Friday, February 23, 2018

EID Journal: Multiple Introductions Of HPAI H5N8 In Egypt

Credit EID Journal


After starting out as an exclusively Chinese and Southeast Asian problem early in the last decade, avian HPAI H5 viruses have spread globally via migratory birds - and while many areas outside of Asia have been affected - no region has reported as much consistent HPAI H5 activity over the past decade as Egypt and the Middle East. 
Despite this, we see relatively few in-depth reports on avian flu viruses coming from that part of the world, and when we do, it is nearly always from Egypt.
Often the reporting of avian flu outbreaks to the OIE is either fragmented, belated, or - far too often -  simply not done by many countries in the Middle East (and elsewhere).  
Admittedly, for many nations, this may be due to the remote location of outbreaks, the reluctance of farmers to report poultry deaths, or a lack of resources.
Even novel human infections may go undetected or reported, with only about 1/3rd of the countries of the world currently self-reporting they have met the core requirements of the 2005 International Health Regulations (see Adding Accountability To The IHR).
The unfortunate result is - at least compared to Europe, North America, and parts of Asia - we don't really have a good handle on what novel viruses are circulating in many places around the globe, or what changes may be occurring in them.
Today, however, we have a Research Letter appearing in the EID Journal that gives us some valuable new insight on the late 2016 arrival, and subsequent multiple introductions of HPAI H5N8, to Egypt during 2017.
Of particular note, four genetically distinct H5N8 viruses were characterized, and all carried previously identified mammalian-adaptation and virulence markers (see Evaluation of phenotypic markers in full genome sequences of avian influenza isolates from California) that raise potential public health concerns.
I've only included some extracts from the letter (bolding mine), so follow the link to read it in its entirety.  I'll return with a brief postscript. 

Volume 24, Number 5—May 2018
Research Letter

Multiple Introductions of Influenza A(H5N8) Virus into Poultry, Egypt, 2017

Ahmen H. Salaheldin, Hatem Salah Abd El-Hamid, Ahmed R. Elbestawy, Jutta Veits, Hafez M. Hafez, Thomas C. Mettenleiter, and Elsayed M. Abd El-Whab


After high mortality rates among commercial poultry were reported in Egypt in 2017, we genetically characterized 4 distinct influenza A(H5N8) viruses isolated from poultry. Full-genome analysis indicated separate introductions of H5N8 clade reassortants from Europe and Asia into Egypt, which poses a serious threat for poultry and humans.

In Egypt, highly pathogenic avian influenza A(H5N1) clade 2.2.1 virus was introduced to poultry via migratory birds in late 2005 (1) and is now endemic among poultry in Egypt (2).
Also in Egypt, the number of H5N1 infections in humans is the highest in the world, and low pathogenicity influenza A(H9N2) virus is widespread among poultry and has infected humans (2).
Despite extensive vaccination, H5N1 and H9N2 viruses are co-circulating and frequently reported (2). In 2014, highly pathogenic avian influenza A(H5N8) virus clade was isolated, mostly from wild birds, in several Eurasian countries and was transmitted to North America. However, in 2016 and 2017, an unprecedented epidemic was reported in Asia, Africa, and Europe (3).
In Egypt, during November 30–December 8, 2016, a total of 3 H5N8 viruses were isolated from common coot (Fulica atra) (4) and green-winged teal (Anas carolinensis) (5). To provide data on the spread of the virus in poultry, we genetically characterized 4 distinct H5N8 viruses isolated from commercial poultry in Egypt in 2017.

The hemagglutinin (HA) and neuraminidase (NA) genes of the 4 viruses shared 95.8%–99.2% nt and 93.1%–99.4% aa identity and shared 96.5%–99.2% nt and 94.2%–99.7% aa identity with viruses from wild birds in Egypt (4,5). Other segments showed 92.6%–99.6% nt and 96%–99.7% aa identity, where the polymerase acidic (PA) genes and proteins of viruses from Dk18 showed the lowest similarity to those of other viruses (Technical Appendix 1[PDF - 1.22 MB - 5 pages] Figure 1).

All viruses possess the polybasic HA cleavage site PLREKRRKR/G and contain mammal-adaptation and virulence markers (9) in polymerase basic (PB) 2 (T63I, L89V, G309D, T339K, Q368R, H447Q, R477G), PB1 (A3V, L13P, K328N, S375N, H436Y, M677T), PA (A515T), HA (T156A, A263T; H5 numbering), matrix (M) 1 (N30D, T215A), and nonstructural (NS) 1 (P42S, T127N, V149A) proteins.
Therefore, protection of humans and risk assessment of bird-to-human transmission is crucial.
These data suggest 4 different introductions of H5N8 virus into poultry in Egypt, independent of viruses isolated from captive birds (4,5). Multiple separate introductions of H5N8 virus into Europe also occurred (10). Further studies are needed to identify the source(s) of introduction. The separate introductions of different reassortants of H5N8 clade virus from Europe and Asia into Egypt indicates a serious threat for poultry and human health.

Mr. Salaheldin is a doctoral student at the Institute of Poultry Diseases, Freie-Universit├Ąt-Berlin. His main interests are molecular virology, vaccine development, and epidemiology of avian influenza viruses.

Thus far HPAI H5N8 (and it's reassorted progenies H5N6 & H5N6) have shown few signs of infecting mammals and no human infections have been reliably reported.

We did see early reports out of South Korea in 2014 of dogs having been infected (see MAFRA: H5N8 Antibodies Detected In South Korean Dogs (Again)) and less than a year ago saw J. Vet. Sci.: Experimental Canine Infection With Avian H5N8.
So we know that mammalian infection with at least some genotypes of H5N8 is at least possible.
Over the past year we've looked at a number of studies that have explored the potential for H5N8 or its spinoffs to evolve into a human health threat. A few include:
J Vet Sci: Evolution, Global Spread, And Pathogenicity Of HPAI H5Nx Clade 
Study: Virulence Of HPAI H5N8 Enhanced By 2 Amino Acid Substitutions

Sci Rpts: H5N8 - Rapid Acquisition of Virulence Markers After Serial Passage In Mice 
Perhaps most telling of these came last September in J. Virulence : Altered Virulence Of (HPAI) H5N8 Reassortant Viruses In Mammalian Models, which found:
Taken together, our study demonstrates that a single gene substitution from other avian influenza viruses can alter the pathogenicity of recent H5N8 viruses, and therefore emphasizes the need for intensive monitoring of reassortment events among co-circulating avian and mammalian viruses.
Last October's J. Virulence Editorial: HPAI H5N8 - Should We Be Worried? reviewed and summarized the literature, and found enough reasons to be concerned over the future evolutionary path of H5N8, stating that:
The extensive distribution of HPAI H5N8, as well as the gene reassortment with other circulating avian viruses already observed for H5N8 suggests there is a potential risk for human cases of H5N8 infections.
While none of this means there is a human adapted H5N8 virus in our future, considering the continual evolution of the virus - particularly in areas of the world where we have little or no visibility - we can't ignore the possibility of someday being blindsided by an abrupt change in the virus's behavior.

Making studies like this one particularly valuable.