EID Journal: Concurrent Infection with Clade 2.3.4.4b Highly Pathogenic Avian Influenza H5N6 and H5N1 Viruses, South Korea, 2023

#18,044

While the rest of the world has been dealing primarily with HPAI H5N1 for the past 3 years, last December and January I wrote several times (see below) about the unexpected return to South Korea of an HPAI H5N6 virus. The first reported since 2018. 

South Korea MAFRA Statement: All-out response to Prevent Additional Outbreaks of Highly Pathogenic Avian Influenza

WOAH: South Korea Reports 10 Additional Poultry Outbreaks With HPAI H5N6

WOAH: South Korea Reports 8 Poultry & Wild Bird Outbreaks With HPAI H5N6

Except for a single report of HPAI H5N6 in a migratory bird in Japan in December, and brief outbreak in the Philippines a year ago, no other countries reported H5N6 in poultry or wild birds to WOAH in 2023.

Over this past winter, South Korea reported to WOAH 26 poultry outbreaks of H5N6, and an additional 11 detections in non-poultry including wild birds.  

As we've discussed often (see HPAI H5N5: A Variation On A Theme) influenza A viruses are very promiscuous, and are able to reinvent themselves into new genotypes or subtypes by swapping genetic material (a process called reassortment) which can result in the creation of a hybrid virus.

While most of these reassortants are relatively short-lived evolutionary failures, a truly successful reassortant can become a game changer.  The emergence of a new clade 2.3.4.4 H5N8 virus in South Korean poultry 10 years ago reinvigorated HPAI H5, which had been slowly declining for several years. 

The rapid evolution and continual reassortment of HPAI H5N1 over the past 3 years has led to literally scores of genotypes spreading around the globe. Some - like genotype B3.13, which recently spilled over into American cattle - are proving to be more formidable than others. 

On Friday, the CDC's EID Journal published a dispatch on the concurrent infection with HPAI H5N1 and HPAI H5N6 of poultry and non-poultry last December in South Korea.  

While the impact of this newly emerged reassortant H5N6 virus remains to be seen, this is a reminder just how quickly a new subtype or genotype can emerge.  

First some excerpts from the dispatch, after which I'll have a brief postscript.

Concurrent Infection with Clade 2.3.4.4b Highly Pathogenic Avian Influenza H5N6 and H5N1 Viruses, South Korea, 2023

Gyeong-Beom Heo, Yong-Myung Kang, Se-Hee An, Yeongbu Kim, Ra Mi Cha, Yunyueng Jang, Eun-Kyoung Lee, Youn-Jeong Lee, and Kwang-Nyeong Lee

Abstract

Highly pathogenic avian influenza H5N6 and H5N1 viruses of clade 2.3.4.4b were simultaneously introduced into South Korea at the end of 2023. An outbreak at a broiler duck farm consisted of concurrent infection by both viruses. Sharing genetic information and international surveillance of such viruses in wild birds and poultry is critical.

(SNIP)

The first suspected case of HPAI in poultry in the 2023‒24 winter season was reported in South Korea. Surprisingly, birds at that farm were found to be concurrently infected with H5N6 and H5N1 viruses of clade 2.3.4.4b. Subsequently, birds at poultry farms as well as wild birds were found to be infected with H5N6 or H5N1 viruses. 

Our study analyzed whole-genome sequences of the virus populations of pooled swab samples from the flocks at the farm that were infected with both H5N6 and H5N1 influenza viruses; we defined the farm as the index case. We compared those sequences with the sequences of viruses isolated from other affected farms and wild birds to determine the origins of the viruses and their relationships.

The Study

On December 3. 2023, a suspected HPAI infection that caused white diarrhea, reduced feed intake, and increased deaths was reported in 39-day-old broiler ducks at a broiler duck farm (D448) in Goheung, South Korea (Figure 1). We detected matrix and H5 genes in the clinical samples from this index farm by real-time reverse transcription PCR. We determined the deduced amino acid sequence of the HA cleavage site of the H5 genes to be PLREKRRKR/GLF, which indicated high pathogenicity. 

For the NA gene, we detected both N1 and N6 genes in some flocks at the farm, at which the flocks were separated in different houses. We analyzed co-infection status at that farm by using whole-genome sequences of avian influenza viruses obtained from pooled oropharyngeal swab samples of 20 live ducks from each of 11 flocks using the Nanopore (Oxford Nanopore, https://nanoporetech.comExternal Link) amplicon sequencing method (Appendix).

