Avian Flu Diary: WHO Novel Flu Summary & Risk Assessment

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As the world battles COVID-19, the zoonotic threats we were following before January 1st, 2020 are still out there - continuing their spread and evolution - and posing the same level of threat to humanity as they did before our current pandemic began.

And while it isn't something anyone wants to hear, there's nothing in the pandemic rule book that excludes the possibility of another pandemic starting before COVID-19 has ended.

It also provides little comfort that while our resources and attention are focused on SARS-CoV-2, our ability to monitor other threats has greatly diminished (see Forgotten Fronts & Global Blind Spots and MERS-CoV: Forgotten, But Not Gone).

Even without a new emerging threat, we'll be battling two concurrent epidemics this fall; COVID-19 and seasonal influenza. And over the past few months, we've seen a worrisome drop in the amount of influenza data being reported by member countries to the WHO.

The bottom line: While things may appear quiet on the avian, swine, and novel flu front - we don't know what we aren't hearing about. And the same can be said for other threats, including MERS-CoV and Nipah - and of course - Clade X (the one we don't know about).

All of which brings us to the latest WHO novel flu summary - the first since early May - that focuses primarily on a couple of novel swine variant viruses (1 in Brazil, 1 in Germany), a pair of H9N2 cases in China, and a risk assessment of the EA H1N1 `G4' virus.

Three of these four cases were previously announced (see Taiwan CDC Alert: 2 New Cases Of Human H9N2 in Mainland China and WHO: Influenza A(H1N2) variant virus – Brazil), and I've written extensively about EA H1N1 `G4' in recent weeks (see here, here, and here).

Due to its length (5-page PDF), I've only included the link and some extended excerpts. Follow the link to read the report in its entirety.

Influenza at the human-animal interface

Summary and assessment, from 9 May to 10 July 2020
New infections : Since the previous update on 8 May 2020, two new human infections with avian influenza A(H9N2) viruses, one human infection with an influenza A(H1N1) variant virus and one human infection with an influenza A(H1N2) variant virus were reported.
Risk assessment: The overall public health risk from currently known influenza viruses at the human-animal interface has not changed, and the likelihood of sustained human-to-human transmission of these viruses remains low. Human infections with viruses of animal origin are expected at the human-animal interface wherever these viruses circulate in animals.

IHR compliance: All human infections caused by a new influenza subtype are required to be reported under the International Health Regulations (IHR, 2005). This includes any influenza A virus that has demonstrated the capacity to infect a human and its haemagglutinin gene (or protein) is not a mutated form of those, i.e. A(H1) or A(H3), circulating widely in the human population. Information from these notifications is critical to inform risk assessments for influenza at the human-animal interface.

Avian Influenza Viruses
Current situation:

Avian influenza A(H5) viruses

According to reports received by the World Organisation for Animal Health (OIE), various influenza A(H5) subtypes continue to be detected in birds in Africa, Europe and Asia.

Avian influenza A(H7N9) viruses
There have been no publicly available reports from animal health authorities in China or other countries on influenza A(H7N9) virus detections in animals in recent months. 4
Overall, the risk assessments have not changed.

Avian influenza A(H9N2) viruses

Since the last update on 8 May 2020, two new laboratory-confirmed human cases of influenza A(H9N2) virus infections were reported from China.

The first case was reported to WHO on 9 May. The infection was detected in a 6-year-old male from Shandong province, China, who had onset of illness on 28 April 2020. The patient was hospitalized on the day on illness onset, was treated with oseltamivir and was discharged on 8 May. The patient had exposure to domestic poultry at his home before onset of symptoms.

The second case was reported to WHO on 13 May. The infection was detected in a 10-month-old male from Fujian province, China, who had onset of illness on 4 May 2020. The patient had mild illness, was not hospitalized and was treated with oseltamivir. The patient had exposure to a live bird market before onset of symptoms.

Both patients were sampled as part of routine influenza-like illness (ILI) surveillance, have recovered, and no further cases were detected among contacts at the time of reporting.
Avian influenza A(H9N2) viruses are enzootic in poultry in Asia and increasingly reported in poultry in Africa.

Swine Influenza Viruses

Current situation: Influenza A(H1N1) variant virus (A(H1N1)v)

Since the last risk assessment of 8 May 2020, one human case of infection with a swine influenza A(H1N1)v virus was reported to WHO from Germany on 3 July. The infection was detected in a 2-year- old male who developed an influenza-like illness on 9 June 2020. The patient received healthcare on 9 June 2020. A sample was collected as part of routine ILI surveillance and an unsubtypeable influenza A virus was detected on 15 June. Whole genome sequencing characterized this virus as a Eurasian avian-like swine A(H1N1) virus (1C.2.2) on 1 July. The case recovered and no further cases were detected among contacts. The patient had visited a swine farm and had close contact with pigs two days before onset of illness.

Antigenic investigations on the virus isolated from the patient indicated some cross-reactivity with seasonal influenza A(H1N1)pdm09 viruses, indicating that immunity against infection with similar swine viruses may exist in the human population due to the circulation of A(H1N1)pdm09 viruses. Serological testing of close family contacts is planned.

Influenza A(H1N2) variant virus (A(H1N2)v)

Since the last risk assessment of 8 May 2020, one human case of infection with a swine influenza A(H1N2)v virus was reported to WHO from Brazil on 22 June. The infection was detected in a 22-year-old female, with no comorbidities, who worked in a swine slaughterhouse in Paraná state. The patient developed an influenza-like illness on 12 April 2020. On 14 April, the patient received medical care and was sampled on 16 April. An unsubtypeable influenza A virus was detected and on 22 June, genetic sequencing characterized this virus as an influenza A(H1N2)v virus. The patient was treated with oseltamivir, was not hospitalized and has recovered. Further genetic and phenotypic characterization of the virus from the patient is ongoing.

