#16,881
Although the number of new human H5N6 infections being reported by China have fallen the past couple of months, since late 2020 we've seen a huge resurgence of human infections on the Mainland. This virus is particularly concerning due to its high fatality rate (40%-50%) in humans.
While undoubtedly an undercount, between 2014 and 2020 China reported only 3 to 4 cases a year, but that number has soared by more than 50 cases since December 2020. Curiously, despite linking most human H5N6 infections to contact with infected poultry, China has not reported a concurrent jump in H5N6 outbreaks in poultry.
Admittedly, getting timely reports from China on outbreaks - in humans, wild birds, or poultry - can be difficult. `Bad news' is often treated as a national security threat or a politically sensitive issue, and is often parceled out strategically by official government sources and/or state controlled media.
In the summer 2017, when the Mainland was facing the dual threat of H7N9 and H5N6, China rolled out a new H5+H7 poultry vaccine, which quickly reduced their avian flu threat. While hailed as a great success, controlling avian flu over the long run with poultry vaccines has a mixed record.
As we've discussed previously (see MPR: Poultry AI Vaccines Are Not A `Cure-all’ & The HPAI Poultry Vaccine Dilemma), AI vaccines don't necessarily stop viruses, sometimes they just suppress their symptoms.
This can allow viruses to spread asymptomatically in poultry - and when new variants invariably emerge (via reassortment or antigenic drift) - vaccines must be continually updated else they lose their effectiveness.
For more than a year we've seen a steady stream of scientific studies describing rapid evolutionary changes in the HPAI H5N6 virus, often with evidence of increasing mammalian adaptation :
China CCDC Weekly: Genetic Characterization of Two Human A (H5N6) Viruses — Guangxi , China, 2021
Two weeks ago, in a particularly stark report (see The Lancet: Resurgence of H5N6 Avian Influenza Virus in 2021 Poses New Threat to Public Health), Chinese scientists warned: "The high genetic diversity and the virulence in mammals of H5N6 viruses in 2021 pose an increasing threat to public health."
Yesterday the CDC's EID Journal published another analysis of reassortant avian H5N6 viruses in China, which describes novel reassortants of H5N6 as moving away from the protection of China's poultry vaccines, and warns its transmission risk is likely to increase.
Novel Reassortant Avian Influenza A(H5N6) Virus, China, 2021
Junhong Chen1, Lingyu Xu1, Tengfei Liu1, Shumin Xie1, Ke Li, Xiao Li, Mengmeng Zhang, Yifan Wu, Xinkai Wang, Jinfeng Wang, Keyi Shi, Beibei Niu, Ming Liao, and Weixin Jia
Abstract
Although reports of human infection with influenza A(H5N6) increased in 2021, reports of similar H5N6 virus infection in poultry are few. We detected 10 avian influenza A(H5N6) clade 2.3.4.4b viruses in poultry from 4 provinces in China. The viruses showed strong immune-escape capacity and complex genetic recombination, suggesting further transmission risk.
Severe human infection with influenza A(H5N6) virus was identified in China in 2014. During 2014–2020, a total of 26 cases of human infection were laboratory confirmed (1,2). Sporadic cases did not attract widespread attention until 2021 (3,4). During February–October 2021, China reported 24 laboratory-confirmed cases of human infection with H5N6 virus and 5 deaths (Figure 1, panel A); the number of human infections within only 8 months was close to the total for the previous 7 years.
The policy of compulsory poultry immunizations in China was adopted to prevent and control infection with highly pathogenic avian influenza (HPAI) subtype H5Nx (5). Although vaccination can reduce the likelihood of severe clinical disease and reduce shedding of virus in poultry, it cannot prevent sporadic infections with H5N6 virus in waterfowl. Because it is difficult to achieve a qualified 100% rate of H5N6 virus antibodies in waterfowl (6), these birds have become a weak link in prevention and control of the virus. In the context of selection pressure for vaccines and the absence of immunity in waterfowl, antigenic drift causes the H5N6 virus to continuously evolve (7), making currently available H5N6 vaccines ineffective.
On November 27, 2020, an outbreak of influenza A(H5N8) virus infections among wild swans was reported in China, resulting in the death of 2 swans (8,9). Since then, H5N8 clade 2.3.4.4b virus has spread throughout China, resulting in co-endemicity of H5N6 clade 2.3.4.4h/b and H5N8 clade 2.3.4.4b viruses. This 2020 outbreak was not the first outbreak of H5N8 virus in China; the earliest introduction of the virus into China was reported in Liaoning on September 12, 2014 (10,11). Because of China’s immunization policies for poultry, H5N8 virus was quickly eliminated, only to reemerge in 2020.
The reappearance and spread of H5N8 virus is a serious threat to the poultry industry. The ecologic environment of the virus has been altered, given the increasing number of influenza A(H5N6) cases in humans. The current prevalence and mode of virus reassortment is of great concern. We discovered a novel H5N6 virus in poultry, which has spread throughout the poultry industry and caused a sharp rise in human infections.
Conclusions
At the peak of human cases, we isolated a total of 10 novel reassortment H5N6 virus strains from local poultry and the environment that were highly similar to the H5N6 (human-origin) virus reported during the same period. The human and avian viruses belong to clade 2.3.4.4b. The initial epidemic strains clustered into 3 geographically characterized subclades, and each avian strain had the same mammalian susceptibility mutation. The apparent antigenic differences between the virus and vaccine antiserum suggest further transmission risk.
While poultry vaccination strategies can be successful, vaccines must be scrupulously applied and continually updated. Failure to do either invites the creation of vaccine escape variants, and the possibility of bigger problems down the road.
A few past blogs on the difficulties involved include:
