You'd think finding that there were some bird flu infections that went undetected would be bad news but it is actually good news. Not tremendous good news but better than no news, and that's unusual in the bird flu world. For some time the absence of mild or inapparent infections has been worrying. It means that the current case fatality ratio of over 60% is the real CFR, not one based on just the most serious cases coming to the attention of the surveillance system. Now scientists gathered in Bangkok at one of the many gatherings of those studying the disease have heard some new data involving 674 people in two Cambodian villages exposed to influenza H5N1 ("bird flu") by infected poultry in their households. Seven children were found to have been infected using a test of their blood for antibodies. Seven is 1% of these exposed people, so it is still consistent with low transmissibility to humans. But scant data from previous investigations of health care workers or villagers in infected areas had not turned up evidence of mild infection, so this is good news. Not all H5N1 cases are serious or fatal disease.
The data were collected in early 2006 in southern Cambodia. Two cases were registered in Cambodia in early 2006, one in April 2006 and one in March 2006. Both were children and both died. Although the locations are different, if we count them both, this suggests that for two clinical cases there were seven mild cases, which means that the case fatality ratio might be considerably lower than the current 100% for the country to 50%. To be more optimistic, one might compare the 2 deaths in 2006 to the seven mild cases for a 22% CFR.
The missed cases were all young, between the ages of 4 and 18 (median age 12). This was much younger than the entire sample of 674 (median age 27).
Results of the Cambodian study support findings from a decade ago in Hong Kong, where human H5N1 cases were first reported in 18 people, six of whom died. Survival rates were higher among children, many of whom weren't severely affected, Peiris said in an interview in Bangkok yesterday.
"Most of the children diagnosed in Hong Kong in 1997 had a very mild course of infection, they basically had a mild flu- like illness and they recovered," he said. "I don't think there is any evidence to say the situation has changed." (Jason Gale, Bloomberg)
We noted in a recent post that a review of the existing cases also shows that the age 10 - 19 children have the highest case fatality, so we should perhaps not read much into the fact that children also have more mild infection. They may just have more infection, both mild and severe. The reasons children are more often among the infected is not known, although that hasn't stopped speculation. We won't go there.
But we think this is good news -- sort of. Or to put it another way, the news could be worse. A lot worse.
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This sounds consistent with a few other surveys I've seen, several of which turned up low (1% - 2%) numbers of surveyed people with antibodies. Given the vast numbers of people exposed to the disease, even 1% would translate into a much larger number of cases than have been officially tallied. The delineation always seems to be: either we are missing much inapparent infection, or the CFR is really as high as we fear. But you don't have to miss very much inapparent infection to drive CFR numbers way down. Which we can only hope is the case.
http://www.recombinomics.com/News/01250801/Birbhum_Cullers_Ill.html
There is a report from Bidhum India which states 257 people have been hospitalized with symptoms that may indicate bird flu. Seven cullers are too sick to work. Other recent reports state 12 more cullers are sick.
Testing for H5N1 in India is inadequate. Vietnam, for example, has a much better infrastructure for bird flu testing. Therefore, many of the 257 hospitalized patients might possibly have bird flu.
I would also like to know if there are experts at the bird flu meeting who believe it is only a matter of time before H5N1 mutates into a strain for efficient human to human transmission. Other bird flu experts have expressed that opinion in the past.
They need to send a WHO team to India to investigate what is happening, before some Indian citizen gets on a plane, infected with bird flu, and arrives in the US.
In Calcutta, they are restricting freedom of movement of the citizens. Please believe me, if a pandemic hits the US,you will not have freedom of movement. And it will not be to control the pandemic. But that is another subject.
Please read the Patriot Act and know what it means.
As H5N1 in birds, which is a bird pandemic, continues to spread, eventually arriving to the United States and South America; and as it spreads to infect birds all over the planet, there will be millions and millions of opportunities for this virus to adapt to humans. People in poor countries do not have the funds to buy protective clothing, and many are unaware of the risks, especially the children, that often play with dead birds. In many countries they are throwing the dead birds into the rivers and lakes. Would you want to drink that water? And many people have no choice but to drink that water, since they have no other source.
It is good news mild cases exist, but please remember the Spanish Flu virus caused a 2 to 3% mortality rate. Even if the mortality rate in Indonesia drops to 40% if a pandemic hits, many people will die. And we in the US are only a few hours by plane from India and Indonesia. If a passenger arrives in New York city with the virus, the game may be over at that moment, as he or she unknowingly spreads the disease. Therefore a pandemic in the US is still a high probablity.
About 25% of general practitioners in the United Kingdom recently reported they would not be able to cope with a pandemic. And there is still a shortage of ventilators in US hospitals, meaning many health care workers will be afraid to report to work, for fear of dying from the virus.
So what good does it do to prepare the community, meaning non-medical people, when many doctors recognize they could not cope with a pandemic, and when we do not have adequate ventilators to protect medical staff in our own hospitals, meaning many will stay home. When you get to the hospital, there may be a sign reading: "If you have bird flu symptoms, go home and die. And be sure to take plenty and aspirin and drink plenty of liquids. Or as they said in 1918, be sure to get plenty of fresh air."
