mobile clinics placed throughout the region? Does that seems like alot of cost and effort for a war-torn region with limited resources to undertake for no reason? I think that’s a good question to ask yourself.
“According to the Kurds, some 50 villages and 400,000 people have been placed under quarantine.”
So what do we have here? We have the Kurdish Regional Goverment quarantining nearly 1/2 million people, mobile clinics (their words, not mine) in 3 northern provinces and only 2 suspected cases? Maybe, but not likely IMO.
I am not saying that I 100% believe that there are 162 suspected cases, I am saying that the ‘rumored’ number does seem plausible in light of the other verifiable facts. IMO the strong questioning of this particular statistic is motivated more by fear that it may be true than by any other reason. I see no more reason to disbelieve this particular article than any other that has been reported from that region. I could be wrong. I hope I am.
Dr. Niman — When you say you “will be updating the “need to know” governmental groups …”, does that mean the common citizens will not be updated by you about such important information? Have you now swithced sides and become part of that which wants to limit what the public knows and control what it thinks? I’m feeling something that feels like a betrayal. Please correct me.
ssal- I am sorry if I was confusing, that was not my intention. To the best of my knowledge, the quotes by the Kurdish officials were originally quoted in the Al-Hayat article, the articles in other news sources expressed it like this…”In the Thursday issue of pan-Arab daily al-Hayat, the head of the pre-emption committee in the Kurdistan Province Najm Eddin Mohammed announced that 162 people have been admitted to the diagnosis center on suspicion of contracting the virus.”
…gs- If there is (MaMa’s husband) at the beginning of a post from me that is my husband’s post. Perhaps it would be simpler if my husband posted under his own ‘forum name’ as long as it isn’t a problem with pogge, melanie, DemfromCT, etc. that two people are posting from the same IP, although I guess we already are in a way. We only have one computer and access site.
As to my estimate, I am not a math-whiz like my hubby, but I will try to explain what I think about it…. I think that the more widespread H5N1 is in the bird population, the more oppurtunities it has to interact with humans.The more times it actually does infect humans, the more chances it has to change (mutate or recombine with another influenza) - This increases the probability of a pandemic occuring from this virus and will increase at a greater rate over time (as it’s spread in birds and humans increases), but I don’t know what the base number should be. That’s my logic-based answer. Every time I wonder how likely it is within the next year, I look at my children and realize that in terms of my personal preparation I better assume it’s pretty high, at least 50%+.
MaMa, I was commenting on the fact that the first report of the 162 was from a Thai news report. This was discussed at the CurEvent board as well. If it was truly first reported by the Pan-Arab news agency Al-Hayat, then I stand corrected. The point is that the number was never been verified, and the number was simply recycled by the other news reports without any verification. Translation difficulties have added to the confusion as I’ve seen the mobile clinics described as ambulances.
Hi, all. I’m new here; just found this discussion tonight. I have no scientific training. But I have been following Dr. Niman’s website and the updates on promed regarding H5N1 for some months, and Niman’s analysis seems quite plausible to me. However, I do not understand why WHO would intentionally obscure data regarding this disease, as Niman seems to suggest. What motivation would WHO have to downplay these events?
niman at 00:16 “I will be updating the need to know governmental groups on the next major change. It will be specific for the time, location, source, and genetic change (just like HA S227N in the Middle East in the fall)”
Was this post was actually from Dr. Niman? I doubt it. Can the moderator confirm this. Perhaps a drawback of this type of forum where there are no user names and passwords. If so seems very odd. It makes no sense to switch from public disclosure to a private “need to know” approach. Militaries and secretive organizations use “need to know” compartmentalized approaches to the flow of information. Something doesn’t make sense here.
Just answered my own question. Similar statement made on CE by niman who is Dr. Niman. Was a similar respose over there to the wordage. Ok. Still doesn’t make sense Dr. Niman. Think your choice of words has got a few people curious. Peer to peer communication is understandable but given the lack of transparency you have accused WHO of perpetrating I doubt if you would also be less than transparent concerning an issue of such import? Or am I being presumptuous?
viralprotein- for the non labtechs, please restate your polymorph list w/ a notation of the viralprotein on which the respective nucleotide revision is expected, HA, NA, PBx, Mx, et al.
MaMa and MaMa’s husband: posting for 2 people from one IP is not really a problem. Identify yourselves separately in advance (Hi, this is xyz, MaMa’s huspand) and try to remember to change the name whe you post (it might stay MaMa when you mean to post as MaMa’s husband).
OTOH your current handle is unique here. I had a husband-wife duo at another board who for a long time posted as a dual name. “We feel that…, etc.” Turns out it was just a writer with a creative streak, but most of us liked it better when they posted as ‘we’. Much more balanced. ;-)
The upcoming change, if it happens as predicted, would probably have a significant effect, so those in the :n “need to know” category should get a heads up and could potentially reduce the likelihood by reducing the target (like the S227N warning, it is very specific with regard to time, location, donor source, and specific mutation).
http://www.recombinomics.com/News/10220501/H5N1_H9N2_Recombination.html
Word will become available to the public shortly thereafter.
petperson,
“Hi, all. Im new here; just found this discussion tonight. I have no scientific training. But I have been following Dr. Nimans website and the updates on promed regarding H5N1 for some months, and Nimans analysis seems quite plausible to me. However, I do not understand why WHO would intentionally obscure data regarding this disease, as Niman seems to suggest. What motivation would WHO have to downplay these events?”
This subject is very thoroughly discussed on this thread. Just make sure you read to the end to get all the different arguments.
http://www.fluwikie.com/index.php?n=Forum.WhyWouldTheWHOHideTheTruth
Tram at 21:55 requested Dr. Niman to elaborate “on your gon the ground reportsh? I hope youfre using more that the single Thai news report (that initially reported the g162 suspected cases in Iraq) to make such bold & responsible statements. Can you tell us the status of the g162” Tram: Dr. Niman does not contribute to this site for the sole purpose of answering your accusations. Your use of quotation marks and such use of “your hope” and “bold and responsible statements” is accusatory in tone. You’ve already made your point several times that you don’t believe anything Dr. Niman has to say, yet you can’t substantiate your own “opinion”. Isn’t that being a little bit hypocritical on your part? I was simply hoping people would take your remarks for what they are and ignore them, but that obviously isn’t the case. Please don’t insult experts who actually do want to contribute to this discussion.
Must read:
This link http://tinyurl.com/bxo4w contains some really interesting comments from/about Tram and where he is coming from. Especially the discussions on ‘proof’ and ‘ethics’ and his support of Dr Gary Butcher’s “there is basically no threat” opinion.
Must read:
anon_22, is the fact that my opinion is different from yours a problem for you or are we all expected to bow at the altar of anon_22? If you go back and actually read the posts in the link you provided I think you might find that my opinion differs from Dr. Butchers as well…
Tram, If you spend a lot of time on this forum you would notice how often people post such links to bring people’s attention to questions which are either already addressed or related to something else. Nothing new in that.
As this thread is getting rather long, I will soon close it and post a Niman II.