We found that 3 flocks, numbers 1, 4, and 5, were co-infected with H5N6 and H5N1 viruses, whereas the other 8 flocks were infected with H5N6 virus only (Figure 2). Analysis of the average coverage at each gene segment as percentage composition showed that birds in flock 4 had more viral reads of H5N1, whereas flocks 1 and 5 had more reads of H5N6 (Figure 2, panel B).

We observed the same co-infection pattern in pooled cloacal swabs of flock 4 (data not shown). Because all the swabs from flocks were pooled at sample collection, no clear evidence was found supporting infection with the 2 viruses in a single bird. Because this farm was located very close to the south sea and seawall lake and had a relatively low level of biosecurity, we considered this farm susceptible to virus introduction by migratory birds (Figure 1, panel A).

We detected HPAI H5N6 virus (WA875) in Jeolla-do province in an apparently healthy wild mandarin duck, which we captured and sampled on December 4, 2023, for the active wild bird surveillance program. Two additional broiler-duck farms in the same province were found to be infected with H5N6 (D449) and H5N1 (D502) virus on December 5 and December 20, 2023 (Figure 1, panel A). 

We assessed the genetic relationships among the HPAI viruses by determining and comparing the complete genome sequences of A/duck/Korea/D448-N6/2023(H5N6), A/duck/Korea/D448-N1/2023(H5N1), A/duck/Korea/D449/2023(H5N6), A/mandarin duck/Korea/WA875/2023(H5N6), and A/duck/Korea/D502/2023(H5N1). Their sequences have been deposited in GISAID (https://www.gisaid.orgExternal Link; accession nos. EPI_ISL_18819959, EPI_ISL_18819961, EPI_ISL_18819826, and EPI_ISL_18819797.

The H5N6 viruses, D448-N6, D449, and WA875, showed high nucleotide sequence identities in all 8 genes among them (>99.8%). The sequences of their polymerase basic (PB) 1, hemagglutinin (HA), and matrix (M) genes were very close (99.53%–99.83%) to the respective genes of clade 2.3.4.4b HPAI H5N1 viruses isolated from wild birds in Japan and South Korea in 2022‒23.

The 4 internal genes of the H5N6 viruses, PB2, polymerase acidic protein (PA), nucleoprotein (NP), and nonstructural protein (NS), were closely related to the respective genes found in the Eurasian low pathogenicity avian influenza (LPAI) viruses of diverse subtypes isolated from wild birds in 2020 and 2022. 

Their N6 genes appeared to be close to the poultry viruses isolated in East Asia in 2021 and 2022, although the nucleotide identities were relatively low (98.1%–98.62%) (Table 1). Of interest, the protein encoded by the N6 gene in the isolates from this study had a deletion of 12 aa residues at positions 58–69; this neuraminidase (NA) stalk deletion has been often observed in poultry-adapted viruses (11,12). From the avian influenza active surveillance program in South Korea in 2019 and 2023, N6 genes were detected only in LPAI viruses isolated from wild birds; we did not observe this NA stalk deletion (data not shown).

We found no HPAI H5N6 viruses showing nucleotide similarities >98.5%, in any of the 8 genes, to the new H5N6 isolates in the public databases. However, a wild bird isolate from Japan (A/peregrine falcon/Saga/4112A002/2023, EPI_ISL_18740267) that was collected on December 6, 2023, was almost identical to the H5N6 Korean viruses (T. Hiono, pers. comm., email, 2024 Jan 11), suggesting that these emerged viruses spread coincidently throughout this winter in East Asia.

The nucleotide sequences of the coding regions of 2 poultry H5N1 viruses, D448-N1 and D502, were very similar (>99.0%) and were very closely related to the sequences of clade 2.3.4.4b H5N1 viruses circulating in Japan and Canada in 2023 (Table 2; Appendix Figures 1–5,7–9). Those clade 2.3.4.4b HPAI H5N1 viruses of diverse genotypes have been prevalent in Europe and North America (3) and had been introduced into South Korea during the epidemics of 2021–22 and 2022–23 (5,8). We did not detect significant mutations related to mammal adaptation or antiviral resistance in the newly isolated H5N6 and H5N1 HPAI viruses.

