#NPM26: Making Preparedness a Priority

 

Note: This is the 29th day of National Preparedness Month. Follow this year’s campaign on Twitter by searching for the #NatlPrep #BeReady or #PrepMonth hashtags

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This month, as part of NPM26, I’ll be rerunning some updated preparedness essays, along with some new ones.

#19,353

Over the summer - and most particularly the past 4 weeks -  we've looked at a number of personal preparedness scenarios (see links below), covering topics such as earthquakes, severe weather, prolonged power outages, and even pandemics. 

#NPM26: It's a 12 Volt Life

#Natlprep 2026: Pandemic Planning At Both Ends of the Spectrum

#NPM26: Preparing For An El Niño Winter

#NatlPrep: 75% of Americans At Risk Of Experiencing A Damaging Earthquake

September Is National Preparedness Month (#NPM26)

We've also looked at a number of governmental concerns and/or reports; with an emphasis on this winter's El Niño, an increasingly stressed power grid, risks to the global food supply, and a plethora of other threats. 

California Declares State of Emergency to Bolster Statewide El Niño Preparedness

FAO: Expect The Unexpected - Guidelines on Emergency Response Preparedness in Agriculture in Europe and Central Asia

NERC Reliability Report: Large Computational Load Risks Due to Voltage Sensitivity

UK National Risk Register 2026 - Urges Citizen Preparedness

NERC Issues Level 3 Alert As Grid Faces `Unprecedented Challenges' Due to Surge In Large Power Consumers

 
While I can't tell you what untoward events may happen in the months ahead, or when or where they might occur, it is a pretty safe bet that some - potentially large - number of people will be affected by one or more local or regional disasters. 

How they will cope with whatever comes will depend in large part on how well they've prepared. 

While I'm a huge proponent of having a good first aid kit (or three), emergency power options, and a full pantry, I can think of no prep more valuable than having one or more `disaster or flu' buddies on whom you can rely in an emergency.

Simply put, a network of family, friends, and neighbors to whom you can turn for help in a emergency, who can turn to you for if they need it. My disaster buddy and I have saved each other's bacon more than once. 

Most disasters boil down to unscheduled camping - for days, or sometimes weeks - in your home, in a community shelter, or possibly even in your backyard. So having the right gear - before an emergency arises - can make life far easier.

Every year I publish a long list of preparedness items that I've either bought for myself, or as gifts for other people. While I'll update that list for the holidays, you'll find my most recent list at The Gift of Preparedness 2025.

Since being sick with the flu, of COVID, during an emergency can seriously degrade your ability to cope, I've long recommended staying current with yearly vaccines (see #NatlPrep: Giving Your Preparedness Plan A Shot In The Arm).

Which is why later today I'll be getting both the fall flu and COVID shots from my local pharmacy. I'm also current with my tetanus shot, and pneumonia vaccines. 

Long time readers know I love to tinker with solar panels and emergency power options, and I've put together some low cost systems for myself, and for a couple of friends (see Emergency Solar Power: Revisited).

For as little as $100, you can buy off-the-shelf plug-and-play components to keep phones charged, and a couple of LED lights powered.  Double that, and you can have comms, fans, and an emergency shortwave radio.

My older (circa 2019) basic $200 kit

While solar generators are the preparedness rage, a system capable of running refrigerators, TVs, and other appliances for more than a few hours can run into the thousands of dollars.  For me, that isn't an option. 

In 2024 I described building a rudimentary LiFePo4 power station (see picture below), which packs a whopping 600 Watt/hour capacity. LiFePo4 batteries are lighter than lead/acid, are far less dangerous, and can be charged and discharged (fully) thousands of times.

My system featured dual 12V Car Cigarette Lighter Sockets, 2 USB outlets, and I added a small 110v inverter (which I will probably never use).  I have both a wall charger and a 100 watt solar panel to keep it charged. 

I now have 3 of these battery systems, and 2 solar panels. They won't run my fridge or big-screen TV, but they will keep lights, radios, MP3 player, fans, DVD player, and other creature comforts going for weeks or even months.  

And most importantly, there is enough redundancy built into these systems than if one (or even two) should fail, I'm not left in the dark.  The old prepper's adage, that `one is none, and two is one' applies. 

I've also got 60 gallons of water stored, water filters, a full pantry, a propane stove, and enough books (audio & physical), MP3 radio shows/podcasts, and DVDs to keep me from going stir crazy for months if need be. 

