IORV: Another Study on The Efficacy of Oseltamivir Against Seasonal Influenza H1N1

Credit NIAID

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Twenty years ago Amantadine - a cheap, generic drug that had been in use for decades - was the preferred influenza antiviral. But in 2005, after reported overuse in Chinese agriculture, it quickly lost its effectiveness. 

By January of 2006, the CDC had pulled the plug on the use of Amantadine and Rimantadine, and a newer, and far more expensive drug - Oseltamivir (aka `Tamiflu') - became the primary influenza antiviral option. 

While occasional instances of Oseltamivir resistance had been observed, in nearly every case, it developed after a person was placed on the drug (i.e. `spontaneous mutations’). Studies suggested that these resistant strains were `less biologically fit’, and were therefore unlikely to spread from human-to-human.

That is, until a `biologically fit' highly resistant H1N1 viruses emerged in early 2008. By year's end nearly all H1N1 viruses were resistant, forcing the CDC to issue major new guidance for the use of antivirals (see CIDRAP article With H1N1 resistance, CDC changes advice on flu drugs).

This resistance was primarily due to an H275Y mutation - where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 275 (Note: some scientists use 'N2 numbering' (H274Y)). 

It seemed as if antiviral crisis was inevitable, but a new swine-origin H1N1 virus - one that happened to retain its sensitivity to Tamiflu - swooped in as a pandemic strain in the spring of 2009, supplanting the older resistant H1N1 virus.

Over the next dozen years - with a few exceptions - oseltamivir remained effective against 99% of seasonal flu viruses, but over the past couple of years we've begun to see some cracks in its veneer.

Eighteen months ago we saw a worrisome report in The Lancet - Global Emergence of Neuraminidase Inhibitor-Resistant Influenza A(H1N1)pdm09 Viruses with I223V and S247N Mutations - which reported a much higher incidence of oseltamivir resistance among samples tested in Hong Kong in 2023.

Unlike the H275Y mutation which caused so much trouble in 2008, these viruses carried dual I223V/S247N mutations.

Since then we've also seen: 

EID Journal: Multicountry Spread of Influenza A(H1N1)pdm09 Viruses with Reduced Oseltamivir Inhibition, May 2023–February 2024

Virus Research: A 15-year Study of Neuraminidase Mutations and the Increasing of S247N Mutation in Spain

And just 3 weeks ago, in Taiwan CDC Statement On Increased Antiviral Resistance in Seasonal H1N1 Cases in 2025, we saw a cryptic report indicating that 6.5% of locally circulating H1N1 viruses in Taiwan were now resistant to Oseltamivir. 

While oseltamivir remains largely effective against seasonal flu, it does appear to be coming under increased pressure. And while there are alternatives to oseltamivir (e.g. Baloxavir) -  oseltamivir remains the most available option. 

All of which brings us to a new study, published this week in Influenza & Other Respiratory Viruses, which - somewhat surprisingly - posits another potential cause of reduced effectiveness of oseltamivir against recent H1N1 viruses. 

Rather than citing previously identified amino acid changes in the NA (e.g. I223V/S247N), Liu et al. propose that an `increase in HA and NA activities' may be responsible for increased resistance in H1N1 viruses.  They state, however:

The reasons for the increased HA and NA activities remain un-clear due to the lack of information on the underlying mechanisms. 

I'll leave it to someone with a substantially higher pay grade to parse this one out.  Suffice to say, they observed higher oseltamivir resistance in 2023 H1N1 viruses, even in H1N1 viruses without previously identified markers. 

The authors then present evidence (in mice) that a baloxavir monotherapy or a baloxavir-molnupiravir combination treatment retained effectiveness against these H1N1 strains, although the combination therapy resulted in better outcomes.  

Note: Baloxavir is far less available here in the U.S., while Molnupiravir (Lagevrio) - a `last resort' COVID antiviral - carries several important warnings; particularly regarding its use during pregnancy, breastfeeding, and in patients under 18.

I've reproduced the abstract below. Those seeking a deeper dive will want to download and read the full PDF.   I'll have a brief postscript after the break.  

