Thursday, April 27, 2023

WHO Novel Flu Summary & Risk Assessment - April 2023

 

#17,426

This week the World Health Organization published their latest novel flu summary, which covers the period from March 4th to April 24th. Of the 7 cases reported in this summary, 6 hail from China, while the 7th is the H5N1 case from Chile

Four of the 6 recently confirmed cases from China (2 H9N2 and 2 H1N1v) were `unofficially' reported in last month's update, obtained via unnamed sources at the February WHO Consultation and Information Meeting on the 2023-2024 Northern Hemisphere Influenza vaccine.

A recurring theme in these reports are reminders to all member nations of their obligation - under IHR 2005 regulations - to report in a timely fashion, all human infections with novel flu viruses. In actual practice, cases are sometimes belatedly reported, and often with far less detail than we'd like. 

In this week's report, at least one of China's H9N2 cases goes back to October of 2022, while one of the H1N1v cases occurred last December.  Others occurred in January and February. 

Due to its length, I've only posted some brief excerpts from this summary, so follow the link to read it in its entirety.  I'll return with some background on H1N1v after the break.  

Influenza at the human-animal interface 

Summary and risk assessment, from 4 March to 24 April 2023

• New infections: From 4 March to 24 April 2023, three human cases of infection with influenza A(H9N2) viruses and two human cases of infection with influenza A(H1N1) variant viruses were reported officially. Two of the A(H9N2) cases and both A(H1N1) variant cases were mentioned in the previous risk assessment of 3 March 2023. 3 Additionally, one human case of infection with an influenza A(H3N8) virus and one human case of infection with an A(H5N1) 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).2F 4 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.    

The most detailed report comes from Chile, on their 1st H5N1 infection, all of which has been previously discussed (see herehere, and here). Details on China's cases, however, remain sparse. The most verbose report, on their 3rd H3N8 case, tells us little more than the original report from the Guangdong CDC last March.

Avian influenza A(H3N8) viruses 

Since the risk assessment of 3 March 2023, China reported one human infection with an influenza A(H3N8) virus to WHO on 27 March. A 56-year-old female from Guangdong province developed symptoms on 22 February, was hospitalized on 3 March and passed away on 16 March. The patient had multiple underlying conditions. She had a history of exposure to live poultry before the onset of illness and there were wild birds reported near her home. Environmental samples from the live animal market that the patient visited before illness onset tested positive for avian influenza A(H3) viruses. No close contacts of the case developed an infection or symptoms of illness at the time of reporting. 

This is the third human case of infection with an influenza A(H3N8) virus reported to WHO. Two previous cases were reported in April and May 2022 .

China's three H9N2 cases reported are summed by by a single paragraph.

Avian influenza A(H9N2) viruses

Flying Blind In The Viral Storm

Since the last risk assessment on 3 March 2023, three human cases of infection with influenza A(H9N2) viruses were reported from China on 9 March (see Table 1 below). The cases were detected in influenza-like illness surveillance. All were children, had mild illness and were not hospitalized. No suspected cases among family contacts of the cases were reported. Two of the A(H9N2) cases were mentioned in the previous risk assessment of 3 March 2023.10

As are the two H1N1v cases reported by China.

Influenza A(H1N1) variant viruses [A(H1N1)v] 

Since the last risk assessment on 3 March 2023, two human cases of infection with Eurasian avian like swine influenza A(H1N1)v viruses were reported from China on 9 March (see Table 2 below). Both were children, had mild illness and were not hospitalized. No information on the likely source of exposure to the virus was available at the time of reporting and no suspected cases among family contacts of the cases were reported. Both of the A(H1N1)v cases were mentioned in the previous risk assessment of 3 March 2023.11 

Although the following plea to member nations to abide by the 2005 IHR is included in every WHO summary, we continue to see disappointing compliance (see Flying Blind In The Viral Storm) with both the letter and the spirit of the agreement.

• In the current COVID-19 pandemic, vigilance for the emergence of novel influenza viruses of pandemic potential should be maintained. WHO has developed practical guidance for integrated surveillance in the context of the cocirculation of SARS-CoV-2 and influenza viruses. The guidance is available here: https://www.who.int/publications/i/item/WHO-2019-nCoVIntegrated_sentinel_surveillance-2022.

All human infections caused by a new subtype of influenza virus are notifiable under the International Health Regulations (IHR, 2005). State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic. Evidence of illness is not required for this report. 

It is critical that these influenza viruses from animals or from people are fully characterized in appropriate animal or human health influenza reference laboratories. Under WHO’s Pandemic Influenza Preparedness (PIP) Framework, Member States are expected to share influenza viruses with pandemic potential on a regular and timely basis with the Global Influenza Surveillance and Response System (GISRS), a WHO-coordinated network of public health laboratories. The viruses are used by the public health laboratories to assess the risk of pandemic influenza and to develop candidate vaccine viruses.


While few details are offered on the two H1N1v cases, the WHO describes them as Eurasian avian-like swine influenza, which opens the possibility that they may be similar to the EA H1N1 `G4' swine viruses that have raised concerns in China, and globally, over the past 7 years.

How similar?  Based on the limited information provided, we simply can't say.  

There are a lot of variants of H1N1v circulating in swine around the globe, some posing much greater threats than others, and the clade and genotype from these infections are not mentioned in this WHO report.  

In 2015 Chen Hualan, director of China's National Avian Influenza Reference Laboratory, was the lead author on a paper that described a new and rising swine flu threat in China (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza).

EAH1N1 is a reassortant virus, with elements from H1N1 avian influenzahuman H1N1pdm, and swine-origin influenza viruses.  Despite sharing the same subtype designation as a currently circulating seasonal strain, it is genetically different enough to pose a genuine public health threat. 


In the `Significance' section the authors boiled it down to this:

Here, we found that, after long-term evolution in pigs, the EAH1N1 SIVs have obtained the traits to cause a human influenza pandemic. 

In 2020, another study on EA H1N1 swine influenza virus appeared in PNAS (see Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China) which reported a greater than 10% seroprevalence for the EAH1N1 virus among swine workers tested, suggesting that EAH1N1 is gaining human infectivity.

That sparked a series of high profile risk assessments being published by the CDC, ECDC, WHO and others (here, here, here, and here).

The CDC added this EA H1N1 G4 virus to their IRAT, and put it at the top of their list in 2021. But their list contains several other North American swine viruses with at least some pandemic potential (2 added in 2019). 

Summary: A risk assessment of Eurasian avian-like swine influenza A(H1N1)[A/swine/Shandong/1207/2016] virus, clade 1C.2.3 and genotype 4, was conducted in July 2020. With point scores ranging from 1 to 10, the overall IRAT risk assessment score for this virus falls into the moderate risk category, which ranges from 4.0 to 7.9. The average risk score for potential emergence of the virus to achieve sustained human-to-human transmission was 7.5, within the upper moderate range. The average risk score for the virus to impact public health if it were to achieve sustained human-to-human transmission was 6.9, also in the upper moderate range.

It is entirely possible that the H1N1v cases reported by China are from a less worrisome H1N1 lineage, but without prompt and detailed reporting, we can only guess at their significance.  

While it is easy to single out China for their belated and parsimonious reporting on disease outbreaks, there are plenty of other countries that - for economic, political or societal reasons - either don't test, or don't tell at all. 

A reminder, that when it comes to infectious diseases, that no news isn't always good news.