While my investments have been small, they have already paid off, since I've been without power twice in the past 10 years - each time for several days - thanks to Hurricanes Irma (2017) and Helene & Milton (2024).  

The road to preparedness needn't be terribly expensive, but it's a journey you need to start before the next crisis occurs.  

So . . . if a disaster struck your region today, and the power went out, stores closed their doors, and water stopped flowing from your kitchen tap for the next 7 to 14 days . . . do you already have:

• A battery operated NWS Emergency Radio to find out what was going on, and to get vital instructions from emergency officials
• A decent first-aid kit, so that you can treat injuries
• Enough non-perishable food and water on hand to feed and hydrate your family (including pets) for the duration
• A way to provide light when the grid is down.
• A way to cook safely without electricity
• A way to purify or filter water
• A way to stay cool (fans) or warm when the power is out.
• A small supply of cash to use in case credit/debit machines are not working
• An emergency plan, including meeting places, emergency out-of-state contact numbers, a disaster buddy, and in case you must evacuate, a bug-out bag
• Spare supply of essential prescription medicines that you or your family may need
• A way to entertain yourself, or your kids, during a prolonged blackout

If your answer is `no’, then I would suggest the time to start preparing
is now.

Cambodian MOH Announces 6th Human H5N1 Case of 2026

 

#19,352

Cambodia's Ministry of Health has announced their 6th confirmed HPAI H5N1 human infection of 2026 - and 40th since early 2023 - this time involving a 49-year-old man from Oddar Meanchey Province who is hospitalized and was confirmed positive on September 27, 2026. 

The man reportedly worked on a farm and had direct contact with sick and dead chickens which were confirmed positive for H5N1 by the National Animal Health and Production Research Institute on September 23, 2026.

Some translated excerpts from the press release, after which I'll  have a bit more. 

   

(Translation)
Kingdom of Cambodia
Nation, Religion, King
Ministry of Health

Press Release

A Case of Bird Flu in a 49-Year-Old Man

The Ministry of Health of the Kingdom of Cambodia wishes to inform the public of a confirmed case of bird flu (H5N1) in a 49-year-old man. The case was confirmed positive for the H5N1 virus on September 27, 2026, by the National Institute of Public Health and the Institut Pasteur du Cambodge. The patient resides in Tuol Kruos Village, O'Svay Commune, Trapeang Prasat District, Oddar Meanchey Province. Currently, the patient is in isolation at the hospital and is receiving attentive care and treatment from the medical team. Inquiries revealed that the patient raised and cared for chickens at a farm and had direct contact with sick and dead chickens; the latter were confirmed positive for the H5N1 avian influenza virus by the National Animal Health and Production Research Institute on September 23, 2026.

National and sub-national Ministry of Health rapid response teams are collaborating with provincial agricultural departments and local authorities at all levels to actively investigate the avian influenza outbreak. They are responding in accordance with established technical protocols and methods to identify sources of transmission—in both animals and humans—and to locate suspected cases and contacts in order to prevent further community spread. Additionally, they are distributing Tamiflu to close contacts and conducting health education campaigns for residents in the affected village. The Ministry of Health wishes to once again remind all citizens to remain vigilant regarding bird flu, as the H5N1 virus continues to pose a threat to public health. If you experience symptoms such as fever, coughing, a runny nose, or difficulty breathing—and have had contact with sick or dead poultry within the 14 days prior to the onset of symptoms—please avoid gatherings or crowded public places. Instead, seek immediate consultation and medical treatment at the nearest health center or hospital to avoid delays that could lead to a high risk of fatal consequences.

Transmission: H5N1 bird flu is an influenza virus that typically spreads among birds; however, it can sometimes be transmitted from birds to humans through close contact with sick or dead poultry. Bird flu in humans is a serious illness that requires timely hospital treatment. Although it does not easily spread from person to person, if it mutates, it could become transmissible—much like seasonal influenza.

Address: Plot No. 80, Samdech Pen Nouth Blvd (289)

Sangkat Boeung Kak II, Khan Tuol Kork, Phnom Penh

1/2

Telephone: (+855) 23 885 970
Email: info@moh.gov.kh
Website: www.moh.gov.kh
Telegram: t.me/MOHCambodia

In February of 2023 an older clade of H5N1 (2.3.2.1.x) reemerged in Cambodia's population after a 9 year absence, spilling over into 6 humans in 2023, 10 people in 2024, and 18 people in 2025.