The CFR was low in Egypt last winter as well. This isn't the case this winter. At least as far as we know. What is currently going on in Egypt is still somewhat clouded. I strongly suspect we aren't going to know what the eventual CFR is until this thing does finally go H2H. What we do know is it is still difficult to get. You need to pull the virus deep into lung tissue. We also have been told from the outset that an immense viral load was the cause of death. So, what if the load was very small to begin with? Or naturally weakened for some reason? UV light would be a possibility. If these children were infected by virus floating on outdoor air currents, then sunlight could have partially disabled the coat. They would then be essentially inoculating themselves. The sample is too small and far too localized to draw any real conclusions. We need to know how and where the children became infected. But, until we know specifics, I remain sceptical.
I'm not sure, this is good news.
It also means that humans can spread H5N1 while
being asymptomatic.
The big problem for the poultry are the
asymptomatic ducks...
But we think this is good news -- sort of. Or to put it another way, the news could be worse. A lot worse.
Well, to stretch it even further, any news could be good news since there is so much that has yet to be discovered and understood.
Dave Briggs :~)
anon: What these data seem to show is that this is not very transmissible. Please keep in mind the difference between transmissibility and virulence, too.
It makes sense, on the surface at least, that some fraction of persons exposed would become infected asymptomatically. It also makes sense that some fraction infected persons would manifest with milder symptoms. That appears to be the case with AIDS, smallpox, and (possibly) Ebola if the events from Uganda around Christmas were reported accuarately so it would be consistent at least if we saw the same phenomena with H5N1. It would also make some sense that the immunological response would vary geographically as the general pathogen environment is different, ergo Cambodian children's immune response might be different than we would see with children in other geographic areas of the planet (not even taking into account differences that might be immunologically relevant with exposure to different subclades of H5N1). I suppose the question would be whether any immunological differences based on local pathogen environment would be significant in different geographic environments with respect to H5N1 immune response.
Following up with Cart's thread, I wonder if these kids ate a significant amount of peanuts? I know it is an extremely unlikely possibility but, I'd love to do see a study investigating indigenous foods that contain naturally occurring antivirals.
There are many factors that might affect the transmissibility (use of incense in the home?), the success of infection (health or phenotype of individual), and the virulence (use of traditional herbal medicine, conventional medicine such as aspirin, vitamins). All of these are important and seem to be lacking in reports or research. Likely, because of cultural or personal bias as well as funding requirements.
Natural products research indicating antiviral activity for a food, constituent or plant extract is not necessarily therapeutically relevant. Such information may offer support, but is supported with ethnopharmacological evidence.
Phytosleuth, elucidate please.
"Natural products research indicating antiviral activity for a food, constituent or plant extract is not necessarily therapeutically relevant. Such information may offer support, but is supported with ethnopharmacological evidence."
I don't understand, why _more_ infections should
mean _less_ transmissiability.
anon: It's a compared to what, question. There were 674 likely exposed and less than 1% infected, even mildly. That's not much transmission. It's consistent with what we've been seeing and nothing like seasonal flu.
Other questions occur to me. I cannot help but wonder if the parents of these kids knew the children were even sick? Did they have asymptomatic infections? Did they have very mild symptoms? Did their parents treat them with any medicines? Do we know the answers to any these questions?
Revere,
Thanks. That is a bit of good news. At a minimum, the skies in the distance may not be as dark as they first appeared. Let's continue to hope the storm misses us.
I'm fascinated with the variables in the equation and especially how the environment might play a role in seasonal flu. Is viral load the tipping point to increase infections during flu season. Are infections during summer months simply asymptomatic due to low viral load and symptomatic infection in winter due to high viral load? Does the environment effect the viral load and how? Or is it not so much viral load, but virus viability that is somehow changed from season to season.
You've said it before and the more we know, the more we don't know.
I'm anxious to read more discussion on this.
herman, that is a clever use of a few facts, several talking points with a "whole lotta drama" thrown in. Very nice. And you note, quite admirably, that if the CFR drops to 40% many people will die. Brilliant! Information like that only confirms my faith in your expert analysis of this issue. Revere has some very good information here. I'd suggest you give it the same credence you give Dr. Nimans. Or at least troll the other way for a refreshing change.
Shannon: Some survey data were collected but we don't have the information at this time. Presumably this paper will be published at some point (I believe it was an oral presentation at the Bangkok meeting or a poster). The diagnosis is based on serology.
Herman,
I can't help but comment.
You continually demonstrate points of ignorance which you use to inflate your sense of panic.
I know this is off topic but here it is anyway..,
First, regarding ventilators. You state: "...And there is still a shortage of ventilators in US hospitals, meaning many health care workers will be afraid to report to work, for fear of dying from the virus" and "pandemic, and when we do not have adequate ventilators to protect medical staff in our own hospitals, meaning many will stay home."
You do not seem to be aware that "ventilators" are devices that are used to help patients get adequate oxygen when their lungs, bronchi, or tracheas are impaired through damage or infection. A tube is inserted in the patient's throat, and they are connected ot a positive pressure system and possibly an oxygen source.
