EID Journal: Changing Geographic Patterns/Risk Factors For H7N9 In China

H7N9 Waves - Credit EID Journal

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In addition to sparking the largest number of human avian flu infections on record (see above), wave 5 saw the emergence of new (HPAI & LPAI) strains of H7N9, along with impressive geographic spread to 8 new provinces in China.

Over the past few months we've seen an avalanche of new studies on H7N9, none of which are particularly reassuring:

J. Virology: Genesis and Spread of Newly Emerged HPAI H7N9 In China

J. Infect. Diseases: Human Clusters Of H7N9 In China - March 2013 to June 2015
  
Sci. Repts: Adaptation of H7N9 in Primary Human Airway Epithelial cells

Obviously worried, for the very first time, China's MOA Ordered An HPAI H7N9 Vaccine Deployed Nationwide This Fall.

Although H7N9 hasn't managed to adapt well enough to human physiology to transmit efficiently, the CDC's IRAT system ranks the newly emerged Yangtze River Delta lineage along with the original Pearl River Delta Lineage (see Updating the CDC's IRAT (Influenza Risk Assessment Tool) Rankings) at the top of their list of viruses with the greatest pandemic potential.

While  human infection during the first three waves was most often linked to exposure at, or through, live bird markets  -  and rarely from farms (see CDC: Risk Factors Involved With H7N9 Infection) - during the 4th and 5th wave that pattern began to change.

Today we've  a new study, published this week in the CDC's EID Journal, that looks at both the increasing geographic range, and shifting risk patterns, from the H7N9 virus in China.  I've only include some highlights, so you'll want to follow the link to read the study in its entirety.

When you return, I'll have a bit more.

Volume 24, Number 1—January 2018
Research

Changing Geographic Patterns and Risk Factors for Avian Influenza A(H7N9) Infections in Humans, China

Jean Artois1, Hui Jiang1, Xiling Wang, Ying Qin, Morgan Pearcy, Shengjie Lai, Yujing Shi, Juanjuan Zhang, Zhibin Peng, Jiandong Zheng, Yangni He, Madhur S. Dhingra, Sophie von Dobschuetz, Fusheng Guo, Vincent Martin, Wantanee Kalpravidh, Filip Claes, Timothy Robinson, Simon I. Hay, Xiangming Xiao, Luzhao Feng, Marius GilbertComments to Author , and Hongjie YuComments to Author

Abstract

The fifth epidemic wave of avian influenza A(H7N9) virus in China during 2016–2017 demonstrated a geographic range expansion and caused more human cases than any previous wave. The factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry, and wetland variables on all epidemic waves. Poultry predictor variables became much more important in the last 2 epidemic waves than they were previously, supporting the assumption of much wider H7N9 transmission in the chicken reservoir. 

We show that the future range expansion of H7N9 to northern China may increase the risk of H7N9 epidemic peaks coinciding in time and space with those of seasonal influenza, leading to a higher risk of reassortments than before, although the risk is still low so far.

The third and fourth epidemic waves of avian influenza A(H7N9) human infections in China showed an apparent reduction in incidence compared to the spring 2013 and winter 2013–14 epidemic waves. However, during the winter of 2016–17, the incidence rose, growing to levels never observed before and reaffirming concerns of a pandemic threat posed by the H7N9 virus (1–3). Since 2013, more than 1,520 human cases of H7N9 virus infection have been reported, mostly located in eastern China, with a case-fatality rate ranging from 30% to 40% (4–6).

(SNIP)

The geographic range expansion and increase in incidence of human cases in the fifth wave of H7N9 brings serious human health concerns. 

First, repeated human infection by avian influenza viruses increases the chances of virus recombination, mutation, or both leading to human-to-human transmission. 

Second, the provinces affected by earlier H7N9 epidemic waves do not have a strong seasonal influenza A peak in January and February (30) that matches the peak of H7N9 cases (Figure 3). 

 However, if the H7N9 virus continues to expand its range northward, in areas with a strong influenza A peak in January and February, there will be a higher chance of local coincidence of peaks of incidence between human cases of H7N9 and seasonal influenza A virus. 

This change may enhance the chances of coinfections that could lead to the emergence of reassortants with the capacity to transmit easily between humans. 

Third, the extent of the geographic range of the expansion is not yet fully known; in the absence of new measures, it may spread further within China and internationally through poultry value chains.

(Continue . . . )

Although the risks are difficult to quantify, the co-infection of a human with a seasonal (H1N1 or H3N2) virus and a novel virus like H7N9 is a concern since the potential for seeing a reassorted `hybrid' virus emerge cannot be ignored.

When the peak of the regular flu season concides with the peak (and increase) in human H7N9 cases, the odds of seeing co-infections rises. While viable reassortant viruses aren't detected often, we've a couple of examples to look at.

• In November of 2015 in J Clin Virol: Influenza Co-Infection Leading To A Reassortant Virus we looked at just such an occurrence. A co-infection between seasonal H3N2 and H1N1pdm09 in a 3 year old Cambodian boy which led to a new, reassortant H3N2 virus.
• In 2011 we saw a similar co-infection in Canada that led to the creation of a unique hybrid reassorted virus (see pH1N1 – H3N2 A Novel Influenza Reassortment) in a 16-month old boy from the Greater Toronto Area. 

In the summer of 2013, in the Lancet: Coinfection With H7N9 & H3N2, we saw the first evidence of co-infection with the newly emerged H7N9 virus and a seasonal flu virus in a human host. The case involved a 15-year-old boy from China - while two influenza viruses were isolated from the same patient - no reassorted virus was detected. 

Once again, in 2014, we saw a report (see EID Journal: Human Co-Infection with Avian and Seasonal Influenza Viruses, China) of two H7N9 co-infections, one with H1N1pdm09, and the other influenza B. 

Upping the ante, in February of 2016, in EID Journal: Nosocomial Co-Transmission Of H7N9 & H1N1pdm09,  we looked at an EID Journal report on another H7N9 - H1N1pmd co-infection from 2014, with the added twist that both strains appear to have been nosocomially transmitted to an immunocompromised patient in a hospital ward in China. 

While a reassorted virus was not detected in either of these events, the risks of eventually seeing it happen are not zero. 

Of course, H7N9 doesn't necessarily have to reassort with a humanized flu virus in order to become a pandemic.  It could simply evolve - perhaps through limited serial transmission in the community - to a more human adapted pathogen.

For now, H7N9 appears to be laying low in China, and while just about everyone (myself included) doubt that happy situation will persist much longer, avian flu often confounds our expectations.

The only thing we can say with absolute certainty is that H7N9 continues to evolve, and that means we need to be prepared for surprises going forward.

Stay tuned.