Presented March 20 at the International Conference on Emerging Infectious Diseases 2006. http://www.cdc.gov/iceid/
An analysis of the first 11 cases of human H5N1 infections in Indonesia starting June 05 showed 8 of these were in 4 clusters (73%) , of which 3 were in Jakarta. Of these, 10 were confirmed and 1 was probable. In addition, the index case of the first cluster was not tested (died) and classified as suspected case.
Some data on these 12 cases:
some of the virus samples were resistant to amantanes, all were sensitive to neuraminidase inhibitors.
Interesting.
This seems to be the type of data that so many of us have been wishing for. Will it be another 9 months before we get this on the clusters in Turkey or Azerbaijan?
Indonesia still heads the list of countries to worry about, with a fast rising trend in cases.
From WHO data, there were 17 confirmed cases in Indonesia for all of 2005, of whom 11 (65%) were fatal. We are less than 3 months into 2006, already there are 12 confirmed cases of whom 11 (92%) died.
anon_22. Indonesia used to be on the top of my list, but the secrecy regarding Turkish results makes me nervous. There is probably alot of bird to human transmission in Indonesia because the Indonesians are not culling. The Turks did cull their birds. So, the absolute number of cases may not be the most important variable. If clusters were larger in Turkey than than they are in Indonesia, I would be more concerned about the Turkish strain (the sequence of which is still blocked) than the Indonesian strain even if there were many more cases in Indonesia.
Monotreme. Would these strains not already be known to the ‘secret seven’ or whatever, and would they not have been accounted for in the recent comments by the CDC and other bodies.
There has to be more strains. If the ones who are supposed to know be are in the dark, should they not have qualified the fact in their reports.
I don’t agree with that. There’s the places we know to worry about (Indonesia and Azerbaijan - ongoing cases) and the places we don’t know whether to worry about (no data like China).
Turkey is not in the mix of my top worries. It’s a place to gain knowledge, though.
China is the black hole that started this thing and maybe the black hole that finishes it.
Sorry, I still think Turkey is important. Not because there are ongoing cases, I assume these have stopped because of effective culling. What I want to know about Turkey are two things:
This issue is, is the virus that infected people in Turkey different from other H5N1 viruses? Without data there is no way to know. When key data is deliberately suppressed, I become suspicious.
Tom DVM: Frankly, I’m not sure who knows what at this point. My understanding now is that Mill Hill doesn’t have access to the sequences they generated. Who does? WHO knows.
I agree about Turkey’s importance. I use “worry” a little differently.
I don’t think they have quite figured out yet, exactly the level of threat they are dealing with. Underestimating your opponent has been a strategic advantage manipulated by many pathogens etc. in the past.
Actually, I don’t have to worry because my Government stated, without qualification, that it appears this particular threat is being overblown by every expert around the world….don’t worry, be happy…and they are still quoting the statistics from the WHO Jan-May 2005.
Monotreme,
I don’t think so. Even though the Indonesians are not culling on a large scale, neither are they seeing massive bird deaths or any other indicator that humans are increasingly exposed.
Even if it is mostly b2h (which we don’t know for sure since the percentage of cases that are in clusters is now 100% vs 73% last year), any improvement in efficiency of b2h still reflects a trend in the evolution of the virus that does not favor us.
Such an improvement in efficiency is only unimportant if you assume that the ONLY selective pressure that will favor formation of a pandemic strain is the one that happens when it passes from one human to another, and not at the b2h step. I believe we do not understand this virus or the formation of any pandemic virus from an avian strain enough to be able to make such fine distinctions.
Dem,
Define “worry” ;-)
Monotreme,
I think the challenges with data from Turkey and the (legitimate) distrust that resulted as a result of how the Turkish information was handled by the WHO are important concerns in their own right. However, I personally think it is important for us as ‘flu-watchers’ to differentiate the behavior of the virus from the behavior of people and organizations managing the response.
And it isn’t just Turkey. The same applies for China, or Burma, or Iran, etc. We would all like to know exactly how many cases there had been, if any. The fact that those governments are not willing to tell us everything does not make it more likely that the truth is drastically different from what we are told. We just don’t know.
Or, put it in another way, just because someone is acting suspiciously doesn’t mean they are guilty.
As Dem would say, no data is just no data.
worry: a place where human cases might accelerate. Turkey’s not on the list.
