Adv. Genetics (Review Article) : Evolution of H5N1 Cross‐Species Transmission - Adaptive Mutations Driving Avian‐to‐Human Infection

#19,019

In the wake of the SARS-CoV-2 pandemic it has become increasingly difficult to find substantive, and verifiable, information on avian flu, COVID, MERS-CoV, (and other) emerging disease outbreaks around the world. 

Many countries simply no longer report outbreaks or incidents. Others do, but only intermittently, and are often parsimonious in the sharing of details.  

Public health organizations - like the WHO, PAHO, and the ECDC - are forced to constantly `remind' countries of their obligation under the IHR to report. But since there are no real penalties for failing to comply, many countries choose silence (see From Here to Impunity).

The public remains largely apathetic (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu), and many governments appear more than happy to downplay the threat for political or economic reasons.

But just because we ignore a threat doesn't make it go away; HPAI H5 continues to evolve at a rapid rate, and over the past 4 years it has increased its affinity for mammalian hosts.

Obviously, no one truly knows what HPAI H5 will do next. 

There could still be some `species barrier' that prevents it from becoming a genuine pandemic threat (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), or it might simply be beaten to the punch by another threat, like H9N2, H3N8, or another coronavirus.

But right now, HPAI H5 remains at the top of our pandemic worry list, for reasons that are covered at length in the following Review/Perspective article  published this week in the journal Advanced Genetics. 

This (12-page) review recounts the evolution of the H5N1 avian influenza virus, with a focus on the 2.3.4.4b clade, and focuses on a number of critical mutations (including HA‐Q226L, HA‐T199I, PB2‐E627K, and NA‐H274Y) which could help enable cross-species transmission or increase NAI resistance.

I've just posted the abstract and a brief excerpt. Follow the link to read the review in its entirety.  I'll have a postscript when you return.

Evolution of H5N1 Cross‐Species Transmission: Adaptive Mutations Driving Avian‐to‐Human Infection
Wenxin Man 1,2, Lin Du 2, Ying Liu 2, Zehan Pang 3, Hongyan Zhu 4,✉, Bixia Hong 2,5,✉, Zhichao Xu 1,2,✉, Huahao Fan 2,✉
PMC Copyright notice
PMCID: PMC12791573 PMID: 41531488

ABSTRACT

First detected in poultry in China in 1996, the H5N1 avian influenza virus has evolved into a significant global public health hazard, primarily owing to its high pathogenicity and potential for interspecies transmission. While primarily affecting avian species, H5N1 has repeatedly breached species barriers, infecting mammals including humans, minks, seals, and cattle. 

This review synthesizes current knowledge on the molecular mechanisms underpinning H5N1's host adaptation, focusing on key mutations in viral proteins‐such as hemagglutinin (HA), neuraminidase (NA), and polymerase subunits (PB2)‐which boost binding affinity to human‐type receptors, increase replicative efficiency in mammalian cells, and facilitate immune evasion. 

Critical mutations, including HA‐Q226L, HA‐T199I, PB2‐E627K, and NA‐H274Y, are discussed in detail, highlighting their roles in altering receptor specificity, promoting antiviral resistance, and expanding viral tropism. The paper also outlines epidemiological trends, global dissemination patterns driven by migratory birds and trade, and current strategies for prevention and control, including antiviral therapeutics and vaccine development. 

Ultimately, this comprehensive analysis underscores the urgent need for continued surveillance, broad‐spectrum countermeasures, and international collaboration to reduce the pandemic risk posed by H5N1.

        (SNIP)

Although the current transmission efficiency of the H5N1 virus among humans remains limited, its highly variable genome provides the molecular foundation for potential evolution toward sustained human-to-human transmission [73].

Significant knowledge gaps remain concerning the key factors that enable efficient human-to-human spread of the virus, its long-term evolutionary trajectory in new mammalian hosts such as cattle, and the impact of continuous surface antigen drift on the efficacy of antibody protection [74-76]. To address these issues, future global surveillance efforts must extend beyond poultry populations to systematically encompass domestic and wild mammalian species, particularly those in outbreak areas, in order to establish a comprehensive ‘One Health’ early warning system [77]. 

