CDC Recommendations On Making PPE Available To Workers on Dairy Farms, Poultry Farms, and in Slaughterhouses

  

#18,048

It is frustrating that six weeks since we first learned that HPAI H5 had been detected in American dairy cows and 5 weeks since the first human infection was reported, the size and scope of this spillover event remains murky. 

• Just 1 case has been identified, but there are credible anecdotal reports of `many' symptomatic farm workers who have refused to be tested. 
• We've seen reports - both in the media and in statements made by APHIS/USDA officials - that they've met `resistance' from farmers who don't want their herds tested. 
• And recent media reports (see here, and here) suggest that some state agencies are not cooperating with the CDC or USDA (Note: The CDC has no authority at the state level unless they are invited in, and apparently some states have elected not to do so). 

As a result, despite strong evidence suggesting the HPAI H5N1 virus is widespread in dairy cattle, only 36 herds across 9 states have been identified.  And only one herd has been added to the list over the past 18 days.  

There may also be community cases of human H5N1 infection which have gone undetected. But without testing, we simply can't know. 

Turf wars between local and federal officials are nothing new, although until fairly recently the CDC appeared immune.  The deep political divide over the agency's COVID response appears to have changed that dynamic. 

I try not to ascribe motivations and intent to people I don't know, who are working under constraints I can only imagine.  But this is a very dangerous game, and if H5N1 gains transmissibility in humans, everyone loses. 

Three weeks ago the CDC came out with strong recommendations for protective gear to be worn by people working with potentially infected animals.  It is unclear however - whether, or how much - they are being used. 

Given the difficulties in trying to do farm work in protective gear, the costs (in lost time and materials), and the public's general distaste for wearing face masks after COVID, I suspect adherence is low. 

As noted above, properly donning and doffing PPEs requires both training, and separate `designated clean areas'.  But when cattle are visibly sick, or when they have tested positive for HPAI, wearing PPEs becomes crucial. 

Yesterday the CDC held a conference call (see readout below) with `state health officials, public health emergency preparedness directors, state epidemiologists, and state public health veterinarians, and leadership from public health partner organizations' discuss farm worker protection using PPEs.  

Quite telling is the following sentence in the last paragraph (emphasis mine).

CDC offers real-time support for state and local public health officials, as well as staff who are ready to deploy within 24 hours, if requested.

First the CDC's statement, after which I'll have brief postscript. 

Readout of CDC Call with State Public Health Partners Regarding Avian Influenza and Farmworker Protection
 
Media Alert

For Immediate Release: Monday, May 6, 2024
Contact: Media Relations
(404) 639-3286
media@cdc.gov


May 6, 2024 – Today, CDC Principal Deputy Director Nirav D. Shah met with state health officials, public health emergency preparedness directors, state epidemiologists, and state public health veterinarians, and leadership from public health partner organizations to discuss farmworker protection and personal protective equipment (PPE) for avian influenza.

CDC asked that jurisdictions make PPE available to workers on dairy farms, poultry farms, and in slaughterhouses. Specifically, CDC asked state health departments to work with their state agriculture department counterparts and partners in communities, such as farmworker organizations, that can help coordinate and facilitate PPE distributions.

Shah recommended that states prioritize distribution of PPE to farms with herds in which a cow was confirmed to be infected with avian flu, noting that some states have already distributed PPE to dairy farms. Jurisdictions were asked to use existing PPE stockpiles for this effort. Shah also briefed state officials on how to request additional PPE from HHS/ASPR’s strategic national stockpile, if needed.

Although CDC’s assessment of the immediate risk to the U.S. public from avian influenza remains low, Shah highlighted the importance of states acting now to protect people with work exposures, who may be at higher risk of infection. CDC has actively engaged with state and local health departments, farmworker organizations and public health veterinarians since first learning about the outbreak of HPAI in dairy cattle herds. CDC is also sharing information with staff at Federally Qualified Health Centers, who may care for farmworkers to help ensure that these staff are aware of the importance of PPE and the options to obtain it.

Shah reiterated the agency’s commitment to support state health officials, who are conducting the on-the-ground public health response to this outbreak. CDC offers real-time support for state and local public health officials, as well as staff who are ready to deploy within 24 hours, if requested. CDC will continue to provide states with the latest situational information and advice to help support their public health response efforts.

I suspect that a lot of people are banking on the idea that H5N1 will eventually burn itself out in cattle, and that since it hasn't sparked a pandemic after 20 years, it never will. While I hope both assumptions are correct, the downsides to getting this wrong are enormous.

