Thursday, May 23, 2019

Eurosurveillance: The re-emergence of HPAI H7N9 Human Infection in Mainland China, 2019



Two years ago pandemic concerns were heightened as the world watched the biggest human outbreak (see chart above) of Avian Influenza on record, in Mainland China.  The culprit was H7N9 - which emerged as an LPAI virus in 2013 - but evolved into co-circulating LPAI & HPAI strains in late 2016.

In the summer of 2017, following the spring surge in H7N9 infections , China's MOA announced plans to test a new experimental H5+H7 poultry vaccine in two provinces (Guangdong & Guangxi).
With fears mounting that H7N9 was moving ever closer to becoming a pandemic strain, less than a month later the MOA Ordered HPAI H7N9 Vaccine Deployed Nationwide that fall. 
While previous poultry vaccination programs had yielded varying levels of success, China's dramatic drop in human infections, reported outbreaks in poultry, and virus detection from routine surveillance has exceeded all expectations.

Last October we looked at an EID Journal Dispatch that found a remarkable reduction in H7 virus detection in Guangdong Province:
Volume 25, Number 1—January 2019
Influenza H5/H7 Virus Vaccination in Poultry and Reduction of Zoonotic Infections, Guangdong Province, China, 2017–18
Jie Wu1, Changwen Ke1, Eric H.Y. Lau, Yingchao Song, Kit Ling Cheng, Lirong Zou, Min Kang, Tie Song2 , Malik Peiris, and Hui-Ling Yen2


We compared the detection frequency of avian influenza H7 subtypes at live poultry markets in Guangdong Province, China, before and after the introduction of a bivalent H5/H7 vaccine in poultry. The vaccine was associated with a 92% reduction in H7 positivity rates among poultry and a 98% reduction in human H7N9 cases.
The year-long drought in human cases ended in April, when China Reported Their 1st Human H7N9 Case Of 2019, at a hospital in Gansu Province, but we later learned the patient was from neighboring Inner Mongolia.
Today the journal Eurosurveillance carries a detailed report on this case, and some recent - and potentially important - changes to the H7N9 virus. 
This is a lengthy and at times, technical, report. Most of my readers will want to follow the link and read it in its entirety.  But briefly, the H7N9 viruses isolated from the patient, and poultry from around his home, carried changes in the HA that may reduce the effectiveness of current vaccines, and a number of mutations that may increase adaptation to mammalian hosts.

Rapid communication Open Access 

The re-emergence of highly pathogenic avian influenza H7N9 viruses in humans in mainland China, 2019  
Deshan Yu1,2, Guofeng Xiang1,3, Wenfei Zhu1,4, Xia Lei1,5, Baodi Li2, Yao Meng4, Lei Yang4, Hongyan Jiao6, Xiyan Li4, Weijuan Huang4, Hejiang Wei4, Yanping Zhang7, Yan Hai5, Hui Zhang2, Hua Yue5, Shumei Zou4, Xiang Zhao4, Chao Li7, Deng Ao6, Ye Zhang4, Minju Tan4, Jia Liu4, Xuemei Zhang6, George F. Gao4,7, Lei Meng2,8, Dayan Wang4,8
Since March 2013, influenza A(H7N9) viruses have caused five epidemic waves of zoonotic infections with a large number of reported human cases (1,567 in total up to February 2018). The first wave lasted until September 2013, and the following four occurred annually between October and September of the next year from 2013/14 to 2016/17. During the fifth wave in 2016/17, the emergence of highly pathogenic avian influenza (HPAI) H7N9 viruses raised wide global concern [1]. 
Compared to low pathogenic avian influenza (LPAI) A(H7N9) viruses, HPAI H7N9 viruses maintained the capacity to bind both human and avian receptors [2] and unreduced transmissibility in mammalian animal models, but exhibited higher virulence and broader tissue tropism [3-5]. Subsequent to 31 human HPAI H7N9 cases being reported in China in the fifth wave, their numbers decreased dramatically from October 2017, with only one additional HPAI H7N9 human case up to February 2018. These 32 latest human cases covered nine provinces of China.
During the following 14 months, neither LPAI H7N9 nor HPAI H7N9 was reported in humans in the country. Several HPAI H7N9 outbreaks occurred in poultry, with the latest in March 2019 in peacocks in Liaoning province (
In late March 2019, a person in Inner Mongolia, China, presenting with severe pneumonia and respiratory failure was confirmed with HPAI H7N9. The re-emergence of a human HPAI H7N9 virus infection after reports of such cases had ceased for more than a year caused high public health concerns. We hereby describe this case and analyse genome features of the viruses causing the infection and of viruses found near the case’s residence. 

Among zoonotic influenza A viruses, influenza A(H7N9) viruses have caused a large number of reported human infections. As one of the strategies for H7N9 prevention and control, vaccination with an H5/H7 bivalent influenza vaccine was adopted in poultry in mainland China since September 2017. It has been reported that vaccination has resulted in reduced isolation rate of H7N9 viruses in poultry by 93.3% [16]. 

No H7N9 human cases was reported since February 2018. However, in late March 2019, we identified one HPAI H7N9 human case with fatal outcome, and HPAI H7N9 viruses with high genome identity to those of the case were detected from environmental samples. Together, these HPAI H7N9 viruses formed a subclade which exhibited a long genetic distance to the previously reported HPAI H7N9 viruses (Figure 1). 

This suggests that H7N9 viruses might still circulate in poultry at a low level in limited locations. In addition, several immune escape mutations, which had not been detected in previously reported HPAI H7N9 viruses, occurred in the HA1 proteins of these viruses (Table 1). The antigenic features of these HPAI H7N9 viruses may differ from the current HPAI H7N9 candidate vaccine strain

Phenotypic features, including antigenic characterisations and receptor binding profiles, need to be investigated in further studies. In conclusion, the detection of this HPAI H7N9 in a human raises a concern for the virus surveillance in both human and avian species, and reminds us that there is still a long way to go to control H7N9 viruses.
        (Continue . . . )

There is little doubt about the success of China's emergency H5+H7 poultry vaccination program. But avian viruses continually evolve, and over time poultry vaccines can become less effective.

Poor vaccine matches can then allow AI viruses to spread silently among flocks, to continue to reassort and to evolve, and even potentially lead to the emergence new subtypes of avian flu.

A few earlier blogs on that include:
Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China).

Study: Recombinant H5N2 Avian Influenza Virus Strains In Vaccinated Chickens

EID Journal: Subclinical HPAI In Vaccinated Poultry – China

While one H7N9 human case after a year's silence does not a crisis make, it is a reminder that flu's evolution never stops, and that Nature's laboratory is fully capable of launching us back into crisis mode at any time.