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UPDATED: CIDRAP NEWS now has an extensive review of this paper up on their website, with expert commentary provided by Dr. Ian MacKay.
Study: H7N9 highly transmissible by airborne route
Highly recommended.
# 7496
While the welcomed lull in avian influenza cases in Eastern China over the past six weeks has taken H7N9 largely out of the daily headlines, history has shown that avian flu viruses often go `quiet’ during the warm summer months, only to reappear again in the fall or winter.
Complicating matters, we still don’t know the source of this virus, or exactly how it managed to spread across tens of thousands of square kilometers of Eastern China - and infect at least 132 people - in a matter of a few weeks.
So over the summer researchers have continued to examine the H7N9 virus, trying to gauge its pandemic potential should it return with colder weather this fall.
Last week we saw two studies in the Journal Nature (see Nature: H7N9 Pathogenesis and Transmissibility In Ferrets & Mice & CIDRAP NEWS article New studies on H7N9 raise pandemic concerns) that suggested the H7N9 virus might be better equipped to spark a pandemic than previously thought.
Researchers determined that while the virus did not appear to transmit as easily as seasonal flu via respiratory droplets between ferrets, once acquired, the virus replicated at a much higher rate than one normally sees with seasonal flu.
Today, we’ve a complex and fascinating new study by scientists from Harbin Veterinary Research Institute and the Gansu Agricultural University appearing in the Journal Science that gives us a detailed look at two critical issues; the pathogenicity and transmissibility of the virus (in mice & ferrets).
Ferrets – whose respiratory system (and susceptibility to flu) are reasonably close to that of humans – are often used in transmissibility and pathogenicity studies of influenza.
Today’s study tested several different H7N9 isolates (acquired from birds, and from humans) for transmissibility, and even though their HA and NA proteins were genetically quite similar, at least one H7N9 isolate transmitted readily via respiratory droplets among ferrets.
The abstract (see below), only scratches the surface of research conducted in this study.
H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet
Science DOI: 10.1126/science.1240532
Qianyi Zhang, Jianzhong Shi, Guohua Deng, Jing Guo, Xianying Zeng, Xijun He, Huihui Kong, Chunyang Gu, Xuyong Li, Jinxiong Liu, Guojun Wang, Yan Chen, Liling Liu, Libin Liang, Yuanyuan Li, Jun Fan, Jinliang Wang, Wenhui Li, Lizheng Guan, Qimeng Li, Huanliang Yang, Pucheng Chen, Li Jiang,Yuntao Guan, Xiaoguang Xin, Yongping Jiang, Guobin Tian, Xiurong Wang, Chuanling Qiao, Chengjun Li, Zhigao Bu, Hualan ChenAbstract (EXCERPT)
We systematically analyzed H7N9 viruses isolated from birds and humans. The viruses were genetically closely related and bound to human airway receptors; some also maintained the ability to bind to avian airway receptors. The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses isolated from humans caused up to 30% body weight loss in mice.
Most importantly, one virus isolated from humans was highly transmissible in ferrets by respiratory droplets. Our findings indicate nothing to reduce the concern that these viruses can transmit between humans.
While I’m sure CIDRAP NEWS will have a more detailed look later today (I’ll post a link), a few of the high points in this study include:
- Researchers tested more than 10,700 samples taken from poultry farms, live market birds, wild bird habitats, and even poultry and swine slaughter houses and only managed to find 52 samples that were H7N9 positive (all but 2 were found in live-markets)
- Chickens intravenously inoculated with two early strains of the virus showed no signs of illness indicating the H7N9 is largely non-pathogenic in chickens
- Isolates taken from humans appeared to be more pathogenic in ferrets and mice than those taken from birds, suggesting adaptation of the virus may occur after the virus jumps to humans.
- All of the human isolates had either the 627K or 701N amino acid changes in their PB2 (both associated with increased virulence and transmission in mammals) - while the avian isolates did not - again suggesting that adaptive mutations may have occurred during replication of the virus in the human host.
- Mice inoculated with avian H7N9 isolates showed no signs of disease signs or deaths.
- Mice inoculated with human derived H7N9 isolates experienced significant weight loss & pathogenesis.
- In ferret transmissibility studies, four of the five viruses tested could be transmitted between ferrets in direct contact with each other, and one transmitted with high efficiency via respiratory droplets.
Being non-pathogenic in chickens, this virus has the potential to spread stealthily, and its rapid spread across multiple provinces in China suggests it transmits efficiently among poultry species.
This research suggests that the H7N9 virus already binds pretty well to human-like (a2,6) receptor cells, and it replicates efficiently in a mammalian (ferret) host.
Additionally, the H7N9 virus appears capable of accruing adaptive mutations that enhance both its virulence and transmissibility once it starts to replicate within a human host.
And perhaps most worrisome of all, at least one isolate tested already demonstrates the ability to transmit readily via respiratory droplets in ferrets.
Complicating matters, earlier this week we saw a study (see mBio: Antiviral Resistance In H7N9) suggesting that antiviral resistance may form quickly in patients infected with the H7N9 virus.
All qualities that could help make the H7N9 virus a formidable foe should we see it return in the fall.