Ventilators are not used to "protect hospital workers."
Second, "protective clothing?" You stated: "People in poor countries do not have the funds to buy protective clothing."
ROTFLMAO!! No one is recommending protective clothing for the masses anywhere. Would you propose that the entire population of Columbia be afforded "moon suits" like you see lab technicians in biohazard level 3 labs wearing when directly handling virus samples? No? I didn't think so. There is no particular brand of "protective clothing" that the general populace anywhere will be using to prevent H5N1 infection. Sorry, your are again misguided.
You continually jack up your personal panic level for no reason other than your lack of knowledge. Posting here as you do you might consider those who are LESS informed than you ( :) ), and not overdo the tension.
How this particular rant of yours relates to higher undetected infection rates in children or the general population of those exposed to H5N1 is beyond me..,
Sorry. It's the effect like those "Kinoki foot pads" have on me.
Still, the Reveres put up with you.
Revere, sorry if I overstate the obvious.
Hooray for expanding denominators without expanding numerators! That is good news. Well, in case-fatality data, anyway.
Shannon: Every culture has different forms of evidence they use to support decisions on use of remedies. What is evidence in one country is ignored by another.
I personally believe that science is a source of good evidence. But I also believe that thousands of years of herbal medicine experience in China and India are equally valuable. In the U.S., conventional medicine states that only clinical, double-blind studies show efficacy and therapeutic relevance. It all depends on who has the power to make therapeutic decisions in your country.
You must understand that scientific information is not necessarily truth or proof. It must be tempered and used appropriately. Natural products research is very reductionistic. Lab research does not transfer automatically to therapeutic use; e.g., licorice root shows antiviral activity against Marsburg virus in a petri dish, therefore we can assume licorice root tea will remedy viral infectious diseases. NOT SO! But such evidence IS a good clue to warrant further investigation. I am assuming your suggestion that peanuts are antiviral is based on such reductionistic natural products research. Or did I misunderstand you?
In my opinion (which does not matter to the AMA, since I am neither a doctor nor a heretic) the antiviral properties of licorice is supported by the 2,000 years use of this plant in Chinese medicine and in Ayurveda in infectious disease formulas. Of course, there are many other herbs even better than licorice root, and not all are "antiviral" but rather may turn on genes and cytokines that protect us from viral infection. This too, is reductionistic and is an overstatement without more evidence to back it up.
When deadly epidemics and pandemics hit, all kinds of remedies (including conventional medicine nostrums) will hit the media and people will be desperate, especially if they cannot access a vaccine or antiviral drug. Such advertising is already evident in the media with news of new vaccines and nanoviricidal techniques.
I am just trying to discourage you from starting a rumor that peanuts are antiviral. Sorry this made my knee jerk. I apologize if I took this wrong, but that's how it sounded.
Personally, I think lots of simple and effective remedies (behavioral, dietary and herbal) are being ignored and there is too much focus on vaccines and antivirals. No one in America seems to be investigating traditional remedies or cultural foods that might protect people from influenza. So I am with you there.
This study was done in early 2006. How bloody pertinent can it be? Bloomberg cites the researchers with being concerned the virus had altered to a form more easily spread between humans.
" Higher rates of milder disease might indicate the virus has found a way to spread more efficiently in humans.
``We need to monitor because the virus can evolve, and this is one of the indicators to see whether it's found a way to penetrate the body,'' said Sirenda Vong, chief of epidemiology with the Pasteur Institute of Cambodia in Phnom Penh, who led the study."
No wonder they suggest little has changed since the emergence of the disease in '96.
"Results of the Cambodian study support findings from a decade ago in Hong Kong, where human H5N1 cases were first reported in 18 people, six of whom died. Survival rates were higher among children, many of whom weren't severely affected, Peiris said in an interview in Bangkok yesterday.
``Most of the children diagnosed in Hong Kong in 1997 had a very mild course of infection, they basically had a mild flu- like illness and they recovered,'' he said. ``I don't think there is any evidence to say the situation has changed.''
On the one hand we have a higher CFR in kids. The stats for the highest incidence of infection and death was in people under the age of 19 and over the age of 10. Now suddenly we are back at the beginning when the survivability was higher amongst children?
So, where are we NOW? How has the virus changed from 2006 to today? I'd feel a heck of a lot better if this information had been a tad more timely. I'd have felt better if we had more to go on then serological studies. And I'd most definitely feel elated if we could get some kind of statistical sampling in more than one tiny place in the world.
Actually, we REALLY need more serologic testing in all countries that have had human H5N1 cases. Such results would give us another angle on how the virus is evolving.
This is epidemiology stuff. I am no expert but I would rather see a benign virus with easy transmission than a virulent virus that doesn't infect humans very easily. The former is the definition of a cold virus.
To find individuals that have antibodies but did not suffer a severe infection is a GOOD indication of a virus becoming benign.
