WHO Mpox SitRep #65 : Report of 3rd Recombinant Mpox Virus With Genomic Elements of Clades Ib and IIb

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While details were scant, just short of 5 months ago (Dec 8th) the UKHSA Identified a New Recombinant Strain of Mpox Virus in a traveler recently returning from an (undisclosed) country in South-East Asia.

For the very first time, genomic sequencing showed an emerging mpox strain with elements from both clade Ib and IIb mpox. 

Two months later the WHO announced a 2nd case, describing the two cases as:

The first case was detected in the United Kingdom of Great Britain and Northern Ireland (hereafter “United Kingdom”), with travel history to a country in South-East Asia, and the second in India, with travel history to a country in the Arabian Peninsula. 

Detailed analysis of the virus genomes shows that the two individuals fell ill several weeks apart with the same recombinant strain, suggesting that there may be further cases than are currently reported. Both cases had similar clinical presentation to that observed for other clades. Neither patient experienced severe outcomes. Contact tracing for both cases in the reporting countries has been completed; no secondary cases were detected. 

With little fanfare, 72 hours ago the WHO announced the third detection of a recombinant strain in their latest SitRep (#65), although they buried the lede somewhat, putting the first mention at the very bottom of their list of highlights. 

Highlights

• Transmission of mpox continues mostly within sexual networks, affecting men and women, often followed by household transmission and, in some areas, affecting all age groups. All clades of monkeypox virus (MPXV)continue to circulate. Rapid containment of mpox outbreaks is essential to prevent community transmission in any setting.

• In March 2026, 48 countries across all WHO regions reported a total of 1235 confirmed mpox cases, including five deaths (case fatality ratio [CFR] 0.4%). Of these cases, 70.4% were reported in the WHO African Region.

• Four WHO regions – the Region of the Americas, African, European, and South-East Asian regions – reported a decline in confirmed cases in March, compared to February 2026, while the Eastern Mediterranean and Western Pacific Region reported an increase in confirmed cases.

• Sixteen countries in Africa reported active transmission of mpox in the last six weeks (9 March – 19 April 2026),with 969 confirmed cases, including three deaths (CFR 0.3%). Madagascar, the Democratic Republic of the Congo,Guinea, Kenya, and Burundi reported the highest number of cases during this period.

• Four countries, Colombia, Denmark, Ecuador and Singapore, reported mpox due to clade Ib MPXV for the first time. Poland and Slovakia reported mpox due to clade I MPXV for the first time, pending subclade identification.

• Outside Africa, Argentina, Denmark, Germany, Pakistan, Portugal, Singapore, Spain, and the United Kingdom of Great Britain and Northern Ireland reported community transmission of clade Ib MPXV, including among men who have sex with men.

• Pakistan has reported a healthcare-associated mpox outbreak in Sindh province, involving neonates, infants, and adults. In the past month, the province has reported 29 confirmed cases, including eight deaths (case fatality ratio: 28%), and one additional death in a suspected case. About half of cases, and all deaths were reported among infants younger than six months of age.

• Qatar has reported a travel-related case of mpox with a clade Ib/IIb recombinant MPXV strain, the third such reported case globally, following previous case reports in India and the United Kingdom of Great Britain and Northern Ireland. The patient has recovered and no secondary cases have been reported to date.

While there is admittedly a lot going on in the world right now, this latest case appears to have escaped the notice of the mainstream press. The WHO report goes on to state (on page 8):

Detection of recombinant MPXV strain in Qatar

On 24 March 2026, Qatar notified WHO of a laboratory-confirmed mpox case infected with a recombinant MPXVstrain containing genomic elements of clade Ib and IIb MPXV. The case is an adult male resident in Qatar, who developed general and genital mpox symptoms on 10 March and was confirmed to have mpox on 21 March.

Genomic sequencing on 2 April confirmed infection with a recombinant clade Ib/IIb MPXV strain.

The individual reported short travel to Saudi Arabia during the incubation period, but no contact with a known mpox case. He did not report any sexual or other known high-risk exposures in either Saudi Arabia or Qatar, and to date, the source of infection for this case remains unknown. Following the initial diagnosis, the case was isolated in a facility and recovered fully. 

Contact tracing was completed with no secondary cases identified.

This represents the third known detection of this MPXV recombinant strain globally, following travel-related detections in India and the United Kingdom of Great Britain and Northern Ireland. Consistent with previous detections, no differences in clinical presentation have been observed compared with infection with non-recombinant MPXV strains. 

While the public health risk associated with this event in Qatar and globally is assessed as low, it highlights the potential for undetected spread of this recombinant strain and the risk of continued emergence of recombinant strains in the context of co-circulation of multiple MPXV clades. Ongoing surveillance, genomic sequencing, and case investigation remain critical.

 
Previously the WHO reported on the first 2 cases:

Detailed analysis of the virus genomes shows that the two individuals fell ill several weeks apart with the same recombinant strain, suggesting that there may be further cases than are currently reported.

But that same report, also said:

After classification of this case and posting in a public database as a novel MPXV recombinant strain, a case of mpox detected in India in September 2025 was retrospectively reclassified as a closely-related recombinant strain based on sequencing data.

This latest report states - `This represents the third known detection of this MPXV recombinant strain globally. . . ' - which strongly suggests all 3 recombinants are genetically similar.

