NOAA/NWS SPC: Another `High Risk' Severe Storm Day

#18,401

While we sometimes can go a year or longer without seeing a `High Risk' forecast from the Storm Prediction Center (SPC), today they've issued their second in just over 2 weeks (see previous).  Although the High Risk region is relatively small, the moderate and enhanced risk areas for today are substantial.  

Somewhere between 1000 and 1200 tornadoes are reported each year in the U.S., although that number has been going up in recent years, possibly because of better detection methods. Roughly half occur between March and May, making the spring - particularly in the South and Central states - prime time for these storms. 

 During the summer, the focus for severe weather moves away from the south (Dixie Alley), and into the mid west (aka `Tornado Alley'). 

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, and 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.

Because it's not a matter of `if' another disaster will strike . .  . 

It's only a matter of where, when, and how bad. 

Media Reports Of Fatal H5N1 Case in Child In Andhra Pradesh, India

 d

#18,400

Overnight the India press has lit up with multiple reports (hat tip FluTrackers and @vinodscaria​) on the death - two weeks ago - of a 2-year-old child from H5N1 in Andhra Pradesh. A quick tour of the local AP MOH website and twitter account, however, turns up no confirmation of the story.

The Indian press, admittedly, has a history of `jumping the gun' when it comes to reporting H5N1 cases (see 2007's India Admits 8 Boys to Hospital With `Bird Flu' Symptoms) - while the government is often slow to confirm - but this one sounds plausible. 

While we've seen many false alarms, there are precedents.  

In the summer of 2021, after several days of unconfirmed newspaper reports, we saw India: MOH Statement On Investigation Of 1st Human H5 Avian Flu Infection. The patient, an 11-year-old boy with acute myeloid leukemia, was infected with the clade 2.3.2.1a virus, and died after a week in the hospital.

According to a 2022 EID Journal Report:

An in-depth interview with family members indicated that the patient often frequented a family-owned poultry business and may have been exposed to birds with undetected infection, although no infected domestic or wild avian sources or any environmental contamination had been reported in or around the residence of the child.

Last May Australia reported their first H5N1 case (see Australia: Victoria Reports Imported H5N1 Case (ex India)) in a 2 year-old child who recently traveled from India. The virus was originally identified as  clade 2.3.2.1a virus, which is known to circulate in poultry in Bangladesh and India.

Last December the CDC's EID Journal published a dispatch which revealed this older clade was actually a new genotype, with contributions from newer clade 2.3.4.4b viruses.

And given the number of confirmed human cases in neighboring Bangladesh (n=8) and Pakistan (n=3) over the years - which are likely undercounts - it seems likely that some actual cases in India have been missed.  

According to the following English Language report from the Deccan Chronical (see AP Reports First Bird Flu Death as 2-Year-Old Succumbs to H5N1) the child was admitted to the hospital on March 4th after falling ill after consuming a small piece of raw chicken. 

The child died 12 days later. Swab samples initially tested positive for Influenza A, but were later confirmed to be H5N1 by AIIMS and the National Institute of Virology (NIV), in Pune.  So far, we have no indication of the clade. 

It is worth noting that India has been reporting as surge in H5N1 in recent months, in poultry, wild birds, and even cats.   Last week Andhra Pradesh reported 8 outbreaks (see WOAH report) in poultry, although none appear to be near to where this child was infected.  

Hopefully we'll get some better information in the next few days. 

Stay tuned. 

Preprint: Population Immunity to HPAI 2.3.4.4b A(H5N1) Viruses in the United States and the Impact of Seasonal Influenza on A(H5N1) Immunity

 

Note: Those already familiar with immune imprinting may wish to skim, or skip, my rather lengthy intro. 

#18,399

A little over 18 years ago, in A Predilection For The Young, I wrote about the disturbing (but curious) skewing of H5N1 cases (and deaths) among younger individuals (see WHO Chart above). 

While there are no records of humans ever having dealt with an H5 influenza pandemic (going back 130+ years), those who were born before before 1967 appeared far less susceptible to the virus - and those born before 1958 - even more so. 

 A lot of theories were proposed, but answers were elusive. Then, in 2013 an equally novel avian H7N9 virus emerged in China - sparking 5 years of seasonal infections - which skewed dramatically toward those over 40 (see comparison chart below).

