CDC's Open Access journal, Emerging Infectious Diseases, has just published an interesting communication from an international team of scientists who surveyed Cambodian villagers in Kampot province immediately after a 28-year old male died of H5N1 infection in March 2005. The team also conducted poultry surveys to estimate the extent to which area birds were infected. The case was said to have handled and eaten sick birds. Medical histories, looking for febrile illness were taken within a week from over 350 villagers. Two months later blood specimens were obtained to see if neutralizing antibodies to Vietnam (clade 1) H5N1 had developed.
The poultry survey revealed evidence of bird die-offs in the period before the fatal case, with 42 flocks considered to have been infected on the basis of greater than 60% mortality and a case fatality of 100%. There was also abundant evidence that many people surveyed had close contact of one kind or another with poultry, many showing evidence of H5N1 infection. The survey produced no evidence of febrile or respiratory illness in the 352 participants during the 12 previous months [this is rather surprising, in our view, but we have no basis to believe the survey was improperly done]. The neutralizing antibody study was also completely negative.
To sum up, a 28 year old man who handled and perhaps consumed poultry presumed infected with H5N1 developed a typical case and died within a week. None of more than 350 neighbors within a 1 km radius, many of whom were also similarly exposed, showed any evidence of infection, either by history or by finding antibodies in their blood after an appropriate interval. Neither the authors nor we have an explanation for this. What are some possibilities?
The antibody test might have been an insensitive measure of infection either because it was not directed at the right antigen or the virus itself provokes too small a response to the particular antibody being measured. More likely one is that none of the surveyed villagers were infected. The authors suggest one obvious answer: there is some unknown host risk factor that makes one person get infected and react fatally while most others, similarly exposed, do not. It is also possible, that the case came from a unique mutated virus allowing infection in this case but no further transmission. Either of these explanations suggest the role of chance: in once case, the chance of having a rare risk factor, in the other, the chance of encountering a mutated virus that can infect you. Both lead to the conclusion that at the moment exposure of humans to this virus leads to illness only rarely.
So we have reliable looking data, from one village in Cambodia in the month of March, 2005. But this virus isn't standing still, so it would be imprudent in the extreme to believe they show the potential for disaster has been overblown or is low. The message of this study is best given by its final paragraph:
This study provides evidence of the low transmissibility of the H5N1 virus from infected poultry to humans, even in circumstances in which human-poultry interactions are regular and intense. In this instance, human H5N1 virus infection manifested as a single case of severe illness without any evidence that the virus could cause either mild disease or asymptomatic infection. However, our findings are limited to the investigation period of 2005. As H5N1 viruses continue to circulate and evolve among poultry, poultry-to-human transmission of H5N1 viruses could increase. Extensive investigations should be routinely conducted for all H5N1 outbreaks among humans and animals to monitor the nature and extent of bird-to-human or human-to-human transmission of H5N1 viruses. Additional seroepidemiologic investigations should be conducted to assess the ongoing risk for bird-to-human transmission of H5N1 among rural and other human populations. (Vong et al., Emerging Infectious Diseases)
Exactly right.
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Third possibility: the person came into contact with an unknown reservoir of H5N1.
4th possibility: bird flu is just a scam to make Rumsfeld and the pharma companies rich, and additionally to trick us all into getting more vaccines. And we all agree vaccines are dangerous and bad, right? Come on, don't you guys read Dr. Joseph Mercola's website?
Snark.
H5N1 isn't standing still, and this study was with clade 1. Isn't it true that the WHO's target strains for a pandemic vaccine do not come from clade 1?
Marissa: There are a variety of possible explanations but not many plausible ones. There seemed to be nothing special about this individual compared to the hundreds of others in his village nearby. Why would he have come into contact with a (presumably prevalent) alternative reservoir and not others? And since others did come in contact with a known reservoir (poultry) we aren't helped in understanding why contact with that reservoir isn't effective but some unidentified one is. So I don't think this is very cogent.
Edmund: I believe the target strains were all Vietnam clade 1 strains but now WHO is advocating adding clde 2 (Indon). See our post here for more info.
Each of us hopes that the skeptics are correct and H5N1 just goes away never to be seen again. However, I think it wise to consider some facts.
