3rd #meeting of #IHR (2005) Emergency #Committee regarding upsurge of #mpox 2024 – Temporary #recommendations

{Excerpts}

The Director-General of the World Health Organization (WHO), following the third meeting of the International Health Regulations (2005) (IHR) Emergency Committee regarding the upsurge of mpox 2024, held on 25 February 2025, from 12:00 to 17:00 CET, concurs with its advice that the event continues to meet the criteria of a public health emergency of international concern and, considering the advice of the Committee, he is hereby issuing a revised set of temporary recommendations.

The WHO Director-General expresses his most sincere gratitude to the Chair, Members, and Advisors of the Committee. The proceeding of the third meeting of the Committee will be shared with States Parties to the IHR and published in the coming days.

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Temporary recommendations

These temporary recommendations are issued to States Parties experiencing the transmission of monkeypox virus (MPXV), including, but not limited to, those where there is sustained community transmission, and where there are clusters of cases or sporadic travel-related cases of MPXV clade Ib.

They are intended to be implemented by those States Parties in addition to the current  standing recommendations for mpox, which will be extended until 20 August 2025. 

In the context of the global efforts to prevent and control the spread of mpox disease outlined in the  WHO Strategic framework for enhancing prevention and control of mpox- 2024-2027, the aforementioned  standing recommendations apply to all States Parties. 

All current WHO interim technical guidance can be accessed on this page of the WHO website. WHO evidence-based guidance has been and will continue to be updated in line with the evolving situation, updated scientific evidence, and WHO risk assessment to support States Parties in the implementation of the WHO Strategic Framework for enhancing mpox prevention and control. 

Pursuant to Article 3 Principle of the International Health Regulations (2005) (IHR), the implementation of these temporary recommendations, as well as of the standing recommendations for mpox, by States Parties shall be with full respect for the dignity, human rights and fundamental freedoms of persons, in line with the principles set out in Article 3 of the IHR. 

(...)

Source: World Health Organization, https://www.who.int/news/item/27-02-2025-third-meeting-of-the-international-health-regulations-2005-emmergency-committee-regarding-the-upsurge-of-mpox-2024-temporary-recommendations

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Quantitative #risk #assessment of #human #H5N1 #infection from #consumption of fluid #cow's #milk

Abstract

The spillover of highly pathogenic avian influenza H5N1 into dairy cattle has raised concerns over the safety of fluid milk. While no human foodborne infection has been reported, this strain has infected dozens of people and milk from infected cows is known to be infectious by ingestion in multiple other species. Investigation into the public health threat of this outbreak is critical. This study uses quantitative risk assessment (QRA) models to represent the United States raw and pasteurized fluid milk supply chains to estimate the risk of human infection from consumption of fluid cow's milk. These models were parameterized with literature emerging from this outbreak, then employed to estimate the H5N1 infection risk and evaluate multiple potential interventions aimed at reducing this risk. The median (5th, 95th percentiles) probabilities of infection per 240-mL serving of pasteurized, farmstore-purchased raw, or retail-purchased raw milk were 5.68E-15 (1.77E-16, 2.98E-13), 1.13E-03 (5.16E-06, 3.82E-02), and 1.02E-03 (5.20E-06, 3.64E-02), respectively. Our results demonstrate that pasteurization is highly effective at reducing H5N1 infection risk. Scenario analysis revealed quantitative real-time reverse transcriptase-polymerase chain reaction (qrRT-PCR) testing of bulk tank milk to be an effective method for reducing risk from raw milk. Additionally, we identify knowledge gaps related to human H5N1 dose-response by ingestion and raw milk consumption patterns. These findings emphasize the importance of pasteurization in protecting public health and will inform the implementation of control strategies to reduce the risk of human H5N1 infection from raw milk.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.12.20.24319470v2

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Immunogenicity and protective #efficacy of an #intranasal NA-based #influenza virus #vaccine adjuvanted ...

