#17,311
There are two broad categories of avian influenza; LPAI (Low Pathogenic Avian Influenza) and HPAI (Highly Pathogenic Avian Influenza). This pathogenicity designation is based on specific genetic signatures, and the virus's mortality in poultry, and not its impact on humans.
- LPAI viruses are quite common in wild birds, cause little illness in poultry, and only rarely death. Prior to 2013 they considered less of threat to human health, but LPAI H7N9 proved that wrong. The other concern (particularly with H5 & H7 strains) is that LPAI viruses have the potential to mutate into HPAI strains when allowed to circulate in poultry.
- HPAI viruses are more dangerous, can produce high morbidity and mortality in wild birds and poultry, and can sometimes infect humans with serious result. The HPAI's of greatest concerns thus far have been H5N1 and H5N6.
Although we've seen the sporadic spillover of a number of LPAI (Low path) and HPAI (high path) avian influenza A viruses into humans - including rare instances with LPAI H9N2 primarily in Asia, LPAI H6N1 in Taiwan, LPAI H3N8 in China, LPAI H7N2 in NYC, and LPAI H7N4 also in China - the biggest players to date (see chart above) have been HPAI H5N1 (870 cases), LPAI & HPAI H7N9 (1568 cases) and HPAI H5N6 (83 cases).
These case counts are all thought to be significant under counts (see Revisiting the H5N1 CFR (Case Fatality Rate) Debate), but so far, none of these viruses has managed to transmit efficiently from human-to-human.
While it remains far from certain that any of the above mentioned avian viruses have what it takes to spark the next pandemic, recent increased spread of H5N1, and the spillover of the virus into mammals (including humans) has raised our level of concern.
As a results, we've seen flurry of statements, and guidance documented, released by public health agencies on avian flu over the past few months, including:
Yesterday the CDC posted a highly informative review of lab-confirmed human infections with LPAI and HPAI avian flu viruses over the years.
Given the amount of hyperbolic misinformation being published by the tabloid press, and repeated ad nauseam in the echo chamber of the Internet, the following information is an excellent reminder that this threat - while genuine - is nothing new.
I'll return with a brief postscript after the break.
Reported Human Infections with Avian Influenza A Viruses
Human infections with avian influenza A viruses are uncommon but have occurred sporadically in many countries, usually after unprotected exposures (e.g. not using respiratory or eye protection) to infected poultry or virus-contaminated environments and have resulted in mild-to-severe illness with a wide range of symptoms and complications. A small number of human infections with avian influenza A viruses have been attributed to exposure to infected wild birds. For some human infections, the source of the virus infection was not determined. Human infections have occurred with different subtypes of low pathogenic and highly pathogenic avian influenza A viruses. The designation of “low” versus “highly” pathogenic avian influenza A virus refers to specific criteria, including mortality in experimentally infected poultry, and not to the severity of illness with human infections. Clinical illness associated with human infections with avian influenza A viruses does not necessarily correlate with virus pathogenicity in infected birds.
Low Pathogenic Avian Influenza A Virus Infections*
Subtypes of low pathogenic avian influenza (LPAI) A viruses that have been virologically confirmed to have infected people include A(H6), A(H7), A(H9), and A(H10) viruses.
A(H6) Virus InfectionsA(H7) Virus Infections
- LPAI A(H6N1) virus infection was reported in one person with moderate lower respiratory tract disease in Taiwan in 2013.
A(H9) Virus Infections
- LPAI A(H7N2) virus infection was reported in a small number of people with conjunctivitis (pink eye), mild upper respiratory tract symptoms, or lower respiratory tract disease in the U.K. and U.S. since 2002. Four infections have been identified in the U.S. since 2002, including 2 that resulted from cat-to-human transmission of an LPAI A(H7N2) virus circulating among cats in 2016.
- LPAI A(H7N3) virus infection was reported in a small number of people with conjunctivitis or mild upper respiratory tract symptoms in the U.K. and Canada since 2004.
- LPAI A(H7N4) virus infection was reported in one person with pneumonia in China in 2017.
- LPAI A(H7N7) virus infection was reported in one person with conjunctivitis in the U.K. in 1996.
- LPAI A(H7N9) virus infection was reported in more than 1500 people in China, particularly during epidemics from 2013-2017, including cases exported to Hong Kong, Macau, Malaysia, Taiwan, and Canada. Clinical syndromes have included mild upper respiratory tract symptoms, lower respiratory tract disease, encephalitis, severe pneumonia with respiratory failure, and multi-organ failure. The case fatality proportion in hospitalized patients is approximately 40%. A very small number of people were reported with asymptomatic infection after investigations in China during 2013. The most recent H7N9 virus infection was reported in China in 2019.
A(H10) Virus Infections
- LPAI A(H9N2) virus infections have been reported sporadically in more than 100 people since 1998 in China, and in Hong Kong, Bangladesh, Cambodia, Egypt, India, Oman, Pakistan, and Senegal. Most cases have been in children and have resulted in mild upper respiratory tract illness symptoms, but lower respiratory tract disease including severe pneumonia, and respiratory failure, including a small number of deaths, have been reported.
