Thursday, April 12, 2018

Sci. Rpts.: Evidence Of H5N1 Exposure In Domestic Pigs - Nigeria


Swine possess both avian-like (SAα2,3Gal) and human-like (SAα2,6Gal) receptor cells in their respiratory tract, making them susceptible to a variety of influenza viruses, including swine, human, and avian varieties.
The 2009 H1N1 pandemic virus was a triple reassortment (swine, human, avian) virus that spread quietly in pigs for years before emerging as a human health threat. 
Since H5 and H7 avian flu viruses tend to produce higher morbidity and mortality in humans, we pay particular attention whenever one of these avian-origin influenza viruses takes up residence in pigs.

After China's discovery of H5N1 in pigs back in 2004, the WHO released a statement called Avian influenza - update: Implications of H5N1 infections in pigs in China which warned:
The chances for genetic reassortment depend upon both the duration of H5N1 circulation in pigs as well as the simultaneous presence of human and pig influenza A viruses (such as H3N2 or H1N1). As long as human and avian influenza viruses are co-circulating - whether in humans or in pigs - the possibility of an exchange of genetic material-exists.
The concerns over finding H5N1 in pigs are actually two-fold. The first is the potential for a reassortment event as described above. The second is the potential for host adaptation of the virus.  
The serial passage of an avian virus from pig - to pig - to pig can, over time, allow genetic traits to emerge that make the virus more adapted to mammalian hosts (see Virology J : Adaptation Of HPAI H5N2 In Mice).
Since H5N1 tends to be asymptomatic (or mildly symptomatic) in pigs, and the virus is found in regions of the world where surveillance of pigs is marginal at best, we only rarely hear of infections. 
Last fall, in Arch. Virology: Isolation & Characterization Of H5N1 In Swine - China 2015, we saw the description of a clade 2.3.2 H5N1 virus isolated from a pig in China which carried a Glu627Lys PB2 mutation with is associated with increased pathogenicity.
What we haven't seen reported - until now - has been evidence of widespread H5N1 exposure in pigs.
Some excerpts from a much long Scientific Report published today in Nature.  Follow the link to read the study in its entirety.  I'll have a postscript when you return.
Evidence of exposure of domestic pigs to Highly Pathogenic Avian Influenza H5N1 in Nigeria
Clement Meseko, Anja Globig,Jeremiah Ijomanta,Tony Joannis, Chika Nwosuh, David Shamaki, Timm Harder, Donata Hoffman, Anne Pohlmann, Martin Beer, Thomas Mettenleiter & Elke Starick


Avian influenza viruses (AIV) potentially transmit to swine as shown by experiments, where further reassortment may contribute to the generation of pandemic strains. Associated risks of AIV inter-species transmission are greater in countries like Nigeria with recurrent epidemics of highly pathogenic AI (HPAI) in poultry and significant pig population.

Analysis of 129 tracheal swab specimens collected from apparently healthy pigs at slaughterhouse during presence of HPAI virus H5N1 in poultry in Nigeria for influenza A by RT-qPCR yielded 43 positive samples. Twenty-two could be determined by clade specific RT-qPCR as belonging to the H5N1 clade and confirmed by partial hemagglutinin (HA) sequence analysis.

In addition, 500 swine sera were screened for antibodies against influenza A virus nucleoprotein and H5 HA using competition ELISAs and hemagglutination inhibition (HI) tests. Serologically, 222 (44.4%) and 42 (8.4%) sera were positive for influenza A virus NP and H5 antibodies, respectively. Sera reacted to H5N1 and A/H1N1pdm09 strains by HI suggesting exposure of the Nigerian domestic pig population to these viruses.

We report for the first time in Nigeria, exposure of domestic pigs to H5N1 virus. This poses potential public health and pandemic risk due to interspecies transmission of avian and human influenza viruses.

