Continued from this thread here .
Using something similar to Nieman’s way of thinking it would appear that when there is a cluster of cases, the distribution of cases should cross bloodlines approximately 50% of the time. It could be expected that in a cluster of four or more people about one half of the cases should be on either side of the blood line.
I selected all clusters with at least four cases from Monotreme’s data and found 10 clusters with at least four cases. I reviewed the cases to determine how often a case occurred that was not related by blood. The numerator is the number of people who are or are likely to be related by blood. The denominator is the total number of cases.
4/5, ¾, 4/4, ¾, 4/5, 4/4, 4/5, 3/6, 2/4, 7/8 (the last is the current case in Indonesia and I am not sure of the denominator.
In 8 of 10 clusters the virus was apparently located on one side of the bloodline.
I also noted that with the addition of Indonesia there are not two but three cases in which the mother and father were both infected.
The use of percentages would not be appropriate in this type of review because of the small numbers in each cluster. It would appear based on all ten clusters, that the virus is found (on average) about 75% of the time in one side of the family. In only two large clusters was the virus found to cross the bloodline 50% of the time.
I have assumed that aunts, uncles (and their children) as well as grandfathers are related by blood. This may or may not be true.
I tend to agree with Racter that Niman’s reasoning is faulty in so far as he only considers infected cases and not idea that one could reasonably expect that all members of a family would be infected given the virulance. None-the-less, for the sake of the argument I have assumed reasoning similar to Niman’s with the attendant problems.
When I use a facsimile of his reasoning there appears to be a blood line connetion. I use this term because I am not persuaded that it is only genetics that drive the infection.
My apologies for spelling Niman’s name.
Spelling errors are NOT a cause for concern.
JoeW—Your ‘statistical’ case isn’t very strong. In particular, your assumptions about second-degree relatives are pure speculation. Also, there may be significant bias in the data due to gender differences in caregivers and food preparers. It seems significant to me that the death of the father who took care of the son occured after the mother had already died, and there was nobody else to care for the sick child, particularly because the neighbors and other relatives were too terrified to take him in. You just don’t know enough about the realities of family dynamics to say much about why certain patterns of exposure are occurring. You really need a diary for all concerned with details of who stayed in what house when to unravel the transmission chain, and we just plain don’t have it.
Hi everyone. It’s been an interesting discussion so far with good points brought up by everybody.
On the genetic predisposition being the reason for the clusters. I think my point earlier on was that H5N1, in it’s immature for not very well adapted, has shortened the infectious period from what would be expected in other seasonal influenza’s.
If the person is not infectious until after they are clinically ill then this narrows the potential contact susceptible population that can be infected by H-H spread.
I think what is confusing us is that the whole susceptible population in the early stages is made up by family…if I am very sick and go home to bed, the only ones who will contact my illness will be my family until I decide to go to hospital…but if the infectious period is shortened the other way to so that respiratory spread does not occur in late clinical cases and the only spread at that point is due to body fluids…then we would not expect spread to hospital workers who are specifically trained to avoid infections by body fluids.
The fact that more healthcare workers have not gotten the infection is only because the respiratory period of spread is over by the time the patients enter hospitals.
This is my opinion and I may be wrong. The point is that this is an intermediate stage in the evolution and adaption of the virus. It could change tomorrow morning to be more fully adapted and spread out that respiratory spread interval and at the same time produce more efficient shedders…more super-shedders like occured with SARS.
If this happens then the next stop is a full blown pandemic and I believe the virus is now set up to do exactly that…I wouldn’t take any comfort whatsoever in the limited nature…
…H-H-H-H is nothing to sneeze at (pun) and represents a significant improvement in evolution to the viruses final goal…now, if we could just figure out what that final goal is…
wetDirt:
That’s true, but it swings both ways. The data are not only sparse, they’re dirty, and we’re all trying to make the best of what we’ve got. Humans are equipped with fine sensitivities to patterns; perhaps too sensitive sometimes — but here, we are compelled to let those sensitivities play freely with the data. It’s like watching a vague form looming out of mist and darkness; some see an elephant, some a circus wagon, others a Sherman tank. For my part, I’m not arguing that genetic predisposition is THE reason for the clusters, but rather that it plays a role. I am willing to consider that it may be a strong role, regardless of whether the route of infection is B2H, H2H, or H2H2H2H (or pig2H, or cat2H, or whatever).
Hi Racter. Just thought I would mention a couple of things…by the way, I see you haven’t lost your skill with the English language…and I am still chuckling over that quote.
I believe that a genetic predispositon may play a role but it would be in the index case infection. H5N1 likes higher body (lung) temperatures…so I assume a person with an abnormally high metabolism rate would be more prone to infection at a immature level of adaption by H5N1. However, the same conditions could also be produced without the genetic predisposition by a child concurrently infected with another influenza which would raise the child’s body temperature accomodating H5N1’s weakness for higher body temperatures…also allowing re-assortments with seasonal flu’s.
As far as the secondary (H-H-H etc.) infections, if the only susceptible population happen to be family members, which I believe is the case with narrow and late respiratory infectiveness, then it would give the false impression of a genetic predisposition to family members. The reason for this may be the interplay in the respiratory infectivity and body fluids infectivity.
How can we prove this is the case? Well, I don’t think the virus has much more adapting to do to produce a pandemic…and the virus is consistently and steadily adapting. As a result, the respiratory infectivity period must widen and when it does we are going to see community illness and much larger clusters over longer periods of time in the range of 50 - 100 persons. The community illnesses will prove that the genetic predisposition was situational. This could be occuring as I write or could occur anytime. This would be the last adaption before a pandemic. The window of opportunity (pandemic) for the virus should open in about Sept. 06 and stay open until June 07.
bumped
I see now why Niman does not like host genetics and infectious disease. It threatens his favored recombination approach. So much for his logic re incidence in relatives in a cluster. Who is engaging in Hocus Pocus ? Intellectual dishonesty is not appreciated. See for instance:
Genetic susceptibility to infectious disease by Segal, S. and Hill, AV. http://tinyurl.com/8gs6u Human genetic variation is a major determinant of susceptibility to many common infectious diseases. Malaria was the first disease to be studied extensively and many susceptibility and resistance loci have been identified. However, genes for other diseases such as HIV/AIDS and mycobacterial infections are now being identified using a variety of approaches. A large number of genes appear to influence susceptibility to infectious pathogens and defining these can provide insights into pathogenic and protective mechanisms and identify new molecular targets for prophylactic and therapeutic interventions. Immunogenetic associations with infectious diseases have considerable potential to guide immunomodulatory interventions and vaccine design.
Host Genetics of Infectious Diseases: Old and New approaches Converge by Adrian V.S. Hill University of Oxford, Oxford, United Kingdom http://tinyurl.com/jzhs4 Our understanding of the variation in individual clinical responses to pathogens has become increasingly relevant, particularly in the face of new emerging epidemics as well as the increasing number of multi-drug-resistant organisms. An effective immune response to infection has contributed to the development of host genetic diversity through selective pressure, with an increasing number of studies characterizing the role that host genetics plays in disease susceptibility. Knowledge of the role host mechanisms play in the pathogenesis of infectious disease can contribute to the design of new therapeutic strategies. Rapid advances in the field of human genomics offer great opportunities for adopting this approach to find new insights into pathogenesis. Influenza 101 by Dr. Mark Loeb, Associate Professor, McMaster University http://tinyurl.com/zhgle Dr. Loeb closed his remarks by stating that more research is required to understand viral and human host genetics underpinning transmission and pathogenesis of influenza, as well as human influenza transmission and community spread, particularly in children and individuals in health care settings. And there was a conference titled: Determinants of Host Resistance, Susceptibility or Immunopathology to Pathogens: Integrating Knowledge from Experimental Models to Human Disease (J2) http://tinyurl.com/oapxr There were 605 references in Google to “Infectious disease” “host genetics” influenza
The statistical case as described by Niman is not string but it is present i the face of his unreasonable constraints. The prior thread (part One) indicates that there is some form of host resistance / susceptibility.
If I could find this information on the web with less than 20 minutes search time, I think that a qualified virologist would certainly be aware of the idea that hundreds of his colleagues (600 odd references on Google) are actively pursuing host genetic susceptibility. I counted 82 presentations at the conference referenced above. Some people may have had more than one presentation. While one might disagree with the work of other scientists it is intellectually dishonest in a public forum made up of people from all walks of life to misrepresent the state of the science and then belittle the efforts of others with the use of misdirection.
Am I angry - yes and Niman has zero credability for integrity with me.
Joe:
I don’t think it does, necessarily, but I think I can see why you would think he would think it would.
String?
string = strong when you type too fast.
I guess spelling errors sometimes ARE cause for concern.
Better typing would add to clarity for all of us.
Yeah, they can be :-) Gave me fits trying to sleep last night because the numbers just seem to indicate that something is going on with regard to suceptibility from an exploratory analysis. For all my musing I did learn that there are a lot of people out there who are concerned with this topic and that is good becasue I sure could not do the work.
