Review
Introduction and enzootic of A/H5N1 in Egypt: Virus evolution, pathogenicity and vaccine efficacy ten years on

https://doi.org/10.1016/j.meegid.2016.02.023Get rights and content

Highlights

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    It has been a decade since H5N1 emerged in birds and humans in Egypt in 2005/2006.

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    Despite the control measures, the endemic virus continues to devastate the poultry industry.

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    Egypt is the country with the highest number of human infections with A/H5N1 worldwide.

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    Virus evolution, pathogenicity in different species and vaccine efficacy studies were summarized.

Abstract

It is almost a decade since the highly pathogenic H5N1 avian influenza virus (A/H5N1) of clade 2.2.1 was introduced to Egypt in 2005, most likely, via wild birds; marking the longest endemic status of influenza viruses in poultry outside Asia. The endemic A/H5N1 in Egypt still compromises the poultry industry, poses serious hazards to public health and threatens to become potentially pandemic. The control strategies adopted for A/H5N1 in Egyptian poultry using diverse vaccines in commercialized poultry neither eliminated the virus nor did they decrease its evolutionary rate. Several virus clades have evolved, a few of them disappeared and others prevailed. Disparate evolutionary traits in both birds and humans were manifested by accumulation of clade-specific mutations across viral genomes driven by a variety of selection pressures. Viruses in vaccinated poultry populations displayed higher mutation rates at the immunogenic epitopes, promoting viral escape and reducing vaccine efficiency. On the other hand, viruses isolated from humans displayed changes in the receptor binding domain, which increased the viral affinity to bind to human-type glycan receptors. Moreover, viral pathogenicity exhibited several patterns in different hosts. This review aims to provide an overview of the viral evolution, pathogenicity and vaccine efficacy of A/H5N1 in Egypt during the last ten years.

Section snippets

Background

In 1997, highly pathogenic H5N1 avian influenza virus (A/H5N1) with a gene constellation that originated from wild aquatic birds was found to replicate efficiently and caused severe mortalities in gallinaceous birds in Hong Kong (Suarez et al., 1998). Unexpectedly, the deadly virus crossed the avian-human species barrier and killed six out of 18 infected patients (Hatta, M. and Kawaoka, Y., 2002, Subbarao, K., et al., 1998). The virus was eradicated successfully after depopulation of all live

Introduction of clade 2.2.1 virus in 2005 via wild birds and establishment of distinct subclades in (vaccinated) poultry and human

In April–June, 2005 unprecedented outbreak of H5N1 occurred in wild birds in Qinghai Lake, in western China and rapidly transmitted to poultry in over 60 countries (Chen, H., et al., 2005, Guan, Y., et al., 2009). Millions of migratory birds pass through Egypt each year via two overlapping migratory routes: the West Asian–East African and Mediterranean–Black Sea flyways of migratory birds (Abdelwhab and Hafez, 2011). During 2005–2006, 203 cloacal swabs out of 1304 migratory birds sampled at a

Variant 2.2.1.1 A/H5N1 viruses displayed steady stepwise-mutations and gradual antigenic drift

Accumulation of clade-specific mutations in the surface glycoproteins of Egyptian H5N1 associated with gradual antigenic drift was observed. Compared to the parent virus in 2006 in domestic poultry, the 2.2.1.1 viruses and 2.2.1.2 differed by 34 and 11 amino acid changes in the HA, respectively (Fig. 2). The majority of mutations in the HA coding region of clade 2.2.1.1 viruses were detected in amino acid residues 110, 140, 141, 144, 185, and 192 (H5 numbering) or residues 74, 97, 162 and 184

Increased affinity of Egyptian A/H5N1 viruses to human galactose-linked sialic acid (SA) receptors

The receptor specificity of the influenza viruses was linked to a number of HA residues: 91, 129, 132, 149, 175, 179, 186, 189–190, 218, 221–222 and 224, which form the receptor binding domain (RBD) (Duvvuri et al., 2009). Switching the receptor binding specificity from avian to mammalian receptors was reported to be associated with Q192R, G222L and Q224S substitutions (Matrosovich, M., et al., 1999, Shtyrya, Y., et al., 2009); nevertheless, Egyptian H5N1 viruses including those isolated from

The internal genes, what is beneath the tip of the iceberg?

Airborne transmission and/or virulence of AIV in mammals are also governed by functions encoded in internal gene segments (Herfst, S., et al., 2012, Imai, M., et al., 2012, Sutton, T.C., et al., 2014). In contrast to the HA and NA genes, there is a paucity of full length sequence information on other gene segments than HA and NA of Egyptian viruses (less than 150 full genome sequences do exist (Abdel-Moneim, A.S., et al., 2011b, Arafa, A., et al., 2012a, Bao, Y., et al., 2008, Gerloff, N.A., et

Chickens

During the first wave of the H5N1 outbreaks in Egypt in 2006, massive mortality of domestic poultry including chickens, ducks, geese, turkeys, and ostriches as well as zoo and feral birds occurred, indicating high level of viral virulence. In 2009–2014, several field observations described decreased virulence in chickens in commercial farms based on the morbidity and mortality rates in chickens where mortality ranged from 20 to 60% (El-Zoghby, E.F., et al., 2012b, Hagag, I.T., et al., 2015,

The recent wave of H5N1 viruses in human and poultry in 2014/2015 in Egypt

In October 2014–March 2015, Egypt experienced an upsurge of H5N1 infections in poultry and humans. The incidence of H5N1 dramatically increased and over 400 outbreaks were reported in commercial and household poultry (Arafa et al., 2015). The isolated viruses were distinguished by only a few mutations in the antigenic sites/immunogenic epitopes and showed no significant antigenic drift compared to viruses from previous years (Arafa et al., 2015). The majority of cases were in backyard birds

Vaccination in poultry against A/H5N1 in Egypt — a double-sided sword

Egypt embarked early (few weeks after introduction of the virus in 2006) on a nationwide blanket vaccination policy based on both H5N1 and H5N2 vaccines (Table 1) attempting to reach all poultry species to control the disease (Aly et al., 2008). Incidence of A/H5N1 outbreaks decreased after the first wave of infections in 2006 but it is unclear whether that was the effect of rigorous culling strategies or of administrating inactivated vaccines on a nationwide scale (Swayne, 2012). The first

Concluding remarks

After the emergence of the A/H5N1 in Egypt in 2005/2006, the Food and Agricultural Organization (FAO) of the United Nations expected that Egypt needs ten years for the eradication of the disease. However, after 10 years, the virus is still deeply entrenched and not only is total eradication far from reach but new waves of infections have been observed. Actually, the infrastructure of poultry industry in Egypt seems a great obstacle for control of the disease. A huge backyard sector, unregistered

Acknowledgment

EMA is supported by a grant from the German Research Foundation (DFG) (DFG-AB 567/1-1). MMN and AM are supported by a doctoral scholarship from German Academic Exchange Service (DAAD) and the Egyptian Government to the FLI and the Institute of Medical Virology, Giessen, respectively. SP conducted this work in the frame of the BMBF-funded FluResearchNet (Grant: 01 KI 07136 to SP), and, the BMBF-funded German Centre for Infection Research (DZIF), partner site Giessen, Germany (TTU Emerging

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