Effect Measure

Indonesia registered its 51st official case and 39th death this week, a 13 year Jakarta boy who had helped his grandfather slaughter sick chickens, took sick a week later and was dead less than a week after that. There’s more discouraging news from this benighted bird flu hotspot.

The Indonesian Ministry of Health says the people in the village where the large family cluster with human to human transmission have refused to be tested or have their chickens tested. WHO has been saying repeatedly that there is no evidence of infection beyond blood relations in this cluster (Jakarta Post). If many villagers refused to be tested, how informative is this statement? Does it mean that all plausible contacts have been tested and found negative or does it just mean that they don’t have evidence? We also learn that the virus from the family cluster did in fact show some mutation, despite earlier denial by WHO this was so. WHO statements were reported in various ways, including “no significant mutations,” but they have done little to clarify what they mean. Now the line is that the virus isolated from one of the cases has changed but not in any “major” way. Presumably this means it is not a reassortant. What else it means is unclear, since we are still in the dark about the changes that would signal enhanced transmission probability between people.

Keiji Fukuda, WHO’s coordinator for the Global Influenza Program in Geneva, said the Indonesian case appears to resemble other family clusters where limited human-to-human transmission occurred following close contact. He said scientists must find out whether anything is different about the way the virus is behaving.

“The really critical factor is why did that cluster develop?” he said. “What’s the reason why people in a cluster got infected?” (AP)

How do they know the changes seen in this virus are not related to critical factors that allowed the cluster to develop? What are the changes that were seen and why aren’t the sequences being deposited in GenBank? If it is the Indon government preventing this, let’s hear it. If it is scientists or WHO or some laboratory dragging their feet, let’s hear it. We”ve tied to be understanding here and I think we’ve cut WHO quite a lot of slack. But our patience is at an end.

Meanwhile the bad poultry infection we thought we knew about turns out to be worse than we thought.

“We thought there was dramatic underreporting, but we never imagined that it would be so pervasive,” said Tufts University’s Jeff Mariner, who is working with the U.N. Food and Agriculture Organization in Jakarta.

He spoke on the sidelines of a three-day meeting that wraps up Friday in the nation’s capital attended by some of the world’s top bird flu experts.

Mariner is coordinating an FAO program that trains local surveillance teams to conduct field interviews with farmers to track backyard poultry that have suddenly died. The teams then use bird flu test kits to identify whether bird flu is to blame.

In the 12 pilot districts on Java Island, the teams detected 78 poultry outbreaks from January to May — roughly one in every 10 interviews resulted in bird flu, Mariner said. He added those numbers cover only about a third of each district due to a lack of manpower needed to conduct the interviews.

“Leaders are now realizing, ‘Boy, this is just the tip of the iceberg,”‘ he said Thursday. “Whereas before, district leaders were saying, ‘Well, we don’t really think we have it.”‘

There are plans to expand the project to Bali and Sumatra islands, but Mariner said the virus will continue to spread unless Indonesia can devise a coordinated approach for local governments to work together to control the disease.

Slaughtering and vaccination are now currently sporadic at best and often outbreaks in poultry are not reported until a human case is discovered.

“It’s gonna be a long struggle,” Mariner said. “It’s 300 million poultry … and it’s a rapid turnover in the population. Essentially, you get an entirely new population after six months.” (AP)

So the Indonesian news comes in three flavors: bad, worse and uninformative. WHO (or whoever has control) needs to release the sequences to GenBank. No one believes WHO’s characterizations any more. Their credibility is going down the toilet.

Comments

#1 Spence - Future Health Solutions
June 23, 2006

Given the apparent change in the improved human-human transmission, as well as WHO putting Roche on notice for their Tamiflu stockpile and the U.S. rushing a Tamiflu stockpile to an “unidentified Asian country”, this is not a surprising development. Many signs were present that the strain from the large family cluster in Indonesia had changed in some way (continued key cumulative mutation pathway)

Hopefully they will also release the genetic sequencing, so a broader group of scientists can be involved in researching the impact.

What is most disappointing, is that it took almost 7 weeks after the outbreak, before WHO finally admitted there was a new mutation. After using language such as “no significant mutations” to describe the strain found in the large family cluster.

I understand that they need a balance between sharing information and not panicking the public. However, we need much more rapid reporting of new findings, as well as stronger transparency from all countries (and academic and public health entities as well) if the world community is going to be able to adequately understand this virus and prepare appropriately.