Phytosleuth, no you understood me perfectly. Peanuts are high in resveratrol. And, I too am very interested in sources of antivirals. I have spent the last three years doing virtually nothing else but locating and sharing studies of phytochemicals and ethnobotanicals. LOL
Shannon: It's a data point and we need data points. If we disregard everything that's occurred until now because the virus is "changing" then we shouldn't bother with many studies. But of course we do. This isn't just sequences. It's biology and we are learning about the biology as we go along. There are many changes in the sequences but we don't know what they mean biologically. This is epidemiology.
Very true, Revere. I just wish it had been more timely. Two years is a long time given the severity of the situation. It will be extremely useful after the fact and prior to the next pandemic. That, however, may not help us now. Put this down as a knee-jerk reaction to frustration.
Let's play with the numbers for a moment. I'm not much good at it, but maybe somebody else can do something with this.
Currently, we have 343 cases with 200 deaths at 58.3% CFR. Remember now, 343 cases are clear cases of BF, with most patients (as I understand it) exhibiting severe symptoms.
Now that we know that it MAY BE POSSIBLE to be assymptomatic or at least exhibit milder symptoms, let's make some positive assumptions, instead of negative ones. With the million or so possible human exposures to BF only 343 (roughly) have displayed severe symptoms. With that many exposures and according to many people on the flu boards, many more people have "probably gone undetected". With only another 343 people, the CFR drops to 29%. With another 343 people the CFR drops to 19%. At 200 deaths, it would take 10,000 cases to reach 2% CFR. Right?
Have we had 10,000 cases in the million or so possible exposures? Don't know. 2% CFR is still darn high. But we haven't factored in what the virus MAY have to give up in virulence to make the jump. And keep in mind, these are in children, where we've speculated the CFR would be the highest.
Revere pushed around some numbers in the original post as well. This is good news....not great news....the clouds are still quite dark. But at least they show a hint of light.
Neil,
Mellow out dude, you are too uptight. I never stated I was a genius, or that knew what I was talking about. The CDC stated that a surgical mask would protect you from bird flu.
That was about 3 years ago. Do hospitals have enough N-95 masks. No. Would you go to work in a hospital, knowing a surgical mask would not protect you, if there were no N-95 masks available. No.
I also do not know how Revere puts up with me. Maybe it is because he knows I am a little crazy. Of course he could fire me into eternity whenever he wants.
No matter what Revere does to me, I want to thank you for hateing my guts. It makes me feel better. Please have a good day.
I admire Revere for his dedication, like I admire Randy, also for his dedication. Randy is not a doctor and neither am I, but he does work hard to understand bird flu, and I respect him for it.
Of course I say stupid things and make mistakes, like talking about ventilators, when I should be talking about N-95 masks. If you want to kick my ass for that, I bless you. Go ahead and kick my ass.
I want to correct one thing. Of course you will attack anything I say, so go ahead.
Human to human transmission of bird flu is very common. Of course I am talking about limited transmission. I am not talking about efficient transmission, which obviously does not exist.
There have been many clusters in Asia involving 2 or more people that had not contact with sick birds. Usually the index case, meaning the first case, is exposed to sick birds. Then due to close and intimate contact, others become infected. Usually they are family members or friends. In Pakistan, there was a cluster involving 10 people that lasted over 6 weeks. That is a record.
Therefore limited human to human transmission, forming sometimes large clusters, is common. The question then becomes, could this virus continue to adapt to humans. The answer is obviously yes, since the is a bird flu pandemic in birds, involving millions of birds all over the planet.
Some virologists state it is only a question of time until the virus completly adapts to humans, meaning efficient transmission.
Neil, also please note many countries specify all the infected humans in a clusters were infected by a common bird source. But please observe that if it had been a common source, they would have all become infected within 2 to 4 days of exposure. But that is not the way it often happens.
Instead, as in the case of the largest cluster ever seen, people continue to become infected, including hospital workers, over a period of more than 6 weeks. And these people had no contact with birds. They were obviously infected by intimate contact with the index case, or others who later became infected.
Neil, please tell me what really pisses you off. Is it really what I am saying. Are you afraid I am correct and that you may eventually die of bird flu? Anyway, I am an easy target.
May peace be with you always, and please have a good day.
http://afp.google.com/article/ALeqM5gTYR7isTn-MX_ok9VfTkZ_TVOm_Q
Neil,
Please read the above report. This is the first time the Chinese Government has acknowledged limited human to human transmission of bird flu, involving a father and son.
Since China does not usually admit anything regarding bird flu if they can avoid it, is it possible there exists in China many of these clusters, and the government knows it will now be impossible to conceal their presence?
Shannon: that's a LOT of peanuts.
ROFLMBO, I said it was an outside chance. There are some nice studies out there on the French Paradox and resveratrol. There are a handful of studies examining the A reduction of inflammation, as well as antiviral capabilities does make for some interesting conjecture.