Addressing this threat necessitates global collaboration in the integration of resources and technologies to continuously monitor viral evolutionary dynamics, with a particular emphasis on its cross-species transmission tendencies from poultry to humans and other mammals.

By implementing comprehensive strategies that encompass surveillance, research, and international cooperation (Figure 4), we can more effectively mitigate future H5N1 virus threats, reduce the risk of a global pandemic, and safeguard both human health and ecological balance.

       (Continue . . . )

Like with nearly every study or review we've looked at (see here, here, here, here, and here), the authors call for greatly improved surveillance, reporting, and international cooperation.

While a few countries obviously `get it', see (see South Korea CDC Announces A 19-day, Nationwide, Mock-Training Exercise to Prepare for Zoonotic Influenza), most nations seem content to ignore the threat, praying nothing happens during their watch. 

A policy that works well up until the point it doesn't anymore. And by then it is usually too late to do much about it.  As the former Secretary of the HHS Michael Leavitt put it 20 years ago:

“Everything you say in advance of a pandemic seems alarmist. Anything you’ve done after it starts is inadequate." 

Public Health Ontario: Hazard Identification and Risk Assessment (HIRA) For the FIFA World Cup 2026 Games in Toronto

 
#19,018

Although we are currently in an interpandemic period, mass gathering and travel events like Carnival in Rio, the Super Bowl, Mardi Gras, Chunyun (aka the Chinese New Year), the Summer & Winter Olympics, Umrah and the Hajj pose unique public health challenges not only for the host country, but for the world at large.

In each of these events - hundreds of thousands, sometimes millions - of people travel from all over the world to spend a few days or a week in a common, usually crowded, location where they can easily exchange viral and bacterial pathogens - mostly common, but occasionally exotic - before returning home.

Since many infectious diseases have relatively long incubation periods (7-10+ days), or may present mildly or even asymptomatically in some people, carriers - traveling both to and from the venue - may not be obvious.

This summer Toronto, Canada will host 6 FIFA World Cup matches in June and early July, with at least 300,000 visitors expected to descend on the city.  In total, 16 cities across 3 countries (Canada, Mexico, U.S) will host the 2026 world cup, with over 5 million fans expected to travel to the various venues. 

While this year's horrendous flu season will be hopefully ended by then, summer has often seen renewed surges in COVID transmission, Canada recently lost its measles elimination status, and food and waterborne illnesses are always a concern. 

But there is a fairly long list of other - admittedly, less likely - infectious disease threats that must be considered. 

While Canada won't be alone in having to plan for - and deal with - potential infectious disease outbreaks, yesterday Public Health Ontario published a 42-page Hazard Identification & Risk Assessment (HIRA) for the upcoming 2026 World Cup Games. 

Hazard Identification and Risk Assessment (HIRA)Infectious Diseases at the FIFA World Cup 2026 Games in Toronto

Purpose

Public Health Ontario (PHO) conducted a mass gathering (MG) HIRA to assess the potential likelihood and impact of infectious disease (ID) hazards while the City of Toronto hosts the Fédération Internationale de Football Association (FIFA) World Cup (FWC) 2026 games.

The tournament will be a global event, and these findings were used to inform public health planning priorities, preparedness and response measures for potential ID hazards. Relevant audiences for this product include the local and provincial public health agencies, public health practitioners involved in planning or response activities, as well as other jurisdictional and international health authorities interested in MG risk assessments.

Risk Question

For the identified ID hazard group, what is the likelihood of the event of interest occurring during May 28,2026, to August 2, 2026 (two weeks before and after the multi-site FWC tournament) and the impact to the public health capacity of Toronto and two neighbouring regions?

Scope

This assessment focused on ID hazards that may arise two weeks before, during, or two weeks after planned MGs as well as public health measures (PHMs) (i.e., non-pharmaceutical interventions to protect the health and well-being of communities)1 and surveillance that can be implemented before and in response to potential ID hazards. Risk to public health capacity was assessed; environmental, non-ID, and bioterrorism hazards were out of scope for this HIRA and will be addressed through other risk assessment work.