Most of these recent Cambodian cases have been due to a new reassortment of an older clade of the H5N1 virus (recently renamed 2.3.2.1e) - which appears to be spreading rapidly through both wild birds and local poultry.

Unlike the recent North American H5N1 clade 2.3.4.4b cases - which have proved far less virulent - Cambodia has seen a 40% fatality rate across these 40 cases. 

While we usually focus on the more dominant H5 2.3.4.4b clade, these cases remind us that there are other lineages of HPAI H5 still in circulation around the globe (see Viruses: Zoonotic Implications of the Co-Circulation of Clade 2.3.4.4b and 2.3.2.1a H5N1 Avian Influenza Viruses in Nepal in 2023), and each is on their own evolutionary trajectory.

H5N1 in Utah Mink (Updated)

 

#19,351

A little over a month ago, in That Touch of Mink Flu (H5N1 in Utah Edition), we looked at a cryptic report of an outbreak of H5N1 at a mink farm somewhere (exact location masked) in Utah. 

The USDA Detections of Highly Pathogenic Avian Influenza in Mammals dashboard reported 7 captive American mink in Utah infected with EA H5N1 (see below).

1 To protect data confidentiality, the county and mapped locations of these detections represent the approximate location of the State capitol.

Other than this, I've found no other official local, state, or federal government statements posted online.  

Thankfully, the The Animal Welfare Institute filed a Utah GRAMA public-records request with the Utah Department of Agriculture and Food (UDAF) on August 26, requesting all records concerning HPAI in American mink from June 1 onward.

On September 17th AWI published a 61-page UDAF GRAMA records release (PDF), along with a press release. Follow the link to read it in its entirety. 

 AWI Newsroom Press Statement

 

Records Request Reveals Unhurried, Inadequate Response to Bird Flu Outbreak in Utah Farmed Mink 

Government records obtained by AWI highlight gaps in disease response protocol, the public health hazards of mink farming, and the urgent need to phase out the practice.

 

September 17, 2026

 

This 61-page GRAMA release consists principally of emails, text-message screenshots, internal correspondence, and one heavily redacted letter (dated Aug 26th) from UDAF to Agriculture Secretary Brooke Rollins.  

Details, such as the size and location of the farm - and number of mink affected -  are blacked out.  No response from the Ag Secretary is included. 

The UDAF qualifies their release by stating `Additional records, or portions thereof have been redacted or withheld because they contain information that is relevant to an ongoing investigation in accordance to Utah Code Ann. § 63G-2-305 (10)(a)'. 

Yesterday (Sept 27th), the Salt Lake Tribune published a sobering report:

‘Watch them die’: Bird flu is ravaging a Utah mink farm, killing 80% of the herd. State agriculture officials have no clear plan.

It’s the first documented outbreak of bird flu in captive mink in the U.S., and an advocacy group is raising concerns about Utah’s response.

As we've discussed often, mink are particularly susceptible to influenza (and coronaviruses), and the way they are raised in captivity can permit the rapid spread - and evolution - of those viruses. 

As an example, in the fall of 2022 H5N1 began spreading rapidly through a large mink farm in Spain (see Eurosurveillance: HPAI A(H5N1) Virus Infection in Farmed Minks, Spain, October 2022).

This mink-derived H5N1 virus from Spain carried a rare mutation (PB2-T271A), which is believed to `enhance the polymerase activity of influenza A viruses in mammalian host cells and mice'.

 

In 2023 the CDC issued an IRAT Risk Assessment On Mink Variant of Avian H5N1, finding its scores had risen in 6 of the 10 parameters used to evaluate their zoonotic potential.

Also in 2023, Finland's fur industry was hit unusually hard by HPAI H5N1, with more than 70 fur farms infected, and > 500,000 animals culled, prompting  Finland's Institute for Health and Welfare (THL) to warn `Avian influenza poses a risk to public health – improvements to health security needed at fur farms'.

During the height of this outbreak, we looked at an excellent opinion piece (see PNAS: Mink Farming Poses Risks for Future Viral Pandemics) penned by two well known virologists from the UK (Professor Wendy Barclay & Tom Peacock) on why fur farms - and mink farms in particular - are high-risk venues for flu.

Since then we've seen several other notable outbreaks, including a reassorted swine and human-origin H3N2 in Canadian farmed mink.  Many farms, and governments, remain reluctant to provide details on outbreaks, and so we are likely only seeing the tip of the iceberg. 