Efficacy of Oseltamivir Against Seasonal Influenza H1N1 and the Efficacy of a Novel Combination Treatment In Vitro and In Vivo in Mouse Studies

Danlei Liu, Ka-Yi Leung, Ruiqi Zhang, Hoi-Yan Lam, Yujing Fan, Xiaochun Xie, Wan-Mui Chan, Kelvin Kai-Wang To, Kwok-Hung Chan, Ivan Fan-Ngai Hung
First published: 20 October 2025
https://doi.org/10.1111/irv.70176

PDF
 
ABSTRACT

Background

Influenza surveillance and drug resistance testing have always been central to clinical efforts. Therefore, researching the virus characteristics and antiviral drugs is essential.

Method

The HA and NA activities were assessed in influenza strains, and mutations were identified through gene sequencing. The effects of oseltamivir, molnupiravir, and baloxavir treatments were evaluated in vitro. The effectiveness of molnupiravir monotherapy and its combination with baloxavir was also evaluated in a mouse model. Changes in body weight and lung tissue were examined, including pathological changes, virus replication, and inflammation levels.

Results

Forty-one seasonal influenza H1N1 strains from 2023 were used. The EC50 of oseltamivir was significantly increased compared to the 2009 reference strain.

Correlation analysis showed that the increase in EC50 was related to the HA and NA activities. The antiviral effects of molnupiravir and baloxavir significantly inhibited virus replication; the combination treatment of molnupiravir/baloxavir showed more potent and synergistic inhibitory effects in vitro. 

In the mouse model, molnupiravir treatment effectively inhibited virus replication and lung inflammation, but the treatment did not improve weight loss or reduce mortality. With the molnupiravir/baloxavir treatment, viral replication was significantly inhibited and proved to be more effective than either monotherapy. The combination therapy also showed the lowest inflammatory response along with a higher survival rate.

Conclusions

The increase in HA and NA activities of seasonal influenza reduced the efficacy of oseltamivir treatment, but the effectiveness of molnupiravir and baloxavir was retained. Combination therapy showed a significant antiviral effect, which provides a reference for the clinical treatment.

        (SNIP)

In summary, the HA and NA activities of the 2023 seasonal influenza have increased, thereby diminishing the antiviral effect of oseltamivir. Molnupiravir has shown certain anti-influenza effects, and its combination with baloxavir can more effectively inhibit viral replication and reduce mortality in mouse studies.

       (Continue . . . )

While oseltamivir continues to be effective against the vast majority of seasonal flu viruses currently in circulation - and we don't appear to be anywhere near a repeat of 2008 - we are seeing some early warning signs. 

Which suggests that public health authorities may need to start thinking about stockpiling alternatives (e.g., zanamivir, baloxavir) should these trends continue.

As we are so frequently reminded -  evolution never stops - and while our modern pharmacological victories over bacteria, fungi, and viruses have been nothing short of remarkable - they are often fleeting.

HK CHP: Mainland China Retrospectively Reports 4 More H9N2 Cases - Cambodian H5N1 Update

#18,917

Last week Hong Kong's CHP reported two relatively recent (Sept) cases of human H9N2 infection on the Mainland, making the 20th and 21st cases announced in the last 6 months (since April 2025).

In the previous 6 month period (Oct 2024 - Apr 2025), China had reported 16 cases.

In today's report, Hong Kong adds 4 retrospectively identified cases from last February.  Details are unusually scant (even for China), with the only identifiers provided being `an individual' and the month. 

Today's report also adds a small detail on the recent H5N1 cases in Cambodia. 

Last Friday, I reported on the Cambodia's 16th H5N1 Case of 2025, although there have been persistent reports of a 17th case that may have gone unreported in  September.  

According to the chart below, a 14 year-old female from Takeo Province was hospitalized (possibly Sept or early Oct).  This case was not included in the most recent WHO report (26 August to 29 September).

I've updated my map (see below) to reflect this 17th case.

Unlike the milder North American H5N1 clade 2.3.4.4b  virus, this is an older clade 2.3.2.1e, which has proved fatal in nearly 50% of cases reported over the past couple of years and has skewed heavily towards younger (< 18) victims. 

