Is it just flu season or something else?

Revere, thank you for giving us your take on recent events. I've been waiting to see what you'd make of them.

One thing I've seen repeatedly claimed is that the sequences of the human cases in Indonesia don't match the sequences from poultry in Indonesia, pointing to a different animal reservoir or h2h transmission. My question is, have the Indonesians had such a turnaround in attitude/behavior that we really have access to poultry/human sequences from the same time and place? Or is this Flublogia lore?

You wrote that if the husband of the dead woman is confirmed to have H5N1, "so much for the 'blood relative' theory."

In an article in the Nov 2005 J.EID, "Family Clustering of Avian Influenza A (H5N1)" (http://tinyurl.com/y834s8), Sonja Olsen et al listed 15 family clusters, in which 3 included a husband and wife pair. (Only two of these pairs had all four members actually confirmed as H5N1+.)

The "blood relative theory" is, so far, too weak to be called a theory. It is an observation, with some reasoning that could support it as a hypothesis (the genetic tendency possibility, for instance).

So much yet to learn, and unlearn, about influenza!

From Path Forward (No relation to "New Way Forward.")

PF: Yes, you are right. I should have been clearer and said, "another nail in the coffin of the blood relative theory" which I have been skeptical of in several posts from the outset.

caia: I believe it is a contention of Henry's, based on some sequence information. The Indonesians seem to be hinting at it, too, as Crof observes in a recent post.

Thanks for this post. The various flu blogs are all covering this.

A couple of points re navigating the details: local press often adds a year, since the convention is to describe the year you're in. Here, you have to get to the end of that year to get credit (you're 10 only after 10 years have passed). A 37 yo here might be 38 years old there.

Also, the 37/8 year old's husband is negative, with the 18 yo son positive. Several reports indicate fowl exposure. I agree there's little H2H data jumping out at us, and details are needed, but it does seem clear that,if nothing else, safe health practices are not being followed in regard to ill or dead birds.

Finally, the press reports a suspected cluster in Bandung, unconfirmed, with a mom and two kids. This bloodline transmission thing remains intriguing.

"A mother and her two children, who were hospitalized in Bandung city, also in West Java, make up the other three of the nine being tested for H5N1, he said"

http://www.bloomberg.com/apps/news?pid=20601080&sid=aR73zJNPLsUw

Dem: Thanks for the update. I also added an update on the father from CP before I saw your comment (was too busy writing a reply to Micahel Fumento; what a waste of bandwidth).

If and when husband and wife are both H5N1 positive, it might be useful to check whether they're cousins.

I am concerned that the negatives in Indo at the moment may be false - esp if they threw Tamiflu at them before testing?
Even in the Canadian Panflu Management Plan it says (roughly from memory)
1. Isolate
2. Tamiflu
3. Test

Well, even if they are false, at least they're recovering. Either we have a whole bunch of false negatives and a considerably lower CFR, or fewer positives. It's good either way, after a macabre kind of fashion.

Juliet...you are such an optimist! Unfortunately I don't think it's a lower cfr: the only reason they are recovering is that they are getting tamiflu, 2 doses a day. What happens if this goes pandemic and the vast majority of victims get no tamiflu?

gharris: exactly the problem, IMO. They have already shown time and again that the tests are unreliable, yet it seems like WHO sticks rigidly with the test results as the only indicator of when to declare a phase 4 or 5.

Let's see, we've got about 56 confirmed or suspect cases in Indonesia since Jan 1st: all of whom have been exposed to either sick poultry (which has tested positive for H5N1 in almost every circumstance, I believe) or exposed to a sick human who has tested positive. Or both. These people are significantly sicker than they should be for ordinary flu (per CDC flu statistics...only about 1 out of a 1000 flu cases get sick enough to require hospitalization), with at least half experiencing respiratory distress - at least 11 severe enough to be put on respirators, (again, way above the statistical odds for ordinary flu) and 4 have died.

Revere: you're an epidemiologist...if there were no PCR tests, and you had to call this one strictly based on epidemiology protocols, what would you say was going on.

MiH: I like to have information before making decisions. If you are asking me for a hunch based on outbreak investigations I'd say most of the negatives are true negatives. That's because there is always a lot of ILI at this time of year and that's what these suspect cases are. But I don't know since I don't have much information.