"reduced by resveratrol and that the phagocytic activity was significantly inhibited by resveratrol. Thus, this study suggests that resveratrol inhibited bacterial phagocytosis by macrophages by downregulating the expression of phagocytic receptors and NF-B activity."
http://aac.asm.org/cgi/content/abstract/52/1/121
Chemical in grapes inhibits flu virus
May 31, 2005 (CIDRAP News) Resveratrol, a chemical found in grapes and other fruits, inhibits the reproduction of influenza viruses in cell culture and mice, according to a recent report in the Journal of Infectious Diseases.
snip
"In an initial cell-culture experiment, treatment with resveratrol at 20 mcg/mL reduced flu virus replication 90%, and treatment with 40 mcg/mL blocked replication completely. However, because the higher concentration damaged the cells, the lower concentration was used in further tests.
The researchers also tested the effects of starting resveratrol treatment at different intervals after infecting cells with the virus. Treatment was most effectivereducing viral growth 87.5%when treatment began 3 hours after virus exposure. Effects were lower but still significant when treatment began 6 hours after infection, and treatment had no significant benefit if delayed until 9 hours after infection.
Given these and other findings, the researchers concluded that resveratrol interferes with the manufacture of proteins made late in the viral replication process, such as hemagglutinin, and limits the transport of viral ribonucleoproteins from the cell nucleus to the cytoplasm. The authors also determined that the molecular mechanism for resveratrol's effects has to do with the inhibition of protein kinase C activity and its dependent pathways.
In the tests on mice, the researchers found that resveratrol treatment increased survival by 40% in treated mice, compared with mice that received a placebo. The level of virus found in the lungs 6 days after infection was 98% lower in treated mice than in the placebo group."
snip
Sorry about the inscrutability of the last post. Hit the post button rather than the preview. The problem with this as in so many other food antivirals is bioavailability. Nonetheless, it does show promise.
Tracking wise, many of the high numbers from notoriously unverifiable sources are meaningless. The fact that cases are reported is a cliche dating back from the first outbreaks of AIDS. None of this is really new news. The most difficult part is separating the wheat from the chaff, and when we get net bounce where once site is generating considerable chaff, which is then posted as fact, fills the lines with unverified, incorrect data. One of the main results of this, is that cases in Pakistan, Israel, Iran, and crucial outbreak points, including cases inside China, are literally being buried by overkill data on India. Enough with India. It is sad and it is spreading and it blackens the sky with data, but it is the spread through 12+ countries, the outbreaks in U.K. and U.S. that fall through the cracks, and the critical news that is very hard to find.
sorry for typos and words missing ect in last post. Cannot edit these posts. MC
The supplementary appendix to last week's New England Journal of Medicine article summarizing what's known about H5N1 listed 8 studies of potentially "at risk" persons who were tested for asymptomatic infection. Overall, 1 was found positive out of a total of 1100 people tested.
The first two studies, from Cambodia, in 2005 and 2006 showed 0/351 and 0/80 who tested positive for H5N1 respectively.
It's hard for me to know what to make of this new report. It's possible that as the virus has evolved in Cambodia, asymptomatic infection has become more common. But I don't know what it tells us about the virus in other locations.
medclinician: As bc notes, almost all serosurveys have been negative so this is definitely new information and potentially significant. The most worrisome thing about previous serosurveys was they were negative, implying an extraordinary CFR. So it is not that we only count the tip of the iceberg (well known, as you say). I am an epidemiologist and early on said there must be many mild and inapparent infections. To my consternation they never showed up in the seroprevalence surveys which was not only unexpected but extremely worrisome. There is still a large gap in our knowledge of prevalence as the data are extremely scant. But don't mistake the idea that only the more serious cases get counted with these data. The former was well known. These data were not and as bc reminds us are different than previous data.
bc: I think we need to know how the various serosurveys different methodologically from each other before we can start to reconcile them.
I would like to present a brief summary of the recent research regarding the binding sugar chains, called glycans, and the implications of this research.
It has been found H5N1 must pick a very specific type of lock to enter human respiratory cells. The chemical linkages between the sugar molecules differ between humans and birds.
The critical issue is the shape of these glycans. To infect humans H5N1 must latch onto the umbrella shaped glycans. In birds the glycans are cone shaped. H5N1 appears to have great difficulty identifying and latching onto the umbrella shaped glycans, but attaches to the cone shaped glycans of birds easily. And now I quote an article:
"Professor Ian Jones, professor of virology at the University of Reading, said: "This new work shows that there are sublevels of sugar that the virus prefers to use to get into cells and the authors suggest this is a significant factor in why H5N1 has not yet spread to humans."
What is disturbing is, with a bird pandemic of H5N1, and with constant interaction between humans and sick birds, the virus may have literally millions of opportunities to identify and latch to the umbrella shaped glycans of humans.
Once that process is completed, efficient human to human transmission may begin, as the virus passes from the upper respiratory tract of one human to another, meaning the virus could be spread through casual contact.
Oh for Crissakes, herman. Do you ever read this blog or just comment?
Do they appear to have any handle on what this one is, at all, Revere? Possible progeny of the one that materialized, when the first cases were recorded, from the cross-border patients from Cambodia; and those who displayed the same set of symptoms, from southern Vietnam, at that time? That one was a monster. A CFR of 100%; and a completely unique signature (at that time) of very remarkable pantropic expression. Is there a possibility that this one has modified its approach, perhaps?