But without more detailed information, it is difficult to say whether all 3 cases stem from a single recombination event. 

As recently as 5 years ago, there were only 2 recognized clades of Mpox (then Monkeypox): The milder West African (now clade IIa) and the more severe Central African clade (now Clade Ia).

But like all viruses, Mpox continues to evolve and diversify, as discussed in the 2014 EID Journal article Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congo, where the authors cautioned:

Small genetic changes could favor adaptation to a human host, and this potential is greatest for pathogens with moderate transmission rates (such as MPXV) (40). The ability to spread rapidly and efficiently from human to human could enhance spread by travelers to new regions.

In recent years we've seen an explosion in the number of Mpox strains, with multiple lineages of clade IIb spreading globally in 2022 - followed in 2023 by the emergence of a new clade Ib, which is slowing spreading internationally as well. 

The detection of 3 (reportedly similar) recombinant strains in 3 different countries raises the possibility that a new - genetically distinct strain - may be emerging.  

While RT-PCR can detect this recombinant a Mpox positive, it doesn't flag it as being `different'. For that, WGS (Whole Gene Sequencing) is needed, and sadly, only a small fraction of samples are sequenced. 

Which means it may be some time before we know if these 3 cases are merely a flash in the pan, or a stronger, more worrisome, signal. But as Ian Fleming once famously wrote; 

"Once is happenstance, twice is coincidence, three times is enemy action"

So we'll be watching this evolving situation closely. 

EID Journal Dispatch: Replication Efficiency of Contemporary Highly Pathogenic Avian Influenza A(H5N1) Virus Isolates in Human Nasal Epithelium Model

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In the past, H5N1 transmission in humans has been thought to be hampered by the generally hostile environment found in the human upper airway; cooler temperatures, the virus's preference for avian (α2,3-linked SA) receptors, and the cytokine signaling defenses of the innate immune system.

While the evidence continues to suggest that HPAI H5N1 viruses are not transmitting efficiently (or often) among humans, it is equally clear that some mild (or asymptomatic) infections have flown under the radar (see MMWR: Serologic Evidence of Recent Infection with HPAI A(H5) Virus Among Dairy Workers).

Over the past year, we've seen growing evidence that contemporary H5 viruses may be evolving towards overcoming some of these obstacles. Some recent blogs include: 

• Last month, in EID Journal: Tropism and Replication Competence of Cattle Influenza A(H5N1) Genotype B3.13 Virus in Human Bronchus and Lung Tissue, we saw a report that the `Bovine' H5N1 virus showed partial adaptation to human respiratory tissue, and replicated in the lung tissue on par with the 2009 H1N1pdm virus. 

• Last January, in Preprint: Bovine-derived Influenza A virus (H5N1) Shows Efficient Replication in Well-differentiated Human Nasal Epithelial Cells Without Requiring Genetic Adaptation, we saw another study - this time on the upper airway - which found H5N1Tex/24 crucially replicated effectively at 33 degrees Celsius, whereas earlier avian H5N1 strains require 37 degrees Celsius.

• And six months ago, in J.I.D.: Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13, researchers demonstrated that D1.1 genotype replicates better in lab-grown nasal and lung tissues than the bovine B3.13 strain, and it binds more tightly to human‑type (α2,6-linked SA) receptors.  

Yesterday the CDC's EID Journal published another in this growing list of studies suggesting that recently emerged strains of HPAI H5N1 clade 2.3.4.4b are becoming better adapted to the human upper respiratory system than older strains.  

This NIAID study compares several HPAI and seasonal flu strains and finds that some strains of HPAI H5 (B3.13 & D1.1) have become better adapted to  human physiology; including tolerance to lower temperatures and the ability to evade some of our innate immune responses. 

While these are incremental changes, and the virus still has a ways to go, this is a worrying trajectory.  Due to its technical nature, I've only posted some excerpts from the dispatch.  Follow the link to read it in its entirety. 

Replication Efficiency of Contemporary Highly Pathogenic Avian Influenza A(H5N1) Virus Isolates in Human Nasal Epithelium Model

Meaghan Flagg1, Christopher J. Winski1, Bridget G. Brackney, Tessa R. Lutterman, Johan A. Ortiz-Morales2, Brandi N. Williamson, and Emmie de Wit 

Abstract

Replication of influenza A virus in human nasal epithelium affects transmissibility and disease. We compared virus replication and immune responses in human nasal epithelium infected with seasonal and highly pathogenic avian influenza A(H5N1) viruses. Contemporary H5N1 viruses replicated better than the historical isolate; however, interferon response to B3.13 genotype viruses was dampened.

Since March 2024, a total of 70 human cases of highly pathogenic avian influenza (HPAI) A(H5N1) have been reported in the United States as a result of sporadic spillover events from poultry and dairy cattle (1). HPAI H5N1 clade 2.3.4.4b genotype B3.13 was responsible for many of the early cases (2).

On January 31, 2025, HPAI H5N1 clade 2.3.4.4b genotype D1.1 was detected in dairy cattle (https://www.aphis.usda.gov/news/program-update/aphis-confirms-d11-genotype-dairy-cattle-nevada-0External Link); D1.1 was later identified in humans (1). Those spillover events sparked global health concerns about the potential for large-scale spread of clade 2.3.4.4b HPAI H5N1 viruses and their risk to human and animal health.

