Wednesday, July 18, 2018

Sci Rpts: Genetic Characterization & Pathogenic Potential Of Avian H10 Viruses


Among avian flu viruses, subtypes H5 and H7 - due to their 20 year history of producing high human mortality -  tend to garner the bulk of our attention. That said, there are a number of other `second tier' avian viruses that pose a zoonotic threat.
Best known, and discussed often in this blog due to its ability to easily reassort with other viruses, is LPAI H9N2 (see recent overview).
Although the true number of human infections is unknown, at least 3 dozen have been identified over the past 20 years (see FluTrackers Global Cumulative H9N2 Partial Case List 1998-2017).
H9N2 is regarded as having at least some pandemic potential (see CDC IRAT SCORE), and several candidate vaccines have been developed over the years.
But also, in 2013 we saw a woman was hospitalized with mild pneumonia from H6N1 in Taiwan. The following year, in the EID Journal: Seropositivity For H6 Influenza Viruses In China, researchers reported a low - but significant - level of H6 antibodies,  particularly among live bird handlers.

While in 2004 the first known human H10 infections (see Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt) were reported, followed in 2012 by a limited outbreak among workers at a chicken farm in Australia (see in EID Journal: Human Infection With H10N7 Avian Influenza).
Most of these avian flu infections were mild or asymptomatic, and self limiting. Often only producing conjunctivitis or mild flu-like symptoms.
But in late 2013 a new H10N8 virus emerged in Mainland China (see Lancet: Clinical & Epidemiological Characteristics Of A Fatal H10N8 Case) infecting three people, killing at least two.

With both H10N8 and H10N7 now shown capable of infecting humans - albeit with widely varying degrees of severity - H10 is now viewed as deserving of more research and respect.
Yesterday, Scientific Reports published the following characterization report on a number of H10 reassortants (H10N1, H10N6, H10N7 & H10N9) found to be circulating in live poultry markets in Bangladesh.
It's a long, detailed, report and you'll want to read it in its entirety.  First the abstract, then I'll return with a couple of snippets from the body of the study.

Genetic characterization and pathogenic potential of H10 avian influenza viruses isolated from live poultry markets in Bangladesh
Rabeh El-Shesheny,John Franks, Bindumadhav M. Marathe, M. Kamrul Hasan, Mohammed M. Feeroz, Scott Krauss, Peter Vogel, Pamela McKenzie, Richard J. Webby & Robert G. Webster

Scientific Reportsvolume 8, Article number: 10693 (2018) | Download Citation


Fatal human cases of avian-origin H10N8 influenza virus infections have raised concern about their potential for human-to-human transmission. H10 subtype avian influenza viruses (AIVs) have been isolated from wild and domestic aquatic birds across Eurasia and North America.

We isolated eight H10 AIVs (four H10N7, two H10N9, one H10N1, and one H10N6) from live poultry markets in Bangladesh. Genetic analyses demonstrated that all eight isolates belong to the Eurasian lineage.

HA phylogenetic and antigenic analyses indicated that two antigenically distinct groups of H10 AIVs are circulating in Bangladeshi live poultry markets.
We evaluated the virulence of four representative H10 AIV strains in DBA/2J mice and found that they replicated efficiently in mice without prior adaptation. Moreover, H10N6 and H10N1 AIVs caused high mortality with systemic dissemination.

These results indicate that H10 AIVs pose a potential threat to human health and the mechanisms of their transmissibility should be elucidated.
        (Continue  . . . . )

In the discussion section of the study, the authors (which include both Webby & Webster from St. Jude Children’s Research Hospital) point out the risks of the co-circulation of H9N2 viruses in Bangladesh.

As we've discussed previously (see The Lancet: H9N2’s Role In Evolution Of Novel Avian Influenzas), these ubiquitous (in Asia and increasingly in the Middle East) LPAI viruses have lent their internal genes to some of the most dangerous avian viruses in the wild.
The H9N2 AIV is endemic in Bangladesh21,44,45,46 and has acquired mammalian host–specific mutations in its internal genes, which have been shown to facilitate transmission from avian species to humans44. H9N2 AIVs are significant donors of genetic material to emerging zoonotic viruses such as H5Nx, H7N9, and H10N8 AIVs posing an enormous threat to both human health and poultry industry. The wide circulation of H9N2 AIVs in Bangladeshi LPMs affords H9N2 with more opportunities for reassortment with other AIV subtypes, such as H10 AIVs. 
While the number of reported H10 infected humans has been small, due to a lack of surveillance and testing, it is likely that those numbers under represent reality. 
In 2014's BMC: H10N8 Antibodies In Animal Workers – Guangdong Province, China, we saw evidence suggesting that people may have been infected with the H10N8 virus in China before the first  case was recognized. 
As the following snippet indicates, a similar serological study published in 2010 showed evidence of H10 infection among American turkey farmers.

Transmission of H10 AIVs to humans has resulted in some fatal cases, and serologic evidence indicates that H10 AIVs were previously transmitted among turkey farmers in the United States47.
This should raise concern about the potential for human-to-human transmission of H10 AIVs. Evaluation of the biologic properties of H10 and other subtypes of AIVs circulating in LPMs is essential for understanding the emergence and evolution of these viruses and to reduce their potential pandemic threat to public health.

While we often hear (for good reason) that the H7N9 virus is the top pandemic contender in the wild, the same was being said about H5N1 until an upstart swine-origin H1N1 virus came out of left field and sparked the 2009 pandemic.

Which is why we need to constantly look beyond the obvious pandemic threats, if we hope to have a head's up over what comes down the pike next.

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