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Mutation of avian influenza A(H7N9): now highly pathogenic for poultry but risk of human-to-human transmission remains low

24 Feb 2017
On 22 February 2017, WHO published the updated cumulative number of human cases of avian influenza A(H7N9) infection, which has now reached 1 223 since the first case in 2013. Nearly one-third of cases have occurred since October 2016 [1]. WHO’s risk assessment states that despite the identification of two small potential clusters of human cases, there is no evidence of sustained A(H7N9) transmission among humans [2]. The likelihood of person-to-person community level spread is therefore considered low.
 
On 19 February 2017, China’s Center for Disease Control and Prevention reported two human infections with a mutant strain of avian influenza A(H7N9) virus in Guangdong. The gene sequencing analysis found insertion mutations in the haemagglutinin gene. One case has recovered, the other case is still undergoing treatment [3].
 
The Veterinary Bureau of the China Animal Disease Control Center notified the World Organisation for Animal Health (OIE) on 18 February 2017 about the detection of a highly pathogenic avian influenza virus A(H7N9) in birds sampled on 10 January 2017 at live bird markets in Guangdong [4].
 
This follows the information shared by the Food and Agriculture Organization of the United Nations (FAO) on 20 February 2017 in an A(H7N9) ‘special edition’ of the FAO EMPRES Situation Update sent by email that ‘the H7N9 virus in China has converted into the highly pathogenic form (HPAI). This strain… shows a mutation leading to multiple basic amino acids at the cleavage site - a sign for high pathogenicity in poultry. The virus was isolated both from live bird market samples and two human cases in Guangdong Province. Following these findings, the MoA [Ministry of Agriculture] China published an emergency notice to strengthen national H7N9 prevention and control’ [5].
 
Health authorities in Taiwan also reported a possible new A(H7N9) genotype in a recent imported case which was ‘slightly different [from the current strain], denoting a possible new genotype, with a highly pathogenic trait in birds.’ It was noted that this virus contains a mutation in the neuraminidase (NA) protein relevant for antiviral resistance against oseltamivir and zanamivir. It is unclear as yet whether this antiviral resistance was acquired during treatment of the patient [6,7].
 
ECDC comment:

The upsurge of human cases in China during the winter 2016-2017 due to A(H7N9) gives cause for concern. On 26 January 2017, ECDC published a rapid risk assessment to remind the EU/EEA Member States of the possibility of travellers infected with A(H7N9) arriving from China [8].

The higher number of infected birds and the observed contamination of the environment in China are considered to have led to greater exposure to A(H7N9) and the increase in human cases.

So far A(H7N9) has had low pathogenicity in poultry, causing no mortality or signs of illness and making it difficult to identify infected birds for any intervention strategy. The evolution of this virus from having low pathogenicity to becoming highly pathogenic offers the opportunity to identify infected animals more readily and to implement the control measures established for all HPAI viruses.

The significant number of cases in both poultry and humans in China represents a risk for the spread of the virus beyond China to Central Asia and Europe. Sequences and viruses containing these new mutations need to be shared internationally (for example, to the Global Initiative on Sharing All Influenza Data (GISAID) and WHO Collaborating Centres) to improve diagnostics and the development of candidate vaccines [9].

Although no virulence factors for increased pathogenicity related to animal-to-human or human-to-human transmission have been described, each human case needs to be carefully assessed so as not to miss further evolution of the virus. Moreover, the above-mentioned antiviral resistance needs to be monitored as only limited treatment measures are available. Vaccines against A(H7N9) have been developed in the US, but their availability is limited [10]. In addition, it is unclear how well the A(H7N9) viruses currently circulating – evolved from the 2013 clade – antigenically match the candidate vaccine strain. Other vaccines against the A(H7N9) strain have been approved for clinical trials by the China Food and Drug Administration (CFDA) [11].
 
The ECDC risk assessment and the options for response have not changed since the last rapid risk assessment in January 2017. However, these new developments need to be monitored and assessed. ECDC will continue to follow the epidemiological and scientific developments related to avian influenza A(H7N9) virus and will continue to work with public health and veterinary experts in the EU/EEA Member States, WHO and other international partners.
 

References

1. World Health Organization (WHO). Human infection with avian influenza A(H7N9) virus – China, 22 February 2017 [22.02.2017]. Available from: http://www.who.int/csr/don/22-february-2017-ah7n9-china/en/
2. World Health Organization (WHO). Human infection with avian influenza A(H7N9) virus – China, 20 February 2017 [22.02.2017]. Available from: http://www.who.int/csr/don/20-february-2017-ah7n9-china/en/
3. Guangdong Provincial Center for Disease Control and Prevention. China Disease Control Center information: human cases detected with H7N9 virus mutant strains 2017 [22.02.2017]. Available from: http://www.cdcp.org.cn/gdsjbyfkzzx/gnwxx001/201702/ce3a2125d5dc46e1b2e906ee42d42c2d.shtml
4. World Organisation for Animal Health (OIE). Immediate notification report 2017 [22.02.2017]. Available from: http://www.oie.int/wahis_2/temp/reports/en_imm_0000022933_20170221_163854.pdf
5. Food and Agriculture Organization of the United Nations (FAO). H7N9 situation update 2017 [22.02.2017] Available from: http://www.fao.org/ag/againfo/programmes/en/empres/H7N9/situation_update.html.
6. Centers for Disease Control ROCT. Press release 2017 [22.02.2017]. Available from: http://www.cdc.gov.tw/info.aspx?treeid=45DA8E73A81D495D&nowtreeid=1BD193ED6DABAEE6&tid=74E691ADCEF52FFA.
7. Centers for Disease Control, ROCT. Taiwan CDC continues to monitor international spread of H7N9 and genetic changes in virus 2017. Available from: http://www.cdc.gov.tw/english/info.aspx?treeid=BC2D4E89B154059B&nowtreeid=EE0A2987CFBA3222&tid=83EDB903CBB4AE70
8. European Centre for Disease Prevention and Control (ECDC). Human infection with avian influenza A(H7N9) virus, fifth update, 27 January 2017 2017 [22.02.2017]. Available from: http://ecdc.europa.eu/en/publications/Publications/rra-influenza-a-h7n9-update-five.pdf
9. The Global Initiative on Sharing All Influenza data (GISAID). Genetic sequence data from the human and poultry isolates of A(H7N9) viruses [23.02.2017]. Available from: http://platform.gisaid.org/epi3/frontend#c6798
10. World Health Organization (WHO). Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness, September 2016 [24.01.2017]. Available from: http://www.who.int/influenza/vaccines/virus/201609_zoonotic_vaccinevirusupdate.pdf?ua=1
11. Ecns.cn. Bird flu vaccines set to undergo clinical trials 2017 [22.02.2017]. Available from: http://www.ecns.cn/2017/02-20/246004.shtml
 
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