Canada: Calgary Zoo Closes Some Venues Over Bird Flu Concerns - Butterfield Acres Update

 

Distance Calgary Zoo to Butterfield Acres 12 mi

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Yesterday, in Canada: Alberta Petting Zoo Closed For HPAI H5 - Recent Visitors Asked to Monitor For Symptoms, we looked at a public health advisory issued after a local petting zoo (Butterfield Acres) was closed for HPAI. 

Although we are seeing some delayed reporting - particularly here in the United States - it is apparent that avian flu has returned earlier than usual - and in force -  both here in North America and in Europe. 

Last year Canada went a full 6 months - (April 10th - Oct 21st) without reporting a single HPAI outbreak in poultry, but their CFIA has already reported 20 outbreaks since September. 

Overnight the Calgary Zoo - which is located just 12 miles from the petting zoo (see map above) discussed yesterday - announced the precautionary closure of several exhibits; citing recent detections of HPAI in `close proximity' to the zoo. 

Protecting our Birds: Viewing Updates Effective October 21

The Canadian Food Inspection Agency (CFIA) has confirmed the presence of highly pathogenic avian influenza in close proximity to the zoo. The health and well-being of the animals in our care remains our top priority. Out of an abundance of caution, we’re proactively implementing the following measures to protect our avian species: 

• The Rainforest Aviary and the Jihad Shibley Rocky Mountain Aviary are closed;

• All birds have been moved indoors, where possible, and may not be viewable (including Chilean flamingoes, ostrich, African grey-crowned cranes, greater rheas, whooping crane, red-crowned cranes, Dalmatian pelicans, and peacocks); and

• The indoor habitat at Penguin Plunge remains open with increased pathway disinfection and disinfectant mats at the entrance.

By limiting access to our beloved birds, we’re helping to protect them from potential contamination from outside the zoo. Thank you for your understanding and continued support as we work to keep the animals we all care about safe.

Meanwhile, CBC News is reporting (see AHS testing people in relation to bird flu outbreak at petting farm, Calgary Zoo taking precautions) that: 

"Alberta Health Services (AHS) has confirmed 12 people have been referred for testing and all “symptomatic workers” at Butterfield Acres Petting Farm are being tested after nine cases of Influenza A H5, commonly known as the avian flu, were identified in poultry."

At this time, no positive cases have been announced. Hopefully we'll get additional information in days ahead. 

Canada: Alberta Petting Zoo Closed For HPAI H5 - Recent Visitors Asked to Monitor For Symptoms

Credit Wikipedia

#18,915

While the risks to recent visitors are likely low, yesterday Alberta Health Services released the following health advisory, after a local petting zoo (Butterfield Acres) was closed for HPAI (presumably, H5N1). 

Visitors to the farm between October 6th and the 12th are asked to monitor for - and report - any flu-like symptoms for the next few days. Anyone who is symptomatic should isolate at home, and call Health Link at 811 for assessment and testing.

 First the link to the Health Advisory (and accompanying FAQ), after which I'll have a brief postscript.

Avian Influenza at Butterfield Acres Petting Farm

October 19, 2025

CALGARY – Primary Care Alberta (PCA) was notified on October 16th, 2025, of nine poultry cases of Highly Pathogenic Avian Influenza (HPAI) at Butterfield Acres in Foothills County located at 254077 Rocky Ridge Rd NW, Calgary, AB, which operates a petting farm.

The facility was voluntarily closed from October 13 - 17, 2025. On October 17th, 2025, AHS issued a formal closure order for the facility. The facility will remain closed until the conditions of the order are met and until public health inspectors and medical officers of health have deemed it safe to reopen.

While HPAI primarily affects birds, rare human infections have occurred through close contact with infected animals. The risk to the public remains low. However, individuals who visited the petting farm between October 6 and October 12, 2025, are asked to consider the following recommendations:

Individuals with symptoms

If you have experienced fever, cough, sore throat, or other flu-like symptoms and visited the farm between October 6 - 12, 2025, it is recommended you isolate at home, and call Health Link at 811 for assessment and testing. When calling 811 select Option “2” and then Option “1.”

