This thread is started to discuss questions concerning basic virology, stuff that people don’t understand about its evolution, pandemics, hosts, etc. The basic science is covered in the Science section of the Wiki. But I thought it might be helpful to have a place for questions etc.
This question was asked on the ‘Ask the Moderators’ thread:
Olymom – at 18:51 Like many others, I am reading the news from Indonesia with concern. I am also wondering what happened to the 1918 flu — did it completely die out or is a version of it still in circulation? I know some fragments of the 1918 flu were unearthed from frozen corpses and analyzed, but I haven’t read if that virus is still in some (moderate) form in humans. Is there an answer to this “still in circulation” question on flu wiki? I’m not sure where to even start looking.
Some general direction pointers would be deeply appreciated.
The best single diagram that summarizes the answer for Olymom’s question is from Webster’s 1992 paper Evolution and ecology of influenza A viruses
I will ask my question here that I asked in the Indonesia thread and hopefully will get a few responses. This thread seems more appropriate, anyway. In several places I have read, some experts think there is a small chance that if the BF goes pandemic and lives in the upper respiratory tract, it may lose some of it’s “punch” and not be as lethal. I don’t understand why some think that is even a remote possibility. Didn’t the 1918 pandemic turn into an upper respiratory infection? And it did not seem to lose it’s “punch”. I know no one should count on the BF becoming less lethal as it spreads, but why do some experts believe that is even a small possibility? That did not happen in 1918 (that I know of) and H5N1 is far deadlier.
Lurker,
You are asking whether H5N1 might have a lower CFR if it goes pandemic. That is the billion dollar question for everyone, I guess. There are several hypotheses, and I’m just laying them out for discussion. It doesn’t mean that I believe in them. :-)
Some have suggested that killing most of its victims makes it less likely that a virus will continue to spread in an efficient manner, the rationale being that dead (or very sick) people do not move around and have less chance of infecting many others. Therefore, a virus has to have a lower CFR to go pandemic. My thought on this is that it depends on how low is low, for the virus to continue to spread. And it also depends on what is the infectious period of the virus. In the case of the flu virus, it is highly contagious just before the person has symptoms, and that could be quite a few days before they get sick enough to not move around.
A second hypothesis is that for the virus has to undergo probably a series of mutations in order to gain increased transmissibility. This changes the characteristics and maybe the behavior of the virus, which may result in a reduction in CFR. I think this is possible but we do not have a guarantee that it won’t go the other way, by the same logic!
The only more-or-less reasonable hypothesis that I have heard is from Malik Peiris, who said that if a pandemic virus emerges as a result of a reassortment event between H5N1 and a human strain, then there is some immunity in the human population to the antigens acquired from the human strain, and thus the CFR could be lower as a result.
That being the case, a pandemic virus that arises NOT from this process can have any kind of lethality, IMHO!
Anon 22- Thanks. I fully expect this virus to be highly lethal in pandemic form. Does anyone know what the 1918 virus did? Did it become less lethal as it turned H2H? I just don’t think there is ANY chance h5n1 will lose any of it’s punch, as a few experts have put it. I have not read the book on 1918 yet.
Lurker,
I missed your question about the upper respiratory tract. Currently H5N1 still has a preference for receptors that are found more commonly in birds (a2,3) than humans (a2,6). These a2,3 receptors do exist in humans and reside in the deepest parts of the lungs, and so to reach them the virus has to survive all the immune mechanisms from the upper airways eg from mucinous secretions. But this preference for receptors deep in the lungs may also explain the tendency to cause devastating lung complications such as viral pneumonia and ARDS (Acute Respiratory Distress Syndrome) which are the major causes of death.
H5N1 currently does not bind as easily to receptors in the upper respiratory tract a2,6, which some suggest account for the difficulty of h2h transmission. If it were to switch preference from a2,3 to a2,6 receptors, then it would be more able to transmit between humans, but it may correspondingly have less preference for inhabiting the deepest parts of the lungs. Therefore, it may become less lethal because of that.
