#16,163
Over the past 10 months we've seen a major uptick in human infection with H5N6 avian influenza in China, with 17 cases reported since last December (see map above). This makes 41 cases reported from China (and 1 from Laos).
While we've not seen any obvious clustering of cases (other than a husband & wife in Hunan province who likely shared an exposure), the recent spate of H5N6 cases - particularly over the summer months - is concerning, as this is normally the slowest time of the year for avian flu transmission.
Details on these cases have generally been scant, but this week the Chinese CDC (CCDC) published a detailed review of 5 recent cases, all in Sichuan Province, in their CCDC Weekly (a publication modeled very much after the CDC's MMWR report).
You'll find my original blogs on these 5 cases here, here, here, here, and here.
To date, a total of 42 laboratory-confirmed cases of human infection with influenza A(H5N6) virus including 22 deaths* have been reported to WHO in the Western Pacific Region since 2014. The last case was reported from China, with onset dates of 31 July 2021 and.
*9 deaths at the time of IHR notification and 13 additional cases resulting in death after IHR notification
I've included the summary, and some excerpts from the Discussion section. You'll want to follow the link to read the full report, including details on the investigation and results. I'll have a brief postscript when you return.
Outbreak Reports: Five Independent Cases of Human Infection with Avian Influenza H5N6 — Sichuan Province, China, 2021
Chongkun Xiao1,&;Jianan Xu1,&;Yu Lan2,&;Zhongping Huang1;Lijun Zhou1;Yaxin Guo2;Xiyan Li2;Lei Yang2;George F. Gao2;Dayan Wang2;William J. Liu2, , ;Xingyu Zhou1, , ;Huiping Yang1, ,
Summary
What is known about this topic?
The emerging H5Ny lineages of the avian influenza virus (AIV) with genomic reassortments have posed a continuous threat to animals and human beings. Since the first case of avian influenza A (H5N6) virus infection in 2014, the World Health Organization has reported a total of 38 cases by August 6, 2021.What is added by this report?
A total of 5 new cases of H5N6 that occurred from May 2021 to July 2021 in Sichuan Province, China were reported in this study. Epidemiological and laboratory information of the five cases were investigated. The genomic analysis of the H5N6 genomes showed the features of AIV genomic reassortments and key residue substitutions.What are the implications for public health practice?
The emergence of human cases infected by AIV H5Ny lineages through time demonstrates a risk of the persistence and evolution of the virus to trigger sporadic outbreaks and even pandemics, which need continuous surveillance.
As a highly contagious virus, the avian influenza virus (AIV) circulates among birds as its reservoir host (1). The spillover to human beings and other animal species occurs frequently, leading to cross-species infection that may trigger mild outbreaks and even pandemics (2). In recent years, AIV H5Ny lineages (i.e., H5N1, H5N2, H5N6, and H5N8) have proved the capacity for zoonotic spread and genomic reassortments amongst this viral group and thus pose a severe threat to animals and human beings (3–4). Among these AIVs, H5N6 was first detected in 1975 (5), and the first reported case of human infection with a novel H5N6 was dated in 2014 (6–7). By August 2021, the World Health Organization (WHO) reported a total of 38 laboratory-confirmed cases of human infection with influenza A(H5N6) virus, including 21 deaths. This year, 10 sporadic human infections have been recorded in Sichuan Province, Anhui Province, Guangxi Zhuang Autonomous Region, and Chongqing Municipality (8).
INVESTIGATION AND RESULTS
Herein, we report the 5 cases infected by AIV H5N6 in Sichuan Province, China in 2021. These 5 independent cases occurred in 5 different districts or counties from 4 cities (Figure 1A, i.e., Jinjiang District of Chengdu City, Kaijiang County and Xuanhan County of Dazhou City, Bazhou District of Bazhong City, and Nanxi District of Yibin City). All four cities are located in the east of Sichuan Province, China (Figure 1A). A case was sampled by nasopharyngeal swabs and sent to the laboratory for quantitative polymerase chain reaction (qPCR) testing. The positive results will be sequenced and sent to China CDC for virus isolation. When a case was found, the local CDC and the municipal and/or provincial CDCs form two or three levels of investigation groups to carry out the epidemiological investigation of avian influenza cases. The timeline and investigation group for each case were shown in Table 1.(SNIP)
DISCUSSION
The AIV H5N6 was first reported as a low-pathogenic AIV (LPAIV) decades ago (5). Since the strain a/gs/gd/1/96 (H5N1) appeared in the 1990s, outbreaks of highly pathogenic AIV (HPAI) have occurred frequently. Before 2010 there was no evidence of reassortment of the H5N1 viruses with NA subtypes other than N1 (11). However, H5 reassorted with different specific NA subtypes, termed H5N2, H5N3, H5N5, H5N6, H5N8 after 2010 (12). These new virus subtypes emerged through multiple genetic reassortments of different subtype viruses within resident domestic and wild bird populations and continued to circulate in domestic poultry populations, leading to wider geographical spread and raising great concern based on their pandemic potential (13).
With the cross-infection of wild birds and poultry, the epidemic of viruses in poultry has accelerated. To date, a total of 38 laboratory-confirmed cases of human infection with influenza A (H5N6) virus, including 21 deaths. Our study found that all the 5 patients had been exposed to live poultry before their disease onset. Given this, more research, enhanced surveillance, including genomic epidemiology, is necessary on wild birds, poultry, and the environment.
The novel clade 2.3.4.4 H5N6 that was first reported in 2013, then reported in Laos and Vietnam in 2014/2015, with evidence of sustained transmission and further geographical spread in both countries. Later on, a series of poultry outbreaks in Japan, Myanmar, and the Republic of Korea have been found to be related by H5N6. By 2017, it began spreading to some European countries such as Greece, Germany, the Netherlands, and Switzerland (14).
Due to the genetic diversity of the virus, the World Health Organization (WHO) subdivided 2.3.4.4 into a–h clades, a total of 8 new clades.
Even if it is so finely divided, recent serological studies have found that the vaccine strains recommended by WHO cannot fully cover the emerging strains in these clades (15). Thus, the balance between viral evolution and the capacity of the candidate vaccine protection needs to be timely updated which will reduce infection events and mortality in humans and animals.
Fortunately, there is no evidence of sustainable human-to-human transmission of H5N6, considering that all cases in this study were independent and have no epidemiological correlation. A one-health approach needs to be strengthened to trace the source of infection in time, block the cross-species spread of the virus, reduce risks, and protect people’s health.
Acknowledgments
Ms. Jie Zhang, Mr. Idrissa Kamara, and Dr. Chuansong Quan.
Although this report cites continued evolutionary changes to the H5N6 virus, they find the virus is still primarily adapted to avian species. The concern is that could change over time.
All 5 of the cases in today's report had either visited a LPM (Live Poultry Market) or had contact with dead poultry, and environmental testing turned up evidence of H5N6 for four cases (2-5). It seems fairly likely that these were bird-to-human transmissions.
China's MOA, however, hasn't reported an outbreak of HPAI H5N6 since April (wild birds in Liaoning Province), raising concerns that the HPAI H5N6 virus - normally deadly in gallinaceous poultry - may be spreading more stealthily due to China's H5+H7 poultry vaccination program.
While H5N6 hasn't shown the ability to transmit efficiently from human-to-human, its high (roughly 50%) Case Fatality Rate - and continual evolution - put this virus near the top of our avian flu watch list.