Bump
The Indonesian cluster includes a husband and wife, which places the genetic score at ZERO. The genetics story is designed to reduce concern about H2H (can only happebn to a very few people who have an odd genetic make-up) and explain H2H in clusters.
It is hocus pocus.
JoeW – at 15:54 , 23 May 2006
‘’I selected all clusters with at least four cases from Monotreme’s data and found 10 clusters with at least four cases. I reviewed the cases to determine how often a case occurred that was not related by blood. The numerator is the number of people who are or are likely to be related by blood. The denominator is the total number of cases.
4/5, ¾, 4/4, ¾, 4/5, 4/4, 4/5, 3/6, 2/4, 7/8 (the last is the current case in Indonesia and I am not sure of the denominator. ‘’
can you post the data of these 49 cases and the relationships ?
It’s not clear to me how you determine the number of people related by blood.
It would be important to have a list of all members of the clusters
how intense their contact with infected members was and how severe their
illness was, if any.
In addition we have no data on the size of the genetic pool in a small and possibly remote village. That is to say how can one speak about genetic susceptibility witout a gene map of the individuals concerned. What are the marrige practises? If genetic resistence to disease follows the same complex path as geneticaly inherited disease, then we can not honestly seperate genetic predisposition from social susceptibility. It seems to me that it is just hocus pocus.
The “no examples of infection of husband and wife” is used as proof that a genetic susceotability to expain the familial clusters. The clusters are considered an anomoly because it is very hard for the general population to get infected by H5N1. This resistance seems to break down in clusters because there are two or more infetced even though such infections are thought to be VERY rare.
However, the “evidence” isn’t real. The latest Sumatra cluster includes a husband and wife (of the 10 year old nephew) and the Haiphong 5 included husband and wife. Similarly, a nurse in Vietnam was infected by his patient, again showing that clusters can include members that are not blood relatives.
Moreover, most clusters are small (2 or 3 members) which limits the chance of infection of both husband and wife, who are the only non-blood relatives in the family.
niman:
I don’t think that’s a fair characterization of the position you’re arguing against. That there are so few examples of clusters involving both husband and wife strongly suggests that genetic predisposition to susceptibility plays a strong role.
When I first saw you make that argument, I thought to myself: “Well, Henry can’t be taking much time to sleep these days, and so might easily be forgiven for the occasional brain fart”. But if you intend to stick with that, I think a few of us would appreciate it if you would walk us through the logic you’re using there. Why couldn’t a cluster simply get larger?
Hi everyone interesting discussion. I wonder how many times in the past thousand years scientists have been sitting at a table or on a rock debating and discussing the nature vs nurture (genetics vs environment) argument.
JoeW…I believe you are a professor and Racter you sound like a professor…and I am the bum that used to sit in the back row, hoping not to be noticed so it gives me great pleasure to say…
…in this situation I would put the three of you at the head of the class and make you debate your opponents position.
To be honest, at this point I don’t understand anyone’s points.
I guess I should discuss a recent analogy. H5N1 by all appearances, is only infecting genetically susceptible people in small genetically susceptible family units…and that is just the point…it looks to good to be true and we have been around enough to know what appears to be too good to be true…usually is.
In the 1980′s AIDS was only infecting gay men in small isolated groups. At that time, the argument was made that gay men were genetically predisposed and heterosexuals were not at risk…women couldn’t get it…and from the epidemiological data at the time, the argument made perfect sense…except it was completely wrong.
I would ask you to consider that if the virus only has the opportunity to infect family members…and it does…then this may give the appearence of genetic factors…the genetic predisposition could be true…but it may also be only an illusion and as the virus continues to adapt it will be seen in the wider community.
History(1918) has clearly shown us that H5N1 can overcome any limitations restricting its develpment at this late intermediate stage of adaption.
let’s cooperate to collect the data and make a serious statistics
Tom:
If it makes you feel any better, my level of concern remains about the same whether genetic susceptibility is accepted as the best explanation for clusters or not. The upside would be that it would indicate that the virus has not already developed better H2H transmissiblity. The downside would be that it may already be better suited than we thought to exploit whatever susceptibility already exists. It might even be that some genetic groups are even more vulnerable than those in which the clusters have occurred to date, but simply haven’t yet encountered the virus. If that is the case, exposure might result in sustained H2H within those groups, providing the virus with greatly increased opportunities for evolving to a full-fledged pandemic strain.
That’s what I meant by “dirty data”. To obtain clean data, we would need to perform experiments using human test subjects. Any volunteers?
From Monotreme’s clusters on the Wiki
Country, Date, N(in cluster), Relationships (girl, boy : no obvious relationship), I think the index case is listed first.
Thailand, 9/04, 4, Mother, daughter, aunt, aunt’s son
Viet Nam, 2/05, 4, brother, sister, grandfather, nurse
Turkey, 1/06, 4, bro, sis, sister bro
Indonesia, 1/06, 5, sister, grandfather, sister, brother, father
Azerbaijan, 3/06, girl, cousin, cousin’s brother, girl, boy, girl
Egypt, 00/06, 4, sister, sister, girl, girl (girls may be in other geographic areas)
In four of ten clusters, the virus is known to cross the bloodline.
In six clusters the virus appears to be in primarily one side of the family with one or more outside people infected.
Twenty seven clusters were reviewed: Parent child relationship n=11 (mother / child relationship n=5) Sibling to sibling n=15 Uncle or Aunt to or from a nephew or niece n = 4. There are 87 people in these clusters and 77 of them appeared to be related by blood (including aunts and uncles) 77/87 = 88% of the people in a cluster are related to another person in the cluster by blood.
Another way to look at this is that in 23/27 clusters (85%) only one parent was infected. How often the other parent was available for infection is not known.
The numbers were supposed to be a pound sign indicating that mother and father had both been infected. I gies PHP doesn’t like the pound sign.
Tom with reagrd to the significance of all this allow me to quote Adrian Hill, Oxford University in the post at 23:26
“Knowledge of the role host mechanisms play in the pathogenesis of infectious disease can contribute to the design of new therapeutic strategies. Rapid advances in the field of human genomics offer great opportunities for adopting this approach to find new insights into pathogenesis”
He says it elegantly. My concern is with the identification of people who might be particularly susceptible and/ or the identification of environmental or behavioral variables that might contribute to catching the flu. Knowledge of these matters might save some lives.
Hi Joe W. Thanks for putting all these numbers together. I know that you’re headed in a direction with these but I am dense.
Could you explain from me what your conclusions are?
Thanks the whole discussion has been really interesting.
In fairness to Niman’s position there are 15, two person clusters and four, three person clusters. 19/27 (70%) of the clusters are composed of two or three people. Obviously there is some substance to his point.
None-the-less there is also a high level of blood relationships. In 13 (48%)clusters siblings are infected and neither parent is infected thus in most of these cases (ages were not considered at this time) the caregiver was not infected.
Knowledge of the role host mechanisms play in the pathogenesis of infectious disease can contribute to the design of new therapeutic strategies. Rapid advances in the field of human genomics offer great opportunities for adopting this approach to find new insights into pathogenesis
Sorry Tom I got a double post from my clipboard. It should have read:
My conclusion to date:
1. There is something that needs to be seriously studied with regard to biological relationships of the people in these clusters. The virus is too often on one side of a family. When the infection is sufficiently intense (?) the other parent is also infected at times. Consider, only the mother and a son were infected in many of these cases. What wasn’t the father infected? Caregiver role is not a sufficient explanation. Approximately, 48% of the time a sibling but not a caregiver was infected.
2. Because the clusters are primarily composed of family members there is a need to study the environmental conditions that would lead one family to acquire the disease and other families in the same area to avoid the infection.
3. What behaviors are some members of the family engaging in that lead to infection while other members of the family are not infected.
JoeW
Sometimes it is incredibly hard to get things in focus. I’ve been trying to figure out a way around this argument.
Genetics may play a role…bad luck may play a role.
So here’s the thing. If I randomly selected similar families in similar areas and innoculated one member with high doses of H5N1, I think I could find a method to produce consistent clusters. Now hypothetially if that was the case then bad luck would play a greater role than genetics unless the whole population in the area were genetically predisposed per Racters earlier comments.
I think the unique nature of these infection patterns is due to super shedders shedding high loads of virus at times when only their families are around them…little beforehand and little later in hospital. Under these conditions then we would expect only family would get the infection and a cluster would result.
I do believe genetics plays a role when we are at the present stage of immature adaption from the virus…but I don’t think this predisposition necessarily plays out in clusters.
Does this make any sense?
Joe W. Man…we are getting really good…or at least you are…you are answering my questions even before I post them…I think I am getting dizzy!!! and confused!!!
Tom,
These are all good questions, but we don’t know the answers yet. The studies haven’t been done.
Okay. The behavioral argument I get. If one families hates chicken and another family eats chicken three times a day…then they would be more likely to get a chicken disease.
On the genetics argument how I understand it…if you take a family then the most closely related members genetically are the children…parents are not that genetically similar to their children. That is why parents can father children with children and not have major birth defects.