Abstract

Influenza virus neuraminidase (NA) has emerged as a promising vaccine candidate due to its relatively stable antigenic structure and the ability of NA-specific antibodies to provide cross-protection within influenza virus subtypes. Since the influenza virus causes respiratory infections in humans, developing mucosal vaccines to protect the entry site of the virus is of high importance. Recombinant NA requires adjuvants to induce a protective immune response after mucosal administration. In the current study, we analyze the immunogenicity and protective efficacy of a recombinant NA-based influenza virus vaccine administered intranasally in combination with adjuvants consisting of outer membrane proteins from Neisseria meningitidis complexed with exogenous lipopolysaccharides (LPS) from Shigella flexneri or endogenous LPS from N. meningitidis. We evaluated the local and systemic humoral and cellular immune responses to adjuvanted recombinant N1 NA, analyzing the dynamics of local follicular T-helper (Tfh) cells and germinal center B cells (GCB) in nasal-associated lymphoid tissue (NALT) and tissue-resident memory T cells in lungs, as well as the levels of IgA and IgG in the upper and lower respiratory tracts. Finally, we performed a heterologous challenge study to test the ability of the investigated vaccine formulations to induce cross-protection. The study demonstrates that bacterial cell membrane-derived adjuvants significantly improve the immunogenicity and protective efficacy of the recombinant N1 NA-based influenza vaccine leading to protection against clade 2.3.4.4b H5N1 challenge. This finding supports the potential of these adjuvanted vaccines in providing effective mucosal immunity against influenza virus.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.26.640278v1

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#USA, #Influenza A #H5N1 in #Humans: #Epidemiology & #Laboratory #Update {as of Feb. 26 '25}

{Excerpts}

(...)

Epidemiology Updates

As of February 24, CDC has confirmed three human cases of H5 bird flu in people who became ill in 2025: 

-- a dairy worker with exposure to infected dairy cows (Nevada), 

-- a poultry worker with exposure to infected commercial poultry (Ohio), and 

-- the owner of an infected backyard poultry flock (Wyoming). 

These are all considered higher-risk exposures. While the dairy worker was not hospitalized, both people with poultry exposures experienced severe illness and were hospitalized. Both hospitalized cases were confirmed positive from lower respiratory specimens, including a bronchoalveolar lavage and sputum. To date, there has been no evidence of onward spread from any of these people to anyone else.

The dairy worker in Nevada had conjunctivitis (eye redness and irritation) and has recovered. Most infections associated with U.S. dairy cows to date have involved mild respiratory symptoms or conjunctivitis. This person was exposed to infected dairy cows and tested positive for avian influenza A(H5N1) virus.

The poultry worker in Ohio had respiratory symptoms and is home and recovering. This person participated in culling activities on a farm with infected poultry. The initial upper respiratory specimens could not be confirmed as positive for avian influenza A(H5) virus at CDC, so CDC initially reported this as a probable case; a subsequent specimen from the person was confirmed positive for avian influenza A(H5) virus at CDC.

The backyard flock owner in Wyoming had respiratory symptoms and is reported to have underlying health conditions that can make people more vulnerable to severe influenza illness. This person has been discharged from the hospital and is recovering. This person had direct contact with poultry infected with avian influenza A(H5) virus that died on their property. Initial upper respiratory specimens were negative for influenza viruses; a lower respiratory specimen collected several days later in the hospital was positive for avian influenza A(H5N1) virus.

Laboratory Updates

CDC has successfully sequenced the viruses from the Nevada and Wyoming cases. Genetic data have been posted in GISAID (Wyoming: EPI_ISL_19749443, Nevada: EPI_ISL_19726293) and GenBank. Sequencing data are not yet available for the Ohio case.

CDC's analysis of the genetic sequence of the virus isolated from the patient in Nevada identified the virus as an avian influenza A(H5N1) virus from clade 2.3.4.4.b (genotype D1.1). The nucleotide sequence was nearly identical to that of the viruses that USDA reported from dairy cows in Nevada that the person worked with. The virus had a genetic mutation in its polymerase basic 2 (PB2) protein that has previously been associated with more efficient virus replication in mammalian cells (i.e., change of PB2 D701N). This change was previously identified in a human case in Chile in 2023. No other changes associated with mammalian adaption were identified in the sequence data. CDC also did not identify any changes that might impact effectiveness of influenza antiviral medications or existing clade 2.3.4.4b H5 candidate vaccine viruses.

CDC's analysis of the genetic sequence of the virus from the patient in Wyoming identified an avian influenza A(H5N1) virus from clade 2.3.4.4.b (genotype D1.1). The virus had a genetic mutation in its PB2 protein that has previously been associated with more efficient virus replication in people and other mammals (i.e., change of PB2 E627K). This change was previously identified in a human case in Texas during 2024. No other changes associated with mammalian adaption were identified in the sequence data. CDC also did not identify any changes in the sequence data that might impact effectiveness of influenza antiviral medications or existing H5 candidate vaccine viruses. Virus was isolated from the case and will undergo further testing and analysis.