Prior to 1997, there were no KNOWN examples of high pathogenic avian influenza viruses crossing the species barrier (if you exclude H1N1 in 1918).
Therefore, we have had three different subtypes do it at the same time in earth's history. This did not happen by chance. Something, whether environmental factors or crowding or something else, is pushing us in a direction we don't want to go.
And it is not just viruses which are mutating to increase virulence but also parasitic, parasitic mediated and bacterial diseases are following the exact same pattern.
In Sept. 2005, Dr. Taunburgher announced that H1N1 did it in 1918. Unless someone comes up with an understandable explanation why H5N1 can't do it, then it can just as easily follow the same pathway.
Is there comfort for me in this report? No. The only comfort for me would come if we discovered that the Case Fatality Rate has been artificially inflated and is actually much lower.
It should be remembered that the experts predicted that by now the CFR would be much lower...it didn't happen.
We are a long way from a victory party yet. Thanks.
If more scientific evidence, in later field studies in Asia, confirms the conclusions of this report, this will be good news.
I wonder if all those who have died of bird flu would celebrate if they had lived long enough to read this report, before they died of bird flu?
And for the citizens of Mexico, if they are notified bird flu will not be a danger, they will have one less thing to worry about, because today is the day a judicial tribunal decides if Felipe Calderon of the PAN will be named the new president of Mexico; if no evidence of voter fraud can be found.
Especially Mexican Army personnel will be glad there is no threat from bird flu. Of course, if Calderon is named president of Mexico, soldiers will have to decide if they really will obey orders to shoot rioters, as these soldiers did in Oaxaca, during the riots caused by the teachers union strike.
The loosing candidate, Andres Obrador of the PRD, will immediately iniciate street protests, if Calderon is named president. Obrador and the street protestors will not have to worry right now about bird flu, but they may have to worry about being killed by a bullet from a Mexican Army rifle, if soldiers decide to continue shooting street protestors. If you were in the Mexican Army, would you obey an order from your commanders to shoot your own citizens?
And the report from China that 1 million pigs have died from some strange disease should not be a cause for alarm. Of course pigs can be infected by bird flu. But since the villagers in the study did not become sick from bird flu, it is obvious the pigs will not infect humans, even if the pigs have bird flu.
Today is a good day for optimism. If you are a street protestor in Mexico, bird flu will not be a threat. But being shot by a soldier of the Mexican Army may kill you today, if Calderon is named president.
And the cause of death of those dead pigs is best ignored.
Ignorance is good, especially in relation to bird flu.
It is better not to worry about what may soon kill you. That way you will die a happy death.
(without the beat)... he had a sweet mistress and took a little trip and didn't tell anyone or lied or tra la la and then when he fell sick neither he nor his family though o it or even re-membered it - it was that some chicken he ate was sick strange some died and the man didn't ask because he was already going batshit about chicks and if he had no they would 'a said Jimmy is not a travellin' man.
My complaint is that it is possible that essential information gets lost in transmission in the flurry of proper sanitary and scientific procedure, and that scientific articles of this type don't unequivocally state that to the best of their knowledge, according to their investigation (points 3a to 3c on a standard form) the man had not been out of that village (area, district, etc., where no other infected have been reported, etc.) for x weeks before his death.
How hard can that be?
It is cogent (see revere responding to Marissa.) Such facts can't be left implicit, presumed. Two sentences.
Edmund, you are right that H5N1 isnt sitting around waiting for the WHO to make its mind up. My friend from the club who is an epidemiologist says that there is really no way to make a vaccine that will work across the board unless we get a huge amount of participation, and in the same breath get it while its hot.
Hot? His statement was simple. We would just about have to vaccinate everyone all at the same time, drag them kicking and screaming in for a mandatory flu shot. Else, its out and running again. Eventually he said though that it will be out and running again anyway, just a different strain.
So far he says, the vaccine is crap. The Chinese are vaccinating for H5N1 with off match vaccine which is a grade B idea slipping into C.
Oh yeah, dont worry about Rumsfeld. If it comes at 20% mortality, the economies of the world will crumble and money will be close to near worthless.
And I buy Ana's argument. Something just isnt right and BS in Switzerland is BS in the US most of the time.
"There seemed to be nothing special about this individual compared to the hundreds of others in his village nearby. Why would he have come into contact with a (presumably prevalent) alternative reservoir and not others?"
