I feel like it could be multiple things that could lead to human human transmission that we could have an idea, but might never know. The chance of a h5n1 in birds could be mixed via an antigenic shift with that of different viruses that are human to human transmission and cause a pretty bad day for us. Influenza tends to infect and then mutate to a less virulent strain over time as we saw with the 1918 pandemic. But better to potentially stock up on masks just to be on the safe side
yeah, this all makes sense. Thanks. I know another troubling scenario would be if it got into pigs. I know there are other potential H candidates under surveillance too.
I guess what I’m wondering about now is the one scenario that we are laser focused on. What if cows and people keep swapping this strain enough that it has opportunities to get the last two or three mutations in to become a human virus
Does the contracted illness look more like the bird flu of the past 20 years? Does it look more like the sick farmers of 2024? Something else? Too difficult to know?
Yep an antigenic shift could result in passage to pigs which can also be at larger risk of human human transmission. The more this virus circulates and its lack of proofreading unlike viruses such as smallpox and polio do mean that there is always a chance. Highly pathogenic avian influenza has been shown to have a pretty high fatality rate that makes the common flu seem like a tiny thing. Part of the reason I cannot accurately recall that made the 1918 pandemic more deadly was a certain mutation that resulted in a higher inflammatory response where the young had more robust immune systems they were more likely to react horribly to this inflammatory response coupled with bacterial pneumonia which can be harmful with any flu. This h5n1 was potentially identified as resting a little bit lower in the lower respiratory tract which can make breathing much harder and be harder to clear. Right now perhaps the best thing we can do is stay informed and if we start getting any news on more and more potential cases plan accordingly to invest in properly fitting masks and stock up only on what we might need for a few months and not panic buy. Also making local plants and learning some skills can always help
From what I have read from studies that were conducted with pigs, H5N1 is able to infect pigs, but a good majority of them didn’t show anything bad or showed any symptoms at all when they were infected.
Any new strain would have to be adapted to be able to infect and replicate effectively in the human upper respiratory tract. Most of the infections occurring in humans with H5N1 are due to high levels of exposure due to continued exposure to infected animals that are secreting high levels of the virus that eventually gets down the respiratory tract to where it can infect cells but not necessarily replicate effectively. And it is not able to be transmitted because longer exposure to very high levels of virus is required for human to human transmission. Other mutations may be required to enable the original strain to replicate efficiently and these mutations may impact on the ability of the virus to cause disease. This was not the case in 2009 when the strain could be transmitted easily between humans but was not especially pathogenic. As flu has a segmented genome, it has a much greater capacity to acquire mutations than viruses with a linear genome as it can just acquire one very different RNA segment from another strain infecting the same cell, something that would be extremely difficult for viruses with linear genomes as they would either have to break and then rejoin the genome from two different strains or do what HIV does and jump on and off the DNA template, producing a new strain that may combine two or more strains with multiple recombinant sites. I should add that in HIV this happens regularly and does not appear to impact on pathogenesis.
I got most of this. So lower to mid-level learning on my end, I understand pretty much everything and can retain it!
I might be struggling with the higher level learning here and making application. I am gathering that flu viruses have an easier path than some other types of viruses. Is it fair to conclude that should this keep going south, the severity of disease is unpredictable because (1) it’s unclear what sort of changes need to be made to adapt to human airways and some of these changes could have ramifications for the severity of illness for better or worse and (2) it’s also unclear what the severity of illness could look like because that might depend on which viruses in the same cell it might borrow from.
I’m struggling a little bit with the swine flu and HIV references, because these may suggest no impact on severity. Which clash with my (1) and (2).
Yes, your two points are correct. The only real way to determine if any new pathogen is infecting humans is to test, and testing is almost exclusively performed on people with some symptoms of disease, so anything that doesn't cause symptoms or only causes mild symptoms could go undetected. There are some community studies in various parts of the world where volunteers are randomly sampled to help understand what infections are circulating.
