Before this year the H7N9 bird flu virus linked to 133 human infections and 43 deaths was never seen in people. All the available evidence suggests that an effective biological barrier apparently kept a pandemic at bay—humans only contracted the novel virus via direct contact with poultry or environments such as live bird markets rather than by human-to-human transmission. New analysis from the Chinese Academy of Agricultural Sciences (CAAS), however, suggests that the virus is closer to becoming a disease transmitted among humans than previously thought.
A large study comparing the genomes of the five reported human H7N9 strains with 37 H7N9 viruses isolated from more than 10,000 poultry market, farm and slaughterhouse samples from across China suggests that the virus would only need small mutations in its protein structure in order to become easily transmissible among humans. Moreover, testing in ferrets—widely considered to the best proxy for humans in flu testing—finds that one lethal strain of the virus that killed the first H7N9 victim in China is transmissible via respiratory droplet, meaning that it could conceivably be spread by coughing and sneezing. The new results are published in Science today. “Our findings indicate nothing to reduce the concern that these viruses can transmit between humans,” says study author Hualan Chen of the CAAS.
The new findings are “worrisome,” says Charles Chiu, an infectious disease expert at the University of California, San Francisco. “For this particular virus, for H7N9, whether or not there is human-to-human transmission is a critical question.”
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Since April the number of H7N9 cases has abruptly dropped, but public health officials are concerned that, like other avian influenza viruses that have seasonal infection patterns, H7N9 could mount a resurgence in the fall. With more cases of H7N9 there would be more opportunities for the virus to mutate among humans and, consequently, make the necessary amino acid changes to create human-to-human transmissible H7N9. The H7N9 viruses isolated from birds and humans are already closely genetically related. In the Science analysis researchers found the viruses can bind to human airway receptors, but they maintain the ability to bind to avian airway receptors, too. In order for the virus to be transmissible among humans, it must further mutate to lose its ability to bind to avian airway receptors—a genetic re-sorting the authors say might be possible with only a few amino acid changes.
The Science paper’s results diverge somewhat from earlier research. A study from the U.S. Centers for Disease Control published in Nature last week also considered H7N9 transmission in ferrets and found that although ferrets housed together transmit the flu, when the animals were physically separated but shared the same air via a net between their cages, the healthy ferrets only rarely contracted the virus. In that work CDC researchers looked at respiratory droplet transmission in two different strains of H7N9 and found that in a strain originating in Anhui Province, China, only two out of six ferrets contracted the virus whereas in a strain from Shanghai, only one out of three ferrets contracted the virus. (Scientific American is part of Nature Publishing Group.)
In the new study researchers also looked at multiple H7N9 strains and found the virus was similarly transmitted via direct contact. But in contrast to the authors of the Nature reports, they found that all three ferrets exposed to the Anhui H7N9 strain contracted the virus when exposed via respiratory droplets. The Science study authors ran the experiment twice and received the same results.
The significance of the conflicting airborne infection figures from the two studies is unclear because both studies looked at very small numbers of ferrets. Some of the discrepancy could have stemmed from differences in the lab environments. Alternatively, the virus may have changed slightly as the samples grew in the labs. What these studies, along with other existing research, make clear is that H7N9 can indeed spread via airborne transmission, but that this mode of transmission is not very effective compared with direct contact, says Richard Webby, an influenza expert at Saint Jude Children’s Research Hospital in Memphis. The new Science report “adds a whole lot of data to the growing list of evidence that this virus is something we need to be worried about,” he says.
Adding to the virus transmission concerns is the fact that chickens, ducks and mice experimentally infected with avian strains of H7N9 show no visible disease symptoms. In outbreaks of H5N1, another flu strain, severely infected poultry served as a warning knell for human infection. But H7N9 could silently spread in poultry markets and there would be no easy way to detect it.
Chiu says that the new findings should prompt more robust surveillance of poultry populations. Other public health measures to combat the virus in humans include washing hands, avoiding touching the eyes, nose and mouth, and coughing into the elbow to help stop the spread of transmission. “Replication in humans,” the authors wrote, “will provide further opportunities for the virus to acquire more mutations and become more virulent and transmissible in the human population.”