Time to get off the soap box, but given the seriousness of the threat, I would expect better behavior from many of these groups.
#2 revere
June 23, 2006

Here’s our general principle for releasing information: Most people can handle the truth.
#3 Kevin
June 23, 2006

Layman opinion: genetic susceptibility is more likely factor in the this cluster than a mutation. All victims were related by blood to the index case. Multiple other family members not related by blood, and HCW, were equally exposed, but no known transmission occurred. If there was virulence related mutation, why did the cluster die out?
#4 Greenhammer
June 23, 2006

The guys running Indonesia say they need $50 million right away to track the disease in birds, and about $900 million over the next three years for surveillance, education, etc.

Where’s the money?
#5 revere
June 23, 2006

Kevin: If this were a susceptibility factor it is a pretty strong one with high penetrance among people not so closely related. I’m not sure they have properly estimated the secondary attack rate. Time will tell.

Greenhammer: The Indons also want a pile of money to buy submarines. It’s all about priorities. I think they have a big cultural problem culling birds. It’s like culling cats and dogs in the US. Not easy to get people to do it.
#6 Dan
June 23, 2006

Revere, I’ve heard this cats and dogs analogy before. I grant the emotional impact of culling family chickens but unlike cats and dogs, there is an important financial aspect that is the center of the Indon bird culling issue. If the Indon government is not reimbursing families for their culled birds, reporting sick birds becomes a real economic threat. And even if they are reimbursed they would likely be quick to replace the culled birds, but from where? Their local neighborhood chicken dealer, whose birds may also have been compromised?

IMO, what’s needed to get a handle on this is a comprehensive program that addresses the economic realities in the villages (including the whole fighting cocks issue).
#7 revere
June 23, 2006

Dan: Well, another way to say it is that there is an economic issue in addition to the place birds have in Indon culture, not instead of. It makes it all the harder. Properly compensating farmers is a necessary prerequisite to a successful culling program, but in this case I doubt it would be sufficient.
#8 Pet Person
June 23, 2006

Reimbursement to these people for their culled chickens is critical to the stability of the country. As a poster pointed out though, the citizens will have difficulty replacing their birds (or pigs if necessary) with healthy stock. What is needed is an alternative method of producing food and income for these people. A thoughtful poster to another forum suggested that rabbit farming might be a suitable activity to replace the chickens. Implementing alternative agricultural programs would be a help.
#9 Healthbizz
June 23, 2006

I triple underline Spence’s remark about it taking 7 weeks “before WHO finally admitted there was a new mutation.” (quoting Spence) I remember reading about the family members, how quickly many died, etc. and thinking, ‘this is trouble.’

On a slightly different but still generally related subject, had a great interview yesterday with the head of Canada’s animal ‘bird flu’ task force, Dr. Jim Clark. Those experts here won’t learn much but he was quite articulate about the P.E.I. situation, their testing, why tests can take so long, etc. A good primer for someone trying to learn the differences between viral severities, transmission methods, and the like. J.U.
#10 JJackson
June 23, 2006

This whole charade of data release just slides from incompetent to criminal.

I think there is little doubt that the only reason the WHO came out with an admission of h2h was that they had seen from the sequence data that the father had been infected from his son. I think this also precipitated the Tamiflu move on the 22 of May and that the “no significant mutations” spin was also crafted in light of incontrovertible evidence of h2h. The bigger cluster with more extended timelines in Turkey only provoked convoluted b2h explanations. They have no idea which mutations are significant. With a few notable exceptions re drug resistance & cleavage sites etc. the complexities of the interactions between mutations across the RNA strands is largely guesswork.

Release the data you don�t know what you are doing, someone else might get lucky.
#11 Mats
June 23, 2006

I am currently in Indonesia and have spoken to a number of laboratory workers and veterinarians. I think that our impression of the situation in Indonesia is not entirely accurate, but this is only my opinion after being here one week.

The veterinarians and diagnostic laboratory scientists have not experienced cultural problems in terms of disease reporting; this could be because they are working with a more informed populations or different sector. I gather that there is a large spectrum of people and many people live in the big cities and may be more informed and thus willing to report. Diagnostic laboratory scientists told me that they are getting more reports because people are becoming more informed. They do some surveillance and told me that 20% of the animals tested positive.