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Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/spotlights/h5n1-response-02262025.html

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Clade 2.3.4.4b #H5N1 #neuraminidase has a long #stalk, which is in contrast to most highly pathogenic H5N1 viruses circulating between 2002 and 2020

ABSTRACT

Since 2020, H5N1 highly pathogenic avian influenza (HPAI) viruses of clade 2.3.4.4b have been rapidly spreading in wild birds but have also caused a large number of mammalian infections and more than 70 known human cases. Importantly, this H5N1 clade has also crossed the species barrier into dairy cattle in the US in late 2023/early 2024. The neuraminidase (NA) protein of the N1 subtype can feature truncations in its stalk domain, which have been identified as putative virulence factors in poultry but seem to have a negative impact on transmission in mammals. Since its emergence, the vast majority of HPAI H5N1 A/goose/Guangdong/1/1996-lineage isolates have featured this truncated version of the NA stalk domain. Here, we report that this changed with the 2020 expansion of clade 2.3.4.4b H5N1 and that the majority of isolates—including the strains circulating in dairy cattle—feature a long NA stalk domain.

Source: mBio, https://journals.asm.org/doi/10.1128/mbio.03989-24

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#Host #cell entry and #neutralisation sensitivity of the emerging #SARS-CoV-2 #variant #LP.8.1

{Excerpt}

Novel SARS-CoV-2 variants continue to emerge, driving waves of COVID-19. The evolution of SARS-CoV-2 took a surprising turn in 2023 with the emergence of BA.2.86, a BA.2-descendant harbouring multiple spike (S) protein mutations, enhancing antibody evasion. Subsequently, several BA.2.86-derived lineages emerged, with JN.1 dominating early and the JN.1-derived variants KP.3.1.1 and XEC dominating late in 2024. Currently, LP.8.1 is on the verge of becoming dominant. This study provides a preliminary virological characterisation of LP.8.1 and its sublineage LP.8.1.1.

(...)

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00113-6/fulltext?rss=yes

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#USA, #Texas announces first #death in #measles #outbreak

The Texas Department of State Health Services is reporting the first death from measles in the ongoing outbreak in the South Plains and Panhandle regions. 

The school-aged child who was not vaccinated was hospitalized in Lubbock last week and tested positive for measles.

As of Feb. 25, 124 cases of measles have been confirmed in the outbreak since late January. Most of the cases are in children. Eighteen people have been hospitalized over the course of the outbreak.

Measles is a highly contagious respiratory illness, which can cause life-threatening illness to anyone who is not protected against the virus. During a measles outbreak, about one in five people who get sick will need hospital care and one in 20 will develop pneumonia. Rarely, measles can lead to swelling of the brain and death. It can also cause pregnancy complications, such as premature birth and babies with low birth weight.

Measles can be transmitted by direct contact with infectious droplets or by airborne spread when an infected person breathes, coughs, or sneezes. People who are infected will begin to have symptoms within a week or two after being exposed. Early symptoms include high fever, cough, runny nose, and red, watery eyes. A few days later, the telltale rash breaks out as flat, red spots on the face and then spreads down the neck and trunk to the rest of the body. A person is contagious about four days before the rash appears to four days after. People who could have measles should stay home during that period.

People who think they have measles or may have been exposed to measles should isolate themselves and call their health care provider before arriving to be tested. It is important to let the provider know that the patient may have measles and to get instructions on how to come to the office for diagnosis without exposing other people to the virus.

The best way to prevent getting sick is to be immunized with two doses of a measles-containing vaccine, which is primarily administered as the combination measles-mumps-rubella or MMR vaccine. Two doses of the MMR vaccine prevent more than 97 percent of measles infections. A small number of vaccinated people can occasionally develop measles. In these cases, the symptoms are generally milder, and they are less likely to spread the disease to other people. DSHS and the Centers for Disease Control and Prevention recommend children receive one dose of MMR at 12 to 15 months of age and another at 4 to 6 years. Children too young to be vaccinated are more likely to have severe complications if they get infected with the measles virus. However, each MMR dose lowers the risk of infection and the severity of illness if infected.

Health care providers can find recommendations for infection control and diagnostic testing in DSHS health alerts. Providers should report any suspected cases to their local health department immediately, preferably while the patient is still with the provider.

DSHS posts additional information about the outbreak cases on the News & Alerts page on Tuesdays and Fridays.