We know virtually nothing about this victim and the possibility of an alternate resevoir is presumed "not cogent?"
The family down the street keeps a pet skunk, and my next-door neightbor was recently bitten by a wild opossum when fishing it out of his window well. I doubt there are any other pet skunks or opossum-bite victims within a 1 km radius.
This is a very useful study, IMHO, for a few reasons.
1. It helps set the baseline of what H5N1 was doing in the early stages, adding weight to the argument that B2H infections are extremely rare, and with high CFR, (as opposed to our not looking carefully enough for the others). So if/when we do start seeing clusters, they can't be dismissed as just better surveillance--we'll be more certain that something significant has changed.
2. It points at the two theories Revere mentioned for follow-up investigation: either the victims were unfortunate enough to encounter a rare mutation, or they had a rare succeptibility. The latter is far less troubling than the former, which suggests H5N1 has already found a useful recipe and now just needs to work out the (re)production logistics to roll-out the global launch of a human pandemic.
Revere, what are your thoughts on the feasibility or usefulness of doing comparative analyses between this individual and the 350 others (DNA, health status, etc), or between his virus samples and others collected from deceased poultry, etc around the village, to further explore these questions?
Known clusters - Turkey, Karo, Vietnam have an eerie similarity in following bloodlines, vs exposure patterns. No matter if source of infection is H2H or a common point source, poultry or otherwise, doesn't this lend some support to 'unknown host risk factors'?
I have a question. What factors in our immune system MIGHT cause antibodies to not be present or be present in such small amounts as to not be dectable. (Assuming the correct tests are used.)
corresponding evidence of this possibly occurring would be the fact that is takes such a large amount of vaccine to stimulate a proper immune response.
Is it possible to have contact with a disease vector and our bodies are unable to mount a sufficient immune response; which would be why the whole "overreaction" response which contributes to the mortality?
Just wondering.......
I also go with ana's argument...whether by accident or design, the amount of disinformation is equal to or exceeds the amount of good information on this subject, and quite consistently.
Often it is just "omitted data" - that black hole of non-information that is hardest to pin down as a lie...which it is, a lie of omission...because it simply isn't there to look at, analyze, argue for or against, prove or disprove.
For example William's comment about the million dead pigs from unknown/suspicious causes in one province in China. No one is talking about it. Does that mean it doesn't exist? Isn't important? We presume it isn't important because no one is talking about it. William presumes this means there have been no human deaths related to it. But that is a presumption only. It could be the authorities are being as silent on human deaths as they are on the pig deaths.
Have you noticed (of course you have) that we seldom get any follow up reports about all those cases of suspect H5N1 flu that kept popping up in Indonesia last month, popping up in places where there had already been verified human and poultry cases of H5N1. Did we ever hear all those cases turned out negative for H5N1? No: It is just presumed they were all negative because no one ever said they turned out positive. I don't want to seem paranoid about this, but while we are searching about in all kinds of complex mental alleyways for the reason behind the seeming anomaly regarding this isolated Cambodian case - or all the rest of the puzzles we grind over re H5N1 - Occam's razor would suggest that the simplest answer is we have omitted or erroneous information.
[i]For example William's comment about the million dead pigs from unknown/suspicious causes in one province in China. No one is talking about it. Does that mean it doesn't exist? Isn't important? We presume it isn't important because no one is talking about it.[/i]
I think the same way about the thousands of birds falling from the sky in Unalaska. No news???
Revere, I'm surprised at your response to my suggestion of a third possibility in the report by Vong et al in the EID journal. Ever good epidemiologist lists the possibilities in the face of inexplicable results. For a long time I've not bought the theory that every case of bf is caused by contact with sick chickens. I know this is not considered "good form." But the fact is in this case at least a good proportion of the 352 villagers had a good opportunity to contract H5N1 but did not do so. The authors may well be right about the susceptibility of this individual--we'll never know; he's dead. However, we need to expand our thinking. What if his susceptibility was ordinary. What then? Where the heck did he get the disease? Was his life in terms of local travel different? Did he indulge in trafficking of birds? Or other animals? All I'm saying is be open minded. Might have been an additional source of H5N1, might not.