Since both H5 and H7 virus exposures had been equally rare, it was obvious that there was more than just prior exposure to - and acquisition of specific antibodies against - these viruses at work. 

While most influenza pandemics see the greatest impact on the elderly, during the 1918 Spanish flu, the death rates among those in their teens, 20s, and 30s was reportedly much higher those in their 50's and 60's.  

In 1977-78, the H1N1 seasonal flu virus - which had been absent for 20 years, suddenly appeared in the Far East, and caused a pseudo-pandemic, primarily affecting those born after 1957. 

And during the  2009 H1N1 pandemic, we saw a similar age shift, where people in their 40's were hardest hit.  Here is what the CDC had to say about the impact of the virus in 2012's First Global Estimates of 2009 H1N1 Pandemic Mortality Released by CDC-Led Collaboration.

2009 H1N1 Pandemic Hits the Young Especially Hard

This study estimated that 80% of 2009 H1N1 deaths were in people younger than 65 years of age which differs from typical seasonal influenza epidemics during which 80-90% of deaths are estimated to occur in people 65 years of age and older.

By early in the last decade many researchers were convinced that the first flu you are exposed to early in life `primes' your immune system to preferentially fight similar influenza infections.  

Over time, this theory was refined to say that the HA Group type (I or II) you are exposed to first could substantially affect your immune response to influenza A (see Science: Protection Against Novel Flu Subtypes Via Childhood HA Imprinting).

The idea is that if your first influenza exposure was to H1N1 or H2N2 (Group 1), you may carry some limited degree of immunity to H5 viruses (H5N1, H5N6, etc.), while if your first exposure was to H3N2 (Group 2), you may carry some degree of protection against H7 viruses instead (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression).

• Those born prior to the mid-1960s were almost certainly first exposed to Group 1 flu viruses (H1N1 or H2N2)

• Those born after 1968 and before 1977 would have been exposed to Group 2 (H3N2) 

• After 1977, both Group 1 and 2 viruses co-circulated, meaning the first exposure could have been to either one. 

Other research suggests exposure to H1N1 (or the seasonal flu shot) may provide some limited degree of protection, since the the NA gene segment in seasonal H1N1 virus is antigenically similar to the NA in the clade 2.3.4.4b H5N1 virus (see EID Journal: A(H5N1) NA Inhibition Antibodies in Healthy Adults after Exposure to Influenza A(H1N1)pdm09).

While none of this is likely to make one fully immune to H5 infection, it could reduce the severity of infection, and decrease mortality. 

All of which brings us to a preprint- published yesterday - from researchers at the CDC and the University of Wisconsin - on potential preexisting population immunity against the HPAI H5 2.3.4.4b virus.  

The good news is this research seems to support previous studies which have suggested that past (age related) H1N1/H2N2 exposure and seasonal flu vaccines may provide some limited protection against severe H5 infection.

This is a lengthy and detailed report, and so I've just posted the link, abstract, and some excerpts.  I'll have a brief postscript after the break. 

Population Immunity to Hemagglutinin Head, Stalk and Neuraminidase of Highly Pathogenic Avian Influenza 2.3.4.4b A(H5N1) viruses in the United States and the Impact of Seasonal Influenza on A(H5N1) Immunity
zhu-nan Li, Feng Liu, Yu-Jin Jung, Stacie Jefferson, Crystal Holiday, F Liaini Gross, Wen-pin Tzeng, Paul Carney, Ashely Kates, Ian York, Nasia Safdar, C Todd Davis, James Stevens, Terrence Tumpey, Min Levine
doi: https://doi.org/10.1101/2025.03.30.25323419

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
 
Preview PDF

Abstract

The unprecedented 2.3.4.4b A(H5N1) outbreak in dairy cattle, poultry, and spillover to humans in the United States (US) poses a major public health threat. Population immunity is a critical component of influenza pandemic risk assessment. 

We conducted a comprehensive assessment of the population immunity to 2.3.4.4b A(H5N1) viruses and analyzed 1794 sera from 723 people (0.5-88 yrs) in multiple US geographic regions during 2021-2024. Low pre-existing neutralizing and hemagglutinin (HA) head binding antibodies and substantial cross reactive binding antibodies to N1 neuraminidase (NA) of 2.3.4.4b A(H5N1) were detected in US population. 

