Tuesday, December 06, 2016

Nature: Risk Assessment of Recent Egyptian H5N1 Influenza Viruses



Over the summer of 2014, HPAI H5N1 picked up several key mutations in Egypt (see Eurosurveillance: Emergence Of A Novel Cluster of H5N1 Clade which are believed to have helped increase its transmissibility from poultry to humans.
Six months later we witnessed the largest human outbreak of H5N1  on record (see EID Dispatch: Increased Number Of Human H5N1 Infection – Egypt, 2014-15), with roughly 160 cases reported over five months.

Last January, in EID Journal: H5N1 In Egypt, we looked at a study that suggested there may have been tens (perhaps, hundreds) of thousands of (mostly mild) human H5N1 infections in Egypt over the past decade.
The authors based their assumption on a limited serological study that found antibodies for H5 in roughly 2% of the people tested.  

Regardless, two facts are clear.  The winter of 2014-15 produced  biggest outbreak of human H5N1 infection ever recorded, and the number of new variants of H5N1 circulating in Egypt has increased markedly over the past couple of years.

For reasons that are far less clear, the number of human infections reported by Egyptian officials over the winter of 2015-16 dropped precipitously.

Yesterday Nature's Scientific Reports published the first detailed analysis of nine recently isolated varieties of H5N1 circulating in Egyptian poultry, and found three of them displayed (limited) transmission via respiratory droplets in ferrets.

While they had difficulty reproducing these results, they suspect that the transmissibility of H5N1 has increased slightly, thereby raising the threat from the virus.

The abstract, and a couple of excerpts follow, but hit the link to read the study in its entirety.

Risk assessment of recent Egyptian H5N1 influenza viruses

    A.-S. Arafa, S. Yamada[…]Y. Kawaoka


Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are enzootic in poultry populations in different parts of the world, and have caused numerous human infections in recent years, particularly in Egypt. However, no sustained human-to-human transmission of these viruses has yet been reported.
We tested nine naturally occurring Egyptian H5N1 viruses (isolated in 2014–2015) in ferrets and found that three of them transmitted via respiratory droplets, causing a fatal infection in one of the exposed animals. All isolates were sensitive to neuraminidase inhibitors. However, these viruses were not transmitted via respiratory droplets in three additional transmission experiments in ferrets.
Currently, we do not know if the efficiency of transmission is very low or if subtle differences in experimental parameters contributed to these inconsistent results. Nonetheless, our findings heighten concern regarding the pandemic potential of recent Egyptian H5N1 influenza viruses.


The HPAI H5N1 viruses were introduced into Egyptian poultry populations in 2006 as descendants of the Qinghai Lake lineage of H5N1 viruses, which belong to subclade 2.2 of the WHO classification system of HPAI H5N1 influenza viruses. Since then, extensive evolution of these viruses has produced several subclades (Supplementary Fig. S1)2,3,4,5,6,7,8. Almost all recent human cases in Egypt have been caused by viruses of subclades 2.2.1 and
In early 2015, a novel cluster within clade was reported that contains all recent human isolates and may have replaced previously circulating clade viruses9. Given that HPAI H5N1 viruses in Egypt evolve rapidly and have caused a substantial number of human infections, we here characterized the respiratory droplet transmissibility of nine Egyptian HPAI H5N1 influenza viruses in ferrets.


None of the several highly pathogenic H5N1 viruses found in nature have previously been shown to transmit via respiratory droplets in ferrets or guinea pigs (reviewed in ref. 29). Previously, our groups speculated that Egyptian HPAI H5N1 viruses may have increased pandemic potential because they encode amino acids in HA that enable binding to human-type receptors, encode the PB2-E627K mutation that allows efficient replication in mammals, and lack a glycosylation site at positions 153–155 of HA30,31. This finding, together with the alarming increase in human HPAI H5N1 virus infections in Egypt in 2014–2015, prompted us to test the respiratory droplet transmissibility of recent Egyptian HPAI H5N1 viruses in ferrets.
While our first study demonstrated respiratory droplet transmission among ferrets for three of nine HPAI H5N1 viruses, this finding was not reproducible in three additional transmission experiments. The transmission efficiency of these viruses in ferrets may be very low, such that subtle differences in experimental conditions (such as the air flow, and health of the animals, and/or animal handling) may have affected the outcomes of these studies.
Collectively, these data suggest that contemporary Egyptian HPAI H5N1 viruses may possess the ability to transmit among mammals, although not at the level of seasonal human influenza viruses.
       (Continue . . . )

A new, potential complication comes with the likely introduction of HPAI H5N8 into Egypt's poultry population.  How that will ultimately affect the continued transmission, or evolution, of H5N1 (or H5N8) is unknown.

But the plot definitely thickens . . . .


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