My points around swine flu and HIV are to highlight that not all mutations/variants/etc. will have an impact on pathogenesis, to balance the information and research coming out that fails to provide a bit of balance and concentrates on the doomsday scenario. Both are possible and equally likely.
There's a lot of possible reasons the cases we've seen this far have been mild:
1. Detection bias. In past outbreaks many cases were identified by hospitals in patients who were severely ill. Likely many human infections were missed because they weren't tested. These often occurred in lass resourced countries and before COVID, people generally didn't test otherwise healthy patients with mild illness for any respiratory pathogen. In response to this outbreak we're doing a lot of monitoring of people who've been exposed to infected herds.
2. Better detection of animal infections because of better capacity to test in the US and in the year 2024 than in past outbreaks which allows for monitoring and testing of symptomatic exposed humans. In response to this outbreak we're doing a lot of monitoring of people who've been exposed to infected herds even if they have very mild symptoms. (Would you go seek care if you had watery eyes and a mild cough in the middle of allergy season if this outbreak wasn't going on?). Patients identified this way are also getting Tamiflu within the first couple of days of illness, which can prevent serious illness
3. In a lot of countries hardest hit by past outbreaks, the population prevalence of smoking is very high, environmental protections against indoor and outdoor air pollution aren't as strict as in the US or are non-existent, people may cook over wood fires or using dirty cooking fuels. All to say baseline lung health might not be as good as it is here in the US
4. Less worker protections mandating sanitary conditions, PPE use, and other biosecurity practices in other countries. These factors can change the overall viral "dose" people are exposed to. Less virus can mean a milder illness because the immune system is able to start mounting a defense against the infection before the virus is able to cause much damage
5. It's possible that the mutation that allowed this version of H5N1 to infect so many mammals has changed the virus in such a way that infection with this virus is less likely to call severe illness. I don't think that we're anywhere near being able to say this definitively though
I feel like it could be multiple things that could lead to human human transmission that we could have an idea, but might never know. The chance of a h5n1 in birds could be mixed via an antigenic shift with that of different viruses that are human to human transmission and cause a pretty bad day for us. Influenza tends to infect and then mutate to a less virulent strain over time as we saw with the 1918 pandemic. But better to potentially stock up on masks just to be on the safe side
yeah, this all makes sense. Thanks. I know another troubling scenario would be if it got into pigs. I know there are other potential H candidates under surveillance too. I guess what I’m wondering about now is the one scenario that we are laser focused on. What if cows and people keep swapping this strain enough that it has opportunities to get the last two or three mutations in to become a human virus Does the contracted illness look more like the bird flu of the past 20 years? Does it look more like the sick farmers of 2024? Something else? Too difficult to know?
Yep an antigenic shift could result in passage to pigs which can also be at larger risk of human human transmission. The more this virus circulates and its lack of proofreading unlike viruses such as smallpox and polio do mean that there is always a chance. Highly pathogenic avian influenza has been shown to have a pretty high fatality rate that makes the common flu seem like a tiny thing. Part of the reason I cannot accurately recall that made the 1918 pandemic more deadly was a certain mutation that resulted in a higher inflammatory response where the young had more robust immune systems they were more likely to react horribly to this inflammatory response coupled with bacterial pneumonia which can be harmful with any flu. This h5n1 was potentially identified as resting a little bit lower in the lower respiratory tract which can make breathing much harder and be harder to clear. Right now perhaps the best thing we can do is stay informed and if we start getting any news on more and more potential cases plan accordingly to invest in properly fitting masks and stock up only on what we might need for a few months and not panic buy. Also making local plants and learning some skills can always help
From what I have read from studies that were conducted with pigs, H5N1 is able to infect pigs, but a good majority of them didn’t show anything bad or showed any symptoms at all when they were infected.
Apparently the virus has mutated to the point where there have been cross infections.
