Monday, May 09, 2022

Serological Surveillance of the H1N1 & H3N2 Swine Influenza in Chinese Pigs between 2016 and 2021

#16,737

Prior to the emergence of our current Coronavirus pandemic we were intently watching several novel avian and swine influenza viruses around the world, each showing some degree of pandemic potential. 

Until the summer of 2017 - when an effective poultry vaccine was finally released by China - avian H7N9 had produced 5 waves of human infection (see chart below) since it emerged in 2013, and was at the top of our watch list. 

Credit FAO

Avian H5N1 and H5N6 were also on that list, as were several H1N1 and H3N2 swine flu viruses endemic in North America. The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having some pandemic potential (2 added in 2019).

H1N2 variant [A/California/62/2018]  Jul    2019  5.8  5.7 Moderate
H3N2 variant [A/Ohio/13/2017]          Jul    2019  6.6  5.8 Moderate
H3N2 variant [A/Indiana/08/2011]      Dec  2012   6.0  4.5 Moderate

Outside of North America, our knowledge of swine flu viruses is considerably less robust, but over the past 7 years China's EA H1N1 `G4' swine flu virus has increasingly raised concerns.. 

First by Chen Hualan, director of China's National Avian Influenza Reference Laboratory, who was the lead author on a paper that pegged a new, rising swine flu threat in China (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza).

EAH1N1 is a reassortant virus, with elements from H1N1 avian influenzahuman H1N1pdm, and swine-origin influenza viruses.  Despite sharing the same subtype designation as a currently circulating seasonal strain, it was genetically different enough to pose a genuine public health threat. 

In the `Significance' section the authors boiled it down to this:
Here, we found that, after long-term evolution in pigs, the EAH1N1 SIVs have obtained the traits to cause a human influenza pandemic.
In an interview, published by Xinhuanet, lead author Chen Hualan stated: 
"Based on scientific analysis and comprehensive comparison of the main animal flu viruses: H1N1, H3N2, H5N1, H7N9, H9N2 and EAH1N1, we found the EAH1N1 is the one most likely to cause next human flu pandemic. We should attach great importance to the EAH1N1."
Six months later, in Sci Rpts: Transmission & Pathogenicity Of Novel Swine Flu Reassortant Viruses we looked at a study where pigs were experimentally infected with one of these Eurasian-Avian H1N1 swine influenza viruses and the 2009 H1N1pdm virus.

Researchers generated 55 novel reassortant viruses spread across 17 genotypes, demonstrating not only how readily EAH1N1 SIV can reassort with human H1N1pdm in a swine host, but also finding:
`Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs'. 
Later that same year, in EID Journal: Reassortant EAH1N1 Virus Infection In A Child - Hunan China, 2016, we reviewed the case report on a 30-month old child from Hunan Province, who was infected with one of these reassortant EAH1N1 - H1N1pdm viruses.     

In 2017 we looked at J. Virology: A Single Amino Acid Change Alters Transmissibility Of EAH1N1 In Guinea Pigswhile in 2018 we saw Emerg. Microbes & Infect.: Effect Of D701N Substitution In PB2 Of EAH1N1 Swine Flu Viruses which described the growing diversity of novel novel H1N1 and H3N2 flu viruses (including EA H1N1) in China's pig population.

In 2019, we saw a number of studies on EAH1H1, including one that documented the virus in farmed mink in China (see Vet. MicroB.: Eurasian Avian-Like Swine Influenza A (H1N1) Virus from Mink in China).

And in 2020, in PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China researchers reported  greater than 10% seroprevalence for the EAH1N1 among swine workers tested, suggesting that EAH1N1 is gaining human infectivity. 

The authors wrote:


Pigs are intermediate hosts for the generation of pandemic influenza virus. Thus, systematic surveillance of influenza viruses in pigs is a key measure for prewarning the emergence of the next pandemic influenza. Here, we identified a reassortant EA H1N1 virus possessing pdm/09 and TR-derived internal genes, termed as G4 genotype, which has become predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses have all the essential hallmarks of a candidate pandemic virus. Of concern is that swine workers show elevated seroprevalence for G4 virus. Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring in human populations, especially the workers in swine industry, should be urgently implemented

This report led to a number of `risk assessments' by public health agencies on EA H1N1 `G4', including:



FAO/OIE/WHO Tripartite Statement on the Pandemic Risk of Swine Influenza

While the overall consensus was that EA H1N1 `G4' was a genuine concern - H1, H2, and H3 swine flu viruses are not considered `reportable animal diseases' to the OIE, so we know far less than we'd like about the threat (see Flying Blind In the Age Of Pandemics & Emerging Infectious Diseases). 

Giving us some new insight on the spread of EA H1N1 (and other) swine flu viruses in China, we have the following study, published in late April, which confirms that EA H1N1 `G4' is still dominant in Chinese pigs, and remains a credible threat to human health. 