Seasonal influenza A and HPAI H5N1 viruses both cause severe respiratory disease despite different tissue tropisms. Seasonal influenza A viruses primarily infect the upper respiratory tract (URT), whereas HPAI H5N1 viruses preferentially replicate in the lower respiratory tract (LRT). This contrast in tissue affinity is explained by differences in receptor specificity and has been implicated in transmission efficiency (3). Specifically, the URT predominantly expresses sialic acids linked to galactose by an α-2,6 linkage; the LRT expresses sialic acid linked to galactose via α-2,3. 

Despite the inefficient human-to-human transmission of HPAI H5N1 viruses, recent emergence and circulation of new genotypes in mammals emphasize the need to characterize these novel viruses in relevant respiratory tract models.

Here, we compare the replication kinetics and host innate immune responses in human nasal epithelium of several seasonal influenza A virus isolates and historical and contemporary HPAI H5N1 virus isolates of 3 different genotypes.

(SNIP)

HPAI H5N1 isolate A/Texas/37/2024 (B3.13 genotype) replicated most efficiently in nasal tissue even when compared with seasonal isolates (Figure 1). Although we noted differences in replication kinetics between viruses of the same genotype, the B3.13 and D1.1 genotype isolates replicated more efficiently than the historical HPAI H5N1 isolate A/Vietnam/1203/2004. The B3.6 HPAI H5N1 isolate A/mountain lion/MT/1/2024 replicated least efficiently (Figure 1). Presence of known mammalian adaptations of polymerase basic (PB) 2 E627K, PB2 D701N, and PB2 M631L was associated with more efficient virus replication (Table; Figure 1).

(SNIP)

HPAI H5N1 virus replication can be affected by the physiologic temperature of the human nasal mucosa, for which the reference is 33°C (11,12). To address the potential effect of temperature on virus replication, we quantified virus replication kinetics at 37°C and 33°C in MDCK cells.

At 8 hours postinoculation, the titers of HPAI H5N1 virus isolates were lower at 33°C than at 37°C (Appendix Figure 2). However, all viruses reached the same maximum titer at 33°C and 37°C. In addition, the relative difference observed between viruses at 37°C were similar at 33°C, suggesting that adjusting the temperature in the nasal epithelial cultures to 33°C would not have substantially altered our results.

Conclusions

Our results reveal that contemporary HPAI H5N1 isolates with known mammalian adaptations replicate more efficiently than historical HPAI H5N1 virus used. Despite high levels of virus replication, ISG induction was limited in response to B3.13 genotype virus infection. Additional studies are needed to further understand how virus replication efficiency and innate immune responses affect mammalian transmission efficiency. Existing immunity to other influenza A viruses might protect against contemporary H5N1 infection and onward transmission.

       (Continue . . . )

 
While it will likely take more than just adapting to the human upper airway to make H5N1 a pandemic contender, increasingly breaching our first line of defense is an important milestone.  

Eurosurveillance: HPAI H5N1 in Poultry & Domestic Cats and Occupational Exposure Among Veterinary and Other First Responders, Germany, February 2026

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We've a detailed report, published yesterday in Eurosurveillance, on a recent (Feb 2026) outbreak of HPAI H5N1 in poultry on a small holding in Germany, where domestic cats (n=9), and a number of people (n=17) were occupationally exposed.

Despite the high number of HPAI H5 outbreaks reported in Germany over the winter of 2025-2026 (see BHVSI-SA graphic below), biosecurity was practically nonexistent on this farm - and based on the lack of PPE use - the index of suspicion for HPAI  appears to have been low for several days into the outbreak. 

While no human infections were detected, testing was less than exhaustive (only symptomatic individuals were tested by RT-PCR & just 11 out of 17 of exposed submitted to serology); despite previous studies (see MMWR: Serologic Evidence of Recent Infection with HPAI A(H5) Virus Among Dairy Workers), suggesting that asymptomatic HPAI H5 cases may be relatively common. 

The authors address some of these shortcomings in their report, stating:

Our analysis has limitations:

Firstly, systematic virological testing of all exposed individuals was not performed, as testing was limited to symptomatic persons, which represents a standard and pragmatic approach in this context. However, asymptomatic or subclinical infections may not have been detected.

(SNIP)

Fourthly, serological assessments of infection have several limitations. Antibody responses may be low or undetectable in asymptomatic or mildly infected individuals, and the timing of sample collection may not capture seroconversion. 

Another concerning aspect to this report is the lack of seasonal flu vaccination among many of the responders (particularly among the Veterinary Authority Staff), and their parsimonious use of PPE (see chart below) during their initial site visits. 

I've provided the link, abstract, and some excerpts from the report below, but you'll want to read it in its entirety.  I'll have a postscript when you return.

Open Access

Highly pathogenic avian influenza A(H5N1) in poultry and domestic cats and occupational exposure among veterinary and other first responders, Germany, February 2026
Aparna Dressler1,2 , Christiane Wagner-Wiening1 , Bettina Tegtmeyer3 , Susanne Haag-Milz3 , Bettina Demattio4 , Ralf Dürrwald5 , Timm Harder6 , Andreas Salditt7 , Judith Köster7

Highly pathogenic avian influenza (HPAI) viruses continue to circulate in Europe, causing outbreaks in poultry and wild birds and occasionally infecting mammals [1-4]. Although human infections remain rare, zoonotic transmission is a recognised occupational risk for persons involved in animal husbandry, outbreak control, and veterinary response activities, and sporadic human infections with HPAI A(H5N1) have been reported globally [5]. An HPAI outbreak in poultry and cats in a small, remote poultry holding in Sigmaringen in February 2026 triggered a One Health investigation with 17 exposed persons.