Source: Department of Health, https://www.dshs.texas.gov/news-alerts/texas-announces-first-death-measles-outbreak

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#Italy - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Follow up report 17

{Excerpt, Feb. 26 2025 Update}

1) HPAI H5N1 was detected in a Yellow-legged Gull (Larus michahellis) found dead in the Municipality of Rimini, province of Rimini, Emilia Romagna region.

2) HPAI H5N1 was detected in an Eurasian buzzard (common buzzard) (Buteo buteo) found dead in the Municipality of Pramaggiore, province of Venezia, Veneto region

3) HPAI H5N1 was detected in a Eurasian buzzard (common buzzard) (Buteo buteo) found dead in the Municipality of Galzignano Terme, province of Padova, Veneto region

4) HPAI H5N1 was detected in a yellow-legged gull (Larus michahellis) found dead in the Municipality of Padova, province of Padova, Veneto region.

5) HPAI H5N1 was detected in a yellow-legged gull (Larus michahellis) found dead in the Municipality of Stanghella, province of Padova, Veneto region.

6) HPAI H5N1 was detected in a Yellow-legged Gull (Larus michahellis) found dead in the Municipality of Porto Recanati, province of Macerata, Marche region. "The Database of Global Administrative Boundaries (GADM) used by WAHIS, provides Loreto as the municipality corresponding to the given coordinates. As a matter of fact the location of the infected premises is the municipality of Porto Recanati."

7) HPAI H5N1 was detected in a black-headed gull (Chroicocephalus ridibundus) found dead in the Municipality of Ortona dei Marsi, province of L'Aquila, Abruzzo region

8) HPAI H5N1 was detected in a common shelduck (Tadorna tadorna) found dead in the municipality of Marano Ligure, province of Udine, Friuli-Venezia Giulia region. Note on 30/01/2025: The start date of the outbreak was changed from 30/11/2024 to 24/12/2024 after more precise information was received by the country.

9) HPAI H5N1 was detected in a common buzzard (Buteo buteo) found dead in the Municipality of Lignano Sabbiadoro, province of Udine, Friuli-Venezia Giulia region

10) HPAI H5N1 was detected in a gadwall (Anas strepera) found dead in the Municipality of Lignano Sabbiadoro, province of Uadova, Friuli Venezia Giulia region.

11) HPAI H5N1 was detected in a little egret (Egretta garzetta) found dead in the Municipality of Lignano Sabbiadoro, province of Udine, Friuli-Venezia Giulia region

12) HPAI H5N1 was detected in a common kingfisher (Alcedo atthis) found dead in the municipality of Trebaseleghe, province of Padova, Veneto region.

13) HPAI H5N1 was detected in a Yellow-legged Gull (Larus michahellis) found dead in the Municipality of Venezia, province of Venezia, Veneto region.

14) HPAI H5N1 was detected in a grey heron (Ardea cinerea) found dead in the Municipality of Villa del Conte, province of Padova, Veneto region

15) HPAI H5N1 was detected in an African sacred ibis (Threskiornis aethiopicus) found dead in the Municipality of San Martino Buon Albergo, province of Verona, Veneto region

16) HPAI H5N1 was detected in an African sacred ibis (Threskiornis aethiopicus) found dead in the Municipality of San Martino Buon Albergo, province of Verona, Veneto region

17) HPAI H5N1 was detected in a yellow-legged gull (Larus michahellis) found dead in the Municipality of Fontevivo, province of Parma, Emilia Romagna region.

(...)

Source: WOAH, https://wahis.woah.org/#/in-event/5912/dashboard

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Mass #mortality #events in the sub- #Antarctic #Indian #Ocean caused by long-distance circumpolar spread of highly pathogenic avian #influenza #H5N1 clade 2.3.4.4b