I've only published some excerpts from a much longer open-access report, so follow the link to read it in its entirety.  

Serological Surveillance of the H1N1 and H3N2 Swine Influenza A Virus in Chinese Swine between 2016 and 2021
Yuzhong Zhao,1,2 Lebin Han,1,2 Ting Chen,3,4 Haotian Sang,1,2 Guofei Ding,1,2 Yingchao Li,1,2 Bin Wang,1,2 Liting Qin,3,4 Sidang Liu,1,2 Yanmeng Hou,1,2 and Yihong Xiao1,2
 
Academic Editor: Marta Laranjo
 
Published 28 Apr 2022

Abstract

Background. 

Swine influenza A virus (IAV-S) is a common cause of respiratory disease in pigs and poses a major public health threat. However, little attention and funding have been given to such studies. The aim of this study was to assess the prevalence of the Eurasian avian-like H1N1 (EA H1N1), 2009 pandemic H1N1 (pdm/09 H1N1), and H3N2 subtype antibodies in unvaccinated swine populations through serological investigations. Such data are helpful in understanding the prevalence of the IAV-S. 

Methods. 

A total of 40,343 serum samples from 17 regions in China were examined using hemagglutination inhibition (HI) tests against EA H1N1, pdm/09 H1N1, and H3N2 IAV-S from 2016 to 2021. The results were analyzed based on a reginal distribution, seasonal distribution, and in different breeding stages.

 Results. 

A total of 19,682 serum samples out of the 40,343 were positive for IAV-S (48.79%). The positivity rates to the EA H1N1 subtype, pdm/09 H1N1 subtype, and H3N2 subtype were 24.75% (9,986/40,343), 7.94% (3,205/40,343), and 0.06% (24/40,343), respectively. The occurrences of coinfections from two or more subtypes were also detected. 

In general, the positivity rates of serum samples were related to the regional distribution and feeding stages. Conclusions. The results of this study showed that the anti-EA H1N1 subtype and pdm/09 H1N1 subtype antibodies were readily detected in swine serum samples. The EA H1N1 subtype has become dominant in the pig population. The occurrences of coinfections from two or more subtypes afforded opportunities for their reassortment to produce new viruses. Our findings emphasized the need for continuous surveillance of influenza viruses.

4. Discussion

EA H1N1 were first isolated from swine in Hong Kong in 1993 [13]. Since 2001, EA H1N1 IAV-S has become the dominant circulating virus in China [9, 14] and will preferentially bind to human-like receptors. Some of the viruses can be efficiently transmitted in ferrets through respiratory droplets [15], and preexisting immunity in humans may not be sufficient to overcome EAH1N1 infections [15, 16]. In fact, isolation of the EA H1N1 subtype has been reported from at least six cases in China [17–22].

In the serum samples from pig farm residents, antibodies specific to the EA H1N1 subtype were also detected with high positivity rates ranging from 10.4% to 11.7% [23–25]. Recently, a genotype 4 reassortant EA H1N1 virus was identified as the predominant strain in swine populations since 2016 and has acquired increased human infectivity [23]. Higher odds of antibody titers against EA H1N1 were detected in swine workers compared to the general population [26]. In this study, the serum samples positive for the EA H1N1 subtype were most abundant, with the highest positivity rate of 24.06% between 2016 and 2021.

Those data further confirmed the predominance of the EA H1N1 subtype [23, 27–29]. The positivity rates based on regional distributions were variable and ranged from 3.7% (Central China) to 35.65% (North China) (Figure 1). The positivity rates were higher in South China from 2016 to 2019 and decreased in 2020, which may partially be due to the increased biosafety of pig farms against Africa swine fever disease. The high positivity rates to the EA H1N1 subtype indicated its predominance and increased in human infectivity, which indicated that it was a substantial threat to human health. Thus, more attention and funding toward the surveillance of the EA H1N1 subtype is urgently needed.(SNIP)

5. Conclusions

Antibodies against the EA H1N1 and pdm/09 H1N1subtypes were easily detected in swine serum samples, which indicated that clinical infections were common from those viruses. The detection of copositive serum was indicative of the strong possibility of reassortment of EA H1N1 subtype with the pdm/09 H1N1or H3N2 subtypes. Thus, great attention should be paid to the appearance of new viral subtypes in the future. The findings of the present study further emphasized the need for detailed surveillance of IAV-S to understand its prevalence and provide a basis for its the prevention and control.

         (Continue . . . )

EA H1N1 `G4' isn't the only swine flu virus with pandemic contender, and it is possible another novel strain will beat it to the punch.  But in early 2021, the CDC Selected Swine-Variant EA H1N1 Virus For The Top Of Their IRAT List of novel flu viruses with pandemic potential. 

Making it very much worthy of our continued attention.