Antibodies to group 1 HA stalk were also prevalent with an age-related pattern. A(H1N1)pdm09 infection and influenza vaccination did not induce neutralizing antibodies but induced significant rise of NA inhibition (NAI) antibodies to N1 of 2.3.4.4b A(H5N1), and group 1 HA stalk antibodies. Understanding population susceptibility to novel influenza is essential for pandemic preparedness.

        (SNIP)

Age-stratified scatter plot of antibodies to group 1 HA stalk in 2023-24, 327 sera were collected from 234 participants from 8 age groups. 

Discussion

Population immunity against new emerging novel viruses is a key factor for influenza pandemic risk assessment16. Amid the ongoing A(H5N1) outbreaks in cattle and poultry and the continued spillover to humans, our study provides a timely and comprehensive assessment of the population immunity in the US to 2.3.4.4b A(H5N1) viruses. 

Results from the current study demonstrate that the levels of the pre-existing neutralizing  antibodies and the HA head binding antibodies to 2.3.4.4b A(H5) viruses in the US population are low, consistent with previous reports of low seroprevalence (mostly measured by HI antibodies) even in populations at increased risk of A(H5) exposure (e.g., poultry workers)12.

 However, our study revealed that the population in the US was not completely immunologically naive to the 2.3.4.4b A(H5N1) viruses: there were substantial levels of preexisting antibodies to the N1 NA of 2.3.4.4b A(H5N1) virus, and group 1 HA stalk antibodies in an age-related pattern. 

Furthermore, these pre-existing cross-reactive immunities to A(H5N1) virus (group 1) were mostly likely from past exposures to seasonal A(H1N1)pdm09 (group 1), not A(H3N2) (group 2) viruses.

While neutralizing antibodies targeting the HAs of the influenza virus are the main correlate of protection in reducing the risk of influenza virus infections, multiple immune mechanisms can contribute to protection from influenza13. Although seasonal influenza A(H1N1)pdm09 virus infection and influenza vaccination did not induce neutralizing and HA head binding antibodies to A(H5N1) viruses (Fig 3-4), both could induce significant rise of cross-reactive functional NAI antibodies to the N1 NA of 2.3.4.4b A(H5N1) (Fig 6). 

Sequence analysis showed that there is significant genetic distance between the HA head of the 2.3.4.4b A(H5N1) and A(H1N1)pdm09 viruses, with amino acid homology at approximately only 53%, and differences across multiple antigenic sites (Extended Table S3 and Extended Fig 2). In contrast, there is a higher level of amino acid sequence homology (86-88%) between the N1 NA sequences of 2.3.4.4b A(H5N1) and recent circulating seasonal A(H1N1)pdm09 viruses (Extended Table S4). 

(Continue . . . )

As we've discussed previously (see SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1), our options during the opening months of a novel pandemic will be limited. Antivirals may be in short supply (or ineffective), and a well-matched vaccine could be 6 months to a year away. 

While not ideal - and with the caveat that it is always possible that H5 swaps out its NA gene for something less compatible - there may be some value in getting the seasonal flu vaccine in the opening days of an H5 pandemic. 

Although the oft-quoted 50% CFR (Case Fatality Rate) of H5N1 is probably greatly exaggerated (see discussions here and here), even a more reasonable 2%-5% CFR would represent a public health crisis unlike anything we've seen in the modern era.

Making any advantage - even a small one - very much worth having. 

A Geospatial Perspective Toward the Role of Wild Bird Migrations and Global Poultry Trade in the Spread of Highly Pathogenic Avian Influenza H5N1

 

Major bird migration flyways - Credit CDC EID Journal

#18,398

Twenty years ago, HPAI H5 was viewed as a regional problem; a poultry virus restricted to Southeast Asia which occasionally spilled over into humans. While it could be carried by waterfowl, most of its spread was chalked up to illicit poultry trade. 

In 2005 a new clade of the virus (2.2) appeared at Qinghai Lake in Tibet, and for the first time managed to escape the confines of Asia (see EID Journal: H5N1 Branching Out), turning up six months later in mute swans in Croatia (cite).  

Changes in the virus appeared to have improved its carriage via migratory waterfowl. By the end 2005, 17 (mostly Asian) countries had reported infections, but in 2006 the virus would appear in an additional 39 countries.

