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| Credit FAO |
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While H7N9 activity in China has been greatly suppressed these past 12 months (see chart above) - likely due to an aggressive national poultry vaccination campaign - the virus continues to circulate and evolve in poultry, and its pandemic threat has not gone away.
The CDC's IRAT (Influenza Risk Assessment Tool) Rankings, places two separate LPAI H7N9 strains at the very top of their list of novel viruses with pandemic potential, and the WHO continues to refine their Candidate Vaccines For Pandemic Preparedness.The runaway outbreak of 2016-2017, which saw nearly as many human infections as had been reported in the previous four outbreaks combined, was notable for not only its size, but for its geographic expansion across China and the emergence of new strains and lineages of the virus.
During this 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, some early evidence has suggested this HPAI version might pose an even greater threat to human health than its LPAI cousin (see Eurosurveillance: Epidemiology of Human HPAI H7N9 Infection - Guangdong Province).
This recent increase in viral diversity is one of the reasons why there is so much concern over the refusal of China to share virus samples with the United States (see New York Times China Has Withheld Samples of a Dangerous Flu Virus).Chinese researchers do, however, continue to publish information on H7N9 (and other) avian flu viruses - and while no substitute for the CDC having access to the actual virus - it does provide us with some valuable data.
Yesterday, the CDC's EID Journal published a new study which has found even more diversity among 5th wave H7N9 viruses than was previously known, and presents evidence of a high rate of adaptive molecular evolution.
This is a long, detailed study, and so I've only excerpted some highlights (bolding mine). Follow the link to read it in its entirety. When you return, I'll have a bit more.
Volume 24, Number 10—October 2018
Research
Molecular Evolution, Diversity, and Adaptation of Influenza A(H7N9) Viruses in China
Jing Lu1, Jayna Raghwani1, Rhys Pryce, Thomas A. Bowden, Julien Thézé, Shanqian Huang, Yingchao Song, Lirong Zou, Lijun Liang, Ru Bai, Yi Jing, Pingping Zhou, Min Kang, Lina Yi, Jie Wu2, Oliver G. Pybus2, and Changwen Ke2
Author affiliations: Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China (J. Lu, Y. Song, L. Zou, L. Liang, R. Bai, Y. Jing, P. Zhou, M. Kang, L. Yi, J. Wu, C. Ke); Guangdong Provincial Institution of Public Health, Guangzhou (J. Lu, P. Zhou, L. Yi); University of Oxford, Oxford, UK (J. Raghwani, R. Pryce, T.A. Bowden, J. Thézé, O.G. Pybus); Beijing Normal University, Beijing, China (S. Huang)
Abstract
The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016–17 raises concerns about the epizootic potential of these viruses.
We investigated the evolution and adaptation of H7N9 viruses by analyzing available data and newly generated virus sequences isolated in Guangdong Province, China, during 2015–2017. Phylogenetic analyses showed that circulating H7N9 viruses belong to distinct lineages with differing spatial distributions.
Hemagglutination inhibition assays performed on serum samples from patients infected with these viruses identified 3 antigenic clusters for 16 strains of different virus lineages. We used ancestral sequence reconstruction to identify parallel amino acid changes on multiple separate lineages. We inferred that mutations in hemagglutinin occur primarily at sites involved in receptor recognition or antigenicity.
Our results indicate that highly pathogenic strains likely emerged from viruses circulating in eastern Guangdong Province during March 2016 and are associated with a high rate of adaptive molecular evolution.(SNIP)
Discussion
Our results show that H7N9 viruses of lineage C, which were prevalent in the recent fifth influenza epidemic wave in China, comprise 2 geographically distinct clades (C1 and C2) that have undergone adaptive evolution.
Clade C1 is found primarily in eastern and central China and clade 2 in Guangdong Province, and both clades appear to have circulated in bird populations for ≈3 years. Our ancestral state reconstruction analysis provides crucial evidence that 2 successful lineages of H7N9 viruses (lineages B and C) have experienced multiple parallel amino acid changes (Figures 4, 5), suggesting the possible action of convergent molecular evolution.
We also observed a higher rate of virus adaptation in the eastern Guangdong Province (C2 clade compared with C1). Although clades C1 and C2 are phylogenetically closely related, serum from a clade C1 virus-infected patient has moderate reactivity with C2 strains from 2015–2016 and poor reactivity to the HP virus from 2016–2017.
The higher adaptation rate and antigenic changes in clade C2 are of concern from a public health perspective. Introduction of HP avian influenza into domestic poultry might constitute a serious risk, as demonstrated by emergence of goose–Guangdong lineage HP H5N1 viruses, which spilled back into wild birds and caused the longest global outbreak of HP avian influenza to date (33).(SNIP)
Recent studies have shown that the HP H7N9 virus is more pathogenic in mice, and more thermally stable, than low pathogenicity A/Anhui/1/2013 virus (47,48). Current surveillance indicates that HP H7N9 viruses have spread to several provinces in China and are responsible for large influenza outbreaks in poultry in central and northern China, that show high mortality rates (http://www.fao.org/ag/againfo/programmes/en/empres/H7N9/situation_update.html).
This finding raises the possibility of global dissemination of H7N9 viruses through migration of wild birds, in a manner similar to that observed for HP H5N1 viruses first identified in Guangdong Province (32). Although vaccination of poultry against H7N9 virus has been now implemented in some regions of China, virus adaptation and spatial distribution should be more closely monitored.
Dr. Lu is a virologist at the Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China. His primary research interests are epidemiology, evolution, and transmission of viruses associated with emerging infectious diseases.While China's massive poultry vaccination campaign over the summer of 2017 appears to have been a huge success, the rapid molecular evolution of the H7N9 virus could allow new, antigenically different strains, to evade its effects.
Over its first 5 years, H7N9 has been a primarily a Mainland China poultry problem, and we've seen relatively little information on it in wild birds.But its recent morphing into a more heat tolerant HPAI version could make it better adapted to wild and migratory birds, which might lead to its regional or even global spread, such as we've seen previously with HPAI H5N1 and HPAI H5N8/H5N6.
Although the year-long respite in H7N9 outbreaks and human infections has been a welcome development, today's report is a reminder that that status is unlikely to last forever.But whether it is H5 or H7, or some other novel flu, another pandemic is pretty much guaranteed. The only real questions are how soon? How bad? And how ready will we be when it comes.
