Opinion.AreHuman-to-HumanAndMammal-to-HumanTransmissionTheSourceOfMostH5N1InfectionsInHumans History
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The following opinion is derived from %newwin%[[http://www.fluwikie2.com/pmwiki.php?n=Forum.AreHumanToHumanAndMammalToHumanTransmissionTheSourceOfMostH5N1InfectionsInHumans|this thread]]. Many thanks to my fellow FluWikians for their comments on the thread which have helped me refine and expand it.
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'''Are Human-to-Human and Mammal-to-Human Transmission the Source of Most H5N1 Infections in Humans?'''
Although we have been conditioned to believe that birds are the source of most human infections of H5N1, what is the evidence that this is so? Certainly, many, many birds have been infected. It is also true that a close association between infected birds and some patients have been observed. For example, the owner of a prize fighting cock applied mouth-to-beak resuscitation when blood was impairing the bird’s ability to breathe.
However, in most cases, the association between human patients and infected birds is either absent or very tenuous - some birds in the village died, or the patient ate chicken a week ago, or the patient walked past a chicken on their way home from work.
It also interesting to note that poultry workers who would be expected to have the most exposure are rarely infected. Nor do they have antibodies to the virus.
Many of the human cases involve clusters. One person is infected, there is a delay consistent with H5N1's incubation period, and then one or more additional people are infected. Which is more likely, 1. first one person was infected by birds, then other family members were infected by birds, or 2. that the first person infected others? Also, why do we expect that it’s easier to get infected from birds than other people? If the spread from birds is fecal-oral, isn’t that route of infection also possible from human to human, especially caregivers? There are many viruses that are spread human to human this way. Think Norovirus.
Other mammals are also possible vectors. Here is a list of the mammals that have been shown to be infected by H5N1. Perhaps human infections of H5N1 are rare because it is really, really hard to get it from birds. But perhaps it’s not so hard to get it from mammals. There may be few human cases because relatively few mammals have been infected thus far.
Strains of H5N1 isolated from humans were more lethal to ferrets than strains isolated from birds reference. Why would this be? I had interpreted this to mean that the virus had mutated while in the patients to become more adapted to mammals. But, there is another explanation. Suppose the virus isolated from patients was more lethal to mammals (ferrets) because it infected the patients directly from mammals. This would have given the virus much more time to adapt to mammals.
Cat H5N1 sequences in Indonesia are apparently more similar to H5N1 sequences from humans than either are to H5N1 sequences from birds. What is the most logical interpretation of these results? I submit that there may be a mammalian reservoir for H5N1 in Indonesia and other countries and that H5N1 is under selection to adapt to mammals in this reservoir. Further, at least some of the human cases may be due to mammal-to-human infections. (See also Dr. Jeremijenko’s post at 23:14 in this thread, and here and here). In the recent large cluster of human cases in Indonesia, no infections of poultry were found in close proximity to the village where the outbreak occured. However, pigs with antibodies to H5N1 were found in this region reference. H5N1 infections in pigs would be particularly worrisome as these animals could serve as mixing vessels for the formation of a human-adapted H5N1 strain.
I cannot prove that specific human infections were due to human-to-human or mammal-to-human transmission. However, it is equally impossible to prove that a specific human infection was due to transmission from a bird. Given that, all three possible modes of transmission should be evaluated according to the same criteria. There is no reason that bird-to-human transmission should be the default explanation.
Implications. Human-to-human spread by close contact may be much more frequent than is currently advertised. There is the potential for large outbreaks if an infected person is in close contact with many others (daycare or school) or handles food for many others (cruise ships, restaurants). Also, the funeral practices of some Africans involve close contact with the body of the deceased and their bodily fluids. Marburg and Ebola have been spread this way. H5N1 might also cause large outbreaks in Africa through this mechanism. Manure from chickens and livestock may be infectious.
The prescence of a mammalian reservoir for H5N1 in Indonesia and possibly elsewhere would result in selective pressure for H5N1 to adapt to mammals. We discussed whether it was possible for H5N1 to be evolving towards a pandemic strain on other threads here and here. Some had argued this would be impossible because the virus would have to start over again every time it jumped from bird to human. But if it starts out in a mammal, it’s got a head start when it infects a human.
Action steps
*Warn people that H5N1 may be frequently transmitted by close contact with an infected patient.
*Warn anyone involved in handling the body of the deceased that bodily fluids may be infectious.