By the end of 2007, the virus was endemic in the Middle East, well established in West Africa, and was a frequent return visitor to Europe. Fortunately, carriage by wild birds was still spotty, and strict culling of infected poultry prevented the virus from getting a solid foothold in Europe.

But repeatedly over the years new clades would emerge - and a new subtype (H5N8) - which incrementally improved the virus's ability to spread via migratory birds.  In early 2014, a clade 2.3.4.4 H5N8 virus abruptly appeared in South Korea, ripping through their poultry industry.  

By the end of that year, this new and improved clade had done what no other H5 had done before; it had crossed from Siberia to Alaska, bringing the first HPAI H5 epizootic to North America. 

While devastating, this epizootic was short-lived, and by summer all traces of the virus had disappeared (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl).

 The virus was still not able to maintain itself long-term in wild and migratory birds. 

The following year, another reassortment occurred in Russia (see EID Journal: Reassorted HPAI H5N8 Clade 2.3.4.4. - Germany 2016), which led to the unprecedented 2016-2017 epizootic in Europe, one which saw numerous subtypes (H5N8, H5N5, H5N2, H5N9, etc.) emerge, and an increased host range among avian species. 

Additional reassortments, several new subclades (e.g. 2.3.4.4b), and the emergence of competing subtypes (H5N6 then H5N1) would appear over the next 3 years, with the virus gaining new abilities to infect - and persist - in a growing number of bird species. 

In 2017, the virus pushed south through Central Africa, reaching the Southern Hemisphere for the first time. 

In 2020, H5N1 would re-emerge, and in 2021 the virus would make another great leap - crossing the North Atlantic and arriving first in Eastern Canada - then spreading rapidly across North America, arriving in South America the following fall. 

The H5 virus continues to expand its avian host range (see DEFRA: The Unprecedented `Order Shift' In Wild Bird H5N1 Positives In Europe & The UK), as well as branching out into many more mammalian species (e.g. cattle, sheep, goats, rodents, cats, etc.). 

Today, the H5 has made it to every continent except Australia, and many scientists fear that conquest is only a matter of time (see Australia : Biodiversity Council Webinar on HPAI H5 Avian Flu Threat).

Like a snowball rolling down a mountainside, H5N1 is gaining both mass and momentum. Where that leads is unknowable, but the H5 virus we face today is not your father's avian influenza. 

All of which brings us to an excellent research article, published in GeoHealth, which looks at this decades-long evolution of the HPAI H5 virus, and how its spread by wild and migratory birds has changed over the years.  

The full open-access report is very much worth reading in its entirety. You'll find the link, some excepts, and a link to a press release below. 

A Geospatial Perspective Toward the Role of Wild Bird Migrations and Global Poultry Trade in the Spread of Highly Pathogenic Avian Influenza H5N1

Mehak Jindal, Haley Stone, Samsung Lim, C. Raina MacIntyre
First published: 25 March 2025
https://doi.org/10.1029/2024GH001296

Abstract

This study presents the interplay between wild bird migrations and global poultry trade in the unprecedented spread of highly pathogenic avian influenza, particularly the H5N1 clade 2.3.4.4b strain, across the world and diverse ecosystems from 2020 to 2023. We theorized the role of migratory birds in spreading pathogens as various wild bird species traverse major flyways between the northern and southern hemispheres.

Simultaneously, we analyzed the global poultry trade data to assess its role in H5N1's anthropogenic spread, highlighting how human economic activities intersect with natural avian behaviors in disease dynamics. Lastly, we conducted spatial hotspot analysis to identify areas of significant clustering of H5N1 outbreak points over different bird families from 2003 to 2023.

This approach provides a strong framework for identifying specific regions at higher risk for H5N1 outbreaks and upon which to further evaluate these patterns with targeted intervention studies and research into what is driving these patterns. Our findings indicate that both the poultry sector and wild bird migrations significantly contribute to global H5N1 transmission, which helps better understanding of H5N1 transmission mechanisms when combined with ecological, epidemiological, and socio-economic perspectives. The results are intended to inform policy-making and strategic planning in wildlife conservation and the poultry trade to improve public health and animal welfare globally.