Here we describe the outbreak, assess potential zoonotic transmission and evaluate the public health response within a One Health framework.

Outbreak detection and initial investigation
 
On 19 February 2026, the local public health authority in Sigmaringen, Baden-Wuerttemberg, Germany, was notified of a suspected avian influenza outbreak in a small poultry holding following veterinary inspections triggered by animal welfare concerns. The holding, which had no biosecurity measures, comprised ca 21 chickens and nine free-roaming cats and was located in a remote rural area. The birds were in a poultry house but had access to the outside and contact with wild birds.

Between 16 and 18 February, veterinary inspectors found four dead chickens and one dead cat on the premises. A further cat showing severe neurological symptoms was euthanised (Tables 1 and 2). Laboratory testing using real-time quantitative PCR (RT-qPCR) confirmed HPAI A(H5N1) infection in all six animals, poultry and cats. All remaining poultry (n = 17) were culled as part of control measures. Subsequently, an additional symptomatic cat tested PCR-positive and was euthanised. The PCR-positive symptomatic cats presented with diverse clinical manifestations, including neurological signs, respiratory symptoms and general sickness.

(SNIP)

This event highlights several important aspects: 

Firstly, early detection through veterinary surveillance, including animal welfare inspections, can facilitate timely identification of outbreaks in backyard poultry holdings.

In this investigation, initial veterinary visits triggered further diagnostic testing after unexplained animal deaths were observed. Secondly, infections in mammals may occur during poultry outbreaks, and cats in particular can serve as indicators of substantial environmental virus circulation. The detection of HPAI A(H5N1) infection in several domestic cats on  the affected premises demonstrates the potential for cross-species transmission under outbreak conditions.

Such spillover events have increasingly been reported and point to an evolving host range of HPAI A(H5N1) viruses [3,4,14]. Serum samples, obtained from all surviving cats, were seropositive for H5-specific antibodies analysed by a commercial ELISA which suggests a close epidemiological link between poultry and feline infections, although the role of cat-to-cat transmission remains unclear.

In this investigation, evidence of predation or scavenging (e.g. poultry carcasses with bite marks) suggests that infection in cats may have occurred through direct contact with infected birds.

Finally, occupational exposure among first responders and veterinary personnel remains an important  pathway for potential zoonotic transmission [1,4,14].  Several individuals involved in the initial response had unprotected contact with animals before confirmation of the outbreak.

        (SNIP)

Conclusions
 
The detection of HPAI A(H5N1) in poultry and domestic cats in Sigmaringen district highlights ongoing zoonotic risks associated with HPAI outbreaks. Rapid interdisciplinary collaboration enabled early identification of the outbreak and implementation of targeted preventive measures.

Overall, this outbreak illustrates the importance of timely coordination between veterinary and public health authorities, early risk assessment of exposed individuals, and implementation of preventive measures within a One Health framework. Appropriate use of PPE, diagnostic testing, and prompt reporting of suspected cases are essential to prevent unprotected exposures and facilitate coordinated investigations. Continued vigilance and coordinated One Health surveillance remain essential to mitigate zoonotic transmission.

        (Continue . . . )

While much of the world's attention remains focused on the impact of HPAI on large commercial poultry farms - which are arguably better prepared to deal with HPAI outbreaks than small holders -  there are more than 11 million backyard poultry flocks in the United States, and tens of millions more in Europe and Asia.

The USDA has reported well over 200 backyard flocks infected since September of last year in the United States, and we've seen at least one death `linked to contact with backyard or wild birds'.

Last October, in UF/IFAS Extension: What Backyard Flock Owners Need to Know about Bird Flu (Influenza H5N1), we looked at two H5N1 related publications; one for backyard poultry owners, and another for consumers of poultry products and milk.

Finding ways to instill better biosecurity practices - and encourage personal protection (vaccination, PPEs, etc.) - before next fall's all-but-inevitable return of avian flu, could go a long way in reducing zoonotic risks.

Because as bad as HPAI has been up till now, it could become a lot worse in the future. 

Vaccines: A Historical Review About Immunity and Vaccines Against H2N2

 

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Although the exact subtypes that sparked influenza pandemics prior to 1918 remain a bit murky, the ECDC graphic (above) from 2015 suggests an H2N3 pandemic likely emerged in 1889, followed 11 years later by an H3 influenza.

The known history of influenza pandemics going back more than 125 years has been a repeating pattern of H1, H2, and H3 viruses (H2, H3, H1, H2, H3, H1 . . .) prompting the question: `Are Influenza Pandemic Viruses Members Of An Exclusive Club'.

Novel H1, H2, and H3 flu viruses appear to have fewer barriers to overcome in order to jump to humans - and while that doesn't preclude the breakthrough of an H5, H7, or H9 outlier - it suggests we should expect an H2 virus to eventually  return as a pandemic threat.

This is hardly a new idea. 

Fifteen years ago, after the furor over the 2009 H1N1 pandemic had finally died down, some researchers suggested it might make sense to add an H2N2 component to the seasonal vaccine to head off the `next' pandemic (see Nature: A Preemptive H2N2 Vaccine Strike?).

