Sunday, October 01, 2017

J. Virology: Genesis and Spread of Newly Emerged HPAI H7N9 In China

H7N9 Reports Showng Seasonality - Credit FAO


October 1st - with the arrival of cooler weather across much of the Northern Hemisphere - is generally regarded as the start of a new avian flu season in China. This is the time of year, after the summer's lull in reporting, when we expect to start seeing new cases begin to emerge.
This fall, we are coming off the biggest H7N9 season on record by far; one where two lineages of LPAI H7N9 expanded their range to new areas of China, and where a newly emergent HPAI (High path) H7N9 appeared in Guangdong Province, and has rapidly spread north (see map below).

Unlike the stealthy LPAI H7N9 virus, which produces no observable signs of infection in birds (while still being highly pathogenic for humans), HPAI H7N9 causes severe morbidity and mortality in poultry and in humans. 
Although data on human infection is limited, there are some hints that HPAI H7N9 might be slightly more dangerous to humans (see Eurosurveillance: Epidemiology of Human HPAI H7N9 Infection - Guangdong Province).

Whether enhanced or the same, the CDC's IRAT (Influenza Risk Assessment Tool) rating on the two better established LPAI H7N9 viruses put both of them at the top of their list of novel viruses with pandemic potential.
China's neighbors, including Russia to the north, and Vietnam to the south, are all on high alert as HPAI H7N9 appears to be spreading faster and farther than earlier LPAI versions of the virus - possibly via migratory birds (see China's Nervous Neighbors).
There are big unanswered questions about this fall's expected return of avian flu across the Northern Hemisphere, with Europe on alert over a feared repeat of last year's record HPAI H5 epizootic, North America wary of a return of HPAI H5 after a two year absence, and Japan, Korea, and the rest Asia on the lookout for both HPAI H5 and H7 viruses. 
Influenza viruses have a habit of zigging when we expect them to zag, and so we won't know what this fall has in store until it actually arrives (see Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1).
All of which brings us to a new report, published last week in the Journal of Virology, that looks at the genesis and spread of this emergent HPAI H7N9 virus.  While the full article is behind a pay wall, we get a pretty good idea of the gist from the abstract below.

J Virol. 2017 Sep 27. pii: JVI.01277-17. doi: 10.1128/JVI.01277-17. [Epub ahead of print]
Genesis and Spread of Newly Emerged Highly Pathogenic H7N9 Avian Viruses in Mainland China.

Yang L1, Zhu W1, Li X1, Chen M2, Wu J3, Yu P4, Qi S5, Huang Y6, Shi W7, Dong J1, Zhao X1, Huang W1, Li Z1, Zeng X1, Bo H1, Chen T1, Chen W1, Liu J1, Zhang Y1, Liang Z2, Shi W4, Shu Y8,9, Wang D8.


The novel low pathogenic H7N9 avian influenza A viruses (LPAI H7N9) have caused a threat to public health for their high mortality and morbidity since their emergence in 2013. Recently, highly pathogenic variants of these H7N9 viruses (HPAI H7N9) have emerged and caused human infections and poultry outbreaks in Mainland China.
However, it is still unclear how the HPAI H7N9 virus was generated and how it evolved and spread in China. Here, we show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze Delta Region and spread southward to the Pearl Delta Region, possibly through live poultry trades.
After introduction into the Pearl Delta Region, the origin LPAI H7N9 virus acquired four amino acid insertions in the HA protein cleavage site and mutated into the HPAI H7N9 virus in late May 2016. Afterward, the HPAI H7N9 viruses further reassorted with LPAI H7N9 or H9N2 viruses locally and generated multiple different genotypes. As of 14 July 2017, the HAPI H7N9 viruses had spread from Guangdong province to at least 12 provinces.
The rapid geographical expansion and genetic evolution of the HPAI H7N9 viruses pose a great challenge, not only to public health, but also to poultry production. Effective control measures, including enhanced surveillance, are therefore urgently needed.


The LPAI H7N9 virus has caused five outbreak waves in humans and was recently reported to have mutated into highly pathogenic variants. It is unknown how the HPAI H7N9 virus originated, evolved, and disseminated in China. In this study, we comprehensively analyzed the sequences of HPAI H7N9 viruses from 28 human and 21 environmental samples covering eight provinces in China that were taken from November 2016 to June 2017.
The results show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze Delta Region. However, the insertion event of four amino acids in the HA protein cleavage site of a LPAI H7N9 virus occurred in late May 2016, in the Pearl Delta Region. The mutated HPAI H7N9 virus further reassorted with LPAI H7N9 or H9N2 viruses that were co-circulating in poultry. Considering the rapid geographical expansion of the HPAI H7N9 viruses, effective control measures are urgently needed.

So concerned are the Chinese over the emergence of this HPAI version of H7N9, over the summer they hastily rolled out a new, experimental poultry vaccine against both H5 and H7 avian flu viruses (see China MOA Orders HPAI H7N9 Vaccine Deployed Nationwide This Fall).
This is China's first attempt to control H7N9 via routine poultry vaccination. Their program to do so with HPAI H5 viruses over the past dozen years has produced - at best - mixed results.
China, which uses roughly 90% of the world's poultry vaccine, has undoubtedly saved tens of millions of poultry from culling, has prevented financial ruin for many farmers, and has lessened food instability.  All positives.
The problem is, vaccines don't always prevent infection - sometimes they just mask the symptoms.
Poorly matched or improperly administered vaccines are actually believed to drive the evolution of `vaccine escape' variants, which increases viral diversity and further diminishes the vaccines effectiveness (see New Scientist: The Downsides To Using HPAI Poultry Vaccines).

A few additional blogs on this topic include:
The HPAI Poultry Vaccine Dilemma
Study: Recombinant H5N2 Avian Influenza Virus Strains In Vaccinated Chickens
         EID Journal: Subclinical HPAI In Vaccinated Poultry – China

While most of the world eschews the use of poultry AI vaccines for these (and other) reasons, China is arguably too dependent upon them to change policies now, and so a lot is riding on just how well this new H7N9 vaccine works, and how effectively it is deployed.

Stay tuned.

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