Abstract

Since 2020, the outbreak of highly pathogenic avian influenza (HPAI) virus clade 2.3.4.4b has turned into the largest documented panzootic to date, reaching the sub-Antarctic region and Antarctica via the tip of South America in 2023. Here, we describe its recent arrival into the Indian Ocean sub-Antarctic archipelagos of Crozet and Kerguelen, where we first detected the virus in October 2024 in dead southern elephant seals, king penguins, gentoo penguins, brown skuas and kelp gulls. While the panzootic is ongoing, it has already caused unprecedented and alarming mortalities of southern elephant seals. We collected brain swabs from various seal and bird carcasses, subsequently isolated the virus and obtained 25 novel HPAI H5N1 clade 2.3.4.4b sequences. Our phylogenetic and phylogeographic analyses show that there have been independent introductions of the virus to Crozet and Kerguelen, from the distant South Georgia Islands in the Southern Atlantic, and not from the more nearby coasts of South Africa. Our results point to a year-long gap in genomic surveillance in the south polar region, obscuring how HPAI H5N1 clade 2.3.4.4b is spreading in the sub-Antarctic and illustrating the difficulties in tracking pathogen dispersal in the region. Locally, our phylogenetic analyses show that the virus is transmitted between different species. Moreover, our serological analyses show that some southern elephant seal pups had mounted an anti-H5 antibody response. With the spread to Crozet and Kerguelen, HPAI H5N1 2.3.4.4b is moving ever closer to Australia and New Zealand, which currently remain free from infections with this strain, and represents a major threat to the sub-Antarctic wildlife. Our results provide key elements to enable stakeholders to anticipate the arrival and spread of the virus in remote areas of critical wildlife conservation concerns.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.25.640068v1

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#Cambodia confirmed a #fatal pediatric case of #H5N1 avian #influenza virus infection

{Original text in Khmer}

Ministry of Health Press Release

A Fatal Case of #H5N1 #influenza in a 2-Year-7-Month-Old Child

The Ministry of Health of the Kingdom of Cambodia wishes to inform the public that there are a case of bird flu in a 2-year-old 7-month-old child has been confirmed positive for the influenza virus H5N1 by the National Institute of Public Health on February 25, 2025.

Location: Tangak Village, Romchek Commune, Preah Sdach District, Prey Veng Province.

According to doctors, the child died on February 25, 2025 due to the parents took the child to the hospital, when him developed a serious condition, including fever, cough, fatigue, and difficulty retreating.

Severe breathing. According to the investigation, the patient's house has a family chicken farm and there are dead chickens. 

About 15 of them were sick and the children were sleeping and playing in the basement near the chicken coop.

The national and subnational emergency response teams of the Ministry of Health cooperated. With the working group of the provincial Department of Agriculture and local authorities at all levels are actively conducting research continue to try to respond to the emergence of avian influenza with technical methods and protocols.

-- Find sources of transmission in both animals and humans and continue to search for suspected cases and victims to prevent transmission

-- Distribute Tamiflu to others in the community and establish close contact.

-- Health education campaign for the people of the village where the incident occurred.

The Ministry of Health once again reminds all citizens to be careful 

-- Beware of bird flu as H5N1 bird flu continues to threaten

-- Health of our people and also ask you to inform yourself if you have fever, cough, runny nose or

-- Difficulty breathing and history of contact with sick or dead chickens during the 14 days prior to the onset date

-- Do not go to crowded or crowded cities and seek advice and counseling.

-- Get medical checkups immediately at a nearby health center or hospital to avoid procrastination.

-- High risk of eventual death.

Transmission: H5N1 bird flu is a common flu that is usually transmitted between sick birds to other birds, but can sometimes be transmitted from birds to humans through close contact with sick or dead birds.

Bird flu in humans is a serious disease that requires timely hospitalization.

Although it is not easily spread from person to person, if it manages to metabolize it, it can be as contagious as the seasonal flu.

How to prevent:

-- Do not touch or eat sick or dead chickens and wear gloves and a mask or cover your nose with a scarf beforehand

-- Grab the chicken and cook it in boiling water before plucking it.

-- Stick to the practice of washing your hands often before handling food.

-- Especially after contact ..., poultry or other objects that can be a source of infection.

-- Cook thoroughly before eating, especially poultry and eggs. Do not eat eggs Or egg yolks and keep raw and cooked foods separate, clean utensils for proper cooking.

-- If there are many sick or dead chickens in the house or village and they have fever, cough, runny nose or

-- Shortness of breath, hurry to seek advice and treatment at the health center or nearby hospitals avoid delays immediately, exposing them to greater risk

Therefore, the public should be aware and take care of their health with the above preventive methods. Health will continue to publish information related to public health issues on the official social media of the Ministry of Health, as well as the official Facebook page of the Department of Infectious Diseases and the website www.cdcmoh.gov.kh.

For more information, you can call the toll-free number 115 of the Ministry of Health Free of charge. 