Enough information available (or that will become available, at some point) to draw any conclusions, here?
herman's expert analysis of receptor bindings...just what I've been waiting for! And so timely.
Revere,
Can you explain what you mean here:
"......There is still a large gap in our knowledge of prevalence as the data are extremely scant. But don't mistake the idea that only the more serious cases get counted with these data. The former was well known. These data were not and as bc reminds us are different than previous data.....
Are you saying that only severe cases get noticed and typed for H5N1? If so, I'm confused by "These data were not and as bc reminds us are different than previous data".
Also, do you think it's possible that the 10-19 age group could have the highest CFR and also have the mildest symptoms as well? Would they have a propensity for both extremes? If so, why might that be? It would seem they would be one or the other, unless it's simply susceptibility and by sheer volume, they would have both extremes?
Dylan: I think this was either a poster or oral presentation (possibly with .ppt slides) at the Bangkok meeting. In any event, all I know is what was in Jason Gale's article (I presume he is there). But this is the first seroprevalence survey that has showed much. I don't know what it's relationship was to the two fatal cases around the same time period. It sounds like it was a survey of two villages that had a poultry outbreak and the subjects lived in houses with poultry (not clear if the poultry were sick or not in each house). So all I know is what I posted. I'd like to know the methodology here and other info they collected, including exposure info.
Patch: In all disease reporting the more serious cases are more likely to be counted because they are recognized and then reported. If you want the ones that don't come to the attention of medical care you need to do a special survey to ascertain less serious or asymptomatic cases. In this instance they took blood from these householders and tested to see if they had antibodies to H5N1 which is presumptive of infection. There is more than one kind of antibody to look for, different ways to do the test (and different thresholds for what is positive) and different criteria for whom to select for testing. Ideally you would want to test twice, once on exposure (to show there were no antibodies at that time) and once two or three weeks later to show that antibodies developed in that interval (this is because antibodies are present over an extended period so you don't know if the infection is recent or more remote). So there is a lot we don't know, including whether the methods were the same as a year earlier when there were no antibodies detected in a similar sounding survey. Regarding the age group, it could just be that this is where most of the infections are occurring, so they have the whole spectrum, from mild to severe.
Dylan: I think this was either a poster or oral presentation (possibly with .ppt slides) at the Bangkok meeting. In any event, all I know is what was in Jason Gale's article (I presume he is there). But this is the first seroprevalence survey that has showed much. I don't know what it's relationship was to the two fatal cases around the same time period. It sounds like it was a survey of two villages that had a poultry outbreak and the subjects lived in houses with poultry (not clear if the poultry were sick or not in each house). So all I know is what I posted.
"I'd like to know the methodology here and other info they collected, including exposure info."
So would I, my friend.
Oh for Crissakes, herman. Do you ever read this blog or just comment?
What the hell is going on here? I read Reveres neat study of glycans, and I did not understand shit he said. So I decided to summarize it in a way I, a lowly retard could understand. What I wrote was brillant. Meaning I could understand it. Whether or not it is scientifically valid is not my problem. Another reviewer, who was actually stupid enough to read it, stated it was timely. What more do you want? Give me a break.
If you were under threat of being exploded into infinity, how would you feel?
Not only that, but I have evidence an atheist mentioned the name of God. If that is not a miracle, I honestly do not know what a miracle is. And I caused the miracle.
Please realize I, a gringo, live in Medellin Colombia. If you ask me why I am stupid enough to live in Colombia, all I can say is I have no excuse. Do you know how fast a Gringo can die here? I do. So another good excuse is I have post traumatic stress syndrome, which is a long description meaning I am nuts or soon will be nuts, because I am scared shitless I will be killed for 50 pesos or less.
Revere has been dumb enough to put up with my stupid comments for more than 3 years. Perhaps he has an emotional problem to do that.
On the serious side, I believe H5N1 has the potential to kill not only millions of birds, but if it unlocks the glycan key, it could possibly produce a pandemic. That is what I was trying to say. There are plenty of people who would insist human to human transmission is not only limited, but some would insist it does not exist.
I sincerely hope they are correct. Because if they are wrong, and I think they are, this virus will sooner or later produce a pandemic.
OK guys, lets hear all the pissed off comments. But please remember I am very sensitive and may cry as I read your posts.
Mellow out dudes, and don't be so uptight, or you will make yourselfs sick.
Ditto Patch,
Herman has a way with words. Long may he blog.
I don't want to be a spoilsport, but I would like to pose a question and suggest an hypothesis.
The question: If the CFR is actually low, why is the case fatality rate in clusters so high? Of course, this could be ascertainment bias, the clusters of death are more noticeable and hence are more likely to be recorded. However, if this is the case, then testing of family members of severely affected cases should find a significant number of infected, but mild cases.
The hypothesis: It is extremely hard to get infected by birds and even if one does get infected, a bird-adapted strain might not be as dangerous in terms of transmissibility or virulence as a mammal-adapted strain. I will further hypothesise that there some strains of mammal-adapted H5N1 that are more transmissible and lethal than bird adapted strains. Finally, I will suggest that the strains that have had a chance to adapt to humans are the most dangerous, both in terms of transmissibility and virulence.