Earlier this month, in The Lancet Regional Health Europe (Comment): If the EU is serious about One Health, it must ban fur farming, we looked at yet another call to action. 

Meanwhile, events such as the one in Utah, continue to occur.  Perhaps, given the reluctance to report, more often than we know.  

And contrary to the old saying, what we don't know can hurt us. 

PLoS One: Occurrence of influenza antivirals and resistance development in influenza A viruses in aquatic environments: A risk assessment

Photo Credit USGS – Wastewater: The Primary Treatment Process
1. Screening 2. Pumping 3. Aerating 4. Removing sludge 5. 

Removing Scum 6. killing bacteria

#19,350

Almost 20 years ago (January 2007), in The Law of Unintended Consequences, we looked at a study by researchers at the Centre for Ecology and Hydrology in Oxford titled Potential Risks Associated with the Proposed Widespread Use of Tamiflu, that questioned what might happen if millions of people simultaneously began taking Tamiflu and releasing it into our environment.

A large percentage (60%-80%) of the Tamiflu (aka oseltamivir) a person takes is eventually excreted in their urine as oseltamivir carboxylate (OC), a factoid that 20 years ago briefly led to internet speculation about the practice of ‘recycling’ our own urine, to stretch out the supply of Tamiflu during a crisis. 

While that thankfully never became an internet challenge, it did inspire a doctor to publish a proposal in Nature on the co-administration of a generic gout medicine - probenecid - which slows the excretion of certain drugs - potentially increasing the effectiveness (and lowering the overall dose) of oseltamivir. 

But I digress . . . 

The 2006 Oxford study specifically warned that large quantities of oseltamivir carboxylate (OC) could be excreted into sewers during a pandemic - which wastewater plants are largely unable to remove - and could end up in rivers and streams, and eventually birds, where it might promote antiviral resistance in avian flu viruses. 

Similar concerns re-emerged in the fall of 2009 (see Everything Old Is News Again) when researchers at Kyoto University tested wastewater discharge from three local sewage treatment plants and water from two rivers into which they drained during the 2008-09 flu season looking for signs of the active ingredient in Tamiflu, oseltamivir carboxylate (OC).

For years Japan has been the largest consumer of antivirals for seasonal flu, and they found exactly what they were looking for; substantial levels of the Tamiflu metabolite in the environment.

In 2011, in Pandemics & The Law Of Unintended Consequences, we looked at not only the potential effects of antivirals in our sewage system, but also how the consumption (and excretion) of antibiotics during a pandemic might affect wastewater treatment plants (WWTPs).

But a proof of concept was published in 2015, in AAC: LPAI H7N9 Acquires Antiviral Resistance When Exposed To Environmental Oseltamivir, which reported that mallards experimentally infected with LPAI H7N9, and then exposed to low levels of oseltamivir carboxylate (OC) in their water, developed antiviral resistance markers (NA-I222T) in as few as 2 days. 

From the Abstract:

In an in vivo Mallard (Anas platyrhynchos) model, we tested if low-pathogenic avian influenza A(H7N9) virus could become resistant if the host was exposed to low levels of OC. Ducks were experimentally infected and OC was added to their water, where after infection and transmission was maintained by successive introductions of uninfected birds. Daily fecal samples were tested for IAV excretion, genotype and phenotype.

Following Mallard exposure of 2.5 μg/L OC, the resistance related NA-I222T substitution, was detected within 2 days during the first passage and was found in all viruses sequenced from subsequently introduced ducks.

Two of those same authors (Lindström & Järhult) are back with today's report, which provides a relative risk assessment of introducing four different antivirals (3 Neuraminidase inhibitors (NAIs), plus Amantadine, an M2 ion-channel inhibitor) into aquatic environments.  

The authors report that the use of PE (peramivir) and OC (oseltamivir) pose the highest environment risk, and suggest using ZA (zanamivir) whenever possible, and limiting the use of oseltamivir in uncomplicated influenza in non-risk groups.

Zanamivir, however, isn't always a good substitute for oseltamivir because it is an inhaled powder, which can be problematic for those with COPD, asthma, or who are experiencing respiratory symptoms. 

They also recommend stockpiling Baloxavir (see yesterday's blog EID Journal: Comparison of Baloxavir-Based Combinations and Monotherapies for Treating Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Mice) to provide additional therapeutic options.

This is a lengthy, and times technical report. Follow the link to read it in its entirety. I'll have a postscript after the break. 