Conclusions

This study describes the simultaneous introduction of H5N1 virus and a new reassortant H5N6 HPAI virus of clade 2.3.4.4b into South Korea in 2023. Better understanding of this spatial and genomic dynamic requires enhanced and timely sharing of genetic information and international surveillance of HPAI and LPAI viruses in wild birds and poultry.

Dr. Heo is a researcher at Animal and Plant Quarantine Agency, South Korea. His research interests include surveillance of zoonotic viruses.

While this particular outbreak may prove to be mostly of academic interest, events like this are occurring - mostly out of our sight - every day around the globe. We live in a threat-rich and increasingly dangerous world, and the more we know about it, the better. 

Sadly, we seem to be getting less timely surveillance and reporting today than we were even a few years ago. Nations have figured out that it can be economically or politically expedient - at least in the short term - to bury `bad news'.  

• In early 2023 China covered up somewhere near 2 million COVID deaths (see EID Journal: Estimate of COVID-19 Deaths, China, December 2022–February 2023). 
• Very few nations track, or bother to report, COVID hospitalization or deaths anymore. 
• China, which often delays reporting, has gone unusually silent on HPAI H5N6 infections. 
• And even here in the United States, we seem incapable of tracking suspected H5N1 cases.

While there may be some who argue that ignorance is bliss, it does carry some substantial risks.   

Referral: Preliminary Genomic Epidemiology H5N1 Influenza A virus Outbreak in U.S. cattle

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While their is an enormous amount of egregious (and dangerous) misinformation on Twitter/X regarding avian H5N1 (and other disease threats), if you look hard enough, you'll find an impressive array of real scientists sharing useful and timely information and perspectives on that platform. 

While governments (including our own) are often slow to release information, experts like Tom Peacock, Michael Worobey, Angela Rasmussen - and dozens of others - are willing to take the time to post data and analysis in a public forum in a timely fashion. 

On Friday, more than 20 researchers combined their efforts on Virological.org to post what is known about H5N1's spread in cattle.  This two-part series was announced by Tom Peacock in a series of tweets. 

You'll find the two parts at the following links: PART 1   and   PART 2

Needless to say, Highly Recommended. 

Welcoming A New Blogger To Flublogia

#18,042

It's been a while since I've been able to welcome a new blogger to Flublogia - this little world of disease hunters and analysts on the internet - which has been going strong now for nearly 20 years.  What began with Crof's blog, Effect Measure, and the Flu Wiki in 2005 quickly blossomed into numerous flu forums and blog sites by 2006. 

Sharon Sanders formed FluTrackers in January of 2006, and I hung out my AFD shingle as well, although we were both denizens of flu forums before that.    

Over the years we've seen flu forums, and bloggers, come and go. It takes a certain degree of mania to do this sort of thing day in and day out - for free - for years.  

In recent years much of the action has shifted away from blogs to platforms like Twitter/X, and collaborative groups like Virological.org. But many of these sites are highly technical and narrowly focused - and if my stats are any indication - `old school' blogs still have a place. 

Those with sharp eyes will have noticed I've put a new site in my sidebar - Hogvet51’s Substack -  which is penned by John Korslund D.V.M., and which began publishing last week. 

Given the recent developments with H5N1 in livestock, having the perspective of a retired USDA APHIS VS staff veterinarian is a welcomed addition to our little group. 

I invite my readers to visit and subscribe to John's substack, and wish him many years of blogging success. 

Sci Repts: Blowflies As Potential Vectors Of Avian Influenza

 

#18,041

A little over 17 years ago in this blog - in Cats and Dogs and Flies, Oh My! - we looked at a 2006 study (see Detection and isolation of highly pathogenic H5N1 avian influenza A viruses from blow flies collected in the vicinity of an infected poultry farm in Kyoto, Japan, 2004 by Kyoko Sawabe et al.) that found that at least 2 types of flies could carry the H5N1 virus.

While flies weren't believed infected with the virus, they could ingest (and subsequently regurgitate or defecate) infected material, or potentially spread it mechanically by their feet or body, thereby spreading the disease.