The list, of course may change.
I know there are no confirmed cases, but I really worry about Nigeria.
anon_22: So, is increased H2H or B2H in Indonesia being acknowledged by the WHO? I don’t see any indication of this in their recent press releases, but I may have missed them. I don’t mean to suggest that I’m not worried about Indonesia, I am. But at least we are getting some information about what’s going on there.
We were told the WHO was going to do very careful and complete epidemiological studies in Turkey. They have had plenty have time to complete these studies and release at least a preliminary report. Yet, we still don’t have basic information like symptom onset dates and the relationships between patients. As I mentioned before, active suppression of information makes me nervous.
I acknowledge that it is not possible to predict with certainty which mechanism is most likely to result in a pandemic with H5N1. However, my personal bias is still to be most concerned about large clusters and the opportunity for the virus to spend more “time” in a human host as most likely to result in complete adaptation to humans and efficient transmission.
anon_22: It is certainly true that sometimes people engage in suspicious behaviour even when they have nothing noteworthy to hide. A certain former dictator of a middle eastern country comes to mind. Of course, more often than not, people who act strangely do have something to hide. And actually we do have some data on Turkey, but not official. There were media reports, in Turkish, describing the relationships between patients and symptom onset dates. These were translated by Oric at CurrentEvents and here at Flu Wiki. Several bloggers arranged these into charts which suggested very large clusters with temporal separation consistent with 3 or more generations of human to human transmission. Of course, since these were never officially acknowledged by the WHO, we can’t be sure that the bloggers got it right. My nightmare is that there was stage 4.5 or 5 cluster in Turkey that was successfully extinguished by aggressive intervention. If so, the virus that caused this is still being transmitted among birds and can reappear again. The developing cluster in Azerbaijan comes to mind.
Monotreme: Bingo! What happened once can happen again. Illuminating as ever.
The sparks fly to more dry brush.
I am mosy worried about the Azerbaijan clusters since there is speculation that there was not contact with birds although there has been some question about contact with “bird feathers”. Soon,the B/B contact may be “they looked at birds through binoculars”.
I am really keeping my eye on the next cluster (as big as or larger than Azerbaijan). I think the next one will be very telling. Anyone want to take a guess where it will break out? My guess would be Africa (outside of the Egypt area). I think if we get a cluster in a back country area of Africa (low immune systems, no surveillance, etc), we could get a very large cluster before the WHO is even aware of it. Again, I think the next one could be a tipping point.
Monotreme, I understand what you are saying and I am not saying one way or the other which ‘worry’ is more valid, cos we just don’t know.
What I AM saying is to be aware of the logic of our thinking, and to separate the (sometimes fixed) notions that we have unconsciously generated for ourselves based on previous experience, and the raw data that we are getting (or not) now. It is important to bear the past in mind. But it is also important to be able to look at every piece of new information on its own merit, and not be too affected by our history. Including the lack of information.
For example, the outbreaks in Turkey in January were worrying. AND there is some suspicion that we were not getting the true story. (BTW bloggers interpretation of previously known data - at least that’s what I think you are saying - does not constitute new data. It’s interpretation of old data.)
But Turkey is no worse on transparency than a whole lot of other countries. And it is certainly not North Korea or Burma, where far bigger clusters or epidemics can be hidden far more easily. Therefore, the fact that there are not any worse new information coming out of Turkey for me is a sign of small (cautious) comfort. Not to be complacent about it, but just to stay vigilant and leave it at that, and focus my energy on things that I _do_ know about.
At some point in the future, if and when more information becomes available for me to form a new opinion about Turkey, that will be the time when I form it. Not now. Not yet. Perhaps never.
The coming months/years may become extremely stressful. All of us may need to come to some triage within ourselves about the kind of things we choose to worry about.
I say this in all sincerity for yours and everyone’s wellbeing. I may be barking up the wrong tree and if that’s so I do apologize. But you have been (and continue to be) such a valuable member of this community and offered so much for all of us that it would be selfish of me to walk away and not say what I think.