Occurrence of influenza antivirals and resistance development in influenza A viruses in aquatic environments: A risk assessment

Hanna Söderström Lindström, Sara H. Norström , Chaojun Tang, Richard H. Lindberg, Josef D. Järhult

Published: September 21, 2026
https://doi.org/10.1371/journal.pone.0358447

Abstract

Influenza antivirals (IAs) have been detected in aquatic environments inhabited by dabbling ducks, the natural reservoir of influenza A virus (IAV), raising concerns about the development of antiviral resistance. Because novel human IAV strains often contain genetic material of avian origin, this may contribute to resistance in viruses with pandemic potential. 

This study aimed to assess the environmental risk posed by four IAs—oseltamivir carboxylate (OC), zanamivir (ZA), peramivir (PE), and amantadine (AM)—based on their potential for environmental release, environmental stability, and induction of antiviral resistance. The assessment combined data from new experiments on (1) environmental release and (2) environmental stability of PE, AM, OC, and ZA, with results from previously published in vivo experiments in a mallard model examining (3) resistance development to OC, PE, and ZA in IAV. 

The risk of environmental release was assessed as high for OC, AM, and PE, and very high for ZA. Environmental stability ranged from very high to low, in the order PE > AM > OC > ZA. The potential to induce resistance in IAV was similar for PE and OC, and lower for ZA.

Overall, the environmental risk ranking was PE > OC > ZA, with PE and OC posing the highest risks. 

Prudent use of IAs requires balancing the risk of resistance development against clinical benefit. In cases of complicated influenza or in high-risk patient groups, the clinical benefits are substantial and justify IA use. However, in uncomplicated influenza among otherwise healthy individuals, the clinical benefit is limited, and the risk of resistance development should be carefully considered. Among the evaluated antivirals, ZA showed the lowest environmental risk and should be preferred when feasible.

        (SNIP)

Conclusions

This is the first study to jointly assess the environmental risk of influenza antivirals (IAs), and the public health risk caused by environmental resistance development in influenza A viruses (IAVs). This comprehensive approach provides new knowledge to support sustainable antiviral use, helping to prevent resistance development in future pandemics and preserve the effectiveness of antiviral stockpiles.

Our study shows that the environmental occurrence of IAs, and resistance development in IAVs in aquatic environments, is a concern for all three IAs (OC, PE, and ZA) studied with a high environmental risk of both PE and OC. Our risk assessment was based on virus experiments on individual IAs which could underestimate the risk for environmental resistance development due to cocktail effects in natural environments.

As antiviral drugs constitute a cornerstone in pandemic preparedness, especially in the first phase before vaccines can be mass-produced, it is crucial to work to retain their effectiveness. Given our assessment of the high environmental risk of both PE and OC, and the risk for the resistance developed to be part of a novel IAV with pandemic potential in humans, non-pandemic use should be prudent. This includes balancing benefits of pre-pandemic use with risks of a resistant pandemic IAV. IAs are important in treating complicated diseases and diseases in risk groups and should be used in these cases. However, in uncomplicated influenza in non-risk groups we argue that the clinical benefit is minimal, and if the use is extensive, it will drive environmental occurrence and risk for resistance development. Therefore, we argue that the risk for resistance development should be considered when treating uncomplicated influenza in non-risk groups.

From our risk assessment, it seems beneficial to use ZA rather than oseltamivir phosphate (the pro-drug for OC) when practically possible. PE is the IA with the highest environmental risk in our assessment, hence highest public health risk and other alternatives should be used when possible. As PE is at present only available as an intravenous formulation, it is likely that the use of this drug will not be extensive.

New influenza antivirals such as baloxavir are a very important addition to the treatment arsenal. They should be considered as additions to stockpiles in pandemic preparedness to have access to alternate antivirals with a different mode of action. This will increase the chances of a viable treatment option in case of a resistant pandemic IAV. At the same time, it is crucial to evaluate the risk for environmental resistance development potential of new antivirals to guide prudent pre-pandemic use.

        (Continue . . . )

Antivirals, antibiotics, and most antifungal medicals all share the same Achilles' heel. Over time - and particularly if they are used recklessly or excessively - the pathogens (viruses, bacteria, or fungi) they were designed to suppress can evolve or mutate enough to render them ineffective.

While many people fear that a hyper-virulent novel virus will someday emerge and kill hundreds of millions of people, the reality is - if we don't protect our limited armamentarium of antibiotics and antivirals - something relatively ordinary, and previously treatable, could do the job equally as well.