Key Points

• We investigated the role of wild bird migration in the inter-continental spread of avian influenza on a global scale

• We analyzed the global poultry trade data to highlight how human economic activities intersect with disease dynamics

• Our findings indicate that both the poultry sector and wild bird migrations significantly contribute to avian influenza transmission

Plain Language Summary

The unprecedented scale and simultaneous infection of avian influenza across multiple species raise concerns about the potential threats to human health, especially in the upcoming years, if not months. The looming increase in bird migrations to the south adds a layer of complexity and urgency to the situation. As we navigate this evolving landscape, it becomes imperative to closely monitor and comprehend the altered dynamics of the virus to implement effective strategies for mitigating the risks associated with human infections.

In this study, we tracked the movement of some wild birds according to their seasonal migration along with the incidence of avian influenza. While the spread patterns revealed that the avian influenza had started in Asian countries, it is not clear how it spread from Asia to Europe because, with the birds we analyzed, it was unable to find a flyway from Asia to Europe. 

However, every spread after the first incidence of avian influenza in Europe can be correlated with the seasonal migration of birds from one country to the other. Europe to Greenland to North America to South America can be established with different wild birds along with the spread from Europe to Africa.

(SNIP)

Analysis from 2005 to 2023 indicated a cyclic occurrence of the H5N1 every 5 years. However, a noteworthy deviation from this established pattern has become apparent in the latest outbreak since 2020. The ecological dynamics of the virus seem to have undergone a significant shift, manifesting in an unprecedented surge in cases compared to previous outbreaks. What distinguishes this event is the simultaneous and extensive infection of poultry, birds, and mammals during the same season—a phenomenon not witnessed in prior instances.

(Continue . . . )

New carrier birds brought avian flu to Europe and the Americas

Unexpected wild bird species, from pelicans to peregrine falcons, are transporting the virus from poultry to new places around the world and changing where the risk of outbreaks is highest

25 March 2025

         (Excerpt)

Far more bird species than ducks, geese and swans are transporting highly pathogenic H5N1 today, the study found. Cormorants, pelicans, buzzards, vultures, hawks, and peregrine falcons play significant roles in spreading avian flu. That makes them both victims and vectors of the disease and upends traditional approaches to monitoring H5N1 spread and predicting and responding to outbreaks. Culling of poultry birds worked in the past to mitigate burgeoning outbreaks, but it has failed to stop the current outbreak.

“We’ve got to think beyond ducks, geese and swans,” MacIntyre said. “They’re still important, but we have to start looking closely at these other species and other routes and think about what new risks that brings.”

Monitoring wild birds at a global scale is very difficult, so managing poultry bird populations is all the more important, she said. “We can do more about factors in our control — agriculture and farming.” Free-range birds, for instance, are more likely to contact wild birds, so managing them requires more vigilance. And pigs are “an ideal genetic mixing vessel” for viruses, so keeping pigs and poultry in close proximity is dangerous, she said.

“It’s a global problem, and it requires global solutions,” MacIntyre said.

          (Continue . . . )

Experimental Infection of Rats with Influenza A Viruses: Implications for Murine Rodents in Influenza A Virus Ecology

Credit CDC

#18,397

Over the years the idea that rats and other rodents could be potential hosts for novel flu viruses has come up a number of times (see 2016's The role of rodents in avian influenza outbreaks in poultry farms: a review), but until recently there has been little evidence to back up those concerns. 

A 2019 study out of Boston found RT-PCR evidence of IAV (Influenza A Virus) in 11% of 163 Norway rats (Rattus norvegicus) trapped and swabbed (note: half came from paw swabs, which may indicate contamination rather than infection). 

But 10 months ago, the USDA reported the detection of rodents (the House Mouse) to their Mammalian Wildlife with H5N1 for the first time, and since then deer mice and black rats have been added as well. 

Today rodents make up 129 of the 574 mammals (22%) on that list, although very little has been released about the circumstances of their discovery.  

The USDA's list is far from exhaustive, since many states have reported zero - or only a few - infections. Reporting is often limited by animals dying in remote and difficult to access places, or by animals that survive the infection. 

But it also seems likely that some states are looking harder for cases than others. 

While the susceptibility of cats (both wild and domestic) to HPAI H5N1 has been long known (see 2015's HPAI H5: Catch As Cats Can), the role that rodents may play in its ecology is less well understood. 

Two recent studies of note, however, include:

• Last August, in Pathogens: Susceptibility of Synanthropic Rodents to H5N1 Subtype HPAI Viruses, we looked at a study where researchers challenged several rodent species (house mice, brown rat, black rat) with two (older 2010, 2007) HPAI H5N1 viruses, and found they are both susceptible to the virus and could potentially play a role it its evolution and spread.