Symptoms of Avian Influenza

Symptoms of avian influenza can range from very mild to severe, depending on the specific virus. The most common symptoms include:

• Pink eye (conjunctivitis)
• Fever
• Fatigue
• Muscle/body aches
• Headache
• Sore throat, cough, stuffy or runny nose
• Nausea and vomiting
• Diarrhea
• Shortness of breath (dyspnea)
• Diarrhea, nausea, vomiting (rare)

Individuals without symptoms

If you do not have symptoms, you do not need to call 811. Continue to monitor your health. If you visited Butterfield Acres between October 6 - 12, 2025 and develop symptoms within 10 days of visiting, it is recommended you isolate at home and call Health Link at 811 for assessment and potential referral for testing.

Anyone with questions or concerns can contact Health Link to speak to a registered nurse 24 hours a day, seven days a week, by dialing 811.

Primary Care Alberta is a made-in-Alberta solution to improve access to the primary care services Albertans rely on. By delivering coordinated services, Primary Care Alberta allows for valued healthcare professionals to do what they do best ─ care for you. Together, we are creating a future where compassionate, timely and effective healthcare is available to every Albertan at every stage of life.

       (Continue . . . .)

Since most of the visitors who might have been exposed are nearing the end of their expected 10-day incubation period, hopefully this will turn out to be a non-event.  

Of course, mild cases may have already occurred - but are not yet reported - and workers at the farm have presumably been exposed far more recently.  We'll probably know more a week from now. 

The concern is that children - the primary demographic for attending petting zoos - have historically been at greater risk of contracting HPAI H5 than adults. 

They are not only more likely to become infected, they are more likely to suffer severe disease. And it has become nearly a cliché that exposure to poultry is usually cited as their likely source of exposure. 

The CDC's recommendations for visiting animal exhibits is pretty clear about the risks, even before adding HPAI to the mix. A few of many outbreaks we've covered include:

• We've seen numerous large outbreaks of Salmonella linked to Easter Chicks, and backyard poultry (see here, here, and here). 
• In 2019 we followed an outbreak linked to a petting zoo in San Diego (see 10 Confirmed, 1 Probable E. coli STEC Cases Linked To County Fair), which resulted in the death of a 2-year old boy. 
• While in 2012's That Duck May Look Clean, But . . . we looked at an outbreak of Salmonella Montevideo involving 66 persons across 20 states linked to the handling of live poultry (baby chicks or ducklings or both) sold via mail-order hatcheries and agricultural feed stores.

The CDC describes the increased risks from petting zoos:

Petting zoos

Every year, many people get sick after visiting an animal exhibit. From 2010-2015, about 100 outbreaks of illness in people linked to animals in public settings like zoos, fairs, and educational farms were reported to public health officials. Some of the most common harmful germs people get from animals at exhibits are E. coli, Cryptosporodium, and Salmonella.

The incursion of HPAI H5 into North America in late 2021 added yet another layer of risk to what once was considered a fairly innocuous endeavor; taking kids to a petting zoo.    

Children - along with the elderly, pregnant women, and immunocompromised individuals - are considered at greatest risk; with the CDC advising that children under 5 not touch or handle poultry at all. 

While the CDC is undoubtedly citing `best practices', good luck with taking a 4 year-old to a petting zoo and then telling them they can't pet the ducks.

We've seen similar warnings issued about visiting agricultural exhibits at state and county fairs (see CDC: Updated Guidance to Help Prevent Spread of Flu at Agricultural Fairs).

The risks - while still low - appear to be greatest during the fall, winter, and early spring, when avian flu activity is typically at its peak.  

After a relatively quite summer, over the past 6 weeks we've seen a huge increase in HPAI outbreaks in commercial and backyard poultry in both the United States and Canada. 

While I dislike the phrase `the new normal', as long as HPAI H5 continues to circulate at high levels, this is likely to remain our new reality. 

J.I.D.: Antivirals for Novel Influenza A Virus Infections

 

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During the opening months of the 2020 COVID pandemic we found ourselves with few pharmaceutical options, since no coronavirus vaccine had previously been developed, and no antivirals had been proven to work against the SARS-CoV-2 virus. 