*Test mammals as well as birds when human cases are observed
*Ask villagers to report suspicious die-offs of mammals as well as birds. Test these mammals for H5N1.
*Compare H5N1 sequences of infected mammals with the sequences from H5N1 infected humans and birds.
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'''Are Human-to-Human and Mammal-to-Human Transmission the Source of Most H5N1 Infections in Humans?'''
Although we have been conditioned to believe that birds are the source of most human infections of H5N1, what is the evidence that this is so? Certainly, many, many birds have been infected. It is also true that a close association between infected birds and some patients have been observed. For example, the owner of a prize fighting cock applied mouth-to-beak resuscitation when blood was impairing the bird’s ability to breathe.
However, in most cases, the association between human patients and infected birds is either absent or very tenuous - some birds in the village died, or the patient ate chicken a week ago, or the patient walked past a chicken on their way home from work.
It also interesting to note that poultry workers who would be expected to have the most exposure are rarely infected. Nor do they have antibodies to the virus.
Many of the human cases involve clusters. One person is infected, there is a delay consistent with H5N1's incubation period, and then one or more additional people are infected. Which is more likely, 1. first one person was infected by birds, then other family members were infected by birds, or 2. that the first person infected others? Also, why do we expect that it’s easier to get infected from birds than other people? If the spread from birds is fecal-oral, isn’t that route of infection also possible from human to human, especially caregivers? There are many viruses that are spread human to human this way. Think Norovirus.
Other mammals are also possible vectors. Here is a list of the mammals that have been shown to be infected by H5N1. Perhaps human infections of H5N1 are rare because it is really, really hard to get it from birds. But perhaps it’s not so hard to get it from mammals. There may be few human cases because relatively few mammals have been infected thus far.
Strains of H5N1 isolated from humans were more lethal to ferrets than strains isolated from birds reference. Why would this be? I had interpreted this to mean that the virus had mutated while in the patients to become more adapted to mammals. But, there is another explanation. Suppose the virus isolated from patients was more lethal to mammals (ferrets) because it infected the patients directly from mammals. This would have given the virus much more time to adapt to mammals.
Cat H5N1 sequences in Indonesia are apparently more similar to H5N1 sequences from humans than either are to H5N1 sequences from birds. What is the most logical interpretation of these results? I submit that there may be a mammalian reservoir for H5N1 in Indonesia and other countries and that H5N1 is under selection to adapt to mammals in this reservoir. Further, at least some of the human cases may be due to mammal-to-human infections. (See also Dr. Jeremijenko’s post at 23:14 in this thread, and here and here). In the recent large cluster of human cases in Indonesia, no infections of poultry were found in close proximity to the village where the outbreak occured. However, pigs with antibodies to H5N1 were found in this region reference. H5N1 infections in pigs would be particularly worrisome as these animals could serve as mixing vessels for the formation of a human-adapted H5N1 strain.
I cannot prove that specific human infections were due to human-to-human or mammal-to-human transmission. However, it is equally impossible to prove that a specific human infection was due to transmission from a bird. Given that, all three possible modes of transmission should be evaluated according to the same criteria. There is no reason that bird-to-human transmission should be the default explanation.
Implications. Human-to-human spread by close contact may be much more frequent than is currently advertised. There is the potential for large outbreaks if an infected person is in close contact with many others (daycare or school) or handles food for many others (cruise ships, restaurants). Also, the funeral practices of some Africans involve close contact with the body of the deceased and their bodily fluids. Marburg and Ebola have been spread this way. H5N1 might also cause large outbreaks in Africa through this mechanism. Manure from chickens and livestock may be infectious.
The prescence of a mammalian reservoir for H5N1 in Indonesia and possibly elsewhere would result in selective pressure for H5N1 to adapt to mammals. We discussed whether it was possible for H5N1 to be evolving towards a pandemic strain on other threads here and here. Some had argued this would be impossible because the virus would have to start over again every time it jumped from bird to human. But if it starts out in a mammal, it’s got a head start when it infects a human.
Action steps
*Warn people that H5N1 may be frequently transmitted by close contact with an infected patient.
*Warn anyone involved in handling the body of the deceased that bodily fluids may be infectious.
*Test mammals as well as birds when human cases are observed
*Ask villagers to report suspicious die-offs of mammals as well as birds. Test these mammals for H5N1.
*Compare H5N1 sequences of infected mammals with the sequences from H5N1 infected humans and birds.