Secondly, the virus infects the young to a far greater extent and efficiency then parents. If we took an overall porportion on young vs. old we would get some indication of preference…so I don’t think it would be that unusual to affect one of two adults without genetics involved, just virus preference.
The problem is when the population that can be infected is small and within a family group, it is hard to come to terms with genetic predilictions but I could be wrong.
I am aware of the idea that at times siblings were caregivers. I simply do not know how often at this point. I have been through this data set one too many times. Somebody else look at it. I am sure the numbers will change as I reviewed quickly (not for publication purposes). I was reasonably sure of my classifications but I did not double or triple check the numbers as I would in a formal presentation. I suspect minor discrepancies would be found. For now, I am satisfied with my conclusions (unless someone can show where they are faulty) and I am going to look at some other topics.
Why are only some people infected?
Sorry Tom, I did not realize that you were still here. Personally, I like the super shedder argument. It seems to encompass much of the argument. There also seems to be some substance to the young people argument. Perhaps that is all there is to it.
I am acutely aware of the idea that with a mutation all bets are off on differential susceptability. But I still think it is worth some serious review by someone who knows about these things.
The genetics story is used to explain away the high number of clusters and it is possible that in some instances it plays a role, but not so much that it would explain many of the clusters.
Contact is a major driver and in almost all instances the number of blood relatives is much high than non-blood. If it is a single parent household, then all are blood relatives. If it is a family of six, then five out ouf six are blood relatives. If its a family of 4, then three out of four are blood relatives, so having 80% as blood relatives is vitually guarantied, even if there is no genetic component.
PS I think the Sumatra cases may if fact ALL be blood relatives, so there may be a genetic conponent in this instance. However, since they are all on the index case side, that relationship may simply be there because those were the people in closest contact. Thus, three were in the same small room, and then more on her side of the family were involved with her care, so the blood line dictated close contact, and genetics were not a factor.
WHO seems to be thinking genetics. “China’s Vice Minister of Health Wang Longde blamed H5N1 cases in the country on the victims’ defective immune systems.” MILLIONS of infected sources? “Only a few people out of tens of millions having contact with infected sources have been infected, so it must have something to do with these individuals’ immune systems,” Gao Qiang, China’s minister of health…`So far our study has yet to find solid evidence to show what kind of defects caused the infection.” MILLIONS have been exposed to sick birds? Maria Cheng: “The question of genetic susceptibility to H5N1 has certainly been raised in the past…It may have some credence, given the millions of people that have likely been exposed to sick birds and the relatively small number of confirmed cases.”
Regarding mutation - is this confirmation? I’m getting confused. I’ve got a headache. “Variants of the H5N1 virus have become progressively more lethal over the past eight years…” the WHO said in February. “The virus is also becoming more capable of causing disease in mammals, the Centers for Disease Control and Prevention in Atlanta said in March.” Webster, same article: “These are all worrying things…[HPAI] has been about for 10 years now and it keeps magnifying. Some of my colleagues are saying if it was going to go human-to-human, it would have happened now. You don’t know.”
glo. That is an excellent summary of things.
First of all, I believe genetics does play a role in susceptibility but only in terms of the index cases. There are many index cases that do not cause clusters (JoeW would have these numbers but he probably needs a break from them at the moment)…
…the difference, in my opinion, between the index cases causing clusters and the index cases not causing clusters is ‘super shedders’. Because H5N1 is still an adolescent it can’t do it in all cases but in some cases, the virus can make people shed large numbers of viruses (like in seasonal influenza) but only for short periods of time (not like seasonal influenza’s). The end result is family members sick just as if H5N1 was a seasonal influenza…
…is this because of a mutation. Well Dr. Niman thinks so and given the fact that these viruses mutate many times within each host they infect then we would have to guess that this large cluster is due to a mutation and further adaption by the H5N1…but we will never know because the WHO knows and they ain’t telling.
This development would correspond to all the statements you listed except regulators say one thing when it suits them and then say something totally different when it suits them…and science integrity and truth doesn’t seem to correlate with which story is told on which day…maybe this will change in the future and maybe it won’t.
But either way we have enough information to pretty well be able to figure out whats going on without them.
Ummm. . . does that mean ? the index case (mother) gets the virus first (from a chicken or pig if we believe WHO) -then it mutates/recombines with her own DNA and then when she sheds it, it especially likes the same DNA found in her children?? So adheres to ‘what it knows’ in the kids?? Dumb question - non-scientist!! Sorry! :-))
Tom DMV, If BF is basicly attributed to water fowl and water fowl consume aquatic life forms, is anyone checking aquatic life for BF?gina
The flu recombination is usually between the viruses. If H5N1 acquires genetic infoprmation in a human, it would most likely come from a human flu virus.
gharris.
It probably goes a child gets it because H5N1 is still an adolescent and hasn’t got its full powers yet and seems to have adapted to the young better as in 1918.
It can’t mutate recombine with a humans DNA…but it can mutate and does many times in each host that it infects and you probably know that it can reassort-recombine with other flu viruses in the same host at the same time.
The interesting thing is that H5N1 likes higher internal lung temperatures so that a child co-infected with a seasonal flu would have that higher internal lung temperature…therefore H5N1 is actually setting itself up to interact with other flu viruses.
In most index cases the immature H5N1 can’t cause a lot of shedding other than mainly in body fluids but in some cases it gains the ability to cause respiratory shedding but only for short periods (doesn’t have all its powers yet) as I mentioned above and that, in my opinion, is where the clusters come from.
The thing is that this virus is adapting now in many species and many mammal species at the same time including humans.
So we ask the skeptics to give us any shred of circumstancial evidence of any kind to back up their assertion that this virus can’t jump because for a virus that can’t jump it seems to be doing a lot and a pretty good job of jumping already!!!
Gina. Your question about aquatic life makes sense but the virus would probably not grow at their body temperatures…however what about virus in water, how long will it remain viable?
gharris—virus= RNA, human-DNA. They don’t mix. So either she had a dual infection with two different H5 strains, or she got it from a creature (mammal, probably, not bird) with a dual infection or which got it from a bird with a dual infection or something. Wouldn’t it be nice to have the sequences so we could line them up and see which ones match? Then we don’t have to waste time and energy speculating.
To understand why the H5N1 follows blood lines, just think of H5N1 as a miniature Willie Sutton.
Gina. Your question was an excellent one from another perspective. How many small mammals live around small bodies of water, ponds or streams etc. These mammals live in close contact with ducks and shore birds of all types. You may have located ground zero for H5N1 adaption. Throw in a few children playing in the water etc. and bingo…a recipe for human disaster!!
>>>>but we will never know because the WHO knows and they ain’t telling.>>>>
Just as a hypothetical, let’s assume WHO does know that there is a genetic preference; let’s say it is “blonde hair” as a wild example (Makes me wonder about blood types?) Anyhow…if WHO were to make public the fact that people with blonde hair were genetically susceptible to this virus, what would happen next. Well, people with blonde hair would have an extra risk factor, and by knowing that they could take extra precautions. But I would also imagine that immediately the health insurance industry would start canceling policies of people with blonde hair, life insurance policies of people with blonde hair would be cancelled, employees might let people with blonde hair be laid off or fired, families would shun neighbors with blonde hair, etc. etc. etc. Do you suppose there is any reasoning of this type by WHO or TPTB in continuing to keep information secret if, in fact, they know something significant?
Tom DVM, Actually, what put me on this tract was the dietary habits of Asians. Fish (fresh and salt H2O) and water greens. Not necessarily in dee[ water. If bacteria can grow there, why not a virus? gina
Hi petperson. I have found through many years of experience that regulatory agencies take the least line of resistance, whatever they determine that to be.
The status quo is all important. It is a known in comparison to change of any kind that is an unknown.
Uncertainties of all kinds are to be avoided at all costs.
Regulatory agencies are deathly afraid of public opinion, because they require the good will of the population to be effective.
Once belief systems are shattered…once credibility is lost…it is almost impossible to get back…
…and they are smart enough to know that this is the corner they have backed themselves into at the moment and this is very likely the main topic of conversation…not Indonesia…
…but this is my opinion and I may be wrong.
Thank you all for the explanations - I think I meant ‘antibodies’ rather than DNA - but I understand a lot better now!!
There are a lot of birds who arent strictly waterfowl who drop fecal sacs into water when cleaning their nests - that would be a *GREAT* source of H5N1??
gina. bacteria can kind of get along on their own but viruses are more labile and require more intimate contact with humans…they usually don’t last nearly as long as bacteria in the environment…
…but that’s not to say that H5N1 won’t have lots of time to interact with many shoreline mammals.
Would anyone care to comment about a hypothesis that favors oral/fecal transmission rather than genetic factors. I was thinking about the limited household utensils and general hygenic conditions of the households affected by BF worldwide. In primitive societies women are more likely to share their living quarters with their blood relatives- children parents etc. obviously. They would be suspected of infidelity if the husband’s cousins brothers etc shared their small homes.
1mother. There are three types of transmission: respiratory, faecal/oral and blood through insects.
I believe that faecal/oral is very unusual for an influenza virus but is definitely part of H5N1…but it is not very efficient and although causing a few cases, could not result in a pandemic.