As a result, treatment was mainly supportive (ventilation, O2, IV fluids, etc.) with a few desperate attempts to incorporate `off-label' drugs, many of which proved to be of little value (see WHO Solidarity Therapeutics Trial: Remdesivir, HCQ, Lopinar/Ritonavir & Interferon Disappoint).

While we will hopefully have better options going into a novel influenza pandemic, a strain-specific vaccine could take 6 - 12 months to reach the masses (see Maggie Fox's SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1), and we've seen recent warnings that our current arsenal of antivirals may be lacking.

St. Jude Researchers: Current Antivirals Likely Less Effective Against Severe Infection Caused by Bird Flu in Cows’ Milk

We've also seen sporadic reports of antiviral resistance turning up in HPAI H5 outbreaks in poultry (see Emerg. Microbes & Inf: Oseltamivir Resistant H5N1 (Genotype D1.1) found On 8 Canadian Poultry Farms), and in a recent EID Journal: Antiviral Susceptibility of Influenza A(H5N1) Clade 2.3.2.1c and 2.3.4.4b Viruses from Humans, 2023–2024, the authors advised:

". . . higher antiviral dosing and combination antiviral treatment (e.g., oseltamivir and baloxavir) should be considered, in particular for patients with H5N1 who are hospitalized or immunocompromised." 

All of which brings us to a narrative evidence review article by the CDC's Dr. Timothy M. Uyeki, MD, MPH, MPP  and Dr. Jessica A. Belser, PhD, which looks at the available literature on use of antivirals in humans with novel influenza A virus infections of avian A(H5N1), A(H5N6), A(H7N7), and A(H7N9). 

Since randomized trials are both impossible and unethical, nearly all evidence comes from observational studies and case reports. Purists may object, but sometimes that is the only type of evidence available. 

The main takeaways from this 19-page article are:

• Most of our observational data comes from the treatment of H5N1 and H7N9 infections

• Early treatment with neuraminidase inhibitors (NAIs), particularly oseltamivir, within 48 hours dramatically improves survival.

• Delayed treatment (>5–7 days) correlates with higher mortality, longer viral shedding, and increased respiratory failure.

• Post-Exposure Prophylaxis  (PEP) evidence exists only for H7N7, but that dataset was small, and confidence is fairly low. 

• Antiviral resistance can emerge, particularly with oseltamivir and baloxavir, reinforcing the need for combination therapy trials.

I've only posted some excerpts from this information-dense report, so you'll want to follow the link to read it in its entirety.  I'll have a postscript when you return. 

Antivirals for Novel Influenza A Virus Infections  
Timothy M Uyeki, Jessica A Belser
 
The Journal of Infectious Diseases, Volume 232, Issue Supplement_3, 15 October 2025, Pages S191–S209, https://doi.org/10.1093/infdis/jiaf296
Published: 17 October 2025

PDF

Abstract

Influenza A viruses of animal origin (such as avian or swine influenza A viruses), which are antigenically and genetically distinct from seasonal influenza A viruses and have infected humans, are referred to as novel influenza A viruses. Sporadic human infections with highly pathogenic avian influenza A(H5N1) viruses of a wide spectrum of illness severity in the United States and worldwide have highlighted the need for evidence-based recommendations on the use of antivirals for novel influenza A virus infections. 

We review the available published data on use of antivirals for humans with novel influenza A virus infections of avian [A(H5N1), A(H5N6), A(H7N7), and A(H7N9) viruses associated with severe human disease] or swine origin, and data from in vivo antiviral studies. We summarize the available evidence on the effectiveness of antiviral treatment and antiviral postexposure prophylaxis of novel influenza A virus infections, discuss considerations for use of combination therapy with antivirals of different mechanisms of action, and identify important questions to improve the evidence base and to further guide use of antivirals for treatment and postexposure prophylaxis of novel influenza A virus infections.

(SNIP)

Taken together, available data from observational studies of patients infected with older clades of HPAI A(H5N1) viruses and from animal studies suggest that early initiation of oseltamivir treatment shortly after symptom onset has the greatest clinical benefit.

There are no data on baloxavir treatment effectiveness for A(H5N1) patients or optimal dosing and duration to achieve clinical benefit and to reduce emergence of resistant viruses, although animal data suggest clinical benefit of early initiation of baloxavir treatment.

