Zoonotic infections with avian influenza A viruses and vaccine preparedness: a game of "mix and match".

Various direct avian-to-human transmissions of influenza A virus subtypes upon exposure to infected poultry have been previously observed in the past decades. Although some of these strains caused lethal infections, the lack of sustained person-to-person transmission has been the major factor that prevented these viruses from causing new pandemics. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) yet again breached the animal-human host species barrier in Asia. Notably, roughly 20% of the A/H7N9-infected patients succumbed to the zoonotic infection whereas two of three A/H10N8 human infections were also lethal. Thus, these events revived the concerns of potential pandemic threats by AIVs in the horizon. This article reviews the various human incursions with AIV variants and provides insight on how continued circulation of these viruses poses perpetual challenge to global public health. As the world anticipates for the next human pandemic, constant vigilance for newly emerging viruses in nature is highly encouraged. With the various numbers of AIVs demonstrating their capacity to breach the animal-human host interface and apparent limitations of current antivirals, there is a need to broaden the selection of pre-pandemic vaccine candidate viruses and development of novel alternative therapeutic strategies.