In 2012, in H2N2: What Went Around, Could Come Around Again, we looked at a study conducted by scientists working at St. Jude Children's Research Hospital - published in the Journal of Virology - that concluded that H2N2 could well pose a threat to humanity once again.

A press release on this research warned:

1950s pandemic influenza virus remains a health threat, particularly to those under 50

St. Jude Children's Research Hospital scientists report that avian H2N2 influenza A viruses related to 1957-1958 pandemic infect human cells and spread among ferrets; may aid identification of emerging threats.

And we revisited the topic in 2018, in J.I.D.: Population Serologic Immunity To H2N2 For Pandemic Risk Assessment, which warned: Population immunity to H2 viruses is insufficient to block epidemic spread of H2 virus. An H2N2 pandemic would have lower impact in those born before 1968.

While it doesn't get much press, avian H2N2 (and other H2 subtypes) continue to circulate in the wild. A few we've covered include: 

• In 2019 we looked at Viruses: Molecular Characterization of a Novel Avian Influenza A (H2N9) Strain Isolated from Wild Duck in Korea in 2018
• In 2017, in H2N2: Everything Old Is Flu Again, we saw a study published in The Journal Of Veterinary Medical Science, which detailed the finding of H2N2 in Siberian Muskrats. (see Genetic characterization of an H2N2 influenza virus isolated from a muskrat in Western Siberia).  
• In 2016's A Novel Reassortant H2N8 In China, described an H2N8 avian flu virus was isolated from a domestic duck in Zhejiang Province, Eastern China, in 2013.
• In 2006 and early 2007, a reassorted H2N3 subtype was detected in pigs on two different Missouri farms, which was the first known appearance of an H2 virus in a mammal since it was supplanted by the H3N2 virus in 1968 (see Recently Emerged Swine Influenza A Virus (H2N3) Causes Severe Pneumonia in Cynomolgus Macaques).

All of which brings us to an excellent review article, recently published in the journal Vaccine, which looks at the history of H2N2, and our waning population immunity to this influenza subtype.

Since this is a lengthy, and detailed, review I've simply reposted the link, abstract, and a brief excerpt.  Follow the link to read it in its entirety.  I'll have a brief postscript when you return.

Seven decades after the Asian influenza pandemic: A historical review about immunity and vaccines against H2N2
Alina Tscherne a, Florian Krammer 
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Abstract

In 1957, a reassortant influenza A virus (IAV) H2N2 subtype emerged in humans and encountered a population that was antigenically naïve to this subtype. The lack of pre-existing immunity to the H2 hemagglutinin (HA) facilitated efficient human-to-human transmission, and by the end of the Summer of 1957, most countries around the world reported increasing influenza cases caused by the new influenza virus subtype. The pandemic lasted until 1958, resulting in millions of infections globally, with 1–4 million estimated deaths.

The first vaccines targeting specifically the H2N2 subtype were available in autumn 1957, but their limited immunogenicity hampered a successful fight against the “Asian influenza pandemic”. After the pandemic, H2N2 became seasonal in the following years. Most individuals developed immunity against both the H2 HA and N2 neuraminidase (NA) proteins of the virus, and vaccines administered in the early 1960s successfully boosted this immunity. 

In 1968, the circulating H2N2 was replaced by the H3N2 subtype, and individuals with pre-existing N2 immunity were partially cross-protected against severe H3N2 infection, as the two N2 NAs were antigenically similar. Since the disappearance of H2N2 from the human population in 1968, global H2 immunity has been decreasing. 

This raises concerns about a possible re-emergence of the H2 subtype from animal reservoirs, where the virus has circulated for decades, into the human population. As preparedness for future pandemics, research on H2-specific vaccines is currently ongoing, with several candidates being tested in preclinical studies and early-phase clinical trials. In contrast to 1957, vaccine technology platforms, but also the assays used to assess vaccine immunogenicity, and efficacy, have significantly improved.

This review aims to summarize the key historical milestones of the Asian influenza pandemic, the impact of H2N2 immunity during and after the 1957 pandemic, the immunogenicity of H2N2-specific vaccines in both a pandemic and pre-pandemic situation, and H2N2-specific antiviral treatment.

        (SNIP)

       (SNIP)

It has been almost 70 years since the H2N2 pandemic and almost 60 years since the virus disappeared from the human population. The virus is still circulating in the avian reservoir, sometimes close to high-density urban areas like New York City, and the risk for another H2 pandemic has increased, as most of the population is now susceptible to H2.

Although vaccine technologies have improved, inducing strong immune responses to influenza viruses to which individuals are naïve remains challenging as seen with H5N1 and H7N9 vaccines. Furthermore, far less effort is being put into preparing for a potential H2 pandemic than into pandemic preparedness for H5N1. However, the H2N2 subtype has already demonstrated its ability to cause a pandemic, while H5N1 – despite very high prevalence in animals globally – has not yet resulted in a pandemic.

       (Continue . . . )

As the following graphic (from today's review) illustrates, H2N2 emerged after an avian virus (this time H2) reassorted with the existing H1N1 seasonal flu (in an unknown host), and produced a newer, more biologically `fit', virus.