Key Findings

• Based on the assessment completed on September 2, 2025, the following IDs or ID categories were assessed as having a moderate risk level for the FWC 2026 games:

• Measles

• Food and waterborne diseases

• Coronavirus Disease 2019 (COVID-19) 

• Food and waterborne illnesses are very common at MGs, as are respiratory illnesses, and have contributed to past public health investigations at Toronto MGs. Uncertainty around COVID-19 seasonality and circulating strains, and global measles activity and vaccination rates contribute to their potential for moderate risk at FWC 2026.

• All other IDs were rated at a low risk level considering outbreaks at past MGs, Ontario trends and existing preparedness, planning and response capacity. While other IDs were estimated as low risk, they still require planning and preparedness activities to mitigate potential exposures and impacts.

• Several planning considerations were recommended including:

• Pre-event assessment activities monitoring local and global epidemiology trends

• Planning for potential surge capacity for outbreak activities and public health investigations 

• Considering the feasibility and utility of enhanced surveillance during the tournament

• Public health planning should consider pre-/during/post-event targeted risk communications and educational messaging for visitors and local populations (e.g., respiratory etiquette, up-to-date vaccinations, hygiene practices), as well as promoting awareness on anticipated illnesses, risk factors, and infection control and prevention (IPAC) guidelines among frontline healthcare workers (HCWs).

Some infectious disease hazards, like vector-borne and zoonotic diseases (VBZDs) may be of greater concern for venues in the United States or Mexico, than for Canada. And admittedly, the risks posed by MERS-CoV, avian flu, and Mpox could change between now and next summer. 

Other health risks could be climate related, particularly in lower-latitude venues this summer, and this HIRA states that environmental, non-ID, and bioterrorism hazards are out of the scope of this report. 

Presumably there will be public (and internal) reports from all of the other hosting cities in the weeks and months ahead. Of course, before we get to the FIFA World Cup, we've got 5 major mass gathering events in February; when subclade K is still expected to be going strong.

• the Super Bowl in Santa Clara, CA,
• the 2026 Winter Olympics in Milan Cortina, Italy
• Carnival in Rio de Janeiro, Brazil
• Mardi Gras in New Orleans
• and the biggest human migration of all; Lunar New Year aka Chunyun; The Spring Festival.

Ramadan runs from mid-February to March 19th, and the Hajj begins in late May. 

While we generally get through these events without a major outbreak, they undoubtedly contribute to the mixing and global spread of infectious diseases each year (see The Lancet: Proactive Surveillance for Avian Influenza H5N1 and Other Priority Pathogens at Mass Gathering Events).

Which is why public health agencies must remain on top of their game, even as the global sharing of valuable infectious disease information appears to be in steep decline.

NPJ Vaccines: Novel recombinant H5-based Vaccine Provides Effective Protection against H5N1 Influenza Virus in Cats

 

Cats As Potential Vectors/Mixing Vessels for Novel Flu

#19,017

Although we've seen HPAI H5 make some abrupt, and unexpected, U-turns in the past (former hotspots Indonesia & Egypt haven't reported a human case in nearly a decade), its recent behavior suggests it is - at least, for now - firmly entrenched in the North American, Asia, South American, and European environment. 

It continues to aggressively spill over into mammals, including livestock, and barring some unpredictable evolutionary twist, seems likely to maintain its endemicity.

As such, it is important we start taking the long view on how we will deal with its continued presence in the years ahead. 

Which is why - despite some logistical challenges and safety concerns - vaccination of poultry and cattle are now being seriously considered both here in the United States and in parts of Europe for the first time.  

HPAI H5's current affinity for felines is another concern, as cats could serve as both a `mixing vessel', and a potential vector of the virus to humans (see JAVMA: Companion Animals and H5N1 Highly Pathogenic Avian Influenza: Cause for Concern?).

Vaccination is an obvious intervention, but - as with poultry, livestock, and even humans - developing a safe, effective, durable, and broadly protective vaccine is a tall order. 

Today we've got a study by researchers from Cornell University, VST LLC dba Medgene, and South Dakota State University on the effectiveness of a novel recombinant H5 vaccine in protecting cats from an H5N1 (genotype B3.13) challenge. 

While the study was small (8 vaccinated, 8 unvaccinated cats), and the end point was 2 weeks post 2nd vaccination (meaning duration of infection wasn't explored), 7 of the 8 vaccinated cats appeared to be fully protected against clinical disease. 