• Also in August 2024, in Emer. Microbe & Inf.: HPAI Virus H5N1 clade 2.3.4.4b in Wild Rats in Egypt during 2023, we a surprisingly high percentage of wild rats testing positive for H5 antibodies in Egypt, suggesting that some number may survive the infection. 

In addition to rodents, we've recently seen a number of studies showing that shrews, voles, and other small (often peridomestic) mammals are susceptible to novel flu (see Virology: Susceptibilities & Viral Shedding of Peridomestic Wildlife Infected with Clade 2.3.4.4b HPAI Virus (H5N1)) 

Last summer, in  Nature: Decoding the RNA Viromes in Shrew Lungs Along the Eastern Coast of China, we looked at a study that found a wide range of zoonotic viruses - including HPAI H5N6 - in shrews. Previously, in 2015's Taking HPAI To The Bank (Vole), we looked at that species' susceptibility to both H5N1 and H7N1.

Today we have a study which looks at the experimental infection of Sprague-Dawley rats with a variety of IAV subtypes, including H5Nx, H7N9, H9N2, H10N8 and the 2009 pandemic H1N1 (see chart below).  Not included: The North American Clade 2.3.4.4b H5N1 Virus.

Somewhat surprisingly, despite all of the viruses causing significant lung injury, none of the rats succumbed to the virus.  A trait that may enable rats to stealthily carry, and transmit, some strains of IAV (including H5N1).  

I've only included the link, Abstract, and a few excerpts from this study. Follow the link to read it in its entirety.  I'll have a postscript when you return.

Experimental Infection of Rats with Influenza A Viruses: Implications for Murine Rodents in Influenza A Virus Ecology

by 

Long Li

 1,

Rirong Chen

 1,

Zhigang Yan

 1,

Qinglong Cai

 1,

Yi Guan

 1,2,* and

Huachen Zhu

 1,2,*

Viruses 2025, 17(4), 495; https://doi.org/10.3390/v17040495 (registering DOI)

Submission received: 28 February 2025 / Revised: 25 March 2025 / Accepted: 27 March 2025 / Published: 29 March 2025

Abstract

Rattus norvegicus (brown rat), a widely distributed rodent and common biomedical model, is a known reservoir for many zoonotic pathogens but has not been traditionally recognized as a host for influenza A virus (IAV).

To evaluate their susceptibility, we intranasally inoculated Sprague-Dawley rats with various IAV subtypes, including H5Nx, H7N9, H9N2, H10N8 and the 2009 pandemic H1N1.

All strains productively infected the rats, inducing seroconversion without overt clinical signs. While replication efficiency varied, all viruses caused significant lung injury with a preferential tropism for the upper respiratory tract.

Investigation of receptor distribution revealed a predominance of α2,3-linked sialic acid (SA) in the nasal turbinates and trachea, whereas α2,6-linked SA was more abundant in the lungs. Notably, both receptor types coexisted throughout the respiratory tract, aligning with the observed tissue-specific replication patterns and broad viral infectivity.

These findings demonstrate that rats are permissive hosts for multiple IAV subtypes, challenging their exclusion from IAV ecology. The asymptomatic yet pathogenic nature of infection, combined with the global synanthropy of rats, underscores their potential role as cryptic reservoirs in viral maintenance and transmission. This study highlights the need for expanded surveillance of rodents in influenza ecology to mitigate zoonotic risks.

(SNIP)

Discussion

The role of rats and other rodents in influenza ecology remains understudied and controversial. This study provides compelling experimental evidence that SD rats, a representative model of the Rattus species, are susceptible to productive infection by diverse subtypes of contemporary IAVs that pose significant threats to both public health and agriculture. These include avian HPAI H5Nx (clades 1.0 and 2.3.4.4a, b, e, g, both human and avian isolates), H7N9 (HPAI and LPAI), H9N2, H10N8, and the mammalian-adapted pandemic 2009 H1N1 viruses (Table 1). 

Notably, these infections occurred without prior viral adaptation, challenging the conventional assumptions that rats are generally insusceptible and not natural hosts of IAV. Our findings, together with previous reports [11,12,13,14,15,16,17,37,38,39,40], underscore the need to reevaluate rodents as potential reservoirs, mechanical vectors, or bridging hosts in the zoonotic transmission of IAVs. 