The authors wrote:

The H5 influenza A virus genes were detected from the intestinal organs, crop, and gut of the two blow fly species, Calliphora nigribarbis and Aldrichina grahami, by reverse transcription-polymerase chain reaction for the matrix protein (M) and hemagglutinin (HA) genes. The HA gene encoding multiple basic amino acids at the HA cleavage site indicated that this virus is a highly pathogenic strain. . . . . Our results suggest it is possible that blow flies could become a mechanical transmitter of H5N1 influenza virus.

Four years later Dr. Sawabe and his team would publish (Blow Flies Were One of the Possible Candidates for Transmission of Highly Pathogenic H5N1 Avian Influenza Virus during the 2004 Outbreaks in Japan) where they conclude:

We have suggested here that blow flies are likely candidates for mechanical transmission of HPAI because of their ecological and physiological characteristics as reviewed here. In fact, blow flies have already been recognized as important vectors for mechanical transmission of several serious infectious diseases, that is, poxvirus [28], rabbit hemorrhagic disease [29], and paratuberculosis [30]. Recently, it has been reported that the H5N1 viral gene was detected in house flies [31] and engorged mosquitoes [32]. 

Last December, we looked at a brief synopsis of an upcoming study (see Kyushu University: The Return Of The Fly), which revisited this topic; testing blowflies for HPAI at the national wildlife reserve in Izumi City, Kagoshima Prefecture, which is the overwintering home for thousands of endangered Hooded Cranes. 

That study got a lot of attention in the Japanese press, with Dr. Ryusuke Fujita quoted as saying,

`Until now, countermeasures have been taken based on the assumption that small animals and people will bring the virus. There was no improvement, and when we suspected it was a fly, a virus was detected.

We will conduct a more detailed investigation, take measures to prevent fly intrusion, and verify their effectiveness."

Given that American dairy farmers are now having to worry about HPAI biosecurity, and flies tend to be abundant around both cows and poultry, this research is certainly timely. We now have the full, English language version, which was published today in Science Reports. 

I've only posted some excerpts, so follow the link to read it in its entirety. 

Article
Open access
Published: 04 May 2024

Blowflies are potential vector for avian influenza virus at enzootic area in Japan
Ryosuke Fujita, Takuji Tachi, Masato Hino, Kosuke Nagata, Masahiro Saiki, Mizue Inumaru, Yukiko Higa, Kentaro Itokawa, Nozomi Uemura, Ryo Matsumura, Izumi Kai, Kyoko Sawabe, Mutsuo Kobayashi, Haruhiko Isawa, Takahiro Kusakabe, Kazunori Matsuo & Shinji Kasai

Scientific Reports volume 14, Article number: 10285 (2024) Cite this article

Abstract

High pathogenicity avian influenza (HPAI) poses a significant threat to both domestic and wild birds globally. The avian influenza virus, known for environmental contamination and subsequent oral infection in birds, necessitates careful consideration of alternative introduction routes during HPAI outbreaks.

This study focuses on blowflies (genus Calliphora), in particular Calliphora nigribarbis, attracted to decaying animals and feces, which migrate to lowland areas of Japan from northern or mountainous regions in early winter, coinciding with HPAI season. Our investigation aims to delineate the role of blowflies as HPAI vectors by conducting a virus prevalence survey in a wild bird HPAI-enzootic area. 

In December 2022, 648 Calliphora nigribarbis were collected. Influenza virus RT-PCR testing identified 14 virus-positive samples (2.2% prevalence), with the highest occurrence observed near the crane colony (14.9%). Subtyping revealed the presence of H5N1 and HxN1 in some samples. Subsequent collections in December 2023 identified one HPAI virus-positive specimen from 608 collected flies in total, underscoring the potential involvement of blowflies in HPAI transmission.

Our observations suggest C. nigribarbis may acquire the HPAI virus from deceased wild birds directly or from fecal materials from infected birds, highlighting the need to add blowflies as a target of HPAI vector control.

          (SNIP)

Blowflies represent a potential vector of HPAI, particularly in enzootic regions. The effectiveness of virus detection from flies relies heavily on the prevalence of infected and deceased wild birds. C. nigribarbis is widespread in human-populated areas across Japan, including semi-rural regions with poultry farms.

Like other insects, C. nigribarbis intermittently disperses its feces, leading to environmental contamination. In this study, we focused on C. nigribarbis because it was the dominant blowfly species in our study field and the season, but we could not exclude the contribution of other necrophagous blowflies in HPAI propagation, especially in geographical areas.