Highly Pathogenic Avian Influenza A Virus Infections*
- LPAI A(H10N3) virus infection was reported in one person with severe pneumonia and respiratory failure in China in 2021, and in another person with severe pneumonia and respiratory failure in China in 2022.
- LPAI A(H10N7) virus infection was reported in a small number of people with conjunctivitis or mild upper respiratory tract symptoms in Egypt in 2004 and Australia in 2010.
- LPAI A(H10N8) virus infection was reported in a small number of people with severe pneumonia with respiratory failure, including a few deaths, in China since 2013.
Subtypes of highly pathogenic avian influenza (HPAI) A viruses that have been virologically confirmed to have infected people include A(H5) and A(H7) viruses.
A(H5) Virus InfectionsA(H7) Virus Infections
- HPAI A(H5N1) virus infections have been reported in more than 880 people with approximately 50% case fatality proportion since 1997, including 20 cases and 7 deaths in Hong Kong during 1997-2003, and more than 860 cases reported in 21 countries since November 2003. Mild upper respiratory tract symptoms, lower respiratory tract disease, severe pneumonia with respiratory failure, encephalitis, and multi-organ failure have been reported. One case of asymptomatic infection was reported in Vietnam in 2011, and another asymptomatic case was reported in the United Kingdom that occurred in late 2021. The spectrum of illness caused by human infection with current H5N1 bird flu viruses is unknown. Since 2016, a small number of sporadic infections have been reported each year globally. Illness in humans from all bird flu virus infections has ranged in severity from no symptoms or mild illness to severe disease that resulted in death. Total case counts reported since 1997 are available.
- HPAI A(H5N6) virus infections have been reported in more than 80 people in China since 2014 and one case was reported in Laos in 2021. Mild upper respiratory tract symptoms, lower respiratory tract disease, severe pneumonia with respiratory failure, and multi-organ failure have been reported. Case fatality proportion in hospitalized patients is approximately 30%.
- HPAI A(H5N8) virus was isolated from one asymptomatic poultry worker in Russia in 2020.
- HPAI A(H7N3) virus infections have been reported in a small number of people with conjunctivitis since 2004 in Canada and in other countries.
- HPAI A(H7N7) virus infections have been reported in more than 90 people, since the first human infection was identified in the U.S. in 1959; although that infection was associated with hepatitis, most infections have been associated with conjunctivitis. However, mild upper respiratory tract symptoms, lower respiratory tract disease, severe pneumonia with respiratory failure, and multi-organ failure have been reported, including one death. Most reported cases were associated with exposures during widespread poultry outbreaks in the Netherlands in 2003.
- HPAI A(H7N9) virus infections have been reported in China since 2016, including lower respiratory tract disease, severe pneumonia with respiratory failure, and multi-organ failure. The case fatality proportion in hospitalized patients is >40%.
Human-to-Human Transmission of Avian Influenza A Viruses
Human-to-human transmission of avian influenza A viruses is rare. Probable limited, non-sustained, human-to-human transmission has been reported in a small number of people without poultry exposures who had close unprotected exposure to a symptomatic index case of HPAI A(H5N1) virus infection, HPAI A(H7N7) virus infection, or LPAI A(H7N9) virus infection. Most reported cases of probable limited, non-sustained, human-to-human transmission have occurred among blood-related family members after unprotected, prolonged close household exposure to a symptomatic family member. However, a small number of reported cases occurred after unprotected, prolonged close exposure to a very sick family member in a hospital. A few cases of probable limited, non-sustained, human-to-human transmission in a hospital have been reported among unrelated patients after unprotected exposures.
*Sources: Adapted from Uyeki T and Peiris M. Infectious Disease Clinics of North America 2019; and World Health Organization reports. For the latest summary, case counts of human infections, and risk assessment, see the World Health Organization Influenza at the human-animal interface summary and assessment: https://www.who.int/teams/global-influenza-programme/avian-influenza/monthly-risk-assessment-summary
Although the threat from these avian viruses is genuine, no one knows for certain whether these H5 or H7 viruses have the ability to adapt well enough to humans to spark a pandemic. While we can only go back a bit over 120 years, the influenza pandemics we've seen have been H2, H3, H1, H2, H3, H1, H1 . . . .
Prior to that, the 1890-93 `Russian flu’ pandemic has often been ascribed as to being caused by H2N2 virus, while the H3N8 virus has been tentatively pegged as causing the 1900 epidemic (see Transmissibility and geographic spread of the 1889 influenza pandemic).
The worst of these - the 1918 H1N1 pandemic - is thought to have killed well over 40 million people, or about 2.5% of those it infected. But those numbers are still debated.
Another pandemic will come, but whether it will be milder or worse than COVID is unknowable. Dire predictions of a 50% fatality rate with avian flu are probably overwrought, but there is nothing to say that 1918 is the worst that nature can deliver.
Admittedly, we could have years or even decades before the next pandemic emerges.
But nature doesn't use calendars, meaning it could just as easily emerge tomorrow. And while H5N1 is currently at the top of our worry list, it could come from any of the viruses mentioned above, or from something completely out of left field.
As weary as we all are after 3+ years of COVID, we need to be preparing ourselves for the next one. Because as bad as COVID has been, the next one could be worse.