Well, of course it's because of the Tamiflu, but people die from this thing Tamiflu or no. Isn't that what virtually all of the other patients got?

Revere: Re the new cluster in Indonesia
Revere:

I have a couple of questions.

Apparently the new cluster in Indonesia represents the first incidence of H5N1 in a husband and wife.

Why is this of significance?

Does this mean that the virus is starting to shed some of its virulence?

Victoria: Bloomberg is reporting this but, as Path Forward earlier in this comment thread points out, there have been three other spousal cases reported in family clusters. Here is the link: http://www.cdc.gov/ncidod/EID/vol11no11/05-0646.htm. The information is in the Table which appears as a link in the paper.

The reason it is considered important is because husband and wife are not blood relations (ordinarily). Since many of the family clusters reported so far have been blood relations, the hypothesis has been floated that there is an important genetic component to susceptibility. There may be, but I have argued against it because it would have to be a very strong genetic effect and many of the cases are not that closely related.

The father is now reported to have tested negative so this is not a cluster of 3, but it is still a mother-son cluster.

Testing results for H5N1 reported in the news media have been extremely unreliable from the very beginning up to the present day.

The tests are unreliable and the samples are unreliable.

Tamiflu given to a patient can alter test results to give a negative result.

Follow-up blood testing on those that recover is either not done or not reported.

To judge what is happening now is difficult, but I say it is getting worse and worse by the day.

Preparing a personal plan for what to do when the pandemic blows would be a wise use of time right now.

There is an interesting contrast between the WHO chart you used here and that prepared from WHO and published in Eurosurveillance.

The pattern of seasonality for reported human H5N1 infections shown in the Eurosurveillance chart shows well-defined peaks in frequency during March for both 2005 and 2006.

Which data were excluded from the WHO chart, I wonder ?

REF: http://www.eurosurveillance.org/ew/2006/061221.asp

Revere: I don't know what "ILI" means. However it seems you are indicating that all these cases of flu with heavy respiratory involvement are not considered "information" on which you could base any kind of decision. 60 some odd cases in 2 weeks, half with serious respiratory problems requiring hospitalization, about 20% or more on ventilators...that's not evidence? That rate of complication if these were "ordinary flu" (which is what the "negative" designation implies) would be about 100 times the normal complication rate...that isn't relevant information either?

You are, however, willing to say "The negatives are probably true negatives". Could you please justify your reasoning then? Let's just go with two cases, Praise A - who had high fever and acute respiratory distress for 10 days, a super low leucocyte count and exposure to chickens confirmed infected with H5N1. That's "negative" number 1. She got better after tamiflu. Then Case 2 - U, the husband of Riyah who died after testing positive, father of A who is still in critical and also tested positive. He is the man who slaughtered the H5N1 chickens that started the whole familial cluster. He also was sick with high fever and respiratory distress for a time, but responded better than his wife and son to tamiflu and now tests negative.

Ok, so you believe these are valid negatives. Based on what.

Thailand is now reporting a confirmed outbreak in the northern province of Phitsanulok.
http://tinyurl.com/y5qu6g
and C A Nidom of Airlangga Univ has found one fifth of stray cats are H5N1 positive
http://www.curevents.com/vb/showthread.php?t=67613

mary in hawaii: I don't know what "ILI" means.

Influenza Like Illness (ILI)

Hi - I perked up when I first heard of the husband / wife infection also since prior discussion from multiple sources had a focus on blood relatives arguing for a genetic predisposition to H5N1 infection. However I did read (somewhere that I can no longer remember)that she had butchered a dead chicken and the husband had helped her defeather it. If true, that might have accounted for the dual infection without HtoH (a varient on the tossing around the chicken head story from Asia last year). Also, as a polysci person I would be skeptical of news reports from the area. All the stakeholders now have a vested political interest in avoiding HtoH. At some point they obviously would not be able to cover it up but prior to that juncture there is a lot of room for misreporting both by error and design.

If Yusef/Yayan (Riyah's husband) had flu symptoms but was H5N1 negative wouldn't that be concerning because there is a chance of H5N1 to mix with another strain? Mary's note above if the only reference I have seen regarding him showing any fever or respiratory distress.