Government officials who don’t seem to be well informed but seem eager to learn more. I am not sure why he did not know some of the basic information we were discussing?

Scientists in Indonesia have a big problem with getting scientific publications, because of cost and lack of internet access. These people are getting a lot of data but do not have the capacity to generate publications.

Regarding sequence information, only a few labs have sequencing capacity. A primary scientist in one of the sequencing facilities told me that they send the sequences and or specimens to flu labs (in the US) and thought that the sequences were being made publicly available.

The diagnostic laboratory that I visited has no idea that Genebank exists and didn?t realize so many people were interested in their data. They also send their sequences and samples to prominent flu labs (not in the US). The scientists are just doing their job and have little idea of what is going on outside their lab. I told them that they would be amazed at how many people would love to have access to their data and they seemed so surprised. I had only a short time with them and tried to convince them to publish or make their sequences available. I am not sure I was able to effectively convey the urgency to them due to the language barrier. I will be here another 5 days and am visiting more laboratories as well as others involved.
#12 Jun
June 23, 2006

…why aren’t the sequences being deposited in GenBank?

Release the Sequences Petition:
http://www.petitiononline.com/h5n12006/petition.html
#13 revere
June 23, 2006

JJ: You can’t tell from the sequence data that the father was infected by the son. That is based on epidemiological data (time sequence). So, yes, there is big doubt that is the reason.

Mats: Sequencing isn’t done in Indon at all as far as I know. It is done either in Hong Kong at Peiris’s lab or CDC, depending on source (Indon lab or NAMRU2). Indon is a complex country with many ethnic groups, some very distrustful of the central gov. The village in North Sumatra is in an area with many Christians and they are very distrustful of the central government.

The GenBank issue is for the sequencing labs and you can be sure they know all about GenBank. But the Indon gov. may also have to give consent to deposit these sequences and they lie through their teeth about this.
#14 Mats
June 23, 2006

The Eijkman Institute for Molecular Biology has three sequencing machines and sends their data to a US lab (not the CDC). They are progressive and seemed sincere, but perhaps I am being naive.

The individuals in the diagnostic laboratories were scientists who were basically collecting data and testing samples. They have little access to the outside world and don’t even have current text books or electronic journals. They try to get free publications when they can, so are largely uninformed. They honestly acted like they had not even heard of Genbank?
#15 tympanachus
June 23, 2006

Spence: “~release the genetic sequencing, so a broader group of scientists can be involved in researching the impact.”

Kindly allow me to inquire one more time (last was lost in the Kruger genocide flap) just who might compose this broader group of interested scientists? I’m all for getting Henry Niman more data but who might these other deprived scientists be?

I can understand the WHO (& CDC, et al.) not wanting to be bothered by every amateur (or pro) sequence flogger who doesn’t subscribe to their reassortment/random point mutation mantra. They might actually have to escape from the iron bounds of doctrine and dogma to spend some time answering/refuting pertinent (or impertinent) attacks on their sacred position. Their theories may in fact be true but their refusal to debate them and the implications of the proposed viral evloutionary schemes by holding the sequence data closely is unethical, if there are other “qualified” researchers.

Niman may or may not be qualified but the history of science, particularly medical science, shows that noisy friction often precedes the change of long held explanations of nature. Henry may be a tad rough but style (personality, pedigree and mode of scientific engagement) should not be an important component in determining bona fides, though I realize that may perhaps be the norm.

So, is this just a “none for you Henry” situation or are there also others they are virtually refusing to debate?
#16 revere
June 23, 2006

Mats: Is this lab actually sequencing H5N1? If they are, I am surprised to hear it. I’m not sure how someone could be trained and adept at sequencing and not have heard of GenBank.

tymp.: This isn’t a Henry Niman issue. This is matter of principle. These sequences need to be available to the worldwide scientific community. There are many ways to analyze the data and too little time to do it. The more people working on it from different points of view the better, not because it will help us in the short run (something I doubt) but because in the long run it is the right thing to do. Hoarding these sequences now is beyond the pale and I am surpised that reputable flu scientits haven’t figured out which way the wind is blowing. You don’t need a weatherman . . .
#17 revere
June 23, 2006

JJ: Earlier (5:33 pm) I commented to you that the sequence data couldn’t tell whether the boy had infected his father. I have now seen news reports that suggest how this was done, so you were right and I was in error. Live and learn.
#18 tympanachus
June 23, 2006

revere: “This is matter of principle. These sequences need to be available to the worldwide scientific community. There are many ways to analyze the data and too little time to do it. The more people working on it from different points of view the better, not because it will help us in the short run (something I doubt) but because in the long run it is the right thing to do.”

