On February 14, China confirmed the first ever human case of H7N4 avian influenza in a 68-year-old patient from Jiangsu province. The woman, who first developed symptoms on December 25, 2017,  was hospitalized for over three weeks in January. She reportedly had been in contact with live poultry before the onset of symptoms. Fortunately, the patient recovered, but it is still a concerning development and highlights the continued threat of zoonotic spillover events that could potentially lead to global pandemics of avian influenza. This week’s post will look at H7N4 and the threat that avian influenza poses to human health.

What is H7N4?

There are four types of influenza viruses: A, B, C and D. Influenza A viruses are categorized by two proteins found on the surface of the virus—hemagglutinin (HA) and neuraminidase (NA).  Most influenza A subtypes can infect birds—including H7N4. The H7 subtype includes nine known virus strains: H7N1-H7N9. These subtypes have been primarily identified in wild birds and poultry, and most are classified as “low pathogenicity avian influenzas (LPAI)”, which means that poultry infected “may show no signs of disease or only exhibit mild illness.” However, this does not mean that it has low pathogenicity in humans, and many LPAI can cause severe illness.

Previous H7 Influenza Outbreaks

Infection in humans by influenza A H7 subtypes is rare, although infections with H7N9, H7N2, H7N3, H7N7--and now H7N4--have been documented. For example, China reported the first case of human infection with an Asian lineage avian influenza A (H7N9) virus in 2013 and is currently experiencing its sixth epidemic of human infection with this subtype. Most of the cases have been caused by exposure to infected poultry or contaminated environments (eg, live poultry markets), and limited transmission among humans has been documented. According to the WHO, a total of 1,565 cases have been infected with the Asian lineage of H7N9 since 2013, with a case fatality of 39% during the previous 5 epidemics. Additionally, human cases of H7N2 have been documented in a poultry culler in Virginia, a New York resident (exposure source unknown), and a veterinarian in New York following exposure to a sick cat. Cases of human infection with H7N7 have occurred in Italy and the Netherlands, and cases of H7N3 have occurred in Mexico and British Columbia.

The Threat of Avian Influenza

Influenza pandemics arise when “a novel influenza viruses emerges with the ability to cause sustained human-to-human transmission, and the human population has little to no immunity against the virus.” Since many subtypes of influenza A currently circulate in poultry, continued contact with these animal populations may lead to spillover events with human infection, much like last week’s case of H7N4. As noted previously, the woman infected with H7N4 reported contact with live poultry before the onset of her symptoms, and the Chinese Centre for Disease Control and Prevention stated that the viruses’ genes “were determined to be of avian origin.”

Once a human becomes infected, the virus may mutate and acquire the ability to transmit from human to human, potentially leading to a pandemic in a human population naïve to that particular subtype. The 1918, 1957, and 1968 influenza pandemics were each caused by a novel type A virus of avian origin. While the 1957 and 1968 pandemics are believed to been caused by coinfection of a host by two different influenza viruses resulting in the subsequent reassortment of avian and human influenza genes, recent data suggests that the much more lethal 1918 virus likely arose from “an avian-like virus that adapted to humans.” However, even without significant genetic changes, some human-to-human transmission—although inefficient—has been demonstrated, including during the outbreak of H7N7 in the Netherlands referenced previously.

Luckily, none of the woman’s close contacts have presented any symptoms during the surveillance period, and hopefully, she will remain an isolated case. This case demonstrates the importance of continued and improved surveillance for avian influenzas in animal populations so that infected animals can be detected and quarantined or culled, as appropriate, and so that their infection can be characterized quickly. Additionally, biosecurity and infection control measures—such as practicing good hand hygiene, using proper personal protective equipment, and avoiding sick animals—can help prevent zoonotic and human-to-human transmission. Measures such as these can help prevent avian influenza A transmission to humans and avoid potentially catastrophic disease outbreaks that could kill thousands, if not millions, of people.

Photo: Chinese Field Epidemiology Training Program (FETP) residents during the H7N9 avian flu investigation in China in 2014.

Photo courtesy of CDC/Shuqing Zhao, China

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