One vaccinated feline briefly shed detectable virus on day 3 post challenge, but all survived. Of the 8 unvaccinated cats, just one survived (the others either died or reached humane euthanization criteria).  

While only the B3.13 genotype was used as a challenge, researchers also showed serological evidence of D1.1 protection based on antibody cross-neutralization in vitro. 

First the link, abstract, and a small excerpt from the study. Follow the link to read it in its entirety.   I'll have a bit more after the break. 

Published: 12 January 2026
Novel recombinant H5-based vaccine provides effective protection against H5N1 influenza virus in cats

Salman L. Butt, Pablo Sebastian Britto de Oliveira, Ruchi Rani, Mohammed Nooruzzaman, Annika N. Diaz, Sherry Glover, Alan J. Young, Bishwas Sharma &
Diego G. Diel 
npj Vaccines , Article number: (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

PDF  

Abstract

The emergence and broad circulation of highly pathogenic avian influenza (HPAI) H5N1 virus in wild birds and its spillover into dairy cows with sustained transmission in this species pose a major risk to felines, which are highly susceptible and often succumb to the infection.

Here, we developed a novel recombinant hemagglutinin H5-based vaccine and evaluated its safety, immunogenicity, and protective efficacy against HPAI H5N1 virus in domestic cats. Immunization of cats with H5-vaccine candidate elicited robust levels of neutralizing antibodies against H5N1 virus and protection against disease, mortality, and infection upon H5N1 virus challenge. The vaccine-elicited immunity significantly reduced virus shedding and viremia, limiting systemic spread and disease severity in immunized animals.

Importantly, beyond protecting susceptible felids, vaccinating cats against the H5N1 virus could also reduce the risk of human exposure - underscoring the One Health impact of implementing such a vaccination strategy in feline populations.

       (SNIP)

It is important to note that in spite of the robust neutralizing antibody responses elicited by the H5-vaccine in cats in our study, cellular immune responses were not investigated, and thus, the contribution of T cells to the observed post-challenge protection is unknown.

Another limitation is the fact that paired tissues from the H5-vaccinated and sham-immunized animals were not collected during the study. Therefore, direct assessment of the H5 -vaccine on limiting the virus tropism and distribution, tissue replication and damage were not determined.

Another aspect of the H5-vaccine developed here that needs further investigation is the duration of the immunity40 . This would be important to determine appropriate intervals for revaccination of felids in the field. 

In summary, we demonstrate the safety and protective efficacy of a recombinant H5-vaccine against HPAI H5N1 virus genotype B3.13 in domestic cats . In addition to decreasing disease severity and mortality in immunized cats, the H5-vaccine developed here dramatically reduced infectious virus shedding, suggesting that it would be an efficient tool to combat H5N1 virus transmission and spread in felines35 .

        (Continue . . .)

As the excerpt above indicates, there are other limitations to this study, but what they were able to demonstrate is encouraging. While more research is needed, it suggests feline H5N1 vaccination could become an important risk-reduction tool.  

Particularly for zoos with big cats, cats on or near infected dairy farms, feral colonies, and shelter or rescue animals.

For more on the threat posed by HPAI H5Hx to cats, you may wish to revisit:

L.A. County Public Animal Health Alert: Another H5N1 Domestic Cat Cluster Linked To Raw Cat Food

One Health: Outbreak of HPAI a(H5N1) Among House Cats: A Case Series Involving Oseltamivir Treatment

Viruses: The Seroprevalence of Influenza A Virus Infections in Polish Cats During a Feline H5N1 Influenza Outbreak in 2023 

JAMA: Maternal Vaccine Receipt and Infant Hospital and Emergency Visits for Influenza and Pertussis

 

#19,016

Over the past two decades we've looked at a number of studies which show that maternal vaccination  (Influenza or Tdap) - usually during the 3rd trimester - can provide valuable protection to the newborn child, who are too young for direct vaccination (usually 6 months for Influenza vaccine, 2 months for DTaP).

• In 2010, in Study: Protecting Two With One Shot we saw a study in the Archives of Pediatric and Adolescent Medicine, that found that that babies born to mothers who received the flu vaccination experienced fewer infections and hospitalizations during their first six months than babies whose mothers did not.