This process was repeated again in 1968 after an avian H3 virus - somewhere in Asia - reassorted with H2N2, producing the H3N2 virus.   While I was only 3 for the H2N2 pandemic - and don't really remember it - I was in high school for H3N2. 

While there are other routes by which an influenza pandemic can emerge, this is the classic scenario, and one that can be repeated at any time with no warning. 

While it is always possible the next influenza pandemic will be an H1Nx, an H3Nx, or something more exotic (H5, H7, H9, etc.); waning population immunity makes an H2Nx virus increasingly likely.  

While we can't know what pathogen will spark the next flu pandemic - or when it will arrive - we can take steps to be better prepared to deal with it.

Assuming, of course, that we can be bothered. 

WHO Influenza at the human-animal interface (March 31st): 13 Novel Flu Infections Detailed

 

#19,132

While avian flu reports may seem to have slowed in the first quarter of 2026, we've a new report from the WHO that announces (for the first time I've seen) at least 4 previously undisclosed cases, including a fatal H5N1 case in Bangladesh. 

Today's Influenza at the Human-Animal Interference contains details on:

• 4 - A(H5N1) cases (3 Cambodia*, 1 Bangladesh)
• 5 - H9N2 Cases (4 China, 1 Italy)*
• 1 - H10N3 Case, China
• 1 - H1N1v Case, China
• 1 - H1N2v Case, China
• 1 - H3N2v Case, Brazil

* Note: We've seen another 4 H9N2 cases reported by China & 1 Cambodian H5N1 case since the Mar 31st cutoff

The first, and arguably most significant of these new cases is this previously unannounced case out of Bangladesh:

A(H5N1), Bangladesh

On 9 February 2026, the National International Health Regulations Focal Point of Bangladesh notified WHO of a laboratory-confirmed human case of avian influenza A(H5) infection in a child from Chattogram Division. The patient, with no known comorbidities, developed symptoms on 21 January 2026 and was admitted to hospital on 28 January. A nasopharyngeal swab was collected on 29 January as part of the Hospital-based Influenza Surveillance (HBIS) platform for influenza-like illness (ILI) and severe acute respiratory infection (SARI) sentinel surveillance in Bangladesh. The patient was referred to a specialized private hospital and admitted to intensive care on 31 January.The patient died on 1 February.

On 7 February, the Institute of Epidemiology, Disease Control and Research (IEDCR), serving as the National Influenza Centre (NIC), received and tested the sample, confirming influenza A(H5) by real-time reverse transcription polymerase chain reaction (RT-PCR) on the same day. Virus characterization and whole genome sequencing was conducted at International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), which confirmed that the A(H5N1) virus belongs to clade 2.3.2.1a of highly pathogenic avian influenza A(H5N1) virus (Gs/GD lineage), similar to the clade of viruses circulating in local poultry since around 2011. 

Genetic sequence data are available in GISAID (EPI_ISL_20367262; submission date 19 Feb 2026; Institute of Epidemiology,Disease Control & Research (IEDCR)).The case had exposure to household poultry, with two ducks and one chicken reportedly dying shortly before the case’s illness onset. Animal and environmental samples were collected and tested with RT-PCR and serology by the zoonotic investigation team of icddr,b. Two samples from ducks in the community and two samples from chicken meat in the freezer of household tested positive for influenza A(H5). Samples from symptomatic close human contacts tested negative for influenza.This is the first confirmed human case of avian influenza A(H5) reported in Bangladesh in 2026.

In 2025, four human cases of avian influenza A(H5) were reported.

This makes the 12th case reported by Bangladesh, and the first fatal outcome.  Today's report also cover the first three Cambodian cases of 2026, which we've previously  discussed (see here, here, and here).

Note: A 4th Cambodian case was announced in April

The report then describes 5 recent H9N2 cases; 4 in China and 1 in Italy (ex-Senegal). 

The two adult cases had underlying conditions. The first two cases had exposure to live bird markets.The last case had exposure to sick poultry. Samples from environments associated with the likely area of exposure of these cases tested positive for A(H9) viruses. The third case likely had exposure to contaminated environments or fomites. No further cases were detected among contacts of these cases.

A(H9N2), Italy, ex-Senegal 

On 21 March 2026, Italy notified WHO of the detection of A(H9N2) virus in an adult male. The case had travelled to Senegal for more than six months and returned to Italy in mid-March 2026. Upon arrival in Italy, the case sought medical care, presenting with fever and persistent cough that had been present since mid-January. Laboratory investigations conducted on a bronchoalveolar lavage specimen on 16 March showed a positive Mycobacterium tuberculosis result, as well as detection of an un-subtypeable influenza A virus. The case was admitted to an isolation room under airborne precautions in a negative-pressure room and received antitubercular and antiviral treatment. As of 24 March, the patient was clinically stable and improving. 

We also get the first details on the Cryptic Announcement of 1 New H10N3 infection last February. 

A(H10N3), China

On 9 February 2026, China notified WHO of one laboratory-confirmed case of human infection with an avian influenza A(H10N3) virus in a 34-year-old man from Guangdong province who developed symptoms on 29 December 2025. On 1 January 2026, he was admitted to hospital and diagnosed with severe pneumonia, severe acute respiratory distress syndrome (ARDS) and sepsis.