But balancing today's needs with those of tomorrow is always easier said than done. For more on the potential environmental risks from wastewater treatment plants, you may wish to revisit: 

Preprint: Spillover of Human Antivirals May Promote Resistant Pathogens in Animal Reservoirs

Study: NDM-1 Bacteria Survive & Thrive In Two Chinese Wastewater Treatment Plants

Study: MRSA In Waste Water Treatment Plants

EID Journal: Comparison of Baloxavir-Based Combinations and Monotherapies for Treating Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Mice

 

Screenshot: CDC's  Interim Guidance on the Use of Antiviral Medications 
for Treatment of Human Infections with Novel Influenza A Viruses Associated 
with Severe Human Disease - July 2025

#19,349

While newer antivirals have been developed (see FDA Approval Of Xofluza : A New Class Of Influenza Antiviral), oseltamivir (aka `Tamiflu') has remained the `Go to' antiviral for influenza treatment in the United States - and much of the world - for more than 20 years. 

Oseltamivir is our most studied antiviral, nations of the world have stockpiled hundreds of millions of doses, and now that can be acquired as a generic drug, its cost has plummeted. 

While exact numbers have never been disclosed, our National Strategic Stockpile supposedly has somewhere around 50-60 million courses of oseltamivir on hand; sufficient to treat 15-20% of the nation during a severe flu pandemic (assuming a single, standard dose).

Stockpiles of Baloxavir (aka Xofluza) are similarly unknown, but according to a media report in 2024 (see The U.S. strategic drug stockpile is inadequate for a bird flu outbreak) likely numbers only in the hundreds of thousands of doses.

But oseltamivir's track record against novel flu is far from perfect. To be effective, it must be started early in one's infection (1st 48 hrs, ideally), and even then, a good outcome is far from guaranteed. 

The first barrier is getting the drug to the patient in a timely manner, something which we've struggled with, even during normal flu seasons (see Sporadic Tamiflu (Oseltamivir) Shortages Reported In U.S. & Canada).

There is also the problem of resistance, something that can develop spontaneously in 1%-2% of people receiving treatment, or worse - can become `fixed' in circulating strains - such as we saw with H1N1 in 2008. 

Last year, in - in Emerg. Microbes & Inf: Oseltamivir Resistant H5N1 (Genotype D1.1) found On 8 Canadian Poultry Farms - we saw a report on a large outbreak of Oseltamivir resistant H5N1 which emerged over several weeks in the fall of 2024.

While we haven't seen that happen on a large scale, 18 months ago concerns over the effectiveness of our current antiviral armamentarium were raised by St. Jude Researchers: Current Antivirals Likely Less Effective Against Severe Infection Caused by Bird Flu in Cows’ Milk. 

Last January, in Nature Comms: Oseltamivir and Baloxavir Monotherapy and Combination Therapy Efficacy Against Clade 2.3.4.4b A(H5N1) Influenza Virus Infection in Ferrets, we saw a CDC study which looked at both mono and combination therapy with oseltamivir and baloxavir in ferrets infected with H5N1 (genotype D1.1).

In short, they found:

• Ferrets infected with H5N1 D1.1 and treated with oseltamivir saw little or no clinical or virologic benefit compared to no treatment, with persistent high fevers, weight loss, and systemic viral replication.
• Ferrets treated with Baloxavir saw significantly less fever, weight loss, and viral replication. Some ferrets, however, saw a late rise in fever (after 4 days) and viral shedding, suggesting a viral rebound. 
• Ferrets treated with both drugs saw similar clinical protection to baloxavir alone, but did not show signs of rebound. 

Note: Ferrets are a good, but not perfect, proxy for humans in influenza research, so these results may not be 100% applicable to humans.  

A month later, we looked at a study (Nature Comms: Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice) by Webby & Jones et al. which suggests that baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating clade 2.3.4.4b (circa 2022) H5N1 avian viruses (in mice).

And last April, in Emerg Microbes & Inf: Antiviral Activities of Multiple Antivirals Against HPAI H5N1 in Vitro and in Mice, the authors reported the existing 5-day course of oseltamivir appears inadequate to treat severe HPAI H5N1 infection (at least, in mice).

The authors reported Baloxavir as being more potent, but even a 5-day B.I.D course (10 times the current dose) only saved 16.7% of treated mice.  Extending treatment to 7 days (14 doses), raised survival to 50%. 

While a 7-day course of Baloxavir (BXM) was the strongest single-drug therapy, extended courses of MNP+BXM and OSP+BXM provided the most effective treatments.