Not too many mild cases in the Karo cluster, were there?
Mono: I don't think CFR is necessarily low, just not 60% which is extraordinarily high. If the true CFR is 10% it's still a monster. Regarding your hypothesis, yes, maybe. Maybe not. There may be many clusters out there and the conditions that lead toward lethality in a location or a family might not necessarily be in the virus but in the hosts or environment. Maybe. Maybe not. But there is no reason to think that transmissibility and virulence are positively correlated at this point. I have discussed here several times why the conventional idea they are inversely related need not be true. It is true in many diseases but not others. So we don't know in this case. You posit they are positively correlated. Maybe. Maybe not.
revere, I agree even a 10% CFR would be devastating.
I will point out that my hypothesis is testable. Simply test and try to isolate virus from family members of people who are definitely infected. My prediction: few mild or asymptomatic cases will be found among children or young people who are in close contact with an infected patient.
Absolute transmissibility may not be correlated with virulence, but I would suggest that there is a considerable body of evidence to suggest that increasing adaptation to a new host is more likely to result in an increase in virulence rather than the other way around. That said, I acknowledge that we do not know for certain what the final CFR of a pandemic strain of H5N1 will be.
10% in the US would be 30 million and change from primary cause flu. Secondary causes of death would follow and this is a little bit inside of the briefing we got, and that is another 25% of the flu surivors would die from bacterial pneumonia post of the flu. Thats another give or take 2 million. Next on the list is the failures of persons and government to perform in their jobs or being too perform those jobs. E.g. power out and unable to produce electricity to make fuel or pump gas to the NE and North parts of the country. This part was supposedly dependent obviously on when it happened so the worst case scenario was used. That was a large number if it happened in a normal winter and for people above the S. border of Kentucky. That was almost as bad as the flu and it was another 15 mil. Finally starvation and that was a ugly little bastard and really the one thing that we the people could actually do something about. 11-20 million as we would be very, very much on our own after the first 30 days.
So 15, mid point 15, and 30 million means about 60 million in the US. Talk about PTSD....
I guess it will depend also on what those death certificates will read. How do you diagnose BF when the WHO only lets it be called H5N1 when there is a certified test in their hands? They adjusted that criteria but it has to be confirmed by a trained HCW. I think we are going to be a tad short on that too.
Monotreme,
As I recall, it's been suggested that the H1N1 pandemic of 1918 (Spanish Flu) started with a mild first wave and become more virulent. I'm not sure on that, or if it's actually ever been proven.
I think the CFR will depend on the form of adaption. A simple mutation of the orginal H5N1 would yeild a high CFR, while a recombination would reveal a lower CFR. I guess that's probably obvious. But not necessary a given.
Patch, I've read the same thing about 1918. Don't know how reliable those reports are, however.
I agree that the CFR may depend on how a pandemic strain evolves. Reassortment or recombination with a "human" flu might lead to a less severe pandemic because there might be enough identical sequence from the "human" flu donor to trigger an effective immune response. However, if H5N1 adapts directly to mammals/humans there is no reason to expect a decrease in the CFR, although we could always get lucky. One of my concerns is that there is a mammalian intermediate reservoir that H5N1 is adapting in. The strains that emerge from selection in mammals may have very different transmissibility properties than the ones that emerge from selection in birds.
What I cannot understand is why the field epidemiologists are not testing mammals in the regions where there are human outbreaks and why there is apparently no attempt to identify the source of human infections other than to say "Oh, he ate chicken" or "Some chickens died there a week ago." The importance of the sequences is that provide a molecular fingerprint which allows one to trace the chain of transmission.
I implore the culling of birds be stopped now and forever: Please read this from an editorial in India.
It was subsequently seen that large-scale culling had not always proved effective in checking the disease. So it becomes difficult to justify the killing of so many birds. The FAO and the World Organisation for Animal Health reversed their decision in 2005, saying that for ethical, ecological and economical reasons, culling should no longer be used as a primary means of control. On April 11, 2005, the FAO (Rome) issued a press release to this effect. This was followed soon by a report in the prestigious journal Nature Vaccination will work better than culling say bird flu experts (April 14, 2005.)
In a review of this disease and related issues Danielle Nierenberg has written even more recently in a WorldWatch publication, More than 140 million birds in Asia have been depopulated since the outbreak first hit. Unfortunately, gathering birds into plastic bags and in some cases, burying or burning them alive did little to prevent the disease from spreading. What is more, the condition in which the birds have been culled in India is likely to have exposed many workers to severe hazards."
It is too late to cull birds. This is a bird pandemic. It is like the little Dutch boy that put his finger in the dyke to stop the ocean. Would you want to be buried alive or burned alive? Don't you realize the horrible suffering of a bird subjected to that? Do humans have no conscience?
Cullers subjected to dead or sick birds will assist H5N1 to adapt to humans. WHO is shit. They should stop the culling now. The scientists at WHO know it is now impossible through culling to control this horrible and dangerous virus.