Here's a stern warning to all scientists who are closed minded (not aimed at you Revere, I assure you). It's called Clarke's Law." "When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong." [Source: Clarke AC. In: Profiles of the Future. London: Pan Books, 1962, p23.
Marissa: I'm not saying it couldn't happen (I like your Clarke, quote, BTW), just that when asked, I didn't think it was a plausible explanation. Much more likely is that it is hard to get infected for one reason or another, not that only this guy was exposed.
Given that there is ongoing smuggling across Cambodia, Laos and Thailand borders, it's worth wondering if a 28 year-old man was involved in illegal smuggling operations. Kampot is a few kilometers from the Gulf of Thailand, with the Vietnam border less than 50 miles to the east.
Floridagirl, I agee. I think negative results should be interpreted as "not found" in that specimen. It isn't very comforting, but that's just the way this universe works.
Ana, I agee. Most of the good stuff never appears in print. Because it isn't usually strong enough to withstand scrutiny. But I think the investigators use that information to direct the investigation whether they can print it or not.
Finally, mary in hawaii, why wouldn't Occam's Razor select that there were no antibodies found in the people tested?
Douglas: Occam's razor is used to find the answer, not the question. The fact of no antibodies is a piece of data. No one is arguing with that. The question is WHY were there no antibodies in the people tested? And in answer to all the possible avenues of speculation, one then applies Occam's razor and tries to find the simplest explanation that works for all the data. Certain presumptions are made: the collection was done correctly, the analyses were done correctly, and there were indeed no antibodies. WHY? Answer one: no infection. People simply did not get infected by the virus even though it was present and prevalent in poultry in the area. Or was it? The article above says there were sick birds, with a high mortality rate, but it never says they were actually tested for H5N1. Were they? Or was it simply a presumption made, a sort of reverse B2H thinking: If a human death by H5N1 was confirmed in the area, then the local sick poultry must have had it. But what if they didn't? Perhaps they were sick from something else and their illness had nothing to do with the human victim's H5N1 infection. That would tend to clear up the matter of why no one else in the village exposed to these infected poultry got sick. But then where did he get it? Like Ana suggests, maybe he was a travelin' man. Like glo says, maybe a smuggler. Personally, I'd like to know if the chickens were ever actually tested for H5N1. Revere?
Just noticed that the current death rate of the Indonesian H5N1 is 76 %.
tinyurl.com/ebz4k
http://www.who.int/csr/don/2006_08_14/en/index.html
Preliminary and secondary tests were negative for avian influenza; however test in August was positive. If more testing was done would the results be different? Are we to believe that only some people are genetically disposed to being infected with this, say like Parkinsons? How odd, I think. Help me out here...
Also, don't we see cases in Indonesia recovering? Not 100% fatalities, so aren't there milder cases or is this just good treatment procedures?
Judy: Most people exposed to infectious agents don't get sick with them. We usually don't know why. In this case we are also in the dark. I'd like to help you out but neither I nor anyone else can. That's why it's a puzzle and why scientists like myself do this for a life's work. the tests might have missed one or two but not likely 350 nor was their evidence of illness. The case fatality depends on a lot of things besides the virus, including medical care, host factors, etc. So we don't know if it's the virus, the environment or the host that is responsible for the higher CFR in Indon.
Revere: "Most people exposed to infectious agents don't get sick with them." This is true and I had not thought a lot about it. My daughter at the age of 18 months contracted cerebrospinal meningitis from another child in a children's nursery. She was already ill when I picked her up from work and was in a coma by the time we got her to the emergency room. She was in the coma for four days before she began to recover. The nursery was closed down immediately, and we learned later that a young worker there had put the two children together in the same crib for a nap. My point is this: none of us, other children, workers, or anyone else in my family contracted this though we were exposed. So my question is this: since everyone who is exposed to H5N1 does not contract this virus (evident even in Indonesia), would this hold true in the event of a pandemic? Can I bring my fear level down just a notch?
Also would like to say how grateful I am to you and other scientists and all those in medical professions for your dedication to your "life's work". Where would we be without you?
Judy: We really don't know how a transmissible H5N1 would behave. In ordinary flu about half the people who are infected are asymptomatic and why the rest don't get infected isn't known (except if they are immune). So we'll have to keep an eye out and try to figure out what's happening on the fly, I'm afraid. Wish I could be more informative, but no one knows.