At least that is one stream of thinking, although I suspect it will have to depend on the virus dose needed to produce those devastating lung complications. Since ARDS is thought to be triggered by ‘cytokine storm’, which is more-or-less a cascade-like event, the relationship between virus dose and its ability to trigger ARDS may not be linear. Or, to put it in another way, the ability to trigger ARDS may not be dose-dependent. Or it may. We just don’t know.
Go to this thread for a more detailed discussion of receptor binding preferences.
Thanks for explaining all that. I appreciate it. Does anyone know what the BF did in 1918 when it settled in the upper respiratory tract? Or did that happen? Did it lose any punch at all? I am guessing it didn’t.
Lurker – at 19:54 “Thanks for explaining all that. I appreciate it. Does anyone know what the BF did in 1918 when it settled in the upper respiratory tract? Or did that happen? Did it lose any punch at all? I am guessing it didn’t.”
I don’t think we have any data to compare when it did or did not settle in the upper respiratory thread. We only know that the second wave was the most lethal, and that after 3 waves, the disease gradually merged into background seasonal flu activity. That was when it probably lost its punch, cos the excess mortalities recorded gave the 3 waves only.
“upper respiratory thread” should read “ upper respiratory track”
You know what kind of tunnel I’ve been down. :-)
There is not a single H1N1 virus. Think of that label as a family tree or race. There were different H1N1 viruses before 1918 and one of them split off and became a human virus. Today we have H1N1 that are descended from the human H!N1 pandemic strain and are less virulent, but there also are H1N1 viruses that descended from the viruses that only infected birds. There are H1N1 swine viruses descended from the 1918 pandemic but only infect pigs now.
The current human H1N1 is less virulent even if you get infected and have no prior exposure to H1, than the 1918 strain. It just mutated down. The virulence seems to be a different factor than the antigen markers. It flared up and then faded down. It’s an ongoing changing train of evolution. We keep expecting a parallel to the 1918 pandemic, but they will likely be different from each other. Just because there are two types of new strains, “reassortment” and “drift”, doesn’t mean all drift mutations will be similiar. The 1918 pandemic did not have bird deaths preceding it or concurrently. The strain killing people was too mammal adapted from the bird version; they don’t see yet that the birds had it (the same sequence). The bird H1N1 is not high pathogenic to birds. The 1918 strain also seems to have started less virulent even before the first wave. In 1917, there were deaths in the European military camps with cyanosis symptoms, and it seemed to build into something worse. It never started with the current CFR that H5N1 has in people and in poultry. Try to not keep thinking it is 1918 pandemic coming again, - we may need to stretch our imagination.
Lurker,
Most viruses become more lethal when they adapt to a new host, not less. The limited evidence suggested that this was true of the 1918 virus. If that happens with H5N1…
Monotreme- That is what I thought too. That’s why I am confused as to why a few experts say it MIGHT lose some of it’s “lethalness” (is that even a word?) if it starts to settle in the upper respiratory tract.
NJ Preppie- Okay well now I am more concerned. Because if the 1918 BF strain was not killing birds then we are in for something awful when the strain that DOES kill birds hits us. I am trying not to compare the two, but it’s all we’ve got, right? Obviously H5N1 is SOOOOOOOO much worse than the 1918 strain.
I can’t give a link for this article from The Lancet, entitled “World War I may have allowed the emergence of “Spanish” influenza”, as it is a subscription site.
(The Lancet Infectious Diseases 2002; 2:111–114) Professor JS Oxford a , A Sefton a, R Jackson a, W Innes a, RS Daniels b and NPAS Johnson c
parial excerpts:
“We present an appraisal of epidemiological and mortality evidence of early outbreaks of respiratory disease in France and the UK in the years 1915 to 1917. Certain of these earlier focal outbreaks—called epidemic bronchitis rather than influenza— occurred during the winter months when influenza was known to be in circulation, and presented with a particular heliotrope cyanosis that was so prominent in the clinical diagnosis in the world pandemic outbreak of 1918–1919 (the Great Pandemic). The outbreaks in army camps at Etaples in France and Aldershot in the UK in 1916–1917 caused very high mortality in 25–35 year olds. Increased deaths from bronchopneumonia and influenza were also recorded in England. We deduce that early focal outbreaks of influenza-like disease occurred in Europe and on the balance of probability the Great Pandemic was not initiated in Spain in 1918 but in another European country in the winter of 1916 or 1917. An almost identical epidemic of purulent bronchitis with bronchopneumonia, with cases showing the peculiar dusky heliotrope cyanosis, and mortality rates of 25–50%, was also described in Aldershot barracks in March 1917.12 The authors of that paper concluded that the unique clinical symptoms together with the pathology delineated a new clinical entity. Furthermore, the same medical team, once they had experienced the 1918–1919 outbreak, noted in retrospect the similarities in pathology to the Aldershot epidemic of 1916.