The absence of overt clinical signs, despite robust viral replication, seroconversion, and histopathological evidence of lung injury (Figure 1, Figure 2, Figure 3, Figure 4 and Figure 5), positions rats as cryptic carriers capable of sustaining IAV infections undetected in natural settings.

A striking feature of IAV-infected SD rats is the dissociation between their subclinical manifestations and significant virological and immunological findings. Unlike mice and ferrets, which develop observable disease or mortality following experimental IAV challenge [32,33], rats exhibited only a statistically insignificant lower rate of weight gain compared to the control group (Figure 1) and no influenza-like symptoms, even when infected with HPAI H5 or H7N9 strains.

This asymptomatic phenotype resembles that of wild waterfowl, the natural reservoirs of IAV [4,5]. The absence of disease presentation and the induction of seroconversion in most rats suggests that rats may use effective immune mechanisms to limit systemic viral spread while allowing local replication in the upper respiratory tract (this study and [19,20,37]). This balance may facilitate viral infection without compromising host survival, positioning rats as potential stealth vectors in ecosystems where they interact with domestic animals, wildlife, and humans.

          (SNIP)

Conclusions

This study redefines Rattus norvegicus as a permissive host for multiple IAV subtypes prevalent in birds or humans and highlights its ability to sustain subclinical infections with potential ecological consequences. The convergence of broad viral susceptibility, synanthropic behavior, and dual SA receptor expression in the respiratory tracts positions rats as underrecognized players in influenza ecology.

While their role as “mixing vessels” remains speculative, the risk of environmental virus amplification and spillover to domestic animals or humans cannot be dismissed. Strengthening surveillance in rodent populations and integrating rats into One Health frameworks will be essential for mitigating zoonotic threats in an era of escalating avian influenza activity.

          (Continue . . .)

Not so very long ago, HPAI H5 was regarded ass pretty much just an avian virus, with occasional spillovers to humans, or to cats unlucky enough to be fed a diet of raw chicken. But 2021 - following a series of reassortment events - we began to see reports of numerous spillovers into a much wider range of mammals (see graphic below).

Credit ECDC/EFSA

While surveillance, testing, and reporting of infected mammals remains severely (some would say, criminally) limited, the growing global impact of HPAI H5 on our shared environment these past few years is unmistakable (see  Nature Reviews: The Threat of Avian Influenza H5N1 Looms Over Global Biodiversity).

As the HPAI H5 virus continues to find new mammalian hosts it only increases the chances that it will find new evolutionary pathways that were unavailable to it when it was primarily a disease of birds. 

  

Where that leads us in anyone's guess, but the more entrenched the virus becomes in the environment, the fewer our options will become to deal with it. 

NPJ Vaccines: Modeling the Impact of Early Vaccination in an Influenza Pandemic in the United States

 

#18,396

Although there are no guarantees that avian H5N1 will spark the next pandemic, it is a pretty good bet that the next pandemic will be caused by a novel `flu-like' virus (with influenza and coronaviruses being at the top of that list).  

While once thought of as a `once-in-a-generation' event, in my lifetime I've already experienced 4 legitimate pandemics (1957, 1968, 2009, 2020), 2 pseudo-pandemics (1977, 2003), and one `near-miss ' (1976).

Given recent trends (see PNAS Research: Intensity and Frequency of Extreme Novel Epidemics) - even at my age - it is entirely possible I'll see another.  While it is unknown what the next pandemic will look like, it is likely we'll go into it without a vaccine and with relatively few therapeutic options. 

Recent studies looking at avian H5 have raised concerns over the effectiveness of current antivirals, and there are a great many barriers to rapidly producing, and distributing, a novel flu vaccine. 

As Maggie Fox explained last year in SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1, our options during the opening months of any pandemic will be limited. Unpopular as they might be, NPIs (non-pharmaceutical interventions like masks, social distancing, etc.) will once again become our first line of defense. 

The rub with any new vaccine is that they tend to arrive late into a pandemic, after most people have already been exposed.  They can certainly be useful for dealing with a `second wave', but they are unlikely to blunt the impact of the opening months.