Blood borne spread also would be very sporadic and inconsistent and unable to produce a pandemic.
Respiratory transmission is the key determinant in whether H5N1 becomes a pandemic or not. If it stays faecal/oral or blood borne they it will never progress beyond a few cases here and there.
The problem is opportunity and I can’t believe the skeptics would not admit that at this point the threshold of opportunity ensures a pandemic…the only question left is when and how bad.
Tom DVM, Thank you for your help.
TomDVM says: …however what about virus in water, how long will it remain viable? Great question. I guess my question is WHAT! We don’t know this? AKK!
Not enough information is available yet to make a genetically predisposed transmission assessment about this virus. And also, Fathers and Mothers do share the same genetic pool through their children. Both a Father and a Mother would become equally susceptible to infection themselves through a progeny child vector. Once a child became infected both parents would share equal risk. I wonder if this is what has happened here?
Are the common practices of family members leading us to false assumptions about this disease transmission being related to genetics? Since I always look at “most likely” answers. I would point to human habits, hygiene, health, food, ritual and religion before I chose to pursue more complex answers. In science there is always the allure of over complexity, perhaps here the answer is much simpler.
I agree.
I disagree that when a child becomes ill that both parents share equal risk. When kids are ill, moms (and aunts and grandmothers) do most of the nose and butt wiping, washing (linens, clothes, dishes), food preparation and disposing of icky stuff. Dads may help out but are more likely to be the breadwinner (or handle other siblings). This is even more true in much of Asia and Africa than in North America.
Bump.
Olymom. I agree with everything you have said.
I think Naplespark was speaking of equal susceptibility of parents in the context of genetics. He was saying that each parent is identical in genetic similarity to children and therefore would be equally susceptible (genetically speaking only).
Being male and a dad, I have avoided the jobs you mention sometimes successfully, sometimes unsuccessfully but I do the best I can to avoid them whenever possible…
…so mothers would, as caregivers, be at greater risk.
I see that I didn’t read Naplespark carefully. Too much skimming of fluwiki! Jared Diamond writes about the biology of people finding partners. If someone’s facial characteristics (such as the width the eyes are set apart) is highly simliar, we are not attracted — which is a biological way of preventing inbreeding. But we happened to travel to Bali one year and visited a local village well known for its ikat fabric (I am a fabric nut) — turns out that particular village had a tradition. On a certain day of the year a girl could throw an item over a high wall. Which ever single male caught/retrieved the item would be her husband == which led to some, well, closely knit families. Maybe there ARE some reasons this is coming out of Indonesia . . . hmm, better not say that too loudly or the world will be looking at my “closely knit” Kentucky branch of the family . . .
bump
JoeW:
1. There is something that needs to be seriously studied with regard to biological relationships of the people in these clusters. The virus is too often on one side of a family. When the infection is sufficiently intense (?) the other parent is also infected at times. Consider, only the mother and a son were infected in many of these cases. What wasn’t the father infected? Caregiver role is not a sufficient explanation. Approximately, 48% of the time a sibling but not a caregiver was infected.
this could also be because H5N1 prefers young people.
Thanks for the data, but the data should be improved.
The relationships are not clear (refer to the index case ?)
Maybe several people can specialize in one cluster and
figure it out ?
We also need age,mild ot severe infection or asymptomatic but exposed
members. We estimate the level of exposure. Also date of symptoms
so we see who infected whom.
The 88% of people related in clusters is not yet conclusive.
When you pick 2 members at random in a family of 4 you have
84% that they are related by blood and 90% in a family of 5.
We also have to estimate degree of blood-relation, is mother-sun
closer than siblings ? Have they looked as the most obvious
genetic factors like blood-groups etc. ?
bump
Bump.
Bump.
Tom:
I’m not changing my tune:
host genetics = virus preference
A map made to a 1:1 scale, which included every detail of the area it represented, down to the last pebble, would be utterly useless. If a map is useful, it is precisely because it does NOT include every detail, and in trying to understand anything which is very complex, the trick is to make good decisions about what to ignore.
The viral genome makes a much more manageable package than does the human genome. It’s much (MUCH) more compact by comparison, and it mutates much (MUCH) more rapidly. We can sample it here and there, and compare one sample to another in the context of observed patterns of virulence in various species with at least some hope of making sense of what’s going on. Taking this approach is further facilitated by treating the human genome as static, and disregarding differences between one human and another as too minor to be of significance. But we need to remember that the map is not the territory, and some of the things we have chosen to ignore may be important nonetheless.
Guenter:
That’s a great question, and one I seem to recall us discussing some time back. (Ah, %newwinhere it is). The only %newwinreference I can find right now (at least it doesn’t have a “shopping cart”) deals with H3N2, H1N1, etc, and does indicate some differences in seroconversion between the different groups. To what extent this may apply to H5N1 remains an open question.
Oops. Sorry, gs. Didn’t mean to bust your anonymity there.
And could some kind markup fairy please fix my botched tags?
but normal flu doesn’t survive in blood or infect multiple organs, while H5N1 does. At least sometimes.
they could easily test this. Probably they did already, but of course won’t tell us if they can avoid.
Distiguishing genetic form contacts would be hard, which is why genetics is still being discussed. The current cluster in Sumatra is a good example. All 8 family members are blood relatives, which on the surface seems to favor genetics - index case, her tow sons, her two brothers and one sister and a child of the sister and one brother.
However, these may have had the seven with the closest contact. Three (her two sons and the recovering brother), were in a small room with the index case on April 29. However, the other relatives are neighbors, so the sister of teh index case as well as the sisters baby could have had direct contact with the index case as could the son of the other brother. This contact may have been closer than family members on the husband’s side of the family. Subsequently, the nephew infected his father, who was said to have care for his son.
Thus, even though all infected are on the sister’s side, that relationship may have simply reflected the circustances of who had the closest or most prolonged contact. Alternative, genetoc could have played a role, but only if it is couples with close contact, so it is hard to seperate the two factors, because they may not be independent.
Proximity = Opportunity is still the strongest argument, mediating for dosage.
Without question, there will eventually be found some correlation between host genetics and susceptability in general or in exaction to a particular H5N1 strain.
Agreed.
And here everyone must agree. There will eventually be found … Emphasis on eventually. Because we are smart and dogged determined researchers. These correlations will be found Post-Pandemic when there is data to observe. Simply put?
Although 600 or even 6,000 researchers merit the host genetics cause primary to their advancement, I easily hold with Niman that we are chasing our tails or another red herring (that the WHO is waving in our face) if we consider this pursuit anywhere higher than tertiary.
Why do I believe we should place this cause tertiary at best?
We are close to a pandemic somehow. Too close to derive answers without large datasets. We have neither the time, nor the large datasets. More importantly, influenza as a body is and always has been indiscriminant in a seasonal variety, even less discriminant in a pandemic mode.
I think it is highly unlikely that we will quickly find a discrete genetic determinant that we can prove for infectivity or invulnerability in time to create an actionable solution that will impact pandemic numbers?
Why chase our tails by looking at the people . . . we are all going to have to fight this beast.
Let’s continue to shine lights on the monster while its still in its cage, to study the movements, to record its responses to stimuli because once it springs through the door, our clever ideas about host susceptability may be no more daunting to H5N1 than a fly-swatter is to a gorilla.
But I guess we’ll feel armed while he’s tearing off our arms.
Let’s focus where we can achieve real returns.
Gather and Solve.
Please.
Aaah, NS1, I just got up because I had a nightmare and since I have a half hour before we’re on the road to camping heaven, I jumped on here. Your post makes me want to crawl back in bed and curl back up with my nightmare. You have a literary knack, and plenty of spooky material to work with here.
To the sciemtists, Are a few chapters in the saga of the BF missing? Now that all of mankinds mental abilities are being focused on how to keep humans from being infected by BF, it appears we may have lost our way. Maybe it is time to back up and regroup. Think outside the box. Here are some of my thoughts. (1) Is H5N1 truely an Avian Flu Virus? We already know birds have the virus and are carriers, but they too are dieing from it. (2)Is it possible this virus lives elsewhere? In our rush to discover where this virus came from, did we miss a few steps along the way? When the birds started dieing off, our first inclination is to test the birds to answer the question “why”. Tests proved that birds had this virus. (3) Where did the birds get this virus? Did the birds get together one day and decide to produce this virus or during the testing was ground zero otherwise ignored? Were other species tested for this virus or was testing cut short (due to lack of funds or whatever) once it was found in birds? (4) Maybe the problem /virus is still viable at ground zero and that is why we keep seeing it come back? The birds are just a host for this virus for now. As we sit and wait for it to recombine and mutate in another species (human), we become the sitting ducks (not punny). (5) Now is the time to ask ourselves the big question. What did we miss? gina
NS1, nice speech. Consider that there are many people looking under many different rocks. While the “boots on the ground” are in the area, when time and the local witch doctor allow, perhaps we should be collecting extensive data sets that just might, (given several thousand researchers and several billion dollars) come upon some unique features of this virus that could limit its ability to spread in some people, times or places.