It is possible, of course, that even if we manage to contain it here, HPAI could spillover to humans in some other country next week or next month.

But a robust, and transparent, investigation might yield valuable data to help us deal with that contingency. Meanwhile, the virus is indifferent to our political divides, economic concerns, or logistical constraints.

HPAI has time on its side, and will do whatever it is going to do, regardless of our plans or assumptions.

Our only realistic option is to face the problem directly, prepare for whatever comes, and hope it is enough.

NOAA SPC Issues A `High Risk' For Severe Weather in Oklahoma/Kansas

 

#18,047

The Storm Prediction Center has issued a rare `high risk' for severe weather across much of Oklahoma, and parts of Kansas, for later today. 

It has already been an active spring for severe storms (see below), with nearly 600 tornadoes reported since the 1st of the year. May is traditionally one of the strongest months for tornadoes, and so people in the warned areas should take these forecasts seriously.

For most Americans, a severe weather event is their biggest regional disaster threat; hurricanes, tornado outbreaks, blizzards, Derechos, and ice storms affect millions of people every year. Having a good (and well rehearsed) family emergency plan is essential for any disaster.

It is important for your plan to include emergency meeting places, out-of-state contacts, and individual wallet information cards - before you need it (see #NatlPrep : Create A Family Communications Plan).

Together with adequate emergency supplies, a solid first aid kit, emergency alerts on your cell phone or an emergency battery operated NWS Weather Radio, these steps will go a long ways to protecting you, and your family, from a wide variety of potential disasters.

As a Floridian I am more than aware that we are only weeks from the start of the Atlantic Hurricane season - and while the worst storms aren't expected until later in the summer - I'm already reviewing my hurricane preps. 

Given the aggressive forecasts we've seen for the hurricane season ahead, anyone living within a couple of hundred miles of the Gulf or Atlantic coast should be doing the same. 

From Escambia County Hurricane Preparedness Information

Preprint: Avian Influenza Virus Infections in Felines: A Systematic Review of Two Decades of Literature

 

Cats As Potential Vectors/Mixing Vessels for Novel Flu

#18,046

One of the topics we revisit with some frequency in this blog is the potential for companion animals (primarily cats) to serve as mixing vessels, and potential conduits of avian influenza to humans (see A Brief History Of Avian Influenza In Cats).

 While only rarely documented, it is not an idle concern.

In late 2016, New York City reported that hundreds of cats across several city-run animal shelters contracted avian an LPAI H7N2 (see NYC Health Dept. Statement On Avian H7N2 In Cats). 

Studies later showed that two shelter workers were infected while 5 others exhibited low positive titers to the virus, suggesting possible infection (see J Infect Dis: Serological Evidence Of H7N2 Infection Among Animal Shelter Workers, NYC 2016). 

Over the years we've looked at dozens of other cat-related spillovers, including these recent reports:

Netherlands: Utrecht University Study Of Stray & Domestic Cats For Evidence Of HPAI H5N1 Exposure

Emerg. Microbes & Inf.: Characterization of HPAI A (H5N1) Viruses isolated from Cats in South Korea, 2023

ECDC Risk Assessment: Avian influenza in domestic cats - Poland - 2023

Nebraska Veterinary Diagnostic Center (NVDC) Report: 2 Domestic Cats Infected With HPAI H5N1

To these we can add recent reports  of cats in close proximity to H5N1 infected dairy cattle succumbing to the virus after presenting with severe neurological manifestations.  That, along with other recent reports, led the CDC to issue Guidance for Veterinarians: Evaluating & Handling Cats Potentially Exposed to HPAI H5N1.

Two decades ago, it was assumed that cats were not particularly susceptible to influenza A infection, but today we know they can even catch seasonal flu from humans (see I&ORD: Evidence of Reverse Zoonotic Transmission of Human Seasonal Influenza A Virus (H1N1, H3N2) Among Cats).

All of which brings us to a preprint which conducts a review of the literature going back to 2004 (when the first spillover of H5N1 to Asia Tigers was reported), and finds hundreds of documented cat infections and deaths, with a substantial uptick in reports since 2023.  

Due to its length I've only posted the link, abstract, and some excerpts.  Follow the link to read the report in its entirety.  I'll have postscript after the break.