It might be possible to shave weeks, or even months, off the delivery time of a pandemic vaccine if an older CVV (Candidate Vaccine Virus) were used instead waiting to isolate a new strain, but it might prove far less effective.  

Which brings us the question: is it better to have a less-well-matched vaccine earlier (at 3 months), or wait (6 months or more) for a well-matched vaccine?

It is not an easy question to answer, because there are so many unknown variables.  As the old saying goes, `If you've seen one pandemic . . . . you've seen one pandemic'.  The speed of transmission (R0), its place of origin, its virulence (CFR and Attack Rate), and even its impact on different age groups, all change the outcome. 

We've a study today that attempts to model the impact of early vs. late vaccination in a variety of pandemic scenarios, juggling virulence (moderate or severe), and vaccine effectiveness (high, moderate, or  low), in order to try to quantify the probable benefits. 

In order to keep all of this manageable the authors had to make a number of assumptions that may, or may not, hold true in the next pandemic; an origin in the Southern Hemisphere, a greater impact on older patients, and a single wave, etc.   

While the full report is well worth reading in its entirety, the take-away is that it is better to have a less-well-matched vaccine available early, than a well-matched vaccine late.  Follow the link to read the full report.  

I'll have a postscript when you return.

Modeling the impact of early vaccination in an influenza pandemic in the United States

Van Hung Nguyen, Pascal Crépey, B. Adam Williams, Verna L. Welch, Jean Marie Pivette, Charles H. Jones & Jane M. True

npj Vaccines volume 10, Article number: 62 (2025) Cite this article

Abstract


We modeled the impact of initiating one-dose influenza vaccination at 3 months vs 6 months after declaration of a pandemic over a 1-year timeframe in the US population. Three vaccine effectiveness (VE) and two pandemic severity levels were considered, using an epidemic curve based on typical seasonal influenza epidemics.

Vaccination from 3 months with a high, moderate, or low effectiveness vaccine would prevent ~95%, 84%, or 38% deaths post-vaccination, respectively, compared with 21%, 18%, and 8%, respectively following vaccination at 6 months, irrespective of pandemic severity.

While the pandemic curve would not be flattened from vaccination from 6 months, a moderate/high effectiveness vaccine could flatten the curve if administered from 3 months.

Overall, speed of initiating a vaccination campaign is more important than VE in reducing the health impacts of an influenza pandemic. Preparedness strategies may be able to minimize future pandemic impacts by prioritizing rapid vaccine roll-out.

          (SNIP)

Discussion

Our analysis shows that the speed of vaccination is key to reducing the impact of an influenza pandemic. Even with a low effectiveness vaccine, initiating vaccination 3 months after the declaration of a pandemic would lower the disease burden compared with initiating a higher effectiveness vaccine at 6 months, with 23–94% incremental benefits across health outcomes and VEs.

While moderately and highly effective vaccines could flatten the pandemic curve if administered from 3 months, none of the scenarios evaluated could flatten the curve if administered from 6 months. Acute and ICU bed availability would also be less constrained under the early vaccination scenario, particularly with higher effectiveness vaccines, but administration of a vaccine at 6 months would not be able to prevent a surge in demand above bed availability thresholds in a severe pandemic, irrespective of VE.

          (SNIP)

In summary, our analysis has demonstrated the importance of rapid initiation of mass vaccination during a future influenza pandemic, with speed of vaccination playing a more important role than VE on population-level health outcomes.

Preparedness exercises such as stockpiling potential pre-pandemic vaccines, as well as pre-emptive collection of data from newer vaccine manufacturing platforms, such as mRNA vaccines, will be paramount for ensuring a rapid and effective response in a future influenza pandemic.

          (Continue . . . )

This study uses a lot of epidemiological assumptions, which may (or may not) be a good fit for the next pandemic.  Much will also depend upon how society reacts to the next pandemic.  

• Will lockdowns be tolerated, or will people refuse masks and social distancing?   

• Assuming a vaccine could be produced in quantity in 3 months, would large segments of the public actually embrace it?  How much extra resistance against an mRNA vaccine? 

• How much tolerance would the public have for (real or imagined) vaccine side effects, particularly in a low VE jab?  

While I'm not particularly hopeful that an emergency vaccine of any VE can be produced and deployed within the first 3 months of a novel pandemic - in the event of a severe disease - this study strongly suggests that the earlier that can happen, the better.