Vaccination and Antiviral Treatment against Avian Influenza H5Nx Viruses: A Harbinger of Virus Control or Evolution

Abstract

Despite the panzootic nature of emergent highly pathogenic avian influenza H5Nx viruses in wild migratory birds and domestic poultry, only a limited number of human infections with H5Nx viruses have been identified since its emergence in 1996. Few countries with endemic avian influenza viruses (AIVs) have implemented vaccination as a control strategy, while most of the countries have adopted a culling strategy for the infected flocks. To date, China and Egypt are the two major sites where vaccination has been adopted to control avian influenza H5Nx infections, especially with the widespread circulation of clade 2.3.4.4b H5N1 viruses. This virus is currently circulating among birds and poultry, with occasional spillovers to mammals, including humans. Herein, we will discuss the history of AIVs in Egypt as one of the hotspots for infections and the improper implementation of prophylactic and therapeutic control strategies, leading to continuous flock outbreaks with remarkable virus evolution scenarios. Along with current pre-pandemic preparedness efforts, comprehensive surveillance of H5Nx viruses in wild birds, domestic poultry, and mammals, including humans, in endemic areas is critical to explore the public health risk of the newly emerging immune-evasive or drug-resistant H5Nx variants.

Keywords: H5Nx; antiviral treatment; avian influenza viruses; vaccination; virus evolution.

Figure 1

Schematic representation of the disseminated IAV subtypes in different mammalian hosts. Human, swine, marine animal, tiger, mink, horse, and domestic dog and cat AIVs are all assumed to have been transmitted from aquatic wild birds and emerged in avian reservoirs, and domestic poultry, to infect mammalian hosts. Unidirectional arrow refers to zoonotic potential of AIVs while bidirectional arrow refers to potential reverse zoonosis events “human-to-animal transmission” following zoonosis.

Figure 2

The migration routes (flyways) of migratory birds all over the world. The eight flyways include one main flyway that passes by Egypt and connects west Asia with east Africa. Global flyway boundaries in this map were created according to Boere and Stroud, 2006 [19].

Figure 3

Timeline of different avian influenza viruses, including H5Nx viruses that emerged in the Egyptian poultry sector. From 2006 to 2017, the HPAI H5N1 virus of clade 2.2.1 and its subclades 2.2.1.1 and 2.2.1.2 resulted in devastating economic losses in poultry and a remarkable public health hazard with zoonotic potential in humans. From 2016 to the present, the HPAI H5N8 virus of subclade 2.3.4.4 has been circulating, resulting mainly in losses in poultry. Recently, in 2022, HPAI H5N1 reassortants of clade 2.3.4.4b have been documented in migratory birds and domestic poultry in Egypt.