The caveat here being that - due to their higher metabolic rate - the half-life of baloxavir is much shorter in mice than in humans. While it remains to be determined, an equivalent dose in humans might be more like 2 or 3 doses spread out over a week's time.

And mice, and ferrets, and other lab animals - while useful - are never a perfect analog for humans. They don't have the same physiology, metabolism, or past virus and/or vaccine exposures that can modify our immune response. 

Adding to this long and winding narrative, we have a new report from the EID Journal which provides additional support for the baloxavir-based strategy described above. 

As in the previous report, the authors found that baloxavir outperformed both oseltamivir and molnupiravir against clade 2.3.4.4b H5N1 in a mouse model, although it should be noted they began treatment just 6 hours after inoculation. 

Combining baloxavir with either oseltamivir or molnupiravir was even more effective in suppressing viral replication and spread beyond the lungs.

The bottom line: both studies suggest oseltamivir monotherapy may be inadequate for severe H5N1, that baloxavir appears more potent, and that combination therapy may prove a more effective regimen - at least in mice. 

How all of this might translate to humans, who would be unlikely to receive antiviral treatment in such short order - remains to be seen. 

I've only posted the abstract and some extended excerpts from the EID dispatch. Follow the link to read it in its entirety.  I'll have a postscript after you return.

Comparison of Baloxavir-Based Combinations and Monotherapies for Treating Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Mice
 
Seong Cheol Min, Ju Ryeong Lee, Beom Kyu Kim, Ji-Hyun Park, Dong Gyu Lee, Gi Chan Lee, Se Hee An, Santosh Chokkakula, Aman Jain, Young Ki Choi, Yun Hee Baek, and Min-Suk Song
 
 Abstract

Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus continues to cause animal outbreaks and sporadic zoonotic infections. In a mouse model of lethal influenza disease, we compared oseltamivir, baloxavir, and molnupiravir monotherapies with 2-drug combinations.

Baloxavir-based combinations improved survival, reduced lung viral loads, and prevented extrapulmonary dissemination, supporting H5N1 preparedness strategies. 

Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus continues to cause widespread outbreaks and sporadic zoonotic infections, underscoring the need to optimize antiviral strategies (1–3). Licensed influenza antiviral drugs can reduce disease severity but might be compromised in severe infections by high viral burdens, treatment delays, and treatment-emergent resistance, motivating evaluation of combination regimens (4–7). 

Recent H5N1 treatment studies using mouse models suggest antiviral performance can vary by exposure route and disease progression (8–11). To inform preparedness-oriented selection, we compared direct-acting antiviral drugs from distinct classes in a lethal mouse model. We tested monotherapies and 2-drug combinations of 2 licensed influenza antiviral agents, oseltamivir phosphate (OSP; neuraminidase inhibitor) and baloxavir acid (BXA; cap-dependent endonuclease inhibitor), and molnupiravir (MPV; nucleoside analog) to assess whether combinations provided synergistic benefit.

(SNIP)

Conclusions

In a lethal clade 2.3.4.4b H5N1 mouse model, monotherapies with OSP, MPV, or BXA improved outcomes in a dose-dependent manner but did not consistently prevent death or extrapulmonary spread. In contrast, 2-drug combinations, particularly those containing BXA, achieved complete survival at both dosing regimens and suppressed pulmonary replication to near LOD while preventing neuroinvasion and cardiac dissemination. 

Those findings are consistent with recent clade 2.3.4.4b A(H5N1) studies showing strong in vivo activity of BXA and BXA-containing regimens and extend those observations by directly comparing BXA/OSP and BXA/MPV with OSP/MPV in a lethal mouse model (8,10,11,14). Our findings extend recent antiviral-combination studies in less virulent influenza models by showing that BXA-containing combinations provided the strongest protection in a lethal clade 2.3.4.4b H5N1 model (14,15). 

Together, our findings provide an experimentally grounded rationale to prioritize BXA-based 2-drug regimens as a preparedness-oriented option for emergent H5N1 infections when antiviral treatment is initiated early after infection, particularly where severe disease or resistance risk can compromise single-agent performance.

        (Continue . . . )

Currently, the CDC's guidance is for prompt oseltamivir treatment of suspected or confirmed novel influenza A infections, while allowing clinicians to consider adding baloxavir in selected severe or high-risk cases.

