#17,935
Divining exactly what is going on with avian flu, COVID, or any other emerging disease threat in China has always been challenging, since the CCP often treats `negative news' as a national security issue, and state run media only publishes what is approved for public consumption.
- We are routinely only belatedly notified of human avian flu infections (see here, here, and here), and then often with few details.
- During the first 3 years of the COVID pandemic, China - with a population of 1.4 billion - only admitted to 5242 deaths from the virus.
- After their Zero-COVID policy collapsed in December 2022, China reported roughly 80K deaths from COVID during Jan-Feb of 2023, but outside estimates (here and here) put that number between 1.4 and 1.9 million.
China isn't alone in holding their cards close to their vest (see here, here, and here), but they do represent nearly 1/6th of the world's population, and China has frequently been ground zero for emerging infectious diseases (see EID Journal: Predicting Hotspots for Influenza Virus Reassortment).
Fortunately, China permits the publication of scientific papers on many of these EID concerns. Although the CCP may still be exerting some editorial control, the focus of these papers may give us some clue as to what is currently on Chinese scientist's radar.
HPAI H5 & H7, and Swine viruses have typically garnered the most attention, but over the past couple of years we've been seeing a growing number of studies on the spread, evolution, and potential public health threat from LPAI H3, H4, H6 and H9 viruses in China.
A few recent examples include:
Viruses: Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice
Genetics and Pathogenicity of Influenza A (H4N6) Virus Isolated from Wild Birds in Jiangsu Province, China, 2023
Transboundary & Emerg. Dis.: Novel Human-Avian Reassortment H9N2 Virus in Guangdong Province, China
Frontiers Microbiology: China's Growing Concerns Over The H3 AIV
Emerg. Microb & Inf.: Emergence of Novel Reassortant H3N3 Avian Influenza viruses, China 2023
While it may be coincidence, for the 2nd time in the space of a couple of weeks, Chinese scientists published a major review article on LPAI H4N6, which is ubiquitous in wild birds both in Asia and around the world, and which has previously shown signs of better adapting to mammalian hosts.
Due to its length, I've just posted some excerpts. Follow the link to read the full report. I'll have a brief postscript after the break.
Genetic and Biological Characteristics of Duck-Origin H4N6 Avian Influenza Virus Isolated in China in 2022
Tian Li 1, Chuankuo Zhao 1, Yuxin Guo 1, Jinze Dong 1, Fanshu Du 1, Sicheng Shu 1, Yang Liu 2, Yachang Cheng 2, Zhiyong Cao 3, Qi Cao 4, Shuiping Shi 5, Yinhua Huang 6, Juan Pu 1 and Litao Liu 1,*
Viruses 2024, 16(2), 207; https://doi.org/10.3390/v16020207
Submission received: 5 December 2023 / Revised: 23 January 2024 / Accepted: 25 January 2024 / Published: 30 January 2024
Abstract
The interaction between migratory birds and domestic waterfowl facilitates viral co-infections, leading to viral reassortment and the emergence of novel viruses. In 2022, samples were collected from duck farms around Poyang Lake in Jiangxi Province, China, which is located within the East Asia–Australasia flyway.Three strains of H4N6 avian influenza virus (AIV) were isolated. Genetic and phylogenetic analyses showed that the isolated H4N6 avian influenza viruses (AIVs) belonged to new genotypes, G23 and G24.All isolated strains demonstrated dual receptor binding properties. Additionally, the isolated strains were able to replicate efficiently not only in avian cells but also in mammalian cells. Furthermore, the H4N6 AIV isolates could infect chickens, with viral replication detected in the lungs and extrapulmonary organs, and could transmit within chicken flocks through contact, with viral shedding detected only in oropharyngeal swabs from chickens in the contact group.Notably, the H4N6 AIV could infect mice without prior adaptation and replicate in the lungs with high viral titers, suggesting that it is a potential threat to humans. In conclusion, this study provides valuable insight into the characteristics of H4N6 strains currently circulating in China.
(SNIP)
Discussion
(Excerpt)
In this study, we conducted genetic and phylogenetic analyses of three newly isolated duck-origin H4N6 AIVs and investigated their biological characteristics. Previous studies have found that multiple genotypes of H4 viruses are cocirculating in the live poultry markets of China [8], and the results of phylogenetic analysis and the genotypes in this study revealed that the three isolated viral strains belonged to novel genotypes, G23 and G24. The genetic sequences of various segments of the isolated strains shared high similarity with virus strains isolated from neighboring countries and regions around China, such as Bangladesh, Mongolia, Vietnam, South Korea, and Japan.Notably, these countries are located along the East Asia–Australasia flyway, a major migratory route for birds. Thus, we hypothesized that the genetic origin of the isolated strains was likely due to the introduction of different AIV subtypes through the migratory activities of birds, which then underwent reassortment with the AIVs carried by domestic waterfowl in China.
Molecular characterization analysis revealed that all three isolated strains had a T160A mutation in the HA gene associated with receptor binding properties. In addition to T160A, G228S, and Q226L play an important role in altering the receptor binding properties of H4 AIV [16]. Subsequently, we conducted an analysis of receptor binding characteristics.The results showed that the isolated strains could bind not only to α-2,3 sialic acid-linked receptors but also to α-2,6 sialic acid-linked receptors, indicating that H4N6 AIVs have the potential to break species barriers and initiate cross-species infections.Pathogenicity experiments on chickens revealed that an H4N6 virus isolate was able to replicate in infected chickens, although no significant clinical symptoms were observed. However, some studies have reported that H4N6 can cause weight loss in broiler chickens and soft-shelled eggs in laying hens [9]. Transmissibility experiments on chickens showed that the isolate had limited transmissibility and was not capable of becoming widespread in chicken flocks, and this characteristic was similar to the previously prevalent H4 subtype AIV, which was mainly found in waterfowl and migratory birds, and failed to adapt well to terrestrial poultry.Surprisingly, the isolate could infect mice directly without prior adaptation and exhibited robust replication in both the respiratory and digestive systems of mice. Other studies have found that some H4 strains have been found to be transmitted between guinea pigs by direct contact, and some can also transmit via respiratory droplet, albeit with limited efficiency [8].
In conclusion, we characterized the genetic evolution and biological properties of the H4N6 virus isolated from waterfowl in Poyang Lake, Jiangxi Province, China. Our study not only offers valuable insights into the prevalence of H4N6 AIVs in China but also highlights the importance of proactive monitoring of wild birds and domestic ducks. This monitoring aids in tracking the evolution of AIVs in waterfowl. It is crucial to monitor AIVs that may pose a threat to poultry or humans and to take appropriate control measures in time.
While the EA H1N1 `G4' Swine virus, and HPAI H5 (and to a lesser extent, HPAI H7) remain at the top of our pandemic watch list, our track record in predicting the `next pandemic' has been notoriously bad.
The next global health crises could just as easily come - as did the 1957 and 1968 pandemics - from the reassortment of an LPAI H2 or H3 virus with seasonal flu, or from an unexpected spillback of COVID from a non-human host, some obscure bat-borne henipavirus, or from some as-yet, unknown zoonotic threat (Disease X).
We live in an interconnected and ever-changing pathogen-rich environment. Which means we need to be preparing for a wide range of pandemic threats, not just the obvious ones.
