Saturday, February 25, 2017

ECDC Comment On HPAI Mutation Of H7N9


It's been less than a week since we were first notified that the LPAI (up until now) H7N9 virus in China had mutated - at least in a few locations in Guangdong Province - into an HPAI (high path) virus (see Guangdong CDC: Two H7N9 `Variants' Isolated From Human Cases).

There are two broad categories of avian influenza; LPAI (Low Pathogenic Avian Influenza) and HPAI (Highly Pathogenic Avian Influenza).  
  • LPAI viruses are quite common in wild birds, cause little illness, and only rarely death.  They are generally not considered a serious threat to human health (H7N9 being the exception), but are of concern since H5 & H7 strains have the potential to mutate into HPAI strains.
  • HPAI viruses are more dangerous, can produce high morbidity and mortality in wild birds and poultry, and can sometimes infect humans with serious result.  The number of HPAI viruses that scientists have been tracking has increased markedly over the past 3 years, and now includes H5N1, H5N2, H5N6, H5N8,H10N8, and others.
Since it was first detected in the spring of 2013, H7N9 has always been an LPAI virus. We've always known there was a possibility that it might mutate into an HPAI virus - since we've seen that occur with other LPAI H7 viruses (see Genome Announcements: LPAI-to-HPAI Mutation Cited in January's H7N8 Outbreak).

Over the past 6 days there's been a scramble to try to understand the significance of this change, a task that has been complicated by the slow release of information out of China.  We are aware of two human cases in Guangdong, and a `similar' exported case (ex Guangdong) in Taiwan (see Taiwan CDC: January's Imported H7N9 Case Carried HPAI Mutation).

Taiwan's case remains in critical condition after nearly a month, and is reportedly infected with an antiviral `resistant' strain of the virus,  although we don't know whether he was infected by a resistant virus, or the virus acquired resistance during his treatment. 
The most immediate effect of H7N9 becoming an HPAI virus is its impact on birds. 

As an LPAI virus, it could spread stealthily among birds, without alerting poultry owners.  Now, this mutated strain is expected to cause morbidity and some degree of mortality among some bird species. Although more costly to poultry producers, this is actually a good thing,  as it may help in the identification and eradication of diseased birds.
While we know this HPAI version can infect humans, we haven't seen any evidence that the virus is any more virulent, or any more transmissible, in people.  Nor do we know how transmissible it is in birds.
The main caveats being, there's obviously a lot we don't yet know about how this new virus works, and that H7N9 (both LPAI and HPAI versions) will continue to diversify and evolve (see Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission).

 Yesterday the ECDC published a summary of events, and a comment, which you'll find below.

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.

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