In this instance if they were infected by a diseased bird/meal there may be no seasonal flu component. Details will be in the sequences. In some cases negative patients in clusters may just be kindling wood. Having multiple flu patients in the same place may actually accelerate the pandemic virus evolution.

MiH: As SCWAZ Gilmore notes, ILI means Influenza Like Illness, the epidemiologic term for a set of diseases from agents that all cause similar symptoms. You asked for why I thought they were true negatives. The reason is that so far the probability of any ILI being H5N1 has been very small and the probability of any random ILI being non-H5N1 is very, very large. There are many ILIs at this time of year in the community without H5N1 and they go unremarked. There are clusters of ILI all over all the time in flu season, most not even from flu of any kind. I was just giving you my reasoning as an epidemiologist. I could be wrong.

Juliet. Revere can cover herald waves but generally they happen in advance of epidemics. The cases are fairly mild depending on the disease. A couple of cases, then blammo the thing fixes the antigen and off to the races it goes. You can put in "herald waves" into a search and pull up all sorts of ugly good stuff on it. Are we there yet? Sheyit I dont know, its certainly not good as it seems to be deepening in geographic reach, depth into mammals and those guys called humans. Basically a death sentence if you get it right now or you'l be so screwed up you cant move for months after you ge a real case of it from organ and lung damage.

Hi - hopefully this is not a violation of any protocol but I saw this from the Austrailan Broadcasting Corporation on News Now site;

Last Updated 16/01/2007, 00:47:26 Select text size:

A hospital designated to treat bird flu cases in the Indonesian capital says it is being overwhelmed with patients with symptoms of the disease amid a spike of new cases this year.

....snip...

Not trying to be melodramatic - hospital could be full for any number of reasons (e.g., a functioning hospital where you need one) anyway..gets to the problem of non-mis reporting of flu

carl: This is typical of the first days of anything. You can't really tell what is happening. Too many possibilities. That is why preparation is so important, because you are ready no matter how it turns out. If it is just seasonal illness or the worried well, no harm done. If you are ready you are ahead than if you weren't. Think of yourself as on guard on the perimenter of the camp. Your (appropriate) reaction is, "What was that noise?"

fred said: Mary's note above if the only reference I have seen regarding him showing any fever or respiratory distress.

In the indonesia thread on fluwikie there are several mentions between Jan 10-12 of this case, and in at least 3 of them it states that the father had the high fever and respiratory infection. These are direct toggle-text translations from the indonesian news source. If I have time I'll go hunt them up and post them here, but you can find them if you look.

ZoKun: According to WPRO, 2 asymptomatic cases from Vietnam were excluded and 7 cases from Egypt, 8 cases from Indonesia and 1 case in Iraq were excluded because there was no onset date.

The latest toggle-texts from Indonesia (see liputan6) state that they've sent home 6 neg patients from the overwhelmed hospital - they're down to 4.

Here's snips from 3 different news articles on fluwikie that mention the husband of Riyah as being symptomatic. These were all on Jan 11 Indonesia thread. I was not able to pull up the next day thread, but I recall a couple more mentions in there.
-------------------------------------------
Bird Flu May Have Infected Relatives of Indonesian H5N1 Patient (Cross posted in News Thread)
By Karima Anjani
Jan. 11 (Bloomberg) -- Two family members of a woman infected with bird flu in Indonesia were hospitalized with symptoms of the virus, said a doctor treating the patients.
The 37-year-old woman, who tested positive for the H5N1 strain of avian influenza two days ago, remains in critical condition at Persahabatan Hospital in Jakarta, Mukhtar Ikhsan, a doctor at the hospital, said today. Her 42-year-old husband and their 18-year-old son have symptoms of fever and respiratory infection, and are being tested for H5N1.
(next articlesame day)
The child and the husband NY Riah, 37, the positive patient bird flu that currently is treated in the Hospital (RS) the Friendship must menjalanai the maintenance because of experiencing the similar sign.
Yayan, 45,dan Wise, 18, arrived in RS the Friendship around struck 14.
30 WIB by being brought by the Tangerang ambulance of the Health Service.
(Snip)
Samsudin, the official of the Health of the Tangerang Regency of the Service said, compared to his father, the Wise condition very weak.
However the awareness both of them still quite good.
(next article)
According to the official from the Health Service of the Tangerang Regency both of them were carried because when the checking of the environment that was carried out, complained about the high fever, the cough, and crowded.
(snip)
Evidently the husband and his child also complained about this sign, he said.