Abrahams, one of the coauthors of the purulent bronchitis paper,12 once he had experienced the large 1918–1919 outbreak, concluded that both outbreaks had the same causation: “We emphasise our view that in essentials the influenza-pneumococcal purulent bronchitis that we and others described in 1916 and 1917 is fundamentally the same condition as the influenza pneumonia of this present pandemic.16 Therefore, not only are we considering a forgotten pandemic17 but a forgotten and overlooked origin.
The protracted period that we postulate for the emergence of the Great Pandemic of 1918, almost 2 years, could be explained by the absence of air travel and the effects of restricted travel during the Great War. The new mutant could have maintained itself in small civilian and military outbreaks while increasing virulence in a stepwise manner, similar to virus adaptation in animal models where sometimes hundreds of passages are needed to increase virulence of a pneumotropic strain.”
Lurker – at 21:59
That’s why I am confused as to why a few experts say it MIGHT lose some of it’s “lethalness” (is that even a word?) if it starts to settle in the upper respiratory tract.
It is possible that H5N1 might decrease in lethalness when it goes pandemic, no-one can say for sure. However, the CDC and the WHO are saying it will definitely drop from a lethality of over 50% to less than 3%. And they are telling governments to make their plans based on that assumption. If brains were dynamite, the epidemiologists at the WHO and CDC wouldn’t have enough to blow their noses.
Obviously H5N1 is SOOOOOOOO much worse than the 1918 strain.
This is what I think, too.
Monotreme-
Why do they feel it will drop to less than 3%? That would be a very drastic drop and I just don’t see that happening.
Thanks all — I got what I needed to know — H5N1 may be around for the next thousands of years but watch the first step as it’s likely to be a doozy.
Lurker – at 23:01
Why do they feel it will drop to less than 3%? That would be a very drastic drop and I just don’t see that happening.
I don’t think they have a good reason. Mostly, they just say no flu virus has ever been worse than 1918, so, therefore, no flu virus can be worse than 1918. Therefore, H5N1 must drop it’s kill rate when it goes pandemic. Dumb, dumb, dumb.
Yes, and I had no idea the 1918 strain was NOT killing birds. If it was mild in birds but still killed humans, then imagine what H5N1 could do? Wow, I just got chills. Not good.
I don’t like starting new threads so I’m posting this article here. The Nipah virus killed a 111 people in Malaysia with a 48% CFR. There have been three more cluster outbreaks more recently in Bangladesh.
Title: “Natural Selections: The Potential Pandemic You’ve Never Heard Of”
- How the connections between pigs, bats, and people could threaten your health.
“The history of this disease, which first struck Malaysia in 1999, offers a cautionary tale of how a potential pandemic was averted. Before SARS, before worries about widespread avian flu, the Nipah virus infected humans with surprising ease. Swift action by Malaysian and international public-health authorities, including the Centers for Disease Control, kept the Nipah outbreak under control for several years. But the disease is having a disturbing second act in Bangladesh….
As suspected, the fruit bats in the region were the only wildlife to test positive for the virus, making them the pathogen’s most likely reservoir….
The circumstances of the Nipah outbreak suggest that the virus needs a large pig population to maintain itself long enough to have a chance of spreading to humans. The farm on which the Nipah virus emerged had over 30,000 pigs, and the branches of fruit trees hung over the walls of their pens, giving bats and pigs plenty of opportunity to come into close contact…
More ominously, at least six of the victims developed acute respiratory distress syndrome, a condition in which fluid builds up in the lungs and prevents normal breathing. These symptoms had not been a feature of the disease in humans before. ..