To say some set of facts are tertiary issues or issues intended to draw attention off the primary area is a non-starter. There are literally thousands of people involved in the solution to this problem and there are many ways to approach it. If one individual or one group of individuals takes one or another tact, that does not make it irrelevant except to a particular person or group who thinks that they have the true description of the elephant.
The news articles keep saying ‘Jones’ is the only surviving member of the family. It would be accurate to say he is the only survivor out of the relatives that got sick. There is no mention of how many total relatives were there was at this pig roast. They came from 4 households. A grown sister (28) and brother (32) to the index case mother died. There is no mention if there were in-law spouses at each of these other households. We haven’t heard if the first mother had a living spouse. Divorced and out of wedlock families are less common in the Asian countries than ours, by a long shot.
Regarding all family clusters, spouses should be at highest risk to transmission. They share the same bed and have intimate contact. If an adult gets sick, who would more likely provide nursing care to them -an offspring or a spouse? If a child gets sick first, obviously a parent should be more exposed through care than a sibling. Yet there is too high a rate of siblings getting infected. Something seems noteworthy about the statistics of 88% of the clusters being blood relatives. If it is explained as simply living in the same households, you need an average of each married couple having 8 children per household, so that only 10% of the time the spouse gets sick. Even then, I would think the other parent/spouse should get sick more than 10% of the time due to the responsiblity of sick children or spouse.
Susceptibility may be giving the opportunity for the virus at the level it is at now. There are more important issues, I think, such as how the virus got the mammal adaptations, how will it get more (pigs-2-humans?), how can we get society to prepare before a pandemic happens. Once the virus becomes unstoppable, there will still be genetic differences in people, as to how sick you get and if you survive or not. I think we should just assume there are genetic differences, and that doesn’t need to be argued.
Apparently while Ginting (if that is the brother’s name) was on the loose he made contact with 38 people and to date none of them have developed symptoms. From what I read he had the Flu and is recovering. There were at least 38 opportunities during the asymptomatic and symptomatic phase and no one but his family got the Flu.
If the cluster lived in four houses next to each other, there were probably other houses in the area. Prior to the index case’s death, I would think that she talked with a few non-family members during the asymptomatic phase over the backyard fence or more importantly at her place of employment – selling vegetables in a market. If nothing else she probably said, “I am not feeling well today, I think I will stay home tomorrow.” So why wasn’t the whole damn place infected given that the common wisdom says that people are asymptomatic for 2–4 days? Perhaps this virus is not as contagious as it appears – at least in its current verion.
JoeW – at 10:43 Ginting wasn’t coughing when he left ICU and later left the Hospital. He was well past that stage. The reason we ducked the bullet this time is because it looks like the bad coughing stage is fairly short, and occurs early, and is accompanied by some prostration, so the affected person doesn’t feel much like going out and coughing on bystanders. It’s looking like the contagion window is early and short. The reason healthcare workers aren’t getting it is the same: the victims show up after the coughing stage, and when it moves deep into the lungs, the virus can’t go airborne.
when the parents are genetically different so one of them can get H5N1 and one not, then won’t we expect that half the children can get it and half not ? This doesn’t seem to be the case.
Thanks wetDirt. I did not know that and I’ll bet lots of other people didn’t either. It is good to learn about one important variable.
I agree with anonymous. It does appear that “many” children get it but we don’t know the family composition. The recent Indosnesian case is the “best” public data set and we do not know how many other relatives lived in the area. For all I know the whole village could be related.
From my perspective the whole thing is a mess and not as eaily sorted out as some would think. Someone, Niman I think, pointed out that 75–80 percent of any family are biologically related so the stats on family member acquisition are certainly vitiated by this simple observation.
However, when I look at the patterns shown above, using Niman’s four people to a cluster idea there seems to be something strange with regard to who is susceptible. And that is the only point that I have tried to make — this is one strange bug but then there must be others who know much much more and have seen similar situations, at least I hope so.
If anyone could solve it, I beleive the Chinese could. They have brilliant well trained scientists. If a high government official is saying some defect in immune systems, they are going up that road. I think blood types, genetic factors, viral overloads from super shedders, poor sanitation, a lot of different small factors become major when properly combined. If the human race is at risk, I think if one thing does make you predisposed it should be put out there. The good of all is primary here, not political correctness of any sort. Perhaps there is a suspicion of official and strange men asking questions in Indonesia. In China, they can trample on your rights and get to the answers. The only thing that might give them an edge in figuring this all out. By our way of thought, not good, in a fight against a virus such a disregard might save us.In my thinking, it is A>Genetics, and then all the smaller triggers once it gets a foothold, from unsanitary conditions. Supershedders, proximity, oral fecal contamination from unhygienic practices, or simply unavoidable given the conditions and cultural practices.
anonymous- you don’t know thw total size of families and how many siblings were not infected. Does anyone have the whole family tree of this cluster? The coughing of the mother could be due to a higher respiratory infection, hence more airborne spread, than is normal for the current virus. That could say more about the mother’s cell distribution difference, than the virus mutation. It doesn’t appear that the average person, is able to get this illness and cough it into the air, or it would be called a pandemic, already. Some families have more cancer, some families have more heart disease, some families have more allergies, and any other disease, etc. you choose. Genetic suceptibility is not worth the effort of argueing about.The more the virus has passage through the susceptible people, one after another, H-2-H-2-H-2-H-2-H, the more it can adapt over to the average type person. I think we are seeing the natural process of how a species crossing can happen, through those who have the genetic edge conditions for virus infectibility.
When you first identify a disease cluster, I always looked at fringe associations as being far more determinant of actual disease pathways. A child will always experience increased susceptibility if a parent falls ill; other family members will always be more susceptible than background, this is the basic nature of the influenza virus. It is the more remote contacts which offer us true insight. Why someone was “not” susceptible to transmission, that is a good question you pose in the field. This is how a working epidemiologist determines rout of transmission quickly and is then able to isolate and prevent vectoring. The biochemistry will later be 20/20, I am sure, but in the field, it is what did not take place more than what did.
Also mortality is very high, this is a window of opportunity passing. Containment is effective remember, the slaughter of entire flocks has in a sense allowed the virus to be come endemic without greater rates of human contact, yet the practice has left migratory survivors immune and their progeny genetically predisposed to lower mortality. If this continues, a pandemic may not develop because mutation opportunities will eventually fall, even though rates will remain static. Many viruses meet this exact end.
Also, I might look at Complement, ours is more active at the interface. This sole difference in Human immunobiology is hard to overcome for the Influenza virus.
Lily, I disagree. A tiny bit. I think, if this problem was easy, we would already have the answer. The fact is, this is an ill-posed problem, the evidence is mainly observational, the parameters are shifty, in short, this is a *HARD* problem. I don’t think any one group is that much smarter than any other group, or workiing that much harder. I think that the problem itself is hard.
Hi Hurricaine RN!
I keep thinking a lot of the the same thoughts as you! How much checking has been done? Did we just stop looking? I feel like this beast is right in front of our eyes and we are stepping right over it.
Now that H5 is reappearing in places, maybe it should have burned itself out in…I wonder about something else. I’m no virologist…in fact I’m just a NO body! Anyway, what about something like Herpes. Doesn’t taht virus become latent in it’s host, then just pop back up to infect others? Couldn’t there be some vector, somewhere, that is harboring this virus…going between a latent faze, then an infectious faze. Maybe it spreads the disease more often in one of it’s life cycles. Perhaps it is infectious in eggs or chicks. Maybe it is latent in some hibernating animal, re-emerging when the aniaml comes back out and it’s body temperature increases. There are thousands of mammals…just how may have we checked? Why didn’t the virus spread back so far…to Europe with the Spring migration? What animals haven’t been checked in the breeding grounds of the wild birds? Questions! Qustions! No answers…I guess!
Variations in the virus geographically mean generational differences as well. There are actually many forms of this virus searching for it’s answer, one dead end in Indonesia is not related necessarily to a dead end in Africa. Epidemiology in Mbomo is quite different than that of Toronto, and presents differing sets of problems to be overcome for the virus, especially at the beginning of a species transition. It perhaps is better to be more general in your approach as that is what the virus is undoubtedly going to be.
This is a fun forum by the way!
It had popped up again in places, with no birds. Didn’t I read something somewhere about the strange re-emergence and they don’t know why. Is it Romania?
Perhaps we should separate us laypeople who have little in the way of a science background, and just let us muck about and debate, and the educated and qualified on a different thread. We amateurs and dilitants seem to be taking this thread over.
Hi Naplespark; Welcome, haven’t seen your name before. Yep it is fun and interesting to try to figure out what is going on. Anything, anything at all, you can contribute to help us all understand is appreciated. Can you tell us more about how an epidemiologist rules out various factors?
Hey Lily, I don’t think that you should do that, I would have to leave too. Besides we all live and learn as best we can. One of the best definitions I have ever heard for “Normal IQ” was by a housewife (not PC but you know what I mean) who said the only thing she knew that was “normal” was the setting on her washing machine. I not only agree, I have used it ever since.
Not if some dominant allele were a significant contributing factor.
