Monday, July 23, 2018

Trans. & Emerg. Dis.:Comparison of HPAI & LPAI H7N9 Potential Threat To Mammals

Credit FAO


Twelve months ago China's H7N9 virus, having evolved into both HPAI and LPAI versions, was on just about everyone's short list for sparking the next pandemic (see NPR: A Pessimistic Guan Yi On H7N9's Evolution).
The CDC's IRAT (Influenza Risk Assessment Tool) Rankings, placed two separate LPAI H7N9 strains at the very top of their list of novel viruses with pandemic potential, and the WHO continued to refine their Candidate Vaccines For Pandemic Preparedness.
While those assessments remain, China's H7N9 activity has fallen off a cliff since last summer (see FAO chart above), with most of the credit likely due to a bold and aggressive poultry vaccination campaign ordered by the Chinese MOA last July.

Despite this welcomed respite from both poultry outbreaks and human infection by H7N9, these viruses continue to circulate in poultry and wild birds  in China.  The vaccine appears to have reduced viral shedding and transmission, but these viruses persist, and will undoubtedly continue to evolve over time. 
During the 5th wave, a new HPAI (highly pathogenic) H7N9 virus emerged in Guangdong province, and quickly began to spread to other provinces. 
Although case reports are limited, there has been some early evidence suggesting this HPAI version might pose an even greater threat to human health (see Eurosurveillance: Epidemiology of Human HPAI H7N9 Infection - Guangdong Province).

Today we've a new report, comparing the potential threat posed by both HPAI and LPAI H7N9 viruses in mammalian hosts.  Among their findings - HP viruses displayed a higher thermostability than did the LP viruses - which you may recall was a topic of considerable conversation last summer.

I've only reproduced the abstract (the full report is behind a pay wall).   I'll return with a brief postscript when you're done.
A comprehensive comparison of the fifth‐wave highly pathogenic and low‐pathogenic H7N9 avian influenza viruses reveals potential threat posed by both types of viruses in mammals

Lihong He,Dong Liu,Jiao Hu, Wenqiang Sun, Ruyi Gao, Lei Shi, Dongchang He, ,Bo Li, Xiaoquan Wang, Min Gu, Shunlin Hu, Xiaowen Liu, Zenglei Hu ,… See all authors

First published: 17 July 2018


Before 2013, zoonotic influenza infections were dominated by H5N1 viruses in China. However, the emergence of the H7N9 viruses in early 2013 changed this dominance greatly, and more than 1,600 laboratory‐confirmed human cases of H7N9 infections have been reported since then.
To understand the underlying mechanism of the emergence of the fifth epidemic wave that shows an unexpected sharp increase, we systematically investigated the biological characteristics of the highly pathogenic (HP) and low‐pathogenic (LP) H7N9 AIVs during this period. 

We first systematically analysed the haemagglutination assay gene of all the isolates available from the website and found that the HP and LP viruses differed a little in the well‐established receptor binding sites and in other potentially important sites. Phylogenetic analysis showed that both the HP and LP viruses belong to the branch of the Yangtze River Delta, whereas they diverged to different small branches. 

To further compare the biological variations in the HP and LP viruses, we selected six HP and six LP strains for in‐depth analysis, including receptor binding characteristics, thermal stability, viral replication and virulence in mice. 

The three major findings of this study were as follows: (a) Other potential  site/sites may affect the receptor binding property of the H7N9 viruses; (b) the HP viruses displayed a higher thermostability than did the LP viruses, quite consistent with the epidemiological data during the summer period; and (c) one‐third of the HP viruses were moderately pathogenic in mice, whereas all the LP viruses were nonpathogenic in this animal model. However, the LP viruses replicated more efficiently in the mouse lung and can spread to the extrarespiratory organs (spleen, kidney and brain). 

Taken together, our results suggest that both the HP and LP H7N9 viruses can pose a potential threat to public health, highlighting the importance of the continual surveillance of the H7N9 AIVs.

The remarkable success of China's H7N9 vaccination campaign has - at least temporarily - reduced the threat from both H7 and H5 avian flu out of China.  But Nature's laboratory is open and running 24/7.  
Earlier this year, we saw the test run of a new subtype - H7N4 (see UK PHE Guidance & Risk Assessment On Human H7N4 In China) - and over the past 5 years we've seen a steady procession of new avian subtypes come out of China (i.e. H5N8, H5N6, H10N8, etc.).
Add in the growing number swine flu (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza), and other novel virus threats, and  the likelihood of our current lull lasting for very long drops dramatically.
The good news is every month we go without a pandemic is another month we have to prepare.  
The bad news is, so few people, organizations, and countries appear to be actively doing so.  For more on the challenges posed by the next pandemic, you may wish to revisit:
The Challenge Of Promoting Pandemic Preparedness

Pandemic Unpreparedness Revisited
Smithsonian Livestream: “The Next Pandemic: Are We Prepared?"
World Bank: World Ill-Prepared For A Pandemic

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