I remember this, but if you'll look, the father always had a milder case - I guess we'll now never know whether he was really positive or not.

FWIW

On the blood relative thing: I think we need to pay attention to patterns, as well as any exception to patterns.

So is clusters being mostly in blood relatives a pattern? I would say there's a lot of data in that direction, even though not enough to be 'proof' of anything. Is an exception always something significant? Not necessarily. You hardly ever find 100% correlation in any epidemiological data.

In addition, we cannot assume that husband and wife are necessarily unrelated genetically. I looked this up specifically when considering the blood-relations theory, and found that the incidence of consanguinity (defined in this instance as first cousin marriages or equivalent) worldwide varies over a very wide range. While it is generally around 1% or less in most western countries, in the Middle East, Africa, India, and some Asian countries, it can be as high as 60+%. I don't have numbers for Indonesia, but Egypt is one of those with >60% quoted in a lot of areas. One interesting finding, which may or may not shed light on this issue, is that the incidence for the Han, the majority Chinese population, is around 1%, but is much higher in some minority groups eg in Sichuan. Souce: http://www.consang.net/

Now this may not mean anything, or it may mean potentially a higher concentration of some recessive traits such as a rare HLA type which could affect response to infection.

A caveat: even if true, this doesn't mean the virus is limited only to those with some sort of genetic susceptibility. Given enough chance to circulate within susceptible populations, which still have huge genetic diversity, whatever barrier there might be currently could be overcome by adaptation.

Go here http://news.bbc.co.uk/1/hi/programmes/newsnight/4442010.stm for an excellent report on cousin marriages in the Pakistani community in the UK and the high incidence of rare genetic disorders.

Quote: "British Pakistanis are 13 times more likely to have children with genetic disorders than the general population - they account for just over 3% of all births but have just under a third of all British children with such illnesses."

sorry, more on the bbc programme. Pay attention to the girl who has fragile skin. Both her parents and grandparents were first cousins. I wonder how long this tradition has been ongoing, and whether Indonesia has the same tradition, maybe because of common religious influence?

anon_22: There may be something to the blood relation thing, but it doesn't seem biologically reasonable to me. Even parents that may be first cousins don't share that much, on the one hand, and most people share almost everything on the other. If there is an inherited factor, rather than, say, the patterns of exposure that make certain family relationships more likely to share them than between spouses, it would have to be a pretty strong factor, which again, doesn't seem reasonable to me. Like everything else, we'll have to see. Everyone wants an answer about everything right away. It takes time and data and we may never have either.

revere,

Sure. The point that I'm making is not to assume no genetic relationship between spouses, that's all.

Hmm, a point of fact: a theory is a reliable, scientific explanation of observed phenomena. A few examples: Theory of Gravitation, Theory of Relativity, and Quantum Mechanics. Should we be using the term "theory" to actually mean supposition or hypothesis?
Thanks,
John

John: Not quite so clear cut. First, theory has a well accepted colloquial use, which is what I was using. But philosophers of science have not agreed on what a theory is, and in my field, the difference between a theory and model is hazy, too. In my usage and teaching, when I portray science in a hypothetico-deductive framework (not the only one, but for these purposes adequate) I take theories to be systems where the meaning filters back from the observables to the unobservables, where models go in the reverse direction. Thus quantum theory, but the Bohr model of the atom. Anyway, I'm comfortable with my usage but I take your point.

There's a news report out of indonesia that 100 out of 500 stray cats in a wetshop distrcit of Jakarta have positive serology for H5N1.

This could be that 'missing link' host that several bloggers have been speculating about for several months.

Also reports of 100 indon cats testing
positive for H5N1 at..
http://www.nst.com.my/Current_News/nst/Tuesday/National/20070116084009/…

Lisa the GP:

I have seen this news item. Does "positive serology" mean that the cats tested positive for antibodies (ie., previously infected but survived) or that they are currently infected? And if the latter, does this mean they are not getting sick? I find it difficult to believe 100 infected cats and not some significant number of them dropping dead before the scientist could put them back out on the street--or, at least being very sick.

Thanks.