Oseltamivir treatment was initiated on 3 January. The patient's condition was stable at the time of reporting. On 12 January, the sample was sent to the provincial laboratory for testing. The result was positive forA(H10N3). On 14 January, the National Influenza Center confirmed the positive result.5 The patient works near two establishments that keep live poultry on the premises and chickens are present at the household.

Environmental samples collected from sites related to likely poultry exposure, including the patient's home, the workplace and a nearby poultry market tested negative for A(H10N3) influenza virus. No further cases were detected among contacts of these cases.A total of 98 close contacts of the patient were traced.Since 2021, a total of seven cases of human avian influenza A(H10N3) virus infection have been reported globally and all were from China

 Lastly, we get two brief descriptions of recent swine variant cases from China, and a more detailed (but belated) report from Brazil.

Swine influenza viruses in humans

Influenza A(H1N1)v, China

On 20 March 2026, China notified WHO of a laboratory-confirmed case of A(H1N1)v influenza virus infection in a child from Yunnan province. The patient had onset of illness on 30 January 2026, was hospitalized on 2 February with pneumonia, and recovered in a few days. The patient had reported exposure to domestic pigs prior to illness onset.

Influenza A(H1N2)v, China 

On 3 February 2026, China notified WHO of a laboratory-confirmed case of A(H1N2)v influenza virus infection in a child from Yunnan province. The patient had onset of mild illness on 20 January 2026, and the infection was laboratory-confirmed on 2 February 2026. The patient had reported exposure to domestic pigs prior to illness onset. This case and the one above are not epidemiologically linked.

 Influenza A(H3N2)v, Brazil

On 26 January 2026, Brazil notified WHO of a laboratory-confirmed case of A(H3N2)v influenza virus infection. On 1 September 2025, a male child residing in the state of Mato Grosso do Sul presented with ILI symptoms and was taken to a health unit on 2 September. The patient had no reported comorbidities or recent travel history and reported being vaccinated against seasonal influenza in the last campaign.

On 9 September, a respiratory sample was collected at the health unit, which is a sentinel unit for ILI. On 12 September, the Central Public Health Laboratory of Mato Grosso do Sul (Lacen/MS) reported that the RT-qPCR test for influenza A virus subtyping amplified the influenza A marker along with the H3 marker, indicating a swine-origin variant of the influenza H3 virus. The sample was sent to the National Influenza Center (NIC) of the Adolfo Lutz Institute, where the A(H3N2)v was confirmed by molecular tests and genomic sequencing. The sequences were entered into GISAID on 1 October. The sample was also shared with the WHO Collaborating Centre at the US Centers for Disease Control and Prevention (CDC), where it was genomically and antigenically characterized.

An epidemiological investigation was conducted, which identified the case as a student at an agricultural school where pigs and laying hens are raised, although the institution's coordinators reported that the students had not had direct contact with pigs recently. It was reported that the case had contact with classmates who presented ILI symptoms during this period. All household contacts were vaccinated against seasonal influenza in the 2025 season, except for the patient's mother. To date, no other human cases of infection with the A(H3N2)v virus have been detected in association with this case.

While avian flu currently has the bulk of our attention, swine variant influenza poses perhaps an even greater pandemic risk. The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).

H1N2 variant [A/California/62/2018] Jul 2019  5.8 5.7 Moderate
H3N2 variant [A/Ohio/13/2017]         Jul 2019  6.6 5.8 Moderate
H3N2 variant [A/Indiana/08/2011]     Dec 2012 6.0 4.5 Moderate

But there is much diversity among swine flu viruses around the globe, with China's EA H1N1 `G4' virus often cited as the biggest pandemic threat. We've also followed repeated spillovers in Brazil, and last year the Eurasian 1C Swine Influenza A Virus was labeled a `high pandemic risk'.

The reality is, surveillance and testing for swine influenza A viruses is notoriously sub-optimal, and many strains circulate under the radar.  

The fact that we are learning nearly 90 days after the fact about a fatal H5N1 case in Bangladesh, and more than 7 months after a novel H3N2 case in Brazil, reminds us that `no news' isn't necessarily `good news'. 

Mpox Clade Ib: 1st Local Transmission in Denmark & Wastewater Detection in Hawaii

 Data WHO SitRep # 64

#19,131

While Mpox is no longer classified as a PHEIC (Public Health Emergency of International Concern) by the WHO - the recently emerged clade Ib continues to make inroads around the globe - and we are watching for further signs of a recombinant strain which has turned up twice; in travelers to the UK and India.

Although it hasn't taken off  the way that clade II did in the spring of 2022, we continue to see scattered reports - such the following one from the San Francisco Health Department - from around the globe.

Health Alert: San Francisco Reports First Clade I Mpox Case 

April 16, 2026
Situational Update

On April 14, 2026, the first clade I mpox case in San Francisco (SF) was confirmed. The case occurred in an unvaccinated adult who was hospitalized and is improving. The individual reported close contact with someone who traveled internationally to an area where clade I mpox is circulating.

Clade I mpox is distinct from clade II mpox. The mpox outbreak in the United States that began in 2022 is due to clade II mpox and has led to 1066 cases in SF as of April 9, 2026. In contrast, an outbreak of clade I mpox in Central and Eastern Africa has been ongoing since 2023, with sporadic travel-associated cases reported in non-endemic countries and increasing reports of locally-acquired clade I mpox in Europe. Over the last two years, 15 clade I mpox cases have been reported in the United States, including 6 in California. Public health officials are monitoring cases to determine if clade I mpox is more severe than clade II mpox in the United States.

