But as we've discussed often, there are other zoonotic or potentially zoonotic avian flu viruses (H3, H4, H6, H9, H10, etc.) which are not reportable, and are often tolerated or ignored because they produce relatively minor financial losses to the poultry industry.

LPAI H9N2, which is now rife in poultry in Asia, the Middle East, and increasingly in Africa, is perhaps the most obvious threat.  We've seen > 140 documented human infections

But increasingly China has warned on the spread (in wild birds and poultry) and zoonotic potential of other LPAI viruses, including H3Nx, H4Nx, H6Nx, and H10Nx. 

If there is a common denominator among these varied LPAI viruses, it is that the longer they circulate in poultry, the greater the zoonotic threat they appear to pose. Their evolution may be far slower than H5 and H7 viruses, but that doesn't make them benign.  

Only easier to ignore.

Twelve years ago - during the opening salvo of H7N9's first wave in China - Taiwan reported the world's first known human infection with LPAI H6N1 (see Taiwan CDC: Epidemiological Analysis Of Human H6N1 Infection).  A year later, Taiwan reported an outbreak in dogs (see EID Journal: Influenza A(H6N1) In Dogs, Taiwan).

Virology Journal: Emerging Zoonotic Potential of H4N1 Avian Influenza Virus: Enhanced Human Receptor Binding and Replication via Novel Mutations

Just yesterday, in Preprint: Progressive Adaptation of H6N1 Avian Influenza Virus in Taiwan Enhances Mammalian Infectivity, Pathogenicity and Transmissibility we looked at a study describing a  `. . . stepwise adaptation of avian influenza viruses to mammalian hosts', which the authors suggest may stem from prolonged circulation in in poultry. 

While none of these LPAI (H3, H4, H5, H9, H10) viruses currently appear to pose the same level of threat as HPAI H5 and H7, they all are purportedly showing signs of gradual adaptation to mammalian hosts. 

Although there may be (unidentified) species barriers that prevent most (or all) of these subtypes from ever posing a serious public health threat, the sharp increase in the number of known HPAI and LPAI viruses with zoonotic potential over the past 12 years has been remarkable.   

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All of which brings us to a new report, once again from China, on the zoonotic potential of LPAI H4N1 viruses, which are commonly found in wild birds and in poultry.  

In 2012's in Seroprevalence Study: Avian Flu In Chinese Pigs, we looked at research that found low levels of H3, H4, and H6 subtypes of avian influenza in Chinese pigs while in 2015 we looked at reports of Avian H4N6 In Midwestern Swine.

While human infection with H4 viruses are believed to be both mild and rare, a 2011 PLoS One study (Evidence of infection with H4 and H11 avian influenza viruses among Lebanese chicken growers) presented serological evidence suggesting that `. . .  H4 and H11 influenza viruses may possess the ability to cross the species barrier to infect humans.'

Today's study finds that - at least in the laboratory - the LPAI H4N1 virus is already surprisingly well adapted to infecting, and replicating within, mammalian hosts. 

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PNAS Research: Intensity and Frequency of Extreme Novel Epidemics

BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover Events

But forewarned is only forearmed, if we take steps now to prepare for the next crisis.