Oh - I am the guy that does IQ assessments, so I gues that makes me an expert in that esoteric field.
JoeW. ‘Imitation is the sincerest form of flattery.’
If this is true then you just got flattered on the ‘chances of a pandemic thread’…read Banshee’s post 13:01
You might as well get some credit for that night with me and Monotreme when we drove you nuts asking for numbers on the clusters.
mom11 12:29
You’re right on the money with herpes undergoing a latent phase and being able to pop back up - one of my favourite phrases that I learned in vet school was “Herpes is forever.” The genetic material of herpes viruses is double-stranded DNA, which means that it can be integrated into the DNA of the host cell - once its integrated, it just kind of hangs out and waits until the host is stressed, which signals the herpes virus to start replicating again.
Influenza, on the other hand, has its genetic material composed of single stranded RNA, so it doesn’t integrate with the host cell nucleus and can’t establish latent infections.
Does that make sense?
This isn’t to say that there can’t be animal species acting as reservoirs, but a reservoir species is different than a latent infection. I think it’s unlikely that there are mammalian species acting as reservoirs for H5N1, but then again the best thing about science is the surprises :-)
I don’t know that I understood the nature of your inquiry entirely but I interpreted it as you wondering if H5N1 could be hanging out in animals other than birds by establishing latent infections.
Finally, another veterinarian…don’t you go anywhere Sasky!!!
If the chinese official, of the depressed immune system quote, was correct, could some of these people have multiple parasitic infections. Worms of various kinds. Now people whose immune systems have nothing to fight, and have various immune diseases are sometimes given a series of pig worm egg infections so their systems have something to battle, and they feel better as a result. Are they anemic, have low B-12 levels. Is there anything they could have prior to their being infected. Of course since they possibly have never had blood work before infection, noone would ever know.
Actually the question of alternative hosts is a very interesting one. Some infections which are spread by mosquitoes can be very transient in their infectious viral load delivery, hence a mosquito which has bitten a sick bird for example, but which did not complete that bite, must bite again quickly to subsequently infect a healthy one. This reservoir can often exist minimally for many years outside any normal path of transmission before mutation tends to select that as the best transmission pathway. This is how mutation adapts to a successful infection route using success as selective pressure. Initially, the ability to transmit is brief, but becomes longer as the virus becomes more effective. Timing is everything it seems. I would not rule out secondary hosts as a transmission route, but I would not search for them either. It is however a very interesting aspect of discussion.
My own feeling is that the longer this latency period of world wide bird infection lasts, the less viable the cross species viability will become. This is the goal of the Epidemiologists now working to stem this infection. To keep bird to human contact low while bird to bird contact reaches it peak and subsequently declines. Unfortunately the peak mutation period has not yet occurred because the virus is not yet endemic in all bird populations geographically. This may very well occur before flu season this upcoming year. If this virus becomes easily transmissible human to human, at that time, well, then there would be a pandemic. I do however, personally have confidence in the way this threat is being handled.
I was asked about epidemiology and methodology, well, that could be a book, or five or ten, but basically it is a matter of biostatistical analysis to build a model of the viral behavior (when it is a virus of course). An advanced form of just what is being done here, not too far advanced either. If you are interested in learning a great deal about the way epidemiologists work, Nick Jewell has a great text, I cannot remember the title but I am sure it is here somewhere. I highly recommend it.
I am sorry, I did not make my point well in my last post. The mosquito pathway is initially a secondary pathway of transmission. It serves to be the reservoir should the first and primary path fail do to adaptation by the target organism. When one vector fails often a virus will search for a second. Often the secondary pathway becomes primary and can be even more dangerous. This is why there is some diversity among exact viral types, to assure some chance of vectoring.
So yes there are often other hosts, other reservoirs which occur in very small amounts, just to make sure perhaps that there is some place for the virus to hide should all else fail. This is why a virus can and does disappear for a hundred years yet re-emerge. It often was found only in very small population of alternative hosts waiting for the reason for it’s initial defeat (immune response and genetic adaptation), to become irrelevant due to generational changes in the primary host. I suspect this virus has done this many times; it already has answers, and is not just expressing itself, it is solving a way to again become pandemic. Some people will have immunity, because some will genetically retain immunity to the last infection which may very well have taken place a thousand years ago.
—1980 in Sumatra. Stayed in a two room, half-dollar a night hostel on the flank of a volcano, back of beautiful Samosir island on lake Toba. Off the perfect cone ran a great hot spring, the restaurant had a mostly egg based menu, the beer was good. The hygienic facilities were a large rock behind which lurked a big pig, there was a stick to keep it at bay for the moment. I will forever remember the look of greed in the eye of the swine.
Times have changed but I guess the same conditions exist today in poorer coastal regions of Sumatra and the same family members would share the same area and get infected somehow.
Human do there
bird pecks poo
cat paws peep
pig packs pickings
kids pets cats
(pig gets infected, the cat is the host and carries H5N1 back to the family?)
It is a pleasure to see humor among the swine…seriously though I think I visited that same rock just last week! (smile). And by the way, I totally agree…
I am continually amazed.
Hi Sasky!
Thanks…Sorry for my confusing whatever…been sick a long time and can’t think straight (or type!)
I am wondering if something, we haven’t tested is just wandering around, happily, carrying the virus. We know some birds have gotten good at this. If the birds , so far haven’t carried this back to Europe, but it appears elsewhere, when they migrate again for Winter, maybe something is hiding out, ready to reinfect the wild birds. Or something, is infecting another source, where the birds can pick it up. Just seems like something else is “out there,” somewhere, lurking, waiting! Like my ghosts!
Could there be breeds of mammals, that are living in the watershed areas and breeding grounds, that may be carrying the H5? Is the H5 always fatal to mammals. I thought some cats, seeemed to be positive for the virus but didn’t appear sick or die. Does anybody have a list of the breeds of animals, thus far monitored for bf?
Just silly questions!
mom11, it seems like I read somewhere that rats can get infected but not die from H5N1.
I really hate rats. Maybe that’s why I suspect them. :(
BTW, that’s a good reason to stock lots of d-con with the prep supplies.
Hi AVanarts!
They’ve carried many dreadful diseases and are everywhere. I hate them too!
My earlier post was meant to illustrate the living conditions in the poorer coastal region of Sumatra. People live there in conditions far removed from the five stars hotel circuit scientists frequent. The typical hygienic area is a semi open space the family share with the pig, ducks, chicken, mice, cat and the occasional H5N1 infected wild bird passing by. If available a large leaf is used to clean back end, or the left hand for the right purpose, no water or soap to clean hand so wipe it in the ground. (toilet paper is for sissies!) This setting might explain a fecal-oral route for the H2H2H infection and the localization of clusters to within a family. Locals presumably eat a low fiber diet mainly based on rice, drop feces every couple of days, explaining the delay between infections barefeet kids kick the dust there, Well one sees the picture…
What we might consider squalid was the norm in any city in Europe a hundred years ago.Rats and Mice must have been checked out by now. Viet Nam seems to be free of it now. What did they do, their living conditions must have been similar to the Indonesians, even if their culture is different.
Westerners have equally disturbing conditions. Think about our high rise buildings, their sealed windows and their heating systems that could blow a flu virus to every person in the highrise within 15 minutes. Our use of rapid transport and our affinity for the inside- most western streets are diserted- everybody is in the Mall.
Re: the genetic susceptibility discussions above (and earlier in this very interesting thread), I have wondered if a small genetic subset of populations have 2,3 sialic acid receptors higher up in their airways than ‘normal’, along with 2,6 recptors.
The only way to determine this would be to examine tissues from the upper airways of those infected. Has anyone looked at this I wonder?
However, even if true, it does not change anything much as the virus will adapt to 2,6 receptors sooner or later if enough human infections occur. But it would be a simple way to close the cluster and susceptibility argument - problem is I gather there have not been many autopsies, and I dont know how viable it would be to get samples from a living person. Just a thought.
yes, and we will all run to the labarotories and get our throat examined so we know whether we can catch H5N1 or not ! Would that 2,3 - thing explain why the cats and tigers die ? Can’t they do some more tests in cats ? (and tell us about the results)
“Would that 2,3 - thing explain why the cats and tigers die ? ”
It might, but there could just as easily be a lot more to it.
“Can’t they do some more tests in cats ?”
It would help to know what exactly to test for. We search within the circle of light our current knowledge casts; but if the answers we seek lie beyond, in the darkness, it is unlikely that we will soon stumble upon them.
Comments on http://www.recombinomics.com/News/05290603/H5N1_Blood_Relatives.html\genetics of H5N1 transmission to humans
Corrected link.