Yesterday, Denmark - which announced an imported case a week ago - announced the detection of 3 more cases, including 1 locally acquired infection.

First case of mpox variant infection in Denmark

Last week, the first case of the mpox variant clade 1b was detected in Denmark, and now three more cases have been confirmed. One of the cases was infected in this country, which is the first example of local transmission.

Last edited on April 27, 2026

Statens Serum Institut (SSI) can now confirm that a total of four cases of mpox clade 1b have been detected in Denmark. In one of these cases, the infection occurred here in the capital area, without prior travel abroad.

Preliminary analyses indicate that there are several independent cases of infection with a common geographical origin outside Denmark.

"It is not unexpected that we are now also seeing local infection in Denmark. Experience from other European countries shows that the infection can spread locally once the variant is introduced," says department head Uffe Vest Schneider from SSI and continues:

"At the same time, it is important to emphasize that the course of the disease has so far been mild, and that the overall risk in the population remains low."

Following the situation closely

In the past year, a number of European countries and countries outside Europe have reported cases of mpox clade 1b with local spread of infection.

Those infected in Denmark have so far had mild illness, and the health authorities continue to assess that there is no cause for concern among the population.

The Danish National Board of Health, the Danish Patient Safety Agency and the State Serum Institut are closely monitoring the situation and collaborating with clinical environments and relevant organizations to track down infection, limit further spread and inform relevant target groups.

At the same time, the importance of vaccination and contraception is emphasized in groups where there is an increased risk of infection.

Also yesterday, the State of Hawaii, Department of Health published the following report on the first detection of clade Ib in wastewater on the island of Oahu. 

MPOX DETECTED AT WASTEWATER SAMPLING SITE ON OʻAHU

Posted on Apr 27, 2026 in Newsroom

HONOLULU — The Hawai‘i Department of Health (DOH) is reporting a wastewater sample from O‘ahu that has tested positive for clade I mpox. The sample was collected on April 13, 2026, from a wastewater treatment facility on Joint Base Pearl Harbor Hickam (JBPHH). This is the first time clade I mpox has been detected in wastewater in Hawaiʻi. To date, no clinical case of clade I mpox has been identified in Hawai‘i.

At this time, the risk for the general public is low. The presence of clade I mpox virus in wastewater does not confirm a clinical case or community spread. Instead, it serves as an indicator to be alert for possible mpox cases. People at higher risk of mpox infection should consider being vaccinated with two doses of the JYNNEOS (mpox) vaccine if not already protected.

The JBPHH facility serves not only on-base military housing and facilities, but public sites that receive large numbers of residents and visitors, including the Pearl Harbor National Memorial Museum.

DOH was notified of the initial detection on April 20, 2026, with positive confirmatory results received on April 24, 2026. Subclade analysis was undetermined due to sample degradation. A subsequent sample, collected on April 20 from the same wastewater facility, has tested negative for mpox. Major civilian wastewater facilities on O‘ahu are routinely tested for clade I mpox, and all samples have tested negative as of April 22, 2026.

Clades are genetically distinct groups, or lineages, of a virus that develop as it evolves over time. There are two types of the virus that causes mpox, clade I and clade II. Both types spread the same way and can be prevented using the same methods. A clade II mpox outbreak in the United States that began in 2022 has led to 65 cases in Hawaiʻi as of April 20, 2026. There has been an ongoing outbreak of clade I mpox since 2023 in Central and Eastern Africa, with recent community transmission in Western Europe. To date, clade I cases in the continental U.S. have been among people who had recently traveled to countries with ongoing outbreaks. So far, there has not been sustained transmission of clade I mpox reported in the U.S. Public health officials are monitoring cases to determine if clade I mpox is more severe than clade II mpox in the U.S.

DOH encourages anyone who has recently traveled to an area with active transmission, or who has been in close contact with a symptomatic individual, to monitor their health and consult with a healthcare provider regarding potential risks. People with mpox often get a rash and may have other symptoms like fever, chills and swollen lymph nodes. The rash, which typically begins as bumps and progresses to blisters and pustules, may be located on the hands, feet, chest, face, or mouth, or near the genitals. If you develop symptoms or believe you are at high risk, contact your healthcare provider to discuss testing and vaccination.

(Continue . . . )

Since the eradication of smallpox in the 1970s, there has been a growing belief that poxviruses are a thing of the past; a near-forgotten relic of the 20th century.

But a 2020 report in the Bulletin of the World Health Organization warned that our waning immunity to smallpox puts society at increasing risk of seeing new poxvirus epidemics (see WHO: Modelling Human-to-Human Transmission of Monkeypox).

The emergence and international spread of 2 new Mpox clades (Ib & IIb) since 2020 - and a new recombinant recently reported in Asia - would seem to reinforce that warning.

Some recent blogs on Mpox research include:

Eurosurveillance: Waning Humoral Immunity Following Monkeypox Virus Infection and Vaccination, Canada, 2020 to 2023

The UK Recombinant Mpox Case: Reactions from the UK Science Media Centre

WHO DON: Broader Transmission of Mpox Due to clade Ib MPXV – Global situation

Preprint: A three-dose MVA-BN Mpox Vaccination Series Improves the Quality of Anti-monkeypox Virus Immunity