OK, If a large portion of our information comes from the news, and if we are not satisfied with the information we are getting, then we must educate the reporters and their editors what facts they need to tell the world. A list of simple questions they need to have on each case. If reporters are to be our first line of defense, then we should get the ear of the news and wire services and train them what to look for. I would prefer the data gathered and released by the scientific community, but that seems too often to fall apart. Lets spam all the newspapers in the world with a form to fill out about BF cases. <g>
anon_22: Its perfectly OK and healthy for us to have different areas of concern. No-one can be certain which country the pandemic will come from. You are quite correct that North Korea or Burma could be have clusters of 50 people for all we know. I realize Turkey is much more transparent than these countries. However, the “old” data from Turkey, from 2 months ago, still bothers me. Not because I think the pandemic is likely to originate in Turkey, in fact I think that’s very unlikely, but rather, because I think the information that is being hidden from us may be valuable in understanding H5N1 evolution. In deciding how large the clusters were in Turkey I have to decide whether to believe the bloggers or the WHO. The bloggers have a better track record, so I believe them. As regards the relative importance of a few large clusters vs. many small clusters, I find the former more worriesome. If I understand you correctly, you are more concerned about the latter. If so, we’ll just have to agree to disagree on this one.
I think our “community” will be served best by people who worry about different things. I’ll rest easier knowing you and DemFromCT will watch Indonesia closely. You two can be assured that I will relentlessly pursue the release of the sequence and cluster data from Turkey.
Monotreme, there’s some new ( I think ) info on the cluster in Turkey, the girl and her uncle. It’s in Fla-Medic’s post near the end of the news thread- interview with Dr. Osterholm.
Gentlemen, I may have missed this in past post. Have you considered why the data is incomplete? I assume you have considered the following,
“Has anyone here, Tram, Anon, etc, the virus experts thought of this (someone ask them if they don’t see this). They keep asking for information they may never get for good reason. Interesting thought. Seems logical to me. It would be hard to posture politically if a pandemic was forming or someone else held the key to creating it. This has to be considered. Unfortunately bioterror is very real. Information in this situation is leverage on the battlefield. This simply can’t be removed from the equation. The bottom line is, prepare for an event. Period. The political climate is not stable in several regions. BF is real, H2H, possible. All intelligent human beings should take the time to store water, food, medical supplies, etc, for several, very real threats.” Roman
MaMa: Just reading the article right now. After my post at 20:47. Thanks for pointing this out. Here’s the quote MaMa is referring to:
Then, when you look at the Turkey virus—that thing mutated. This is the case of the young girl in Turkey who died from her infection, and so did her uncle. We definitely have clusters where it’s not just bird contact [spreading the virus]. The uncle’s only exposure to this virus was riding in the ambulance with her from hospital one to hospital two. He became ill three days later and died. Her virus has now been fully sequenced, and there were three mutations that occurred in that virus, between the bird version and hers. One was the substitution of a glutamic acid with lysine at the 223-hemagglutinin position. That is what changes it from a bird-receptor virus to a human-receptor virus. The second thing was two other substitutions that served to make it look more and more like a human virus.
Roman1
Yes, the bioterror factor is something to fear. People keep quoting odds of H5N1 mixing with a human flu as high. But the odds really change if someone tries to mix them.
Monotreme, you’re welcome!
Dennis, And spreads mis-information to prevent a solution. Or hides information for a military/economic advantage (US, etc). This applies to a possible natural Bf or manufactured. Once again, this possibility can not be removed from the equation/solution. There is no way they could be transparent with information concerning this situation. You will never know the whole story. Period. A clear picture provides too many opportunities.
I am very thankful for the attempt by some of you to track this situation and will follow the post daily.
Roman
MOnotreme,
“Not because I think the pandemic is likely to originate in Turkey, in fact I think that’s very unlikely, but rather, because I think the information that is being hidden from us may be valuable in understanding H5N1 evolution.”
In that case I do agree with you.
However, I also think that there’s a limit to how much viral sequences can tell us about whether a pandemic is imminent, which I assume is one major concern of yours. We simply do not know enough about how flu viruses cause pandemics and exactly what molecular conditions are necessary for that to happen. So the experts can hypothesize all they want, they still have to look at whether there is any epidemiological correlation with their findings.
An analogy can be found in the development of pharmaceutical products, including vaccines. In the process of developing a new drug, drug companies do everything to create the components that based on previous knowledge are most likely to get them to the results they want. And they can achieve a very high level of precision and sophistication. But unless and until the drug is tested in vivo, animals then human, we just don’t know how it will behave. The recent tragic events in London where 6 previously healthy people suffered catastrophic reactions is a case in point.