Tuesday 13 Roch Khemak, Rong Chhasak, BE 2561 - Royal Decree, February 25, 2025, Kingdom of Cambodia - Ministry of Health

Source: Ministry of Health of the Kingdom of Cambodia, https://moh.gov.kh/kh/notice/detail/58

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Structural basis of #receptor-binding #adaptation of #human-infecting #H3N8 #influenza A virus

ABSTRACT

Recent avian-origin H3N8 influenza A virus (IAV) that have infected humans pose a potential public health concern. Alterations in the viral surface glycoprotein, hemagglutinin (HA), are typically required for IAVs to cross the species barrier for adaptation to a new host, but whether H3N8 has adapted to infect humans remains elusive. The observation of a degenerative codon in position 228 of HA in human H3N8 A/Henan/4-10/2022 protein sequence, which could be residue G or S, suggests a dynamic viral adaptation for human infection. Previously, we found this human-isolated virus has shown the ability to transmit between ferrets via respiratory droplets, with the HA-G228S substitution mutation emerging as a critical determinant for the airborne transmission of the virus in ferrets. Here, we investigated the receptor-binding properties of these two H3N8 HAs. Our results showed H3N8 HAs have dual receptor-binding properties with a preference for avian receptor binding, and G228S slightly increased binding to human receptors. Cryo-electron microscopy structures of the two H3N8 HAs with avian and human receptor analogs revealed the basis for dual receptor binding. Mutagenesis studies reveal that the Q226L mutation shifts H3N8 HA’s receptor preference from avian to human, while the G228S substitution enhances binding to both receptor types. H3N8 exhibits distinct antigenic sites compared to H3N2, prompting concerns regarding vaccine efficacy. These findings suggest that the current H3N8 human isolates are yet to adapt for efficient human-to-human transmission and further continuous surveillance should be implemented.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01065-24?af=R

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#Dynamics of a #Panzootic: Genomic #Insights, #Host Range, and #Epidemiology of the Highly Pathogenic Avian #Influenza A(#H5N1) Clade 2.3.4.4b in #USA

Abstract

In late 2021, Eurasian-lineage highly pathogenic avian influenza (HPAI) A(H5N1) viruses from HA clade 2.3.4.4b were first detected in the United States. These viruses have caused severe morbidity and mortality in poultry and have been detected in numerous wild and domestic animals, including cows and humans. Notably, infected cows transmitted the virus to cats, causing extreme pathogenicity and death. While human-to-human spread of the virus has not been recorded, efficient transmission of the bovine-origin virus has also led to extreme pathogenicity and death in ferret models. Recently, markers in PB2 (E627K) and HA (E186D, Q222H), indicating mammalian adaptation mutations, were detected in an H5N1-infected patient manifesting critical illness in Canada. These, combined with instances of interspecies spread of the virus, have raised global public health concerns. This could highlight the potential for the virus to successfully adapt to mammals, posing a serious risk of a global outbreak. A One Health approach is, thereby, necessary to monitor and control the outbreak. This review aims to analyze the epidemiology, transmission, and ecological impacts of HPAI A(H5N1) clade 2.3.4.4b in the U.S., identify knowledge gaps, and inform strategies for effective outbreak management and mitigation.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/312

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#Efficacy and #safety of #sipavibart for #prevention of #COVID19 in individuals who are immunocompromised (SUPERNOVA)...

Summary

Background

Sipavibart is an anti-spike monoclonal antibody that neutralises SARS-CoV-2 with exceptions, including Phe456Leu-containing variants (eg, KP.2* and KP.3*). This trial assessed sipavibart efficacy and safety for prevention of symptomatic COVID-19 in participants who are immunocompromised.

Methods

In this ongoing, double-blind, international, phase 3 trial, we enrolled participants who were immunocompromised and aged 12 years or older at 197 hospitals, university health centres, and clinical trial units in 18 countries. Participants were randomly allocated 1:1 to a sipavibart group (intramuscular sipavibart 300 mg on days 1 and 181) or a comparator group (tixagevimab 300 mg–cilgavimab 300 mg on day 1 and placebo on day 181 or placebo on days 1 and 181), stratified by previous COVID-19 vaccination and infection status and use of tixagevimab–cilgavimab. The primary efficacy outcomes were symptomatic COVID-19 caused by any variant or symptomatic COVID-19 caused by non-Phe456Leu-containing variants within 181 days of dosing, assessed in the SARS-CoV-2-negative set, comprising all participants without a positive RT-PCR test for SARS-CoV-2 at baseline and who received at least one trial intervention dose. