Monday, December 23, 2019

BMC Vet. Rsrch.: Continuing Evolution of H6N2 Influenza A Virus in South Africa













#14,596


After more than two decades in the scientific limelight, the pandemic threat from avian influenza viruses remains only partially understood.  We've seen our attention broaden from primarily H5N1 during the first decade of the 21st century, to include H7N9, H9N2, and a short list of other avian viruses over the past decade. 
The CDC's Influenza Risk Assessment Tool (IRAT) currently lists 16 `high risk' novel viruses, and of those, 14 are of avian origin (5 - H5s,  6 - H7s, 1 - H9, 1 - H10, and 1 - H1). 
This is far from a complete list, and as avian flu viruses evolve, swap genetic material (reassort), acquire new characteristics, and spread geographically, this list will undoubtedly change and probably expand further. 

There are two broad categories of avian influenza; LPAI (Low Pathogenic Avian Influenza) and HPAI (Highly Pathogenic Avian Influenza).
  • LPAI viruses are quite common in wild birds, cause little illness, and only rarely death.
  • HPAI viruses are more dangerous, can produce high morbidity and mortality in wild birds and poultry
Before the middle of the last decade, there was no uniform requirement to report or track LPAI infections. That changed in 2006 when the OIE made reporting of LPAI H5 & H7 viruses mandatory, primarily because they can sometimes mutate into High Path viruses once they begin to circulate in poultry.

Despite having a place on the CDC's IRAT list, LPAI H9N2 is not considered to be a `reportable' infection by the OIE. Andt there are other LPAI viruses - not currently on either list - that we keep an eye on as well.

One of those that we revisit from time to time are H6 viruses, which have demonstrated an unusually wide host range.


Since H6 is not a reportable disease, rarely causes human illness, and doesn't usually inflict losses to poultry, it isn't nearly as well studied as H5 and H7 viruses. Like H9N2, it has demonstrated its ability to share gene segments with HPAI H5 viruses - and when combined with its ability to jump species - makes it a virus to watch.

To that end we've a long, detailed analysis of H6N2 viruses circulating in South Africa - a region where HPAI H5N8 arrived a little over two years ago - that highlights its continual evolution, and our general lack of knowledge of its evolution and status in neighboring countries.

While H6 viruses have only demonstrated a limited ability to infect humans, the authors point out the high number of immunocompromised poultry workers in South Africa, which might provide the virus with an easier route to human infection and adaptation.
Zoonotic threat: sub-lineage I strains are gradually gaining mutations associated with acquiring affinity for human receptors. The continuing genetic and antigenic drift in H6N2 viruses will have to be closely monitored so that human health authorities can be alerted in time. South Africa has one of the highest HIV/AIDS positive populations in the world, and agricultural workers were estimated to have an infection rate double that of the national average [48].
The  full research article - which is both lengthy and at times fairly technical - is available at the link below. I've only included some excerpts from the Abstract.  I'll have a postscript after the break:

Continuing evolution of H6N2 influenza a virus in South African chickens and the implications for diagnosis and control

Celia Abolnik  Christine Strydom  Dionne Linda Rauff   Daniel Barend   Rudolph Wandrag Deryn Petty
Open Access Research article
First Online: 18 December 2019
Background
The threat of poultry-origin H6 avian influenza viruses to human health emphasizes the importance of monitoring their evolution. South Africa’s H6N2 epidemic in chickens began in 2001 and two co-circulating antigenic sub-lineages of H6N2 could be distinguished from the outset. The true incidence and prevalence of H6N2 in the country has been difficult to determine, partly due to the continued use of an inactivated whole virus H6N2 vaccine and the inability to distinguish vaccinated from non-vaccinated birds on serology tests. In the present study, the complete genomes of 12 H6N2 viruses isolated from various farming systems between September 2015 and February 2019 in three major chicken-producing regions were analysed and a serological experiment was used to demonstrate the effects of antigenic mismatch in diagnostic tests.
Results
Genetic drift in H6N2 continued and antigenic diversity in sub-lineage I is increasing; no sub-lineage II viruses were detected. Reassortment patterns indicated epidemiological connections between provinces as well as different farming systems, but there was no reassortment with wild bird or ostrich influenza viruses. The sequence mismatch between the official antigens used for routine hemagglutination inhibition (HI) testing and circulating field strains has increased steadily, and we demonstrated that H6N2 field infections are likely to be missed.
More concerning, sub-lineage I H6N2 viruses acquired three of the nine HA mutations associated with human receptor-binding preference (A13S, V187D and A193N) since 2002. Most sub-lineage I viruses isolated since 2015 acquired the K702R mutation in PB2 associated with the ability to infect humans, whereas prior to 2015 most viruses in sub-lineages I and II contained the avian lysine marker. All strains had an unusual HA0 motif of PQVETRGIF or PQVGTRGIF.
Conclusions
The H6N2 viruses in South African chickens are mutating and reassorting amongst themselves but have remained a genetically pure lineage since they emerged more than 18 years ago. Greater efforts must be made by government and industry in the continuous isolation and characterization of field strains for use as HI antigens, new vaccine seed strains and to monitor the zoonotic threat of H6N2 viruses.
          (Continue . . . )

Admittedly, when you think of hotspots for avian flu reassortment - or of seeing a spillover to humans - you don't normally think of Southern Africa.  Eastern Asia, Egypt, and India are generally pegged as the most likely places for new avian flu subtypes to emerge (see 2013's EID Journal: Predicting Hotspots for Influenza Virus Reassortment).
But the recent introductions of HPAI H5 viruses to West, Central, and Southern Africa over the past 6 years makes it another region to watch.  
Not quite three years ago, in The Challenge Of Avian Flu Surveillance In Sub-Saharan Africa, we looked at the general lack of surveillance, testing, and reporting on avian flu on the African continent, and the very strong likelihood that some human infections have gone unreported. 

All of which makes surveillance studies - like the one above - an important part of any avian flu early warning system. 

Posted by at