The dense populations of humans and flying foxes in a country like Bangladesh may provide the conditions under which the Nipah virus will finally acquire the ability to explode into a pandemic. ..
So while avian flu continues to make headlines, Nipah is also a virus to watch.”
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Additional information on emerging diseaese from bats-
Bats have been the reservior behing Ebola, Marburg, Sars. One species of bats in China tested 71% positive for Sars antibodies. The bats transmitted Sars to the civet cats, and Ebola to primates, which then was transmitted to humans eating bush meat. Other viruses have been transmitted to people through farm animals. Roosting barn bats transmitted Hendra virus to race horses, killing 13 horses and two human trainers in Australia. Another incident, Hendra killed 2 horses and one farmer.
A big consideration is that human influenza -H3N2- has been found in bats!!! That’s what this news has to do with H5N1. Can bats share a virus from a bird and allow it to acquire mammalian adaptations passing through its large colony nesting sites? There appears to be not so much a species barrier between bats and humans as a mammalian bridge. Bats descend from a common shrew ancestor that rodents and primates have descended from too.
Would the fact that monkeys (primates), bats, and birds all hang out in trees contribute to the fact that they may be transferring virus back and forth, allowing for even more mixing and matching of RNA?
Likewise, omnivorous pigs root under trees, consuming whatever has fallen out of the branches — dead bats, dead birds, and any other droppings of partially eaten fruit or previously eaten fruit? Chickens and ducks also forage under trees for fruit seeds and so forth, some of which may have been passed through infected bats, birds, and monkeys.
The moisture of trees, and the shaded ground underneath, and the moist fruits and droppings would all be reservoirs of virus that could maintain viability for some time. In addition, one pig could pick up remnants of a hundred or more separate tree living animals and their droppings in rooting around under just one tree. So the odds of some kinds of mixtures of virus would be incredibly high. Under certain temperatures and moisture conditions, the circulation of viruses through all these animals would be constant. So the odds of some kinds of mixtures of virus would be incredibly high.
In the event of a drought, natural disaster of some sort, great change in natural conditions or forage shortages, the forced changes in preferred diets may cause increase and decrease of the animal populations and changes in virus circulation allowing even more novel combinations.
So, if one virus is emerging easily, so many more are probably in the crucible to come out in quick succession.
Oh, I hope we don’t burn out on Influenza — there’s probably more waiting!
the 1918 (2nd wave) virus did become less lethal as the pandemic was going. I guess, the mortality halfed each 2 or 3 months. H5N1 could be different - the transmission is not (yet) as with normal flu. H5N1 can survive longer in the surroundings, can survive in blood, can travel through the lymph-system.
1918 H5N1 is still there. It gave 5 genes to 1957 H2N2 and 6 genes to 1968 H3N2, so our normal flu (H3N2) still has 5 genes from 1918. Although a lot of point mutations occurred. But you can clearly see how our PB2,PA,NP,M,NS are similar to the 1918 virus while PB1,HA,NA are more different. One chance for H5N1 to acquire better transmissability is to reassort with H3N2 or H1N1 , viruses who already “know” how to go pandemic. When H5N1 could keep its HA (and to a lesser grade its NA) then we would have no immunity. But with the other genes it might loose its virulence, simply because H3N2 and H1N1 are not so virulent. When OTOH. H5N1 contributes genes other than HA, then we might have some immunity. And then there is also the possibility that H5N1 doesn’t have to reassort to go pandemic.
Here’s an article by Taubenberger as a reference for the previous discussion about the source of the 1918. Notice the difference in how H1N1 evolved compared to the current H5N1. This is not an exact repeat. CDC/Taubengerger
title- “1918 Influenza: the Mother of All Pandemics”
Jeffery K. Taubenberger* and David M. Morens†
“…On the contrary, the 1918 virus appears to be an avianlike influenza virus derived in toto from an unknown source (17,19), as its 8 genome segments are substantially different from contemporary avian influenza genes. Influenza virus gene sequences from a number of fixed specimens of wild birds collected circa 1918 show little difference from avian viruses isolated today, indicating that avian viruses likely undergo little antigenic change in their natural hosts even over long periods (24,25)…
Because the 1918 gene segments have more synonymous changes from known sequences of wild bird strains than expected, they are unlikely to have emerged directly from an avian influenza virus similar to those that have been sequenced so far…
At the same time, the 1918 sequences have too few amino acid differences from those of wild-bird strains to have spent many years adapting only in a human or swine intermediate host. One possible explanation is that these unusual gene segments were acquired from a reservoir of influenza virus that has not yet been identified or sampled. All of these findings beg the question: where did the 1918 virus come from?
Like the 1918 virus, H5N1 is an avian virus (39), though a distantly related one. The evolutionary path that led to pandemic emergence in 1918 is entirely unknown, but it appears to be different in many respects from the current situation with H5N1. There are no historical data, either in 1918 or in any other pandemic, for establishing that a pandemic “precursor” virus caused a highly pathogenic outbreak in domestic poultry, and no highly pathogenic avian influenza (HPAI) virus, including H5N1 and a number of others, has ever been known to cause a major human epidemic, let alone a pandemic…
Even with modern antiviral and antibacterial drugs, vaccines, and prevention knowledge, the return of a pandemic virus equivalent in pathogenicity to the virus of 1918 would likely kill >100 million people worldwide. A pandemic virus with the (alleged) pathogenic potential of some recent H5N1 outbreaks could cause substantially more deaths.”
This is cross-posted from the News Thread
InKy ¨C at 15:25
Re Tom DVM at 11:00 - Thanks. It seems the alternative to asking dumb questions is remaining ignorant, so I¡¯ve asked quite a few in my lifetime ;¡ú. Is it the case that strains of endemic low-path H5N1 simply mutated in Southeast Asia to become the high-path H5N1 we are now worried about? I had the impression that H5N1 was something new altogether, so word of a ¡°low path¡± virus of the same name that¡¯s been around for years requires that I refine my understanding.
You probably know this already but just in case and for lurkers who don’t :-)
The difference between LP and HP is in the presence of a unique configuration of the HA protein (chain of basic amino acids at the cleavage site where the protein splits into 2 before viral replication can occur) that, for unknown reasons, the virus acquires when infecting domestic chickens, causes a severe systemic disease resulting in close to 100% death. The origin of the HP H5N1 in Asia is thought to be from reassortment with possibly H9N2 or other unknown avian subtypes, but the acquisition of that cleavage site is a characteristic of only H5 and H7 subtypes. Since 1997, different strains of HP H5N1 have arisen from the same ‘parent’ strain in Guangdong in southern China. We don’t know exactly why but it seems that this is something that happens uniquely in that part of the world, and is still continuing.
Every case is a test tube and H5N1 may as well be a mad scientist feverishly at work, so I wasn¡¯t really thinking that intentional exposure would be a good idea, just wondering if these viruses are similar enough that the low-path strain would produce an immune response to any degree whatsoever.
Well, I don’t think we know the answer to that, except maybe to say that since LP H5N1 does not infect humans, you can’t really deliberately acquire immunity that way. Also, when they try to develop vaccines, they found that the H5N1 virus, for unknown reasons, is not very immunogenic, and there is very little cross-immunity between different clades, such that the WHO has had to provide different virus seed samples for vaccine manufacturers. This probably tells us that being infected with any one clade of HP H5N1 does not necessarily produce immunity anyway, let alone LP H5N1.
Somehow I don¡¯t think this is the case. There must have been low-path strains of H5N1 in Indonesia, Thailand, China and Vietnam if there have been cases in Maryland, Pennsylvania, and who knows where else, going back 20 years or more, before the high-path strain emerged. High-path H5N1 is high-path precisely because it trumps resistance. Have I answered my own question?
Yes, I think you have. :-)
Closed to maintain Forum speed.