Wednesday, November 22, 2017

EID Journal: Human Clusters Of H7N9 In China, 2013 - 2017

Credit WHO


Last September, in J. Infect. Diseases: Human Clusters Of H7N9 In China - March 2013 to June 2015, we looked at an analysis of suspected and probable human-to-human transmission of H7N9 during its first three epidemic waves in China.
That study described 21 H7N9 clusters (involving 22 contacts) from the first three waves, and found that at least 12 infections were likely the result of human-to-human transmission, another 4 were considered `possible', while 6 were determined to be unlikely.
But, as I pointed out at the time, the H7N9 virus has undergone a great many changes over the past couple of years.  A new LPAI Yangtze River Delta lineage of H7N9 has emerged, and become the dominant strain - while perhaps more ominously - an HPAI virus emerged in Guangdong Province and has quickly spread to other provinces.

Early reports (see Eurosurveillance: Epidemiology of Human HPAI H7N9 Infection - Guangdong Province) have suggested this recently emerged HPAI version might pose a greater threat to human health than the two LPAI lineages, but until recently, we've had little data to go on.

Over the past month or so, the research floodgates have opened, and we've seen:
Cell Host & Microbe: HPAI H7N9 Lethality & Transmission In Ferrets
Cell Research: Another Cautionary H7N9 Study Out Of China
J. Virology: Emergence & Adaptation Of HPAI H7N9 In Birds and Humans
EID Journal: H7N9 Viruses Co-circulating In Chickens In Southern China, 2016–2017

All of these studies suggest that HPAI H7N9 has acquired important mammalian adaptations that may increase both its virulence, and its transmissibility, and together they may enhance its pandemic potential.

While all very concerning, particularly on top of seeing a record number of human H7N9 infections during the 5th epidemic wave (see chart at top of blog), we haven't (yet) seen any signs of increased human-to-human transmission in the field. 
At least, not based on the limited real-time reporting provided by the Chinese government, the quality of which seriously declined in the spring of 2015 (see H7N9: No News Is . . . . Curious).
After slow rolling the release of dozens of cases last December, in January the momentum of the 5th wave was so great the Chinese government began releasing weekly updates  (see HK CHP: China Reports An Additional 83 H7N9 Cases For December), albeit with only limited epidemiological details.  
The good news is that studies coming out of China - while delayed by many months - often do an excellent job filling in those blanks.
Yesterday the EID Journal published a new study which examines human clusters from all 5 epidemic waves (through mid-summer 2017), and while the number of clusters has nearly doubled (n=40) over the past two waves, they did not find any signs of increased or more efficient H-2-H transmission.

I've posted some excerpts, but you'll want to follow the link to read it in its entirety. 

Volume 24, Number 2—February 2018

Clusters of Human Infection and Human-to-Human Transmission of Avian Influenza A(H7N9) Virus, 2013–2017

Lei Zhou1, Enfu Chen1, Changjun Bao1, Nijuan Xiang1, Jiabing Wu, Shengen Wu, Jian Shi, Xianjun Wang, Yaxu Zheng, Yi Zhang, Ruiqi Ren, Carolyn M. Greene, Fiona Havers, A. Danielle Iuliano, Ying Song, Chao Li, Tao Chen, Yali Wang, Dan Li, Daxin Ni, Yanping Zhang, Zijian Feng, Timothy M. Uyeki, and Qun LiComments to Author


To detect changes in human-to-human transmission of influenza A(H7N9) virus, we analyzed characteristics of 40 clusters of case-patients during 5 epidemics in China in 2013–2017. Similarities in number and size of clusters and proportion of clusters with probable human-to-human transmission across all epidemics suggest no change in human-to-human transmission risk.

Since December 2016, the number of human infections with avian influenza A(H7N9) virus in China has increased markedly (1,2), prompting concerns of pandemic influenza. Early signals of greater human-to-human transmissibility might be increased number and size of clusters of epidemiologically linked human infections and clusters of case-patients who are not blood relatives or increased numbers of case-patients with mild illness (3). 

To elucidate whether the increase in humans infections during the fifth epidemic (2016–2017) in China was associated with increased human-to-human transmissibility of A(H7N9) virus, we compared the characteristics of clusters of A(H7N9) case-patients during the fifth epidemic with those of clusters of case-patients identified from the previous 4 epidemics (2013–2016).



Despite the surge in human infections with A(H7N9) virus during the fifth epidemic in China, the similarity in numbers and sizes of clusters and proportions of clusters with probable human-to-human transmission during 2013–2017 suggest no change in human-to-human A(H7N9) virus transmission risk over time.
These findings suggest that the increase in human infections during the fifth epidemic probably reflects an increase in sporadic poultry-to-human A(H7N9) virus transmission over a wide geographic area in China (1).
Although we restricted the assessment of human-to-human A/(H7N9) virus transmission in probable clusters to secondary case-patients without identified poultry exposure, we may have overestimated human-to-human transmission in clusters if not all poultry exposures were identified and reported. We could have underestimated human-to-human transmission by excluding infections in possible clusters with exposures to both poultry and symptomatic case-patients. Only symptomatic close contacts of index case-patients were tested, possibly underestimating the size of clusters of patients with asymptomatic infections (4). 

Clusters of probable limited human-to-human A(H7N9) virus infections, including in healthcare settings, underscore the value of adhering to recommended infection prevention and control measures to prevent nosocomial A(H7N9) virus transmission (5-8). Ongoing assessment of the epidemiology of human infections with avian influenza A(H7N9) virus to identify any increase in human-to-human transmission will inform pandemic risk assessment, preparedness, and response (9).

Dr. Zhou is deputy chief of the Branch for Emerging Infectious Diseases, Public Health Emergency Center, China CDC. Her research interests are prevention and control of emerging infectious diseases and pandemic influenza preparedness and response.
The fact that we are not waist deep in an H7N9 pandemic right now is pretty good evidence that the virus is not quite ready for prime time, but it is (at least temporarily) reassuring that Chinese researchers have not been able to detect any signs of increased transmissibility between humans.

That said, the virus that returns this winter may have gained additional mutations over its `summer vacation', and we'll be watching closely for any changes in its behavior.

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