Avian Influenza Virus Infections in Felines: A Systematic Review of Two Decades of Literature

Kristen K. Coleman, Ian G. Bemis

doi: https://doi.org/10.1101/2024.04.30.24306585

          PDF 

As an avian influenza virus panzootic is underway, the threat of a human pandemic is emerging. Infections among mammalian species in frequent contact with humans should be closely monitored. One mammalian family, the Felidae, is of particular concern.

Felids, known as felines or cats, are susceptible to avian influenza virus infection. Felines prey on wild birds and may serve as a host for avian influenza virus adaptation to mammals. Feline-to-feline transmission has been demonstrated experimentally [1], and real-world outbreaks have been reported [2,3]. Domestic cats are a popular human companion animal and thus provide a potential pathway for zoonotic spillover of avian influenza viruses to humans.

Here, we provide a systematic review of the scientific literature to describe the epidemiology and global distribution of avian influenza virus infections in felines reported from 2004 – 2024. We aim to provide a comprehensive background for the assessment of the current risk, as well as bring awareness to the recurring phenomenon of AIV infection in felines.

          (SNIP)

 Avian influenza virus infections in felines reported over time The annual number of articles reporting avian influenza infections in felines drastically increased in 2023 (Figure 2), with a recent spike in the total number of domestic cat infections reported in 2023 and 2024 (Figure 3) from multiple regions (Supplementary Figure 1). 

This spike is commensurate with the emergence and increased spread of avian influenza virus H5N1 clade 2.3.4.4b among birds and mammals. As publication year may not be representative of the actual year(s) in which reported feline infections occurred, we provide data on the specific year(s) each study took place (Table 1). The overall case fatality rate among the reported RT-PCR-confirmed feline infections identified in our review was estimated to be 63%. 

Among the publications that described the illness experienced by the reported feline infections, respiratory and neurological illness were the most common and often resulted in death. Blindness and chorioretinitis were also recently observed in two AIV-infected domestic cats exposed to the virus through drinking raw colostrum and milk containing high viral loads from infected dairy cattle [5]. This clinical observation was unique to these feline cases and suggests that exposure route and dose of AIV might impact disease presentation and severity. 

Among all the reported feline infections, highly pathogenic avian influenza A(H5N1) was the most frequently identified subtype, followed by H5N6, H7N2, H9N2, and H3N8. H5N1 clade 2.3.4.4b was first detected in felines in 2022, including a wild lynx during an outbreak among pheasants in Finland [24], and a domestic cat living near a duck farm in France [25].

All studies reporting feline infections occurring since that time have identified H5N1 clade 2.3.4.4b as the causative agent [4,26–32], aside from one serology study in Spain which did not report the specific clade of the H5 virus identified [33]. Overall, clade 2.3.4.4b accounted for 112 of the reported feline cases and 75 deaths, yielding a mortality rate of 67%

          (SNIP)

Discussion and Conclusion 

Through our systematic review, we identified 486 avian influenza virus infections in felines, including 249 associated feline deaths, reported in the English scientific literature from 2004 – 2024. The reports represent cases from 7 geographical regions, including 17 countries and 12 felid species. 

Of particular interest are domestic cats infected with H5N1 clade 2.3.4.4, which represents a variant in the hemagglutinin serotype 5 gene of IAV which became the dominant IAV H5 serotype among poultry in 2020 [35]. Clade 2.3.4.4b was first reported in felines in 2022, and among the feline infections reported, it has yielded a mortality rate of 67%. 

Clade 2.3.4.4b is also responsible for the ongoing AIV outbreaks among dairy cattle in the U.S. [5], representing a significant threat to feline companion animals. Furthermore, subclinical infections of H5N1 in cats have been reported [6]. 

Thus, we argue that surveillance among domestic cats is urgently needed. As feline-to-human transmission of AIV has been documented [2,3], farm cat owners, veterinarians, zoo keepers, and cat shelter volunteers may have a heightened risk of AIV infection during outbreaks among poultry and mammalian farm animals. 

          (Continue . . . )

While dogs are also susceptible to H5N1 (see Microorganisms: Case Report On Symptomatic H5N1 Infection In A Dog - Poland, 2023), they tend to have milder (often asymptomatic) infections.  Both, however, are believed capable of serving as `mixing vessels' for the virus. 

We recently reviewed the CDC's Updated Advice On Bird Flu in Pets and Other Animals, which warned the public to avoid contact between their pets (e.g., pet birds, dogs and cats) with wild birds.

While the risk of cat-to-human transmission of H5N1 is still believed to be low, HPAI H5 continues to exceed our expectations, and so taking extra precautions would seem prudent at this time.  