Therefore, the fact that the virus is acquiring certain mutations is always a ‘cause for concern’. But the mutated strain still has to (unfortunately) go through ‘clinical trials’ to tell us how it will perform. Thus, while keeping an eye on the molecular side (or keeping an eye on your posts), I am a lot more focused on the epidemiological trend and the likely response from countries and/or the WHO.
As you said, it is just as well that different people focus on (or worry about) different things.
:-)
anon_22: I don’t think we are really in any disagreement. I agree that epidemiology will be the most accurate indicator of an imminent pandemic. I want the sequence data and the epidemiological data from Turkey. Both are currently being blocked. Correlating sequence data with animal studies and epidemiology is the best way to get this done. The fact that the WHO, WHO collaborating scientists and some countries are preventing this important work from being accomplished is shameful. The consequence is that when the strain of the virus that caused the large clusters in Turkey pops up again, as it may be doing in Azerbaijan, the general public is unaware of exactly how much danger they are in - with tragic consequences.
sequences, seroprevalence and clusters. Or, as Scott Layne describes here, epidemiologic, genotypic, and phenotypic data. It’s all important. We need it all.
DemFromCT: The modernization of data collection relating to influenza is overdue. So, no argument with that part of Dr. Layne’s article. However, he also slid this in:
The release of data to other users or entities would be controlled by the submitting organization or authority.
To which I say, screw that. Bermuda Rules: Deposit all sequence data in GenBank within 24 hours. Anyone who hoards the data is a vile monster, in my book.
editors of journals could just refuse to take articles unless the sequences where posted.
Monotreme – at 22:25
I’m prepared to allow proposals without prejudice. The end result, I am confident, is what we all want… full disclosure and transparency of data.
“I swear to uphold the sacred principles of Fluwikieism in my appointment as judge and jury in the trial of all individuals who have allegedly acted to withhold information on viral sequences which contributed to the unnecessary death of humanity.” My oath taken after TSHTF and we come out on the other side and go after all of these kind folk. <g> but it is not funny. “I want to thank….”
The points I took from the Osterholm interview that really hit home (just as the Western news media is getting gung-ho about the virus “having a problem” jumping to humans):
anon_22: Do you have any more information on the Indonesia clusters? Here is the informtion on these clusters that I have so far. From the Indonesia page?.
The first confirmed human case of H5N1 was a 38 year old man from Tangerang, a suburb of Jakarta, who died on July 12 2005. His 1 year old daughter died before he did, but she was not tested. Another daughter, 8 years old, also died. She was reported to be H5N1 positive, but was later judged by the WHO not to have an acute H5N1 infection.
On September 10 2005 a 37 year old woman from Jakarta died of confirmed H5N1. Her 9 year old nephew became sick with respiratory symptoms. Initially he tested postive with PCR. It was later reported that he was not infected with H5N1.
On September 20 2005 a 21-year-old man from Lampung province developed symptoms. On September 24 2005 he was hospitalized; H5N1 infection was confirmed. On October 4, the 4 year old nephew of this man became ill. H5N1 infection was confirmed. The WHO judged these cases not to involve human to human transmission.
On October 19 2005, a 19 year old woman from Tangerang became ill. She died on October 28. Her 8 year old brother became ill on October 25. H5N1 infection was confirmed in both cases.
On November 3, two brothers, ages 7 and 20, from West Java province developed fever and respiratory symptoms. They died on November 11. On November 6, their 16 year old brother also developed fever and respiratory symptoms. He was hospitalized on November 16. H5N1 infection was confirmed in the 16 year old. The 7 year old and 20 year old were not tested for H5N1.
On January 6 2006, a 13 year old girl became ill. She died of H5N1 influenza on January 14. On January 8 2006, her 4 year old brother became ill. He died of H5N1 influenza on January 17. Their 14 year old sister was hospitalized with respiratory symptoms on January 14 2006. Their 43 year old father was hospitalized on January 17 with respiratory symptoms. On January 19 2006, a 9 year old girl from a neighboring village was hospitalized, but later recovered. H5N1 infection was confirmed.
A 12 year old girl from Boyolali, Central Java became ill on February 19 2006. She died on March 1. H5N1 infection was confirmed. Her 10 year old brother also became ill on February 19 and died February 28. He was not tested for H5N1.