There has been some scientific examination of the transmission of H3N8, canine influenza, which recently jumped species. As I recall, it is estimated that in a kennel situation with H3N8 infection, approximately 20% of the dogs will not develop symptoms, but will be asymptomatic carriers. For how long they remain carriers, I don’t know. Why those particular dogs develop asymptomatic disease, I don’t know. Perhaps it has to do with their immune system? There are other diseases in dogs that are dependent on compromised immune function, demodectic mange being one that seems to be an inherited susceptibility. Also, as I recall, there are always a percentage of persons who do not develop immunity as a result of vaccination against disease. There again, presumably, the individual immune system is at fault. Possibly the infected families share the same genetically acquired immune system fault that allows H5N1 to take hold. Perhaps other individuals in the community have resistance from prior exposure to a similar virus which has given them immunity. It would probably take a great deal of work to track these theories down; more than what can be done practically, I think.
petperson:
I think we need to be careful here to distinguish between “susceptibility” and “immunity”.
There are lots of potential reasons why a particular individual’s immune system might fail to produce antibodies to a particular virus, genetic factors included. But since H5N1 is a virus to which effectively none of our immune systems has any previous experience, no one is going to have antibodies to begin with — so while the ability to produce antibodies certainly will have a great deal to do with whether a person survives the virus, it can’t have anything to do with whether or not a person contracts the virus in the first place. If we then propose that the genetic trait shared by members of these clusters has something to do with compromised functionality in the non-specific first line of defense, the so-called innate response, the question arises as to why these same individuals have not previously shown an unusual propensity for contracting viruses in general (assuming, of course, that if that were the case, someone would have noticed).
Racter: >>>But since H5N1 is a virus to which effectively none of our immune systems has any previous experience, no one is going to have antibodies to begin with — so while the ability to produce antibodies certainly will have a great deal to do with whether a person survives the virus, it can’t have anything to do with whether or not a person contracts the virus in the first place. >>> Are we sure of this?? The fact that there have been many persons in contact with infected chickens that did not get sick - take cullers for example - makes me wonder if there are not people, and perhaps the majority of people, that do have an immunity of some sort to this virus. Is it possible that some previous exposure to a related virus has left a residual measure of immunity to this one? Otherwise, why would only a few people get infected? It seems to me that we are missing something here.
I made a post on this thread on May 26th @ 09:18. It must have been wet because it got hung out to dry. I really would like some feedback on this, so my brain will shut-up. Someone save me! gina
Does it not seem strange that for all of the cluster inforamtion and in the face of the idea that 75+% of a family are related that many people in the immediate area do not become infected. I am not talking about occassionaly but consisently, and with few exceptions, the virus stays within a family.
I am aware of the cartaker argument and find it lacking in some respects as cartakers are not “always” infected. I can agree that there is a “window” of opportunity, and I can even agree with a super shedder argument. In the face of all of these alternatives, the simple consistency of staying within a family is, to say the least confusing.
I am not one to hod to an argument long after it is dead, I am simply too impressed with the within the family problem. It is logical, I believe that in at least some of these cases people other than family members shoud be infected and I am disturbed by the idea that others were NOT infected.
I agree that family infection is confiunded with method of transmission and perhaps what is needed is more information about the development of the flu over time. Are there any references to how the disease unfolds?
I agree that family infection is confounded with method of transmission and perhaps what is needed is more information about the development of the flu over time. Are there any references to how the disease unfolds?
petperson:
No. Unfortunately, there seem to be very few things related to this virus of which we can be absolutely sure. All we’ve got right now is to try to make the best of what little evidence we have.
Being exposed and developing immunity is not the same thing as being exposed and not being affected at all. If the former were occuring, one way to confirm that would be to test for antibodies among cullers and caregivers. Everyone is crying for more such studies, and while there has been some debate over this, the consensus seems to be that those studies conducted thus far do not strongly indicate significant numbers of subclinical or asymptomatic cases among those most likely to have been exposed.
Chicken pox is a common childhood illness; most American kids had it. Probably most of you. One kid in the family caught it from the neighbor kid and the rest of the kids in the family usually got it too. Sometimes. Not always. Regularly enough, one of the kids didn’t. Maybe they did some other time. Mom and Dad didn’t get it, babysitters didn’t get, Uncle Leo didn’t get it, the entire neighborhood didn’t get it, the entire class and the entire school didn’t get it. Why not? It was NOT because every single contact was immune due to previous contraction/exposure, because they weren’t ALL immune. So how is that explained? I don’t think it can be - too many variables, and it just has to be taken for what it is. My brothers and I didn’t get it. Neither did our immediate cousins, who did not live in our house, nor have the same contacts and lifestyle. A little epidemiological mystery story: as a HCW, I had to undergo work-related immunization review. On chart review and med history, it was discovered that I had no documentable chicken pox history. So they did a titer, which demonstrated lack of antibody/antigen to chicken pox, so I got the vaccine along with my brothers. Long story short, by the time they rounded everybody up, my adult male cousin got it from his kids. Not good. NONE of us had had chicken pox, with the exception of a much younger brother who got it as a freshman in boarding school. My kids, the brothers’ and the cousins’ kids did. My mom had it as a child, but not my dad. Probably not my grandparents either, but we don’t know. ALL of us traveled, lived other places, went to different schools, attended different public events, went to slumber parties; we had to have been exposed.
The tuberculosis epidemic: some people got it - some people didn’t. Kids, caregivers, big family groups, etc. No particular pattern, but not everyone was diagnosed and treated. My grandma was sent off to a santitorium for several years. My grandpa wasn’t, nor were any of the other 10+ family members living in close proximity in a small cabin. My aunt was an infant; she didn’t contract it.
My thoughts on AI contagion: 1. Some number has it in a less dramatic form, so aren’t being seen and included in a count. 2. Some number is exposed and generating antigen/antibody response, but are asymptomatic. 3. Another number are not seeking medical treatment, for whatever reason. 4. With respect to the younger ages contracting AI, older individuals must have had some kind of previous exposure. For example, possibly a low-path H5N1 circulating that caused no or minimal random illness, but genetically related enough to kick in the right antibody response.
Anonymous above is me. I think it would be a fascinating study to do sero studies and oral specimens from older asymptomatic contacts, as well as from certain other populations. For example, older generation rural Alaskan and Canadian wild bird subsistence users/hunters that have had routine contact with wild birds for decades (bare-handed handling, defeathering, butchering, egg collecting) and zero contact with domestic poulty. Also very little contact with the ‘outside’ world, so very few variables to confuse data. Even someone like me - in my lifetime, I’ve handled hundreds of geese and ducks, as well as picked seagull and arctic tern eggs each spring. We’ve not done that this year… ;} I have never handled domestic birds. But of course, this would have to be done BEFORE a human illness is demonstrated in North America; once that happens, the study would be compromised.
The development and progression of Influenza in the individual
Influenza is a syndrome (a recognizable complex of symptoms and signs, which indicate a specific disease or condition for which a direct cause is not necessarily understood. Thus in practice doctors refer to the famous “viral syndrome” as such because we are never really sure just which of the legion of viral agents is causing the illness. Once medical science identifies a causative agent or process with a fair degree of certainty, we call the process a disease, not a syndrome.)
This progression is for “normal” influenza. I could not find information for H5N1 so unless someone has better data it would appear that individuals can and do infect others from Day 1 through Day 14.
Day 1 High fever (usually between 100 – 106 degrees F) may last for one – five days.
Other symptoms include flushed face, tiredness, some with dizziness and vomiting, headache, fatigue, and muscle ache. Some gastrointestinal symptoms such as vomiting, nausea, and diarrhea may be present. Sweating, shortness of breath, and chills may be present and may be accompanied by a loss of appetite.
Day 2 or 3 Respiratory symptoms are more prominent than whole body symptoms. These symptoms range from cold like to laryngotracheobronchitis. Sore throat, bronchiolitis, runny nose and ear infection are other symptoms. The most prominent of the respiratory symptoms is usually a dry cough.
Day 4–7 Symptoms other than dry cough disappear. Fever may return.
Day 8 – Day 14 (or longer) Cough and tiredness linger.
The source for this information is “Influenza Treatment,” http://tinyurl.com/muzqm
Apparently on Day One the individual basically feels pretty down but not badly enough for everyone to stay home. Some individuals could be expected to be away from home and at work given a fever of 102 – 103. This of course depends upon individual will power, need to work etc.
By Day Two or Three the respiratory symptoms appear. It could be expected that most (but not all) people would be in bed and having someone take care of them. There is a need for a caregiver. Note that some people may be able to function on day two and they might be coughing and spreading the virus in this way. Apparently the sick individual could be spreading the flu for one to three days (with cough) before they are bedridden.\\\
Apparently, somewhere around Day Four or Five the person and their family are going to perceive a need for hospitalization (if available and acceptable to the family). It is at this point that the sick individual continues to exhibit a dry cough and it could be expected that in some cases could infect others through Day 14.
From this expected progression of influenza it could be expected that the sick individual is capable and may infect everyone with whom they come into contact and there are ample opportunities for contact during the first three days for at least some of the observed clusters. None-the-less by a very large margin only family members are infected. My question concerning why other people are not infected given ample opportunity is unanswered. Help would be appreciated.
An epidemiologist from Italy posted on another thread and said that the flu could have been hiding in some other animal species for thousands of years and that it continues to seek ways of spreading. In this scenario, he thought it possible there might be some genetic resistance in humans that has been around for many years. It is possible that the current clusters are individuals who do not have this resistance.
