Saturday, October 01, 2016

J. Virology: Pathogenesis & Transmission Assessments Of HPAI & LPAI H7N8 Viruses


Last January, after waiting for months to see if HPAI H5 would return to the United States, we saw instead an outbreak of HPAI H7N8 At A Commercial Turkey Farm In Indiana. This was the first detection of a highly pathogenic H7N8 virus, although LPAI H7N8 viruses had previously been detected in wild birds. 
Nine farms were affected (1 HPAI & 8 LPAI), but the outbreak was quickly contained, and no other farms or wild birds in the area have tested positive for the HPAI virus since.

In March APHIS released an Epidemiology Report On Indiana H7N8 Outbreak, stating it appeared to be the result of both a reassortment in wild birds, followed by a mutation from LPAI to HPAI in infected poultry.

This was followed last July by a report published in Genome Announcements: LPAI-to-HPAI Mutation Cited in January's H7N8 Outbreak that concluded that a spontaneous mutation had occurred in one of the outbreaks after the LPAI virus was introduced into the commercial flock.

While spontaneous mutation from LPAI-to-HPAI doesn't happen all that often, the risk is considered great enough that all LPAI H5 and H7 outbreaks must be reported to the OIE, and immediate steps must be taken to contain and eradicate the virus. 

HPAI viruses have been generated in the lab by repeated passage of LPAI viruses through chickens (cite FAO) but exactly how and why this occurs naturally is poorly understood (see JVI  Emergence of a Highly Pathogenic Avian Influenza Virus from a Low Pathogenic Progenitor).  
Since we don't know whether this HPAI H7N8 outbreak was a one-off event or if it will emerge someday again, it is important to get a sense of just how dangerous this subtype might be. 

Although the full report is behind a paywall, the following abstract informs us that HPAI H7N8 viruses are able to replicate in mammals and cause severe disease, but they did not observe transmission among ferrets.

Limited transmission, but less virulence, was observed with the LPAI H7N8 virus.

While HPAI H7N8 doesn't appear quite ready for prime time, it does have at least some of the characteristics that put it on our watch list, and it also serves to remind us just how quickly, and unexpectedly, a new avian influenza subtype can emerge.

Pathogenesis and transmission assessments of two H7N8 influenza A viruses recently isolated from turkey farms in Indiana using mouse and ferret models.

Avian influenza A H7 viruses have caused multiple outbreaks in domestic poultry throughout North America, resulting in occasional human infections in close contact. In early 2016, the presence of H7N8 highly pathogenic avian influenza (HPAI) viruses and closely related H7N8 low pathogenic avian influenza (LPAI) viruses were confirmed in commercial turkey farms in Indiana. 

These H7N8 viruses represent the first isolation of this subtype in domestic poultry in North America, with their virulence in mammalian hosts and the potential risk for human infection largely unknown.

 In this study, we assessed the ability of H7N8 HPAI and LPAI viruses to replicate in vitro in human airway cells and in vivo in mouse and ferret models. Both H7N8 viruses replicated efficiently in vitro and in vivo, but exhibited substantial differences in disease severity in mammals.

In mice, while the H7N8 LPAI virus largely remained avirulent, the H7N8 HPAI virus exhibited greater infectivity, virulence, and lethality. Both H7N8 viruses replicated similarly in ferrets, but only the H7N8 HPAI virus caused moderate weight loss, lethargy, and mortality. The H7N8 LPAI virus displayed limited transmissibility in ferrets placed in direct contact, while no transmission of H7N8 HPAI virus was detected.

 Our results indicate that the H7N8 avian influenza viruses from Indiana are able to replicate in mammals and cause severe disease, but with limited transmission. The recent appearance of H7N8 viruses in domestic poultry highlights the need for continued influenza surveillance in wild birds and close monitoring of the potential risk to human health.


H7 influenza viruses circulate in wild birds in the U.S., but when the virus emerges in domestic poultry populations, the frequency of human exposure and the potential for human infections increases. 

An H7N8 highly pathogenic avian influenza (HPAI) and an H7N8 low pathogenic avian influenza (LPAI) viruses were recently isolated from commercial turkey farms in Indiana. To determine the risk that these influenza viruses pose to humans, we assessed the pathogenesis and transmission in vitro and in mammalian models. 

We found that the H7N8 HPAI virus exhibited enhanced virulence and, although transmission was only observed with the H7N8 LPAI virus, the ability of this H7 virus to transmit in a mammalian host and quickly evolve to a more virulent strain is cause for concern. Our findings offer important insight into the potential for emerging H7 avian influenza viruses to acquire the ability to cause disease and transmit among mammals.

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