I am sick and tired of reading statements of so called virologists with their thumb up their ass declaring this virus will very probably not cause a pandemic. Are they tring to shit us or what? If this virus adapts to humans after unlocking the glycan key, humans will be in deep shit.
Please listen to what Randy and Monotreme are saying, before the Titanic hits the iceberg.
herman, please don't cite me in your rants. I support culling the birds, with appropriate PPE, of course. It is the only way to limit the spread to mammals.
Absolutely ludicrous! herman...where were you when Randy was talking about nuking countries who spawned pandemic H5N1? You lift him up as your hero while in the same breath condemning culling practices?
Furthermore, while many chickens are pets I'm guessing few are allowed to die a peaceful death after a full life. They are a major source of protein, remember. Chickens are usually killed by pulling off their head.
I won't comment further on such idiocy, but I do wonder what effect culling has had. It's certainly possible that we have deprived the virus countless replications and therefore mutation opportunities. Perhaps "the" pandemic strain was destroyed along with it's immediate host in a cull. I do agree that we should be keeping our eyes open for mammalian hosts. I would bet well informed agencies, such as the WHO are looking at alternative hosts.
1) the virus has undermined much of the animal world in species and geography.
Normally, this wouldn't be a problem at all because viruses rarely...very very rarely ever jump species.
There is no other virus that has affected so many animal species at the same time.
2) The virus is opportunistic.
It can be assumed with some certainty that it is evolving on at least two fronts...avian species and mammals...as many small mammals feed on carrion...and domestic animals cats, dogs, pigs, goats also will feed on carrion.
It is circulating in many wild and domestic mammals due to the eating of carrion.
3) The continuing spread and efficiency of CFR in poultry is a crisis of immense porportions...as it is the most efficient (inputs) and easily grown meat protein source for poor families in developing countries.
4) If it gets into pigs or goats or cattle efficiently...it doesn't have to get into humans to cause significant collateral damage...and result in political instability.
No other virus in human history has the unique threat potential of H5N1...and that is an absolute. For those who might think this is farfetched...be my guest...give me another virus that has done what this one has done in a very short biological time period.
For what it is worth. H5N1 is following a well worn path...and I have watched most other pathogens taking the same pathway succeed.
Herman are you nuts old son? Patch is right. I advocated the use of neutron weapons on a country/area where BF had gotten loose. Its too late for that now as the area has spread along with the birds. The latest is that goats are dropping like flies and in a 3 day time frame from the first signs. Bird flu? I dont know and neither do they. The only way they'll find out is via testing and none of the newsies are indicating they are doing any testing. There are 2300 plus Bangladeshi children in hospital now with acute respiratory problems... No they didnt say distress because if you did that it would raise the flag.
As for the burning of live birds. First PPE! Gimme a break. Second....Barbeque the little two legged virus carrying sacks of shit in a emolation if you cant find dry ice to drop them into a garbage can with. It takes about 3 minutes. I read somewhere that viruses cant stand dry ice because it causes the cell membranes where they are frozen to rupture....I think thats right. Same with liquid nitrogen if it contacts the cells. Whatever. But it would and will take at least a month or two to cull them all. But WTF, they are eating the damned things!
I do agree that they cant kill all of the birds. But they could go to a cleaner bird and that is one thats factory processed. Is it the transient birds infecting the chickens or is it now endemic in the water, soil, feces and dirt? I dont know and neither do they. I can tell you for a fact that another two districts in India were closed today and its now only one hour drive on a shitty road before it hits Calcutta. Human cases? No, none reported. But then again to get a human case you have to test and to test costs about 100 USD.... No, they arent going to do any testing for that single obvious reason. The humans are going to be the mine canaries in Bangladesh and India. When they start dropping, it will already be too late.
Tom has a very valid point. I think it was the sixties and smallpox broke out in India and it ran like a striped assed ape with a gasoline fire on his hickories. We are due and due big for something...H5 is the bug of choice. What if it isnt? I wont be dissapointed but like I said...XDR-TB with no chance of cure? I think I might start skydiving again...without a chute.
Herman, again I think you are too far into this and you need to take a break. If you are prepped up and you are in a foreign land then I suggest you either shelter in place or the second you hear of it going H2H in an extended fashion that you haul ass back to the States. Not that it will be any better but your passport would be better recognized here. I have said it many times... embrace the horror and do what you can. Quit getting so worked up about it. If this is your reaction to it now, think what it will be if it comes.
Wow, this thread is running hot. Don't know if kids are eating peanuts in eastern India but I am certain that garlic, onion and tumeric are used (usually on a daily basis, even by the very poor) and all three of these foods are said to have some anti-viral properties. It will be interesting to see if TIMING of anti-virals (food or otherwise) continues to be important. It sounds like Tamiflu is most effective when given quite early in the infection and somewhat worthless when given late.
Herman, hang in there. I can tell you care -- a lot. We miss a couple things in e-postings, including volume and tone of voice. For some reason that seems to make people post "hotter" than if they were speaking in person (IMHO). Sorry to see it happen though. We do all need the "hive" mind working on this stuff.