• Combination antiviral treatment (e.g., oseltamivir and baloxavir) can be considered for hospitalized patients with novel influenza A virus infection because it is possible that some novel influenza A viruses might become resistant to oseltamivir and peramivir during antiviral treatment with one of these agents 36789
• Oseltamivir resistance has been reported in hospitalized patients with HPAI A(H5N1) virus infection, resulting in fatal outcome 3. If a hospitalized patient treated with oseltamivir or peramivir manifests progressive lower respiratory disease, the presence of a resistant virus should be considered. After consultation with CDC's Influenza Division, investigation for antiviral resistance should be performed.
• Combination treatment with a neuraminidase inhibitor and baloxavir did not have clinical benefit compared with neuraminidase inhibitor and placebo in a randomized clinical trial in hospitalized patients with seasonal influenza, but the addition of baloxavir reduced duration of infectious viral shedding 10

Added to this are the logistical considerations: The global supply of oseltamivir is far greater than baloxavir, while the cost is far lower.

The reality is, even oseltamivir may be hard to get - at least during the first critical 24-48 hrs of infection - during any global influenza pandemic. It seems likely that `extended' baloxavir or combination therapy will be limited to hospitalized patients with severe disease.

Combine that with an expected wait of at least 6 months before having any large quantities of vaccine, and we will once again have to rely heavily on preventing infection; wearing face masks, hand washing, improved indoor ventilation, staying home while sick, and avoiding crowds.

While I would certainly avail myself of whatever antivirals are available in an influenza pandemic, my primary strategy is always one of prevention. I've already got my supply of masks, hand sanitizer, and OTC meds in the hall closet, and have stayed current with all of my vaccines.

If you aren't similarly prepared, you may want to revisit:

#Natlprep 2026: Pandemic Planning At Both Ends of the Spectrum

H5N1’s Summer Lull: Getting Shorter?

 
Chart generated by Gemini using USDA Data

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As the above chart illustrates, for the past few years we've witnessed a similar avian flu pattern; a summer lull followed by a sharp increase in outbreaks starting in either September or October, and running through late spring. 

While the amplitude of poultry outbreaks during the winter has fallen (possibly due to better biosecurity measures) a bit, the number of months with elevated activity has increased. 

Avian flu outbreaks in September 2025 and 2026 have far exceeded outbreaks for the same month in 2023 and 2024, while last spring's avian flu activity extended well into May. 

Our summer lull remains, but appears to be shrinking.  

• In 2023-2024, the U.S. saw 3 months of strong activity (> 25 outbreaks/mo). 
• In 2024-2025 that number jumped to 5 months
• And in 2025-2026 we saw 6 months with > 25 outbreak/mo. 

And while September isn't completely in the books - and there are often delays in reporting - over the past 30 days the United States has already reported 20 poultry outbreaks (18 in September). 

After reporting zero outbreaks during June, July, and August - Canada has reported 6 outbreaks in Manitoba over the past 2 weeks (Sept 10th-24th).  

In 2024, Canada's summer break in avian flu reports ran from April 10th to October 21st (194 days). In 2025, the lull lasted from May 15th to September 9th (117 days).  This year, from May 16th to September 10th (also 117 days).

As we saw yesterday in ECDC/EFSA Quarterly Avian Influenza Overview June-August 2026, Europe saw unprecedented levels of HPAI in wild birds over the 2025-2026 season.

And South Korea reported both increased diversity and infectivity among avian flu viruses which sparked a difficult and lengthy 2025-2026 avian flu season, which began 47 days earlier than the 2024-2025 season. 

These shifts aren't necessarily permanent, nor are they reliable indicators of what this fall and winter avian flu season will look like. But we shouldn't ignore them, either. 

By now most commercial poultry producers are presumably well practiced in implementing biosecurity measures to protect their flocks (despite which, outbreaks still happen). But the APPA estimates `Eleven (11) million U.S. households own backyard chickens (a 28% increase from 2023)'.

A recent survey (see MMWR: Knowledge, Attitudes, and Practices Regarding Avian Influenza Among Owners of Backyard Flocks), found significant gaps in their knowledge of dealing with avian flu.

Although the risks of infection are believed low, we've already seen at least two fatalities (here, and here) in the United States from H5Nx following `. . . exposure to a combination of a non-commercial backyard flock and wild birds.'

In an attempt to avoid future incidents, last year the University of Florida's Extension office (UF/IFAS) released two H5N1 related publications; one for backyard poultry owners, and another for consumers of poultry products and milk.

Given what may be on the horizon, both are recommended reading.