Infections of swine with AIV in nature seem to be rare, and only very few studies have described detection of HPAIV H5N1 in healthy domestic pigs in Indonesia and China15,16. In those studies, the virus appeared to have been transmitted from poultry. Our investigation revealed natural exposure of HPAIV H5N1 clade possibly from infected poultry in Nigeria to domestic pigs as we could find H5N1 RNA in 43 tracheal specimens of swine sampled in December, 2015 to February, 2016 in the slaughter house in Jos, Plateau state, Nigeria.

The significance of our study is the detection of HPAI H5N1 RNA of clade and H5 reactive sera in apparently healthy pigs in Nigeria. Nigeria recorded the highest number of outbreaks of HPAIV in West Africa since 2006 and from 2015 to 2016. Similarly, A/H1N1pdm09 strain is dominant in domestic pigs in the region following 2009 pandemic with seroprevalence in the range of 27.4 to 29% reported in different studies7,32,33.

If AIV is sustained and adapted in pigs, the consequences comprise suggestions by some investigators34,35 that a reassortant H5N1 with A/H1N1pdm09 internal genes may have enhanced replication and transmissibility competence compared to the parent H5N1. A previous serosurvey of H5N1 in pigs in Nigeria during 2006–2008 epidemic returned negative results36. However, the viruses that circulated in Nigeria at that time belonged to a different clade of Asian origin H5 HPAIV (clade 2.2.). Sera analysed by HI in the present investigation was negative to that clade further showing that exposure of pigs to H5 virus is a recent event.

Thus detection of H5N1 in the current study suggests possibilities of enhanced factors including increased contact rates between avian and swine and widespread H5N1 virus dissemination in the environment, which could aid exposures and biological adaptation in swine host.
Furthermore, a large proportion of serum samples showed antibodies against IAV most of which were reactive to A/H1N1pdm09 and therefore calls attention to the theoretical possibility of simultaneous infections with different avian and mammalian influenza A viruses in the population, the basis for reassortment of genes in pigs being a mixing vessel. This also indicates that possibly, human pandemic H1N1 infections (or porcine adapted variants thereof) play the main role for swine influenza in Nigeria. Alternatively, other swine-adapted viruses may circulate which are antigenically distinct from those of Europe or other regions.
In conclusion, the exposure to H5N1 HPAIV from avian to swine, poses yet unknown public health risk if subclinical infection in pigs is sustained and may combine with A/H1N1pdm09 also detected in the population. This might allow the generation of new potentially zoonotic viruses by gene reassortment. The potential of this IAV transmission to humans thus requires further monitoring and investigation of the swine population in Nigeria, especially in regions with high swine density and endemicity of HPAIV in poultry though the risk is up to now theoretical.
        (Continue . . . .)

As we've discussed before, there can be a great deal of variation in behavior and virulence among avian flu viruses - even those that carry the same designation.  Subtypes (like H5N1) are divided into clades (like or, and clades can be made up of numerous genotypes. 
Although Nigeria was initially hit with clade 2.2 of H5N1 back in 2006, in 2014 we saw a new clade arrive (likely via migratory birds) (see EID Journal: HPAI A(H5N1) clade In West Africa).
Clade (including subtypes A(H5N1), A(H5N2), A(H5N6) and A(H5N8)), has gotten the bulk of our attention the past few years, having sparked epizootics in Asia, Europe, North America, the Middle East, and parts of Africa.
Clade, meanwhile, has been reported primarily in poultry and wild birds Vietnam, China, India, Bulgaria, Indonesia, and west Africa.
This clade was also isolated from a nurse who returned to Alberta, Canada from a trip to China (see Alberta Canada Reports Fatal (Imported) H5N1 Infection) in late 2013, and similar to one that killed a captive tiger in Jiangsu Province in 2013.

Clade also gets our attention because it has been linked to unusual neurological symptoms in human - and feline - infections (see Novel H5N1 Reassortment Detected In Migratory Birds - China).

A reminder that we aren't dealing with just one H5N1 virus, but rather dozens, all on their own evolutionary path. The same can be said for H7N9, H5N6, and a host of others.
While H5N1 has only shown limited ability to infect pigs in the wild, as long as it remains in circulation and continues to evolve, it will have more opportunities to figure that out.