Monotreme,
Thank you for giving us the details on these cases. I know of some of these but you have better details.
The most significant one is actually the first cluster. This is no rural poor farming family. This is an affluent family in a big house and garden in Jakarta. The father was a senior civil servant with an office job, the family had no pets, the girl had not gone to any markets, the family had no history of having recently slaughtering chicken, and so on.
After the deaths, there was intense speculation as to how the girl caught the virus. The only hypothesis given by the authorities at the time were a couple of rather lame ones that the virus was found in chicken droppings in the garden (never confirmed) or that the people living across the street had a pet parrot that was H5N1 positive. This latter was again unconfirmed but in any case the family home was large and gated and the girl had never gone across the street to the neighbour’s house.
In most if not all of the other clusters, one can always use the argument of common exposure to an avian source. This is the one cluster where none of the patients had any known exposure at all. So we are looking at both H2H and the issue of infection from environmental source.
Concern about environmental infection (i.e. viruses in droppings, soil etc) is real although data from both Cambodia and Vietnam suggest that such infections have (at least up to end 05) been very uncommon and none have officially been recognized. For the Indonesian cluster, the official answer is ‘we don’t know’.
This and the cluster of the 3 brothers (fifth on your list) also illustrate the issue of unrecognized positive cases, which you and I have suggested for a long time. The suggestion that the CFR should be lower because of under-counting of mild cases has been overturned by the low seroprevalence that we now (finally!) know about from Indonesia and Cambodia. The under-counting of positive cases would mean a higher CFR instead of lower.
In any case, the current official CFR for Indonesia 06 is at an alarming 92% (11 out of 12 dead).
I see more and more threads which I’d like to read but which are too long already. Is this a common syndrome ?
A screen flash on MSNBC this morning said that “Indonesian officials confirmed that a one year old had died of the Bird Flu.” No other details. Now, a 1yo is obviously too young to be tending chickens. Obviously babies are crawling/on the ground a lot and everything goes in their mouths. But, it does make one wonder if perhaps someone else in her family was/is ill?
anon_22: “In any case, the current official CFR for Indonesia 06 is at an alarming 92% (11 out of 12 dead).”
Yes. That is truly alarming. I suspect that in countries, like Turkey, where a lower CFR has been reported, its because of better and more rapid treatment. In Indonesia, we may be seeing what the “real” mortality rate would be like during a pandemic, unless the lethality of H5N1 declines when it becomes easily transmissible. This is our only hope, I’m afraid.
Thank you Monotreme and Anon 22 for the Indonesian reporting.
gs- more people must mean more posting and we can’t keep up with all the reading material. Titles of threads are going to be more important. Sometimes I discover I have been missing a great thread because the title sounded uninteresting.
DennisC- nice idea about the editors of journals, they should get on board!
DennisC,
“editors of journals could just refuse to take articles unless the sequences where posted.”
I wish (and they probably also wish too) that they are as free as you suggest. :-)
But that would also take us down the slippery slope of censorship for political ends. Does the end truly justify the means? Giving the public access to even partial material is still better than not having any.
to summarize:
the Qinghai strain (Turkey,Aserbaidjan,Africa,Europe) is rather stable. The S227N mutation occurred (at least) once in Turkey.
the Indonesian strain is different and evolves (apparantly, although the sequences are withheld). The Indonesian human viruses have another cleavage site than the bird-viruses (all, or most, we don’t know exactly). This is a bit strange and unusual - we had in no other H5N1 so far. Maybe not even in other flu-viruses at all, I don’t know. How can this happen ? Either the viruses mutate inside the humans or only (Indonesian) viruses with that mutation can infect humans, while the mutation is rare in birds.
These strains have not reassorted,recombined so far but there could be a dangerous potential if these strains combine their abilities. I haven’t yet read about this, but what if we change the Qinghai=Africa virus in the cleavage site to match the Indonesian virus ? Has it been examined ?
Government has a reaction time to respond to bird flu clusters. Pick a number - ?2 weeks? Six months ago the cluster sizes were 2 to three people. Now there are cluster sizes of 8 people. This is going from one double to 3 doubles. If it increases to 5 doubles it is not obvious that cluster sizes of 32 in two weeks can be controlled.
Older thread, closing for speed purposes.
check dates