        (SNIP)

The detection of oseltamivir-resistant HPAI A(H5N1) virus with H274Y in NA circulating among poultry in British Columbia, Canada [106], is notable because if unprotected exposure to oseltamivir-resistant novel influenza A virus is known or suspected, then use of other antivirals that have activity against such oseltamivir-resistant viruses, such as inhaled zanamivir or baloxavir, for postexposure prophylaxis is indicated.

       (SNIP)

Optimal dosing and duration of antiviral treatment in outpatients and hospitalized patients with novel influenza A virus infections remain to be determined. 

Availability of assays in clinical settings or rapid sequencing of target genes that can detect antiviral resistance to NAIs, polymerase inhibitors, adamantanes, and other antivirals in respiratory specimens and provide timely results, can help guide specific treatment. 

Because of the ongoing, unpredictable evolution of influenza A viruses among birds and other animals, susceptibility to antivirals in the past or now does not necessarily inform susceptibility to antivirals in the future, and antiviral treatment decisions for patients with novel influenza A virus infections may vary on a case-by-case basis, depending upon antiviral susceptibility data and what antivirals are available. 

Therefore, ongoing, rapid sharing of data on antiviral susceptibility of novel influenza A viruses currently circulating in animals and infecting humans is important to guide public health and clinical recommendations for use of antivirals and for pandemic influenza preparedness. 

       (Continue . . . )

While the United States and other countries have tens of millions of courses (of mostly oseltamivir) stockpiled, there isn't nearly enough to treat everyone during a pandemic, particularly when the optimum dose and duration have not been established.  

Even during moderately severe flu seasons, we've seen spot shortages and difficulties getting antivirals to patients who need them in the crucial first 48 hours of infection (see CDC HAN #0482: Prioritizing Antiviral Treatment of Influenza in the Setting of Reduced Availability of Oseltamivir).  

While I wouldn't hesitate to take antivirals for pandemic flu infection, their effectiveness and availability are not guaranteed. Which means our initial response  - once again - must focus heavily on preventing infection. 

That means the use of NPIs (non-pharmaceutical interventions); like face masks, hand washing, improved indoor ventilation, staying home while sick, and avoiding crowds. 

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

ECDC Summary: Human Infection with Avian Influenza A(H5) virus - Mexico - 2025

Credit Wikipedia

#18,913

Three days ago in the latest PAHO H5N1 Epidemiological Report, there was a brief mention of an H5 case in Mexico.  While I've been hoping for a more detailed report, so far, details remain scant.

What we do know is the patient - a woman in her 20's - developed symptoms  on September 14th, and after two weeks of increasing respiratory distress was finally hospitalized and a bronchoalveolar lavage sample was obtained, which tested positive for an unsubtypable influenza A on Sept 29th. 

The sample sent out for further testing, and Avian influenza A(H5) was confirmed on September 30th. The patient was then put on oseltamivir. Determination of the NA type remains pending. 

This is the third H5 case reported from Mexico since 2024, and the source of all three remain undetermined.

The first occurred in April of 2024 (see Mexico announced the death of a 58-year-old man) when a patient - who also suffered from serious comorbidities - tested positive for H5N2, becoming the first laboratory-confirmed human case of influenza A(H5N2) infection reported globally.

A year later (April 2025), a 3-year old girl from Durango State died following an H5N1 infection (see WHO DON Update On Mexico's Fatal H5N1 Infection). 

While this latest case went > 2 weeks with symptoms before being diagnosed, the good news is once hospitalized, the infection was quickly identified and treatment was begun. 

First the ECDC summary, after which I'll have a postscript.

Human infection with avian influenza A(H5) virus - Mexico - 2025

Overview: On 15 October 2025, Pan American Health Organization, PAHO/WHO reported a new human case with avian influenza A(H5) virus infection in Mexico City, Mexico. A young woman in her 20s with no recent travel history and no recent influenza vaccination developed respiratory symptoms (rhinorrhea and cough) on 14 September 2025. 