Although the extent of blowfly intrusion into poultry houses and their role as infection sources has not been extensively studied, it is important to pay equal attention not only to the intrusion of small animals or birds but also to the entry of flies into poultry houses15. Unfortunately, due to the lack of comparable data on virus prevalence in each vector and their invasion rates into poultry farms, we could not determine which vector poses a higher risk for HPAI transmission on poultry farms.

Unlike house flies, which often originate within poultry houses and are visibly active, C. nigribarbis does not exhibit such behavior. While they may appear elusive, they can be readily captured in winter using baits or traps. Considering the possible involvement of blowflies in HPAI transmission, it would be advisable to implement fly control measures in poultry settings, such as utilizing fine mesh nets, fly traps, or insecticides.

(Continue . . .)

 

Gen. Virology: Iceland: An Underestimated Hub for the Spread of HPAI Viruses in the North Atlantic

 

#18,040

Despite nearly 30 years of dealing with H5N1, we have an unfortunate habit of underestimating what the HPAI H5Nx virus is capable of.  In the early 2000s, the virus was believed to be restricted to Southeast Asia, since the nearly everybody `knew' that sick migratory birds don't fly. 

Even after the virus winged its way to Europe, the Middle East, and Africa (following the 2005 Qinghai Lake event ) many experts still doubted the ability of the virus to spread efficiently via migratory birds (see 2014's Bird Flu Spread: The Flyway Or The Highway?).

This peculiar bit of self-delusion persisted until December of 2014 when HPAI H5Nx crossed the relatively narrow Bering Straits and began spreading across Canada and the United States, sparking the biggest avian epizootic (to that time) in North American history.

 

By the time it finally burned itself out in the summer of 2015, avian flu had affected 15 states and several provinces in Canada, and resulted in the loss of over 50 million commercially raised birds (see map above).

Luckily, HPAI wasn't sustained in North American birds (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl) and the outbreak did not resume the following fall.

While another Pacific crossing was always possible, most (but not all) experts believed the Atlantic was simply too vast to allow the virus to spread from Europe. A few contrarian studies from the last decade, with an emphasis on the potential role of both  Iceland and Greenland, included:

PLoS One: North Atlantic Flyways Provide Opportunities For Spread Of Avian Influenza Viruses

H5Nx: Why North America Must Remain Alert

Iceland Warns On Bird Flu 

In late 2021, the inevitable happened, and HPAI H5 arrived in Eastern Canada and Western Canada via two different routes; across the Pacific and the Atlantic (Multiple Introductions of H5 HPAI Viruses into Canada Via both East Asia-Australasia/Pacific & Atlantic Flyways).

Unlike older versions of HPAI H5, this reinvented avian flu was able to persist in a wide array of avian (and a few mammalian) hosts. Meaning it no longer requires re-introduction of the virus every year.  

While we've seen no evidence of west-to-east spread of North American HPAI viruses to Europe, we have seen evidence that some North American LPAI viruses  have crossed over into Asia.

According to the Icelandic Institute of Natural History, birds from both Canada and Europe regularly visit Iceland, making an exchange of avian viruses plausible (see below).

A total of 75 bird species regularly nest in Iceland, and a number of others occasionally choose to breed here, although they have been slow to establish themselves permanently. Some Arctic birds spend the winter in Iceland but nest at more northerly latitudes. Iceland is an extremely important stopover for geese and waders migrating between breeding grounds in Greenland and Canada and wintering grounds in Europe.

In late 2022, in Iceland as Stepping Stone for Spread of Highly Pathogenic Avian Influenza Virus between Europe and North America, we looked at an EID Journal Synopsis on the role Iceland, and migratory birds, played in introducing HPAI H5Nx to the North America. 

All of which brings us to a new study, by many of the same authors, that identifies Iceland as a likely, but underestimated, hub for the intercontinental spread of HPAI viruses. 

I've only included a few excerpts, so follow the link to read the full report. 