• The following year, in Pssst! Immunity . . . Pass it On, we saw a study in the American Journal of Obstetrics and Gynecology, that found that maternal receipt of the flu vaccine was linked to more than a 45% reduction in infant hospitalizations with laboratory confirmed flu.

• And in 2016, in Pediatrics: Maternal Flu Vaccination Extends Protection To Infants, reported `. . . Infants born to women reporting influenza immunization during pregnancy had risk reductions of 64% for ILI, 70% for laboratory-confirmed influenza, and 81% for influenza hospitalizations in their first 6 months.'

Despite excellent safety profiles, uptake of these vaccines in pregnant women remains suboptimal.  As the following CDC chart illustrates, there has been nearly a 33% drop in uptake of influenza vaccine by pregnant women since 2019.

While the following Italian study published this week in JAMA probably won't change a lot of minds, it supports the benefits we've seen reported by previous studies on the benefits of maternal vaccination. 

In a nutshell, the authors report that offspring of pregnant women who received the Tdap or Influenza Vaccine were far less likely need hospital or ER care for those illness in the first 6 months of their lives.  Flu shots reduced infant risk by roughly 70% and Tdap cut whooping cough risk by nearly 90%. 

While these numbers are impressive, the confidence intervals (CIs) were very wide - likely due to the limited number of hospital/ER cases - making the absolute impact less certain.  

That said, these results are largely consistent with what we've seen in past studies.  

I've only posted the link and abstract below. Follow the link to read the full study, including the author's list of limitations. 

Maternal Vaccine Receipt and Infant Hospital and Emergency Visits for Influenza and Pertussis
Gabriella Morabito, MSc1,2; Giovanni Corrao, PhD3; Carlo Giaquinto, MD4 et al
 JAMA Netw Open
Published Online: January 8, 2026
2026;9;(1):e2553179. doi:10.1001/jamanetworkopen.2025.53179

Key Points

Question Are maternal influenza and Tdap vaccinations associated with influenza- and pertussis-related hospitalizations and emergency department (ED) visits in infants younger than 6 months?

Findings In this cohort study of 84 348 mother-infant dyads in the influenza cohort and 171 141 mother-infant dyads in the Tdap cohort, a strong negative association between maternal influenza and Tdap vaccinations and influenza- and pertussis-related hospitalization or ED visits in infants younger than 6 months was found, with an estimated vaccine effectiveness of 69.7% and 88.6%, respectively. Additionally, our findings confirm the suboptimal vaccine uptake in Italy.

Meaning These findings suggest support for the current recommendations for administering the Tdap and influenza vaccines during pregnancy and underline the urgent need to implement strategies to improve their acceptance.

Abstract

Importance Influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccinations during pregnancy offer protection to infants from infections. However, evidence about their effectiveness against hospitalization and emergency department (ED) visits associated with influenza and pertussis remains limited.

Objective This study aimed to evaluate the association of maternal influenza and Tdap vaccinations with influenza- and pertussis-related hospitalizations and ED visits in infants younger than 6 months.

Design, Setting, and Participants This population-based cohort study used the health care utilization databases from the Lombardy region of Italy. Pregnant individuals who received the influenza and Tdap vaccine among all live-birth pregnancies in 2018 to 2022 were included. Each vaccinated mother was matched with a nonvaccinated counterpart based on month and year of delivery, gestational age at birth, and pregnancy multiplicity. Analyses were performed from April 2024 to February 2025.

Exposures Exposures of interest were influenza and Tdap vaccinations during pregnancy.

Main Outcomes and Measures The primary outcomes were infant hospitalizations or ED visits due to influenza and pertussis. Cox regression models were fitted to estimate the hazard ratio (HR) of each outcome associated with the corresponding maternal vaccine. Vaccine effectiveness (VE) was calculated as VE = (1 − HR) × 100%.

Results This study included 53 448 pregnant individuals who received the Tdap vaccine and 5347 who received influenza vaccine. The maternal vaccination coverage (ie, proportion of vaccinated pregnant individuals among those eligible) was 5359 (6.4%) for influenza and 70 119 (41.0%) for Tdap, respectively. Infants born to mothers who received the influenza and Tdap vaccine had a lower risk of hospitalization or ED visit for influenza (VE, 69.7%; 95% CI, 8.7%-90.0%) and pertussis (VE, 88.6%; 95% CI, 11.5%-98.5%), respectively.