The symptoms progressed to fever and odynophagia followed by hemoptysis and chest pain between 21 and 28 September when she was hospitalised at the National Institute of Respiratory Diseases (INER as per acronym in Spanish). On 29 September bronchoalveolar lavage sample was collected and tested positive for unsubtypable influenza A. Avian influenza A(H5) was confirmed on 30 September by real-time RT-PCR (designation of the influenza virus neuraminidase is pending), same day the patient received treatment with Oseltamvir. The patient was discharged on 11 October 2025.

During the epidemiological investigation, 41 contacts were identified. All samples taken from the contacts tested negative for avian influenza; all contacts received prophylactic treatment with Oseltamivir.

Several animals (two pigeons, a pet dog in the domicile of the case, and poultry birds) were identified in the courtyard of the residential place of the individual. Bird droppings were identified in several areas of the house, including a poorly sealed water cistern that supplies water to all apartments in the building. Samples taken from some animals tested positive for avian influenza A(H5) at the Official Laboratory of the National Service for Agrifood Health, Safety, and Quality (SENASICA, per its acronym in Spanish). Results of the testing of the environmental samples are pending.

This is the third human case with avian influenza A(H5) infection reported in Mexico since 2024. The previous case (with avian influenza A(H5N1)) of infection was reported in April 2025. Since 2003 and as of 13 October 2025, 991 human cases of avian influenza A(H5N1) virus infection, including 476 deaths (CFR 48%), were reported from 25 countries worldwide.

Acknowledgements: we gratefully acknowledge all data contributors, i.e. the authors and their originating laboratories responsible for obtaining the specimens, and the submitting laboratories for generating the genetic sequence and metadata and sharing via the GISAID Initiative.

ECDC assessment:

Sporadic human cases of different avian influenza A(H5Nx) subtypes have previously been reported globally. 

Despite widespread transmission of avian influenza viruses in animals, transmission to humans with avian influenza remains infrequent and no sustained transmission between humans has been observed.

Overall, the risk related to zoonotic influenza for the general population in EU/EEA is considered low.

Direct contact with birds and other infected animals, their secretions or a contaminated environment is the most likely source of infection, and the use of personal protective measures for people exposed to dead animals or their secretions will minimise the associated risk. The recent severe cases in Asia and the Americas in children and people exposed to infected, sick or dead backyard poultry underlines the risk of unprotected contact with infected birds in backyard farm settings.

Actions:

ECDC monitors avian influenza strains through its influenza surveillance programme and epidemic intelligence activities in collaboration with the European Food Safety Authority (EFSA) and the EU Reference Laboratory for Avian Influenza in order to identify significant changes in the virological characteristics and epidemiology of the virus. Together with EFSA and the EU Reference Laboratory for Avian Influenza, ECDC produces a quarterly report on the avian influenza situation. The most recent report was published in September 2025.

Once again, we don't know if this is H5N1, H5N2, or some other subtype.  

The lack of positive tests among the 41 close contacts is reassuring, but the window for detecting an influenza A infection via PCR testing is relatively narrow, with best results obtained during the first week of infection. After 7 days, the ability to reliably detect Influenza A infection drops off sharply.

 

Making the negative results from close contacts - who are often tested weeks after exposure - less probative than they might appear. 

 

While most known human H5 infections have been epidemiologically linked to a specific agricultural exposure (cows, chickens, wild birds, etc.), over the past 18 months we've seen a handful (U.S. x 4, Mexico x 3, Canada x 1) where the source of exposure remains unexplained.

Given the limits of surveillance and testing (see above), it would not be terribly surprising if there are other cases in the community that have not been officially confirmed.

Particularly since some percentage of infections are asymptomatic or very mild (see MMWR: Serologic Evidence of Recent Infection with HPAI A(H5) Virus Among Dairy Workers).

Had this patient's condition not worsened enough over 2 weeks for her to seek hospital care - and the proper tests were performed -  it would likely never have come to light.  

While there is still no evidence of efficient human-to-human transmission, that is something that can likely only be detected after it's begun in earnest (see UK Novel Flu Surveillance: Quantifying TTD).

Although the lack of new human cases reported in the United States in recent months may be reassuring, our ability to detect novel flu viruses in the community remains limited.