NYC HAN Advisory: `Substantial' Increases In Mpox Infections Over Past Few Months

 #18,045

While HPAI H5Nx currently has most of our attention, we continue to watch a number of other emerging disease threats, including Mpox (formerly Monkeypox) which continues to evolve as it spreads both in endemic regions of Africa, and around the world.

Although the global health emergency for the international spread of a new clade (IIb) of Mpox ended nearly a year ago, we continue to see sporadic infections around the globe, while a more dangerous clade I mpox virus continues to rage (>12,000 cases in 2023) in the DRC.

In November of last year, the WHO Reported the 1st Confirmed Cluster Of Sexually Transmitted MPXV Clade 1 in the DRC, warning that `The risk of mpox further spreading to neighbouring countries and worldwide appears to be significant.'

The changing epidemiology and genetic evolution of mpox clade I in central Africa has sparked a number of risks assessments over the past few months, including:

CDC HAN Advisory #00501: Mpox Caused by H-2-H Transmission with Geographic Spread in the Democratic Republic of the Congo

ECDC Risk Assessment On Transmission & Spread of Clade I Mpox From The DRC

Two months ago a study was published Eurosurveillance: Ongoing Mpox Outbreak in South Kivu Province, DRC Associated With a Novel Clade I Sub-lineage, which contained the first genomic analysis of samples from a previously unaffected region of the DRC (the city of Kamituga). 

That study revealed a novel clade I sub-linage had emerged - most likely from a zoonotic introduction - with changes that may render current CDC tests unreliable.

 Three weeks ago, in Preprint: Sustained Human Outbreak of a New MPXV Clade I Lineage in Eastern Democratic Republic of the Congo, we saw a further analysis, which called for this new lineage to be named Clade Ib, and warned of its potential to spread globally. 

Whether it is the international spread of the classic clade I virus, the spread of this new (proposed) Clade Ib strain, or a resurgence of the milder clade IIb clade which began its world tour two years ago, the threat from mpox has not gone away. 

On Friday, May 3rd the New York City Health Department published the following HAN (Health Alert Network) Advisory citing increasing numbers of Mpox cases reported in the city, and the concerns over the introduction of these more dangerous clades of the virus. 

I've only posted some excerpts, so follow the link to read the release in its entirety.  I'll have a bit more on the JYNNEOS vaccine after the break. 

2024 Health Advisory #12: Updates on Mpox in New York City

• Mpox continues to circulate in New York City (NYC), with a substantial increase in reported cases since October 2023. 

• An outbreak of the more severe Clade I monkeypox virus (MPXV) in the Democratic Republic of the Congo poses risk for the introduction of Clade I into the U.S. 

• Consult with the NYC Department of Health and Mental Hygiene about testing if a patient is suspected of having Clade I MPXV. Treatment and vaccination strategies for Clade I are similar to those for Clade II. 

• Individuals with potential risk of exposure to mpox should be fully vaccinated. Continue to encourage and offer vaccination or refer to vaccination sites. 

• Commercialization of the JYNNEOS vaccine is underway. Begin to identify processes and funds to purchase vaccine on the commercial market. 

May 3, 2024 

Dear Colleagues, 

Mpox continues to circulate in New York City (NYC). Overall, the number of cases is low compared to the 2022 outbreak, but there have been increases in cases since October 2023. This, along with the large outbreak of the more severe Clade I monkeypox virus (MPXV) in the Democratic Republic of the Congo, highlight the need for ongoing vigilance, especially approaching the summer when increased transmission may occur. 

The U.S. continues to see only Clade II cases. Reported case numbers in NYC were relatively low for most of 2023, ranging from two to 20 cases per month between January and September. Since October, there has been an increase to an average of 36 cases per month, with a peak case count of 51 cases in January 2024. Of the 256 cases from October 2023 through April 15, 2024:

• 73% (188) were not vaccinated or had received only one dose.

• 94% were among men who have sex with men. 

• Most were Black or Hispanic and between the ages of 25-44. 

• Most were mild; ten (3.9%) people were hospitalized. 

Clade I Outbreak in the Democratic Republic of the Congo 

There is an outbreak of concern of Clade I MPXV in the Democratic Republic of the Congo. There have been no reported cases of Clade I in the U.S. and no evidence of transmission outside of endemic countries of Central Africa. However, it is possible that Clade I could be introduced into the U.S. by a traveler to the Democratic Republic of the Congo or other endemic countries, or with epidemiological links to those regions.