Conclusions and Relevance This study found that maternal influenza and Tdap vaccinations were associated with reduced influenza- and pertussis-related hospitalization or ED visits in infants younger than 6 months. Given the low vaccination coverage, it is crucial to implement maternal vaccination campaigns to enhance infant health outcomes.

       (Continue . . .)

As we've discussed often, influenza or COVID infection during pregnancy carries significant risk for both the mother and the unborn child (see 2024's CIMB Review: Maternal Influenza and Offspring Neurodevelopment).

Historical accounts and studies following the 3 influenza pandemics (1918, 1957, and 1968) of the 20th century all showed distinct increases in maternal mortality, the number stillbirths, and evidence of impaired fetal development.

The best records come from the most recent, and mildest, of these flu pandemics (2009).

• In 2011, in BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection a study found pregnant women who were admitted to the hospital with an H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.
• And in 2019, Study: Outcomes Of Infants Born To Women With Influenza A(H1N1)pdm09 found that women admitted to the ICU with H1N1 were more likely to deliver preterm infants, low birth weight infants, and infants with low Apgar scores than women in the other groups.

All of which only strengthens the case for pregnant women getting the recommended flu/COVID and Tdap vaccines. 

PAHO Epidemiological Alert: Simultaneous Circulation of Seasonal Influenza and Respiratory Syncytial Virus - 9 January 2026

 

#19,015

While it is not exactly `news' that the Northern Hemisphere is being battered by a particularly intense H3N2 flu season (see When Seasonal Flu Exceeds Expectations), on Friday PAHO released an updated Epidemiological Alert that also warns of a slow rise in RSV (Respiratory Syncytial Virus) activity. 

This double-viral whammy has the potential to put even more pressure on already stressed healthcare delivery systems.  As we saw yesterday, we've already seen Sporadic Tamiflu (Oseltamivir) Shortages Reported In U.S. & Canada. 

Yesterday PAHO published a press release (excerpts below) summarizing the Alert.

PAHO issues alert on simultaneous circulation of seasonal influenza and respiratory syncytial virus in the Americas

Washington, D.C., January 10, 2026 (PAHO) – The Pan American Health Organization (PAHO) has urged countries across the Americas to remain vigilant and strengthen health system preparedness in response to the simultaneous circulation of seasonal influenza and respiratory syncytial virus (RSV). This situation could place additional pressure on hospitals and clinics for the remainder of the winter season in the Northern Hemisphere.

The epidemiological alert updates an advisory released on December 4, 2025, which warned of the possibility of an earlier or more intense respiratory season than usual.

       (SNIP)

"The simultaneous circulation of influenza and RSV is a significant challenge that requires us to prioritize vaccination—which protects against severe cases that may require hospitalization—and maintain close surveillance, enabling timely action to prevent larger outbreaks and avoid hospital overcrowding," said Dr. Marc Rondy, PAHO Regional Adviser in Epidemiology of Epidemic- and Pandemic-Prone Diseases.

PAHO emphasizes that interim studies show current influenza vaccines are effective at preventing hospitalizations (30–40% effectiveness in adults and 75% in children), and calls on countries to achieve high vaccination coverage, especially among priority groups such as children, pregnant people, older adults, and those with chronic conditions.

In light of this situation, PAHO recommends that countries in the region:

• Strengthen integrated surveillance of influenza, RSV, SARS-CoV-2, and other respiratory viruses, reporting weekly data to FluNET and FluID to support regional and global monitoring.
• Prepare and adjust health service response plans to address possible simultaneous increases in influenza and RSV cases and hospitalizations.
• Prioritize influenza and COVID-19 vaccination for at-risk groups, including older adults, young children, pregnant people, individuals with chronic conditions, and healthcare workers.
• Implement RSV prevention strategies, including maternal vaccination and long-acting monoclonal antibodies for newborns and infants, in line with PAHO/WHO recommendations.
• Strengthen risk communication, promoting key preventive practices.

PAHO reminds the public that vaccination against influenza, frequent handwashing, covering the mouth when coughing or sneezing, wearing masks indoors if symptomatic, staying home when experiencing fever or respiratory symptoms, and seeking prompt medical care for severe symptoms are simple and effective ways to protect themselves and their families, especially young children and older adults

 
The full 22-page Epidemiological Alert provides nation-specific data for the Americas, and recommended guidance for public health authorities, with sections on Surveillance, Clinical management and prophylaxis, Vaccination, and Risk Communications. 

While PAHO reports that Respiratory Syncytial virus levels remain below last year's, the combined impact of a `drifted' H3N2 virus - which has impacted young children and the elderly the hardest - and an expected further rise in RSV (which affects the same cohorts), is a concern. 

PAHO's advice is pretty straightforward; those at high risk should get vaccinated, everyone should practice good `flu hygiene' (wash hands, wear masks, stay home if sick, etc.), and those who are ill should immediately seek medical treatment in case of respiratory distress. 

But getting people to follow it remains a challenge.

Sporadic Tamiflu (Oseltamivir) Shortages Reported In U.S. & Canada

 

FluView Week #53

#19,014

With seasonal influenza raging in North America, Europe, and Asia it isn't terribly surprising that we are - once again - seeing reports of sporadic shortages of the antiviral oseltamivir by both the media, and industry watchdogs. 

Two days ago, Becker's Hospital Review published Tamiflu shortages emerge during severe flu season, which reports in some regions pharmacists - and even hospitals - are scrambling to find doses. 

Similarly, on the 7th, Bloomberg reported Flu Patients Struggle To Find Tamiflu As Virus Surges Across US.  But the problem isn't limited to the United States; Drug Shortages Canada lists both actual and anticipated shortages of several strengths of oseltamivir.

While not every community is affected, shortages are concerning since delays in starting tamiflu can reduce its effectiveness. The CDC urges: 

There are prescription flu antiviral drugs that can treat flu illness; those should be started as early as possible and are especially important for patients at higher risk for flu-related complications.1

We've looked at the importance of starting oseltamivir early (1st 48 hrs. of illness) many times before, including in 2024's Clinical Inf. Dis.: Benefit of Early Oseltamivir Therapy for Adults Hospitalized with Influenza A: An Observational Study.

While the FDA hasn't weighed in on these most recent reports, the American Society of Health-System Pharmacists’ (ASHP) drug shortage database lists (as of Jan 7th) 10 oseltamivir products (various manufacturers and strengths) are in short supply. 

Sporadic shortages and delays in getting Tamiflu are not uncommon, as we saw in 2022 in the CDC HAN #0482: Prioritizing Antiviral Treatment of Influenza in the Setting of Reduced Availability of Oseltamivir. 

That shortage led to the HHS Releasing Some Tamiflu Supplies From the Strategic National Stockpile.

Since the demand for oseltamivir is elevated globally, it isn't clear how long it will take for supply chains to adjust, alleviating these delays.  While there are other options such as Baloxavir, they aren't well stocked by many pharmacies in the United States. 

All of which makes it more important than ever to take steps to avoid, or at least reduce the impact, of getting the flu. 

As we discussed yesterday in Preprint: Antibodies elicited by the 2025-2026 influenza vaccine in humans, serological evidence suggests this year's flu shot isn't a complete miss - and while it might not prevent infection - for many it may  help reduce its severity. 

Masking, avoiding crowds, increasing indoor ventilation, and using hand sanitizers can add additional valuable layers of protection. And if you do get sick, stay home.

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 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.

How to get those vital medications from the government warehouses, to thousands of hospitals and pharmacies, and then the `last mile' to the patient (who will need to start them within 24-48 hours of falling ill) - is a legitimate logistical challenge. 

While I'm hopeful our antiviral armamentarium will help `take the edge off' the opening months of the next pandemic, it is by no means guaranteed. Meanwhile, vaccines may be a year or more away (see SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1).

Once again, our first line of defense will likely rely heavily on NPIs (non-pharmaceutical interventions), like face masks, hand washing, ventilation, staying home while sick, and avoiding crowds.

Which is why I'm recommending that people consider now (see #Natlprep 2025: Personal Pandemic Preparedness).what they will do if another pandemic flu should embark on a new world tour.