One Flu Over the Cuckoo’s Nest: Has the New Avian Influenza Virus Achieved Human-to-Human Transmission?


By Asu Erden

Human cases of H7N9 – a new avian influenza A virus – were first reported in China between February and March 2013. It is believed that infection with this virus requires exposure to poultry but when and how the virus crossed the species barrier remains elusive. The Centers for Disease Control (CDC) originally estimated that up to 20% of the people that become infected with this virus die. There are currently no vaccines available against this avian flu virus, although clinical trials are under way with the help of the World Health Organization (WHO). The disease caused is severe and mainly affects the respiratory tract. Li et al. recently published a study in the New England Journal of Medicine that sheds light on the epidemiology of the disease caused by H7N9 and suggests that the virus might have achieved human-to-human transmission.


In their study, Li et al. investigated 139 confirmed cases of H7N9 from 12 different areas in China (including Shanghai and Beijing). Their aim was to better understand the epidemiology of the lower respiratory illness caused by this avian flu virus newly infecting humans. They were able to identify cases thanks to the Chinese surveillance system for pneumonia of unknown origin, which was put in place in 2004 at the time of the H5N1 avian influenza outbreak. The study confirmed that infection with H7N9 is most likely caused by exposure to live animals (poultry, birds, or swine). Most of the studied cases (77%) occurred in older individuals with the median age of patients being 61. Despite an older age distribution, the H7N9 virus seems to infect people from a broader age range than H5N1 did a decade ago.


This emerging zoonosis seems to be particularly virulent. After an incubation period of 7 days, H7N9 caused an acute illness characterized by severe lower respiratory symptoms – including pneumonia and respiratory failure – in all studied patients. The case fatality rate was also high, with 34% of patients dying. This rate is significantly higher than originally estimated by the WHO but remains lower than for H5N1. Further studies are required to establish the true case fatality rate of the disease caused by H7N9 in the overall population.


Li’s group also carried out family cluster analyses based on four families in which two or more individuals had confirmed cases of H7N9. In each cluster, one of the individuals became infected due to close contact with poultry (e.g. visits at poultry markets) but the other infected individuals never came in close contact with live animals. This suggests that the virus might have evolved to achieve human-to-human transmission. On the other hand, Li et al. also followed over 2500 close contacts of their 139 confirmed cases and only 1% developed respiratory symptoms, none of which tested positive for H7N9. Of note, however, is that these individuals were only followed for 7 days after contact and only single swabs were collected from them. This likely decreased the likeliness of detecting H7N9 cases among close contacts.


The most significant finding from this study also happens to be the only negative data that were presented:  Li et al. were unable to discard the possibility that H7N9 can transmit from human to human. Given the virulence, case fatality rate, and ongoing outbreak of the H7N9 avian influenza virus, the possibility of human-to-human transmission is cause for concern. The establishment of a putative human reservoir would allow for fast spread of the virus worldwide and should be scrutinized by public health officials.