Clade I appears to be more transmissible and cause more severe disease. Isolation vaccination (JYNNEOS, ACAM2000), and treatment (e.g., tecovirimat, brincidofovir, vaccinia immune globulin intravenous) strategies used for Clade II infections are expected to be effective for Clade I infections.

Vaccination Update

People with potential risk of exposure to mpox should receive two doses of the JYNNEOS vaccine to be fully vaccinated. It is estimated that only one in four people recommended to receive the vaccine in the U.S. are fully vaccinated. Increasing vaccine uptake is essential to preventing infections and severe disease.

On April 1, 2024, the JYNNEOS vaccine began transition to the commercial market, though no cost federal supplies are available until early summer 2024. JYNNEOS vaccine will be made available through the Vaccines for Children (VFC) Program (for eligible adolescents), likely within a few months of commercialization. 

Recommendations for health care providers 

1) Testing 

• Given mild signs and symptoms reported by most cases since the 2022 outbreak, maintain a low threshold for mpox testing to reduce the potential for missed cases. Testing should be provided to any individual who requests it and has a sore or skin lesion that can be swabbed. 

• Refer to the GOALS Framework for Sexual History Taking in Primary Care to assess testing needs and facilitate the patient-provider relationship by normalizing discussions about sexual health and behavior as a routine part of health care. 

• Submit mpox specimens to a commercial or facility-based laboratory that has been approved to conduct mpox testing by New York State. If testing is not feasible, call the NYC Department of Health and Mental Hygiene (Health Department) Provider Access Line at 866-692-3641 to arrange for testing, following the NYC Public Health Laboratory specimen collection guidelines. 

• Be alert to the possibility of Clade I MPXV and need for specimen collection for people with symptoms and a history of travel or epidemiological links to a region of endemicity, including the Democratic Republic of the Congo, within 21 days of symptom onset. 

• If Clade I MPXV is suspected, call the Provider Access Line at 866-692-3641 for immediate consultation and to arrange for testing by the Centers for Disease Control and Prevention (CDC) (currently, only CDC can test for Clade I).

2) Vaccination 

• Continue to encourage vaccination for individuals for whom it is recommended and especially those with a higher risk of mpox complications (e.g., people with advanced HIV or other severe immunocompromise).

• Advise those who have not yet received a second vaccine dose to do so as soon as possible, regardless of how much time has passed since their first dose. 

• Start to identify processes and funds for ordering JYNNEOS on the commercial market. • Order no-cost vaccine by emailing poxvax@health.nyc.gov. The NYC Health Department anticipates being able to fulfill requests until early summer 2024. 

• If you do not offer vaccination, refer to vaccinefinder.nyc.gov to find a vaccination site.  

(Continue . . . )

Complicating matters, recent studies have suggested that the effectiveness of the JYNNEOS vaccine (approved in 2019) wanes significantly between 1 and 12 months, even when a person has received two doses. 

Five weeks ago, in ECCMID 2024 Study: Mpox (monkeypox) Antibodies Wane Within A Year of Vaccination) we looked at a study by researchers from Erasmus MC in Rotterdam that found:

. . .  recipients of the 2-Dose JYNNEOS/ IMVANEX/ IMVAMUNE mpox vaccine who did not receive a childhood smallpox vaccination (discontinued in the 1970s) experienced substantial drops in their immune response after 12 months. 

Another presentation, released at roughly the same time from Sweden (see Immune response to MPXV wanes rapidly after intradermal vaccination with MVA-BN (Jynneos)) found an even quicker loss (> 28 days) of detectable neutralizing antibodies after the second vaccination, writing:

Our findings corroborate previous data showing that intradermal MVA-BN vaccination results in neutralizing antibodies only in a proportion of vaccinees, and that a significant decline occurs already during the first months post-vaccination. Immunity after MPXV infection mounts a higher and more robust neutralizing response. In conclusion, the findings merits the study of booster doses.

Immunity is based more than just detectable neutralizing antibodies, and anecdotal reports suggest the vaccine provides significant protection, but boosters may be required sooner than originally planned (see ACIP Evidence to Recommendations for Use of JYNNEOS (orthopoxvirus) Vaccine Booster Every 2 Years).

While it remains to be seen whether the two (known) clade I strains follow clade IIb out of Africa, the virus continues to mutate and evolve, and will remain a tangible threat unless and until concerted efforts are made to contain it at its source. 

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

#18,043

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.