On 26 June 2020, local authorities started a retrospective and prospective investigation in the slaughterhouse where the patient worked as well in nearby municipalities where the slaughterhouse workers live. According to the preliminary epidemiological investigation, a second individual who also worked at the slaughterhouse developed respiratory symptoms during the same timeframe as the confirmed case, but no sample was collected from this person. No other suspected cases amongst contacts of the confirmed case have been identified.

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We've covered the growing risks from the avian H9N2 virus numerous times in the past (see Viruses: Characterization of the H9N2 Avian Influenza Viruses Currently Circulating in South China ) and last May, the CDC added a new lineage of the H9N2 virus to their IRAT (Influenza Risk Assessment Tool) short list of novel flu viruses with pandemic potential.

H9N2: Avian Influenza A(H9N2) Y280 lineage [A/Anhui-Lujiang/39/2018] Virus

Low pathogenic avian influenza A(H9N2) viruses are enzootic in poultry in many countries in Africa, Asia, the Middle East, and Europe. Since the late 1990s when the first human infections with avian influenza A(H9N2) virus were identified, detection of this virus has been reported infrequently in humans and in swine and other mammals. In 2018, there were 7 reported human infections, most with known exposure to poultry and with the majority involving viruses of the Y280 lineage.

Summary: A risk assessment of avian influenza A(H9N2) Y280 lineage A/Anhui-Lujiang/39/2018 virus was conducted in July 2019. The overall IRAT risk assessment score for this virus falls into the moderate risk category. The summary average risk score for the virus to achieve sustained human-to-human transmission was 6.2. The average risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission was 5.9, also in the moderate range. For a full report click here pdf icon[356 KB, 5 pages].

And although we've been watching it since late 2015 (see PN AS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza), a new study - published late last month (see PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China) - has raised fresh concerns over an evolving swine flu threat in China.

This new study found this virus replicated well in human epithelial cells, can be spread via respiratory droplets among ferrets, and a seroprevalence study of swine workers found that 10% (35/338) showed antibodies to this emerging strain.

Today's WHO report also contained a risk assessment on this emerging EA H1N1 `G4' virus:

Eurasian A(H1N1) swine viruses

In June 2020, the China Institute of Microbiology, Center for Influenza Research and Early-Warning, published a report entitled “Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection”.5 The article described swine influenza viruses detected through swine surveillance from 2011 to 2018 in China – the viruses had genes from Eurasian avian-like A(H1N1) lineages and internal genes from the human, seasonal A(H1N1)pdm09 virus and swine influenza triple reassortant viruses. These swine influenza viruses were classified based on their genetic make-up and termed genotypes G1-G6. The paper focuses on the zoonotic potential of the genotype G4 (termed by the authors of the paper) which emerged in 2013 and became predominant in swine population since 2016. The paper reported a seroprevalence of approximately 10% in swine industry workers and efficient direct contact and respiratory droplet transmission of the viruses in a ferret model.

5 Sun H, Xiao Y, Liu J, Wang D, Li F, Wang C et al. Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection. Proceedings of the National Academy of Sciences Jun 2020, 201921186.
Available at: doi.org/10.1073/pnas.1921186117.

Risk assessment

The viruses discussed in paper are not new. Viruses with similar gene combinations including the G4 genotype were reported previously in swine in China by the Harbin Veterinary Research Institute, China in a 2016 publication, and G4 genotype viruses have been the dominant genotype in swine population in China since 2016. The reported seroprevalence rate was based on a moderately small sample size and might not be solely attributed to the “new” G4 viruses. Other factors e.g. study design and context need to be taken into consideration. On the other hand, it highlights the importance of surveillance of swine influenza.

Sporadic zoonotic infections in humans with G4 genotype swine influenza viruses have been reported from China with the most recent human case reported in November 2019. In line with the findings of this paper, the influenza division of the Centers of Disease Control and Prevention (CDC) in the United States (US) has performed risk assessments of related viruses (though not G4 genotype) in 2019 and confirmed that they are transmissible in a ferret model by both direct contact and respiratory droplet. In collaboration with the OIE-FAO Network of expertise on animal influenza (OFFLU), the WHO Global Influenza Surveillance and Response System (GISRS) has been monitoring swine influenza viruses from the public health perspective. A candidate vaccine virus (CVV) from a closely related Eurasian avian-like A(H1N1) virus has been developed by the WHO Collaborating Centre at the Chinese Center for Disease Control and Prevention (China CDC) and is available for vaccine development for pandemic preparedness purposes.

Preliminary evaluation shows that the CVV covers well the G4 viruses from human infections, and evaluation with viruses from swine is ongoing. The G4 genotype and other swine and avian influenza viruses are continuously evolving. WHO, in collaboration with partners from the animal health sector, will continue monitoring their evolution and assess the associated risk. Animal influenza viruses continue to challenge human public health; surveillance of swine influenza viruses is as equally important as avian influenza viruses. Effective surveillance of these viruses significantly improves pandemic preparedness.

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While neither EA H1N1 `G4' or avian H9N2 appear to pose an imminent threat, we have a notoriously bad track record of seeing pandemics threats coming. The only thing we can say with any certainty is that, sooner or later, another pandemic virus will emerge.