>>>Being exposed and developing immunity is not the same thing as being exposed and not being affected at all. If the former were occuring, one way to confirm that would be to test for antibodies among cullers and caregivers. >>> But maybe we are not looking for H5N1 antibodies. Maybe antibodies to H1N1 also confer protection against H5N1. I think a better question would be, what Did they have antibodies to - and then see if there is a common denominator among those that have been exposed to H5N1 but not infected. I have no scientific background; but if, for example, you examined 100 cullers that did not become ill, and you found none had antibodies to H5N1, but you also found they All had antibodies to H1N1, then you might be on to something.
From and Indonesian doctor treating a patient with Bird Flu, “But we still must monitor this patient’s condition daily, because bird flu initially seems like an ordinary flu. We’ll see in 2–3 days from now.” Source Flu Wiki “News Reports May 29” at 21:48
Joe:
Genetic resistance is, by definition, not the same thing as aquired immunity.
petperson:
It is precisely the assumption that this is NOT the case that has everyone so concerned. Though less prevalent than H3N2, H1N1 is commonly encountered as seasonal influenza, and it would not be the least surprising to find antibodies to it among the patients comprising the H5N1 clusters as well as those who remain unaffected.
Regarding genetic susceptibility — don’t forget that in some countries (including Indonesia) marriage between cousins or closely related family members isn’t unusual. In some cases it’s preferred; in others, i.e., a small town where everyone has lived there going back ten generations — everyone’s related anyway and they have no choice. *shrug* Different culture.
This could skew the results in either direction. It could:
1. Make it appear that the virus prefers close relatives. (It had no non-relatives to infect. Everybody in the village was related one way or another, most likely multiple ways.)
2. Make it appear that the virus HAS infected a non-relative, i.e., both a husband and a wife are infected — but they’re both first cousins as well, and moreover their family tree is a bit braided together if you start tracing the lineage back …
Leva
I agree that genetic resistance is not, by definition aquired immunity. And I am grasping at straws in an attempt to understand the within family problem. The idea that all humans may have some immunity and that some (very few) familes may not have this immunity is a conceptually appealing idea with significant ramifications. The usual caveat re until it mutates may or may not apply. Is it likely that humans have some form of immunity to the flu? My guess, it makes sense.
There may be some atypical features of bird flu victims cells that allow the virus entry. Some of the autopsies revealed systemic damage to organs, brain inflammation, and virus present in the blood. For a virus that is not “human adapted” yet, it shouldn’t be getting around some people’s bodies like that. The gateways in these people’s cells are opening to the virus. IMO, this appears that the virus is very much on the cusp of being able to get into the mainstream human cells. It could be just one little doo-hickey on the normal receptor key shape that makes the difference.
Excuse the last link, I forgot I put it there. I’ll explain it next.
Yes- Bats are believed to be the originators of Sars, Ebola, Nipah, Marburg. Read article from Scientific American. -http://tinyurl.com/qgadl
Diseases do well in species that live in dense population colonies, like bats, birds. -Humans are newcomers as good hosts, since the domestication of animals and agriculture some 10,000 years ago, which gave us the higher population communities for infectious diseases. So the much older colony species have developed viri for far longer, and have much to share with us. H5N1 is a bird creation as all influenza are, I’m not implying bats made it. But if mammals such as ferrets,cats, rodents can get infected, I wonder if bats could too? They are probably very hardy to viruses, like ducks, and possibly could contribute to spreading it. A lot more mammals need to be tested to fully understand how we are getting all these outbreaks. They have been too chicken oriented, but how are the chickens getting it!???
bump
oops. my prior post should have referred to “resistance” not “immunity.” Nothing like a little muddle headed thinking
I’m on a bat roll. I think besides pigs, bats could also allow mammalian adaptian to occur. Notice that they are closer to primates than to rodents. From wikipedia- http://en.wikipedia.org/wiki/Bat
“There are estimated to be about 1,100 species of bats worldwide: about 20% of all mammal species.
Bats are mammals. Though sometimes called “flying rodents”, “flying mice,” or even bugs, bats are neither mice nor rodents.
Bats are traditionally grouped with the tree shrews (Scandentia), colugos (Dermoptera), and the primates in superorder Archonta because of the similarities between Megachiroptera and these mammals. However, molecular studies have placed them as sister group to Ferungulata, a large grouping including carnivorans, pangolins, odd-toed ungulates, even-toed ungulates, and whales.”
They are responsible for transmitting many diseases to humans, so there is a viral compatibility. Besides the above mentioned Sars, Ebola, Marburg, and other less famous diseases, there is Rabies and Histoplasmosis. Here is another deadly cross species virus-
http://news.bbc.co.uk/1/hi/health/226702.stm
“One of the new viruses was first identified in thoroughbred horses in a Brisbane suburb. (Australia) The horses came down with a respiratory disease in 1994 and 13 died. So did their trainer, Vic Rail. Experts tracked the source of the disease to a variation of a virus related to measles and canine distemper. They called it megamyxovirus. A year later, a sugar cane farmer in northern Australia developed severe muscular seizures and died. It is thought that the horses may have caught the virus from the uterus fluid from female bats which had just given birth. Experts believe the fluid may have dropped onto the ground from the trees where the bats were nesting and entered into the horses’ bloodstream after they ate or licked it. It may then have passed to the farmer through cuts on his arms. Other new bat viruses which may infect humans include paramyxous virus, which causes flu-like symptoms; Ross River fever, a virus carried by mosquitoes; and Japanese encephalitis, a potentially fatal brain infection.”
Bats hang out in the roof of barns and sheds, where their droppings can infect farm animals. Hmmmmm -
I’m including the mention of Histoplasmosis because of it’s commoness to people- up to 80% in Illinois show exposure. I had a serious case of disemminated Histoplasmosis, which has an 80% fatality rate. http://tinyurl.com/oznyk -
“Histoplasmosis-The disease is transmitted to humans by airborne fungus spores from soil contaminated by pigeon and starling droppings (as well as from the droppings of other birds and bats). Although almost always associated with soil, the fungus has been found in droppings (particularly from bats) alone, such as in an attic. In some areas, including portions of Illinois, up to 80 percent of the population show evidence of previous infection.”
Previously someone talked about chicken mites spreading disease. There could also be mites that go from bats to birds in the same roost area.
“Bird or bat roosts can harbor parasites that may invade buildings. Although these parasites can bite and irritate, they are unlikely to transmit diseases to humans. The northern fowl mite and chicken mite are usually the main culprits.”
My local bats are great for eating mosquitos, I’ve even found an occassional bat in one of my hanging baskets. Tiny as a mouse. Could there be some link, mosquitoes, bats, droppings, then on and on in a chain. Of course this is a chain, but where does it begin, and where will it end. If its in the soil too. When does a virus truly die.
As for the mosquitos…
Influenza in general is not considered to be a vector-borne disease. Though RNA segments have been found in blood samples from infected patients, as far as I can tell there has been only one instance (a 5-year-old boy from Thailand) of live H5N1 virus having been found in blood (there are a few — but very few — other confirmed instances of influenza viraemia in humans). No virus in blood, no transmission by mosquito. I say, take whatever good news we can get.
Kay, my wife, has two deceminated retinas due to Histoplasmosis. So I know a little about that one. She had been a nurse specializng in cardiology and is now (has been for 15 years) legally blind. Seems the disease in throughout the Ohio Valley, among other places and can be aggravated by stress. I wonder if stress can aggravate H5N1?
most illness are aggraveted by stress, stress reduces the immune response over time and makes our bodies more suseptable to illness.
I have to post this here as it simply belongs in this thread, “Rutnani do not believe bird flu is spreading H2H. She said if H2H, she’d already be infected, as she treated Antap and Antap’s child.” From mamypoko translation of the news in Indonesia. Posted on News Reports May 30 at 23:41. Rutnani states that she is the sister-in-law of the index case (Antap). This is not any proof but it is suggestive for my thesis that there is something about the sensitivity of members of a family to the current version of the Flu.
Re: Sumatra family has roast pork feast, dies of flu. Here in rural Bolivia a good pig is worth as much as a small cow, so it is used as a cash reserve say for the kids clothing or schoolwares. Rarely would a poor family eat it for no reason.
Possible scenario: The mother seeing their family pig getting weak and sick takes care of it, tending and feeding better until finally the animal is about to expire she decides to butcher it with the help of husband and kids as she feels already a bit feverish.
The family pig lives off scraps from the kitchen and scavenges the yard for greens, bugs and grubs, also cleans the toilet area and eats the occasional dead chicken or wild bird mauled by the cat. (they tell me here pigs don’t eat dead cats-!fur?) So index case would be the pig eating infected bird, mother gets infected from tending it, and later the rest of the family from handling the raw meat. No onelse gets invited to the party because the roast has an off flavour a bit.
Would this explain the delay in onset dates and the localization of the cluster?
Maybe I’ll skip breakfast this morning.
Yes, what was the reason for the barbeque if any, outside of pig infected and showing signs of illness. Can this scenario be verified?
Excellent thread, but long. Continuing to Part 3 here.