Iceland: an underestimated hub for the spread of high-pathogenicity avian influenza viruses in the North Atlantic

Ann Kathrin Ahrens1​, Stefán Ragnar Jónsson2​, Vilhjálmur Svansson2​, Brigitte Brugger3​, Martin Beer1​, Timm C. Harder1​ and Anne Pohlmann1​
 
Published: 02 May 2024 https://doi.org/10.1099/jgv.0.001985

High-pathogenicity avian influenza viruses (HPAIVs) of the goose/Guangdong lineage are enzootically circulating in wild bird populations worldwide. This increases the risk of entry into poultry production and spill-over to mammalian species, including humans. Better understanding of the ecological and epizootiological networks of these viruses is essential to optimize mitigation measures. 

Based on full genome sequences of 26 HPAIV samples from Iceland, which were collected between spring and autumn 2022, as well as 1 sample from the 2023 summer period, we show that 3 different genotypes of HPAIV H5N1 clade 2.3.4.4b were circulating within the wild bird population in Iceland in 2022.

Furthermore, in 2023 we observed a novel introduction of HPAIV H5N5 of the same clade to Iceland. The data support the role of Iceland as an utmost northwestern distribution area in Europe that might act also as a potential bridging point for intercontinental spread of HPAIV across the North Atlantic.

         (SNIP)

 

In conclusion, our data confirm that Iceland is involved in the circulation of clade 2.3.4.4b HPAI H5N1 viruses both as a sink for viruses from continental European and as a source for North America. It is therefore reasonable to assume that Iceland could act as a gateway for avian influenza in the transatlantic transmission pathway.

However, to date there is no evidence of west-to-east transmission.

Nevertheless, Iceland remains an important sampling area for the detection of novel avian influenza incursions. Iceland also remains a focal point for ongoing monitoring with regard to the potential impact of the HPAI epidemic in seabirds on biodiversity and the protection of endangered species.

         (Continue . . .).

While HPAI H5 has yet to crack the code on how to infect and spread efficiently in humans, it continues to exceed most other expectations.

Our focus today is understandably on the recent spillover into American cattle, but we need to remember that the virus is following hundreds of divergent evolutionary pathways around the globe, most of which are occurring outside of our view. 

Most will result in failure, but the virus only has to get `lucky' once.  

Which is why we need to cast a wide net, be prepared for surprises, and the strong likelihood that some will come from out of left field. 

Upcoming WHO EPI-WIN Webinar (May 6th) on Public Health Risk of H5N1 in Cattle

#18,039

On Monday, May 6th,  the World Health Organization will hold a new live Epi-Win Webinar on the public health risk of H5N1 recently found in American Cattle. A little over a year ago they held a webinar on H5N1 which you can view at this link. 

Although this is a rapidly evolving situation, and everyone is working with limited data, this should be an illuminating presentation. 

The time of the webcast (13:00 CET) works out to 7am EDT in the United States. Registration is required for the Zoom call, but the video will be posted on the WHO's YouTube Channel sometime after the broadcast.

WHO EPI-WIN Webinar: Public health risk of avian influenza A(H5N1) detected recently in dairy cattle
6 May 2024 13:00 – 14:00 CET

Background:

The highly pathogenic avian influenza (HPAI) A(H5N1) clade of viruses which arose in 2020 from previously circulating influenza A(H5Nx) viruses led to unprecedented numbers of deaths in wild birds and in domestic poultry. It spread globally and has been reported in non-avian species including, and most recently in dairy cattle. This has led to widespread concern. On 24th April 2024, WHO, FAO and WOAH published a joint risk assessment. This EPI-WIN webinar will explain the public health risks of the recent avian influenza detected in dairy cattle.

Tentative agenda:


Moderator: Dr Wenqing Zhang, Head, Global Influenza Programme (GIP), WHO
Opening remarks: Dr Maria Van Kerkhove, Director a.i., Epidemic and Pandemic Prevention and Preparedness (EPP), WHO

Speakers:
Dr Aspen Hammond, Technical Officer, GIP
Dr Moez Sanaa, Unit Head, Standard and Scientific Advice on Food Nutrition, WHO

Panel:
Dr Charles(Todd) Davis, CDC, USA
Dr Magdi Samaan, GIP, WHO
Dr David Swayne, Influenza Veterinarian, USA
Dr Mia Torchetti, USDA, USA
Dr Richard Webby, WHO CC, St Jude Children’s Hospital, USA


To register, please click here.

Participants will be able to submit questions during the webinar by using Zoom's "Q&A" feature. You may also submit questions in advance by sending them to epi-win@who.int.