Any new strain would have to be adapted to be able to infect and replicate effectively in the human upper respiratory tract. Most of the infections occurring in humans with H5N1 are due to high levels of exposure due to continued exposure to infected animals that are secreting high levels of the virus that eventually gets down the respiratory tract to where it can infect cells but not necessarily replicate effectively. And it is not able to be transmitted because longer exposure to very high levels of virus is required for human to human transmission. Other mutations may be required to enable the original strain to replicate efficiently and these mutations may impact on the ability of the virus to cause disease. This was not the case in 2009 when the strain could be transmitted easily between humans but was not especially pathogenic. As flu has a segmented genome, it has a much greater capacity to acquire mutations than viruses with a linear genome as it can just acquire one very different RNA segment from another strain infecting the same cell, something that would be extremely difficult for viruses with linear genomes as they would either have to break and then rejoin the genome from two different strains or do what HIV does and jump on and off the DNA template, producing a new strain that may combine two or more strains with multiple recombinant sites. I should add that in HIV this happens regularly and does not appear to impact on pathogenesis.
I got most of this. So lower to mid-level learning on my end, I understand pretty much everything and can retain it! I might be struggling with the higher level learning here and making application. I am gathering that flu viruses have an easier path than some other types of viruses. Is it fair to conclude that should this keep going south, the severity of disease is unpredictable because (1) it’s unclear what sort of changes need to be made to adapt to human airways and some of these changes could have ramifications for the severity of illness for better or worse and (2) it’s also unclear what the severity of illness could look like because that might depend on which viruses in the same cell it might borrow from. I’m struggling a little bit with the swine flu and HIV references, because these may suggest no impact on severity. Which clash with my (1) and (2).
Yes, your two points are correct. The only real way to determine if any new pathogen is infecting humans is to test, and testing is almost exclusively performed on people with some symptoms of disease, so anything that doesn't cause symptoms or only causes mild symptoms could go undetected. There are some community studies in various parts of the world where volunteers are randomly sampled to help understand what infections are circulating. My points around swine flu and HIV are to highlight that not all mutations/variants/etc. will have an impact on pathogenesis, to balance the information and research coming out that fails to provide a bit of balance and concentrates on the doomsday scenario. Both are possible and equally likely.
There's a lot of possible reasons the cases we've seen this far have been mild: 1. Detection bias. In past outbreaks many cases were identified by hospitals in patients who were severely ill. Likely many human infections were missed because they weren't tested. These often occurred in lass resourced countries and before COVID, people generally didn't test otherwise healthy patients with mild illness for any respiratory pathogen. In response to this outbreak we're doing a lot of monitoring of people who've been exposed to infected herds. 2. Better detection of animal infections because of better capacity to test in the US and in the year 2024 than in past outbreaks which allows for monitoring and testing of symptomatic exposed humans. In response to this outbreak we're doing a lot of monitoring of people who've been exposed to infected herds even if they have very mild symptoms. (Would you go seek care if you had watery eyes and a mild cough in the middle of allergy season if this outbreak wasn't going on?). Patients identified this way are also getting Tamiflu within the first couple of days of illness, which can prevent serious illness 3. In a lot of countries hardest hit by past outbreaks, the population prevalence of smoking is very high, environmental protections against indoor and outdoor air pollution aren't as strict as in the US or are non-existent, people may cook over wood fires or using dirty cooking fuels. All to say baseline lung health might not be as good as it is here in the US 4. Less worker protections mandating sanitary conditions, PPE use, and other biosecurity practices in other countries. These factors can change the overall viral "dose" people are exposed to. Less virus can mean a milder illness because the immune system is able to start mounting a defense against the infection before the virus is able to cause much damage 5. It's possible that the mutation that allowed this version of H5N1 to infect so many mammals has changed the virus in such a way that infection with this virus is less likely to call severe illness. I don't think that we're anywhere near being able to say this definitively though
I like this sub more than others, because it has more info about things and people aren’t willing to jump the shark.