Can’t argue with this but are there any out there besides Henry who are waiting on sequences?

Like Prospero: “I can call creatures from the vasty deep.” Aye but will they come?
#19 revere
June 23, 2006

tymp: There are many flu researchers who look at sequences. Even I have an interest in them, although it is not the same as Henry’s. Henry is a bit player in all this, although he looms large on internet boards. I don’t mean to take anything away from him, except that there is a vast community that looks at sequences.
#20 Tom DVM
June 23, 2006

Mats. I don’t know how you found yourself in this position but the information you have forwarded is vital. Please, keep up the good work!! and Thanks.
#21 tympanachus
June 23, 2006

revere: “~there is a vast community that looks at sequences”

Well, maybe they should make themselves heard if their H5N1 sequence buffer is empty and they’re feeling as exposed as the rest of us. I don’t see them commenting on Declan Butler’s blog or writing letters to the Journals or whining on Fox (I suppose they could be there – I don’t watch Focks) or the WSJ. Are they gathering around Ilaria Capua? Maybe they don’t want to rock that sacred boat.

Let’s hope there’s a bit player somewhere that will get us out of this jam after we’ve shamed the hoarders into being more forthcoming.
#22 GaudiaRay
June 24, 2006

Might someone here draft an informational letter to Indonesian labs doing the work, inviting them to post their data at GenBank?

If this letter were posted here and then translated by a reader here, it could be posted to the named individuals at the probably dozen or so labs in the entirety of Indonesia.

As I’ve observed before, though probably not here, Jakarta has more in common with Los Angeles than it does with Karo or any of the Indo countryside. Only the major population centers, no more than six to ten total in all of Indonesia, host those diagnostic facilities.

So, 10 letters informing and inviting may do as much as the Petition, this being said, in no way do I wish to detract from the continued posting of the Petition for Full Disclosure of Sequences.
#23 tan06
June 24, 2006

I have posted an e-mail to the WHO Influenza Centre National Institute for Medical Research in London,
although maybe not at the right person, but he may pass it to the others there

Email ahay@nimr.mrc.ac.uk

to thank them for the publication of 8 gene segments of 4 human isolates from Turkey (see Niman at:)

http://www.recombinomics.com/News/06230603/H5N1_S227N_Turkey_Cases.html

When someone drafts an informational letter to the Indonesian laboratories, I have Indonesian neighbours who can possibly translate the text.
#24 Mats
June 24, 2006

Eijkman may or may not know about Genbank. They started sequencing by doing forensics work and are now doing AI work. The people at Eijkman thought that thier US collaborators were sharing the data? I am fairly confident that most individuals in the smaller disease investigatons centers are not aware of it.

I met with an university scientist today who has been studying AI. He indicated that the lack of transparency may be caused by the government, so I don’t know how this would affect trying to get data from these small labs. They really need someone to help them interpret and analyze their data because it is clear that they can’t do it alone. The university scientist is starting some rudimentary epidemiological studies on other mammals but his laboratory does not have the personnel or resources to undertake large studies and produce results rapidly.

The Indonesians do not currently have adaquate laboratory capacity. Their scientists are bright but lack the resources to present and publish their data in major scientific journals.
#25 revere
June 24, 2006

Mats: OK, here are two questions. Who is actually sequencing H5N1 isolates in Indon? What do they do with the sequences? I had not heard anyone was actually sequencing H5N1 in Indon but I would be glad to know if that is incorrect.
#26 Mats
June 24, 2006

A variety of overseas labs are doing the sequencing, through “collaborations”. I believe the Indo facility is doing some but I don’t know the source. From what I understand, the small labs get some of the sequences back but again, they don’t have the capacity to publish or analyze. I apologize for not being more specific.
#27 Marissa
June 25, 2006

Mats: If the scientists at the Indonesian lab need help in getting info or help with papers or manuscript, this is what we do in our day jobs with many of our clients. Just e-mail me and let me know what we can do to help.