NEW DEVELOPMENT WITH REGARDS TO HIGHLY PATHOGENIC AVIAN INFLUENZA (HPAI)
I am interrupting my blog series on a comprehensive update of COVID-19, due to a concerning development relating to a virus that is one of a number on my watch list of potential pandemic threats – the HPAI A(H5N1) influenza virus.
Why was this virus on my watch list?
When I pick viruses for my list, the criteria I use are:
1st level selection: Viruses with airborne transmission.
2nd level selection: Of those viruses with airborne transmission, then I rank highest on the list those that are novel viruses or known viruses with novel mutations, recombinations or reassortments for which there is expected to be little population-level immunity.
(Levels 1 and 2 select for viruses with pandemic potential, then level 3 selects for severity of the pandemic)
3rd level selection: Then, of those viruses that satisfy the first and second levels of selection, I rank those viruses with any of the following traits higher up the list, and even higher up the list for the more of these traits that they have:
- Relatively high levels of morbidity (illness, but not death) and mortality (death) across all age groups, or at least many age groups;
- Significant presymptomatic or asymptomatic spread of infectious virus;
- School-aged children able to transmit the virus efficiently;
- High infectious load of virus in infected persons;
- Low infectious dose required for transmission;
- The virus is not particularly susceptible to environmental factors (temperature, humidity, UV light) and is able to remain infectious in the air and on surfaces for an extended period of time;
- No existing test or the only available tests are high complexity tests that can only be conducted in certain specialized laboratories;
- Widespread zoonotic and reverse zoonotic spread (the virus can transmit among humans, to our pets and farm animals, and back to humans)
- Non-durable immunity from infection and vaccination;
- No existing vaccine that is effective or that could quickly be modified to be effective in preventing severe disease;
- No known existing medications with antiviral effect against the virus;
- High degree of viral fitness and rapid evolution to increase transmissibility;
- Significant levels of infection among health care workers and nosocomial spread in health care facilities.
Among the viruses with airborne transmission, influenza viruses are a prime example. Therefore, this influenza virus makes it to the list based on level 1.
What has caused concern about this particular virus?
HPAI A(H5N1), an influenza A virus, has circulated in birds since at least 1997 (the first infection was detected in 1996 in China in a domestic goose) when it caused an epidemic among birds and was first detected, thus the reference to this virus being an avian (bird) influenza virus, which accounts for the A and the I in HPAI. The good news is that since 1997, only a total of 902 sporadic human A(H5N1) cases have been reported from 23 countries, caused by different HPAI A(H5N1) virus clades. However, the introduction of H5N1 into North America is not known to have occurred until late 2021 through migratory birds. The bad news is that with ongoing transmission in animals, the virus does evolve and there is always the chance that it could mutate or reassort in a manner that would increase transmission to humans. In fact, the reference to “caused by different HPAI A(H5N1) virus clades” is a reference to significant genetic changes to the virus warranting assignment to a new clade. The other bad news is that thus far there is a cumulative case fatality rate of greater than 50% in humans.
In the last century, there have been four occasions when influenza viruses with genes that originated from swine (pig) or avian (bird) reservoirs entered the human population with wide-spread, efficient and sustained human-to-human transmission causing pandemics [1918 Spanish flu A(H1N1), 1957 Asian flu A(H2N2), 1968 Hong Kong flu A(H3N2), and 2009 swine flu A (H1N1)].
Thus far, while the H5N1 virus has infected humans, it has not shown the ability for efficient human-to-human transmission. Most of the infections have been in people with close contact with infected animals, and we have not seen much forward transmission, even to family members.
Then, why all the concern? The concern is that the virus is spreading globally, even to remote areas (including Antartica), with an alarming expanded range of hosts. Waterfowl are natural hosts for low pathogenic influenza viruses. These wild and migratory birds then move to new locations and carry the virus with them. They congregate with domesticated ducks and geese to which they can transmit the viruses. Influenza viruses mutate frequently and while the virus started out as a low pathogenic virus (promoting its spread by these migratory birds that are not too sick to relocate geographically and find new domestic birds to transmit the virus to), there is the potential for the virus to evolve to a highly pathogenic form of virus that can result in loss of many domestic birds (some involved in our food chain) as it is transmitted among these birds and then potentially back again to migratory birds that can carry the virus to new areas of the state, country or world further infecting more domestic poultry before these birds die.
What has been alarming during the past year is that this particular HPAI A(H5N1) has been increasingly identified in mammals that generally have not been impacted by previous avian influenza viruses and we have seen the evidence that this particular virus can be highly pathogenic in many of these species of animals, as well, including ocean animals.
Human transmission of avian influenza viruses has historically been rare, as opposed to swine influenza viruses, which are much more suited for human transmission, but still relatively uncommon (for example, we had three documented cases in 2023 (two in Michigan and one in Montana – all from direct exposure to pigs at fairs) and just had our first of 2024 – in Pennsylvania). Swine flu is endemic to pigs. But pigs can be the intersection between birds (poultry on farms or even wild birds that transiently stop on land shared with pigs, or in the case of HPAI, where their carcass remains following their death) and humans (farmers, visitors at fairs, live markets, etc.) and pigs can serve as a “mixing bowl” for human, swine and avian viruses. That is a reference to the fact that coinfections of pigs with these different strains of influenza virus can result in the influenza viruses swapping segments of their genetic material, a process referred to as reassortment, in which the resulting virus has an increased ability to transmit from the pig to humans, and most worrisome, when the resulting reassorted virus also has the ability to transmit efficiently from humans to other humans. In fact, this is exactly what happened with the influenza A virus that caused the 2009 pandemic [A(H1N1)pdm09]. Genetic sequencing of this virus revealed eight gene segments of the virus were from a mix of avian, human and swine origins.
My concern arises from the first detection of HPAI A(H5N1) virus in cows, a week ago. In fact, one of the identifications came from cows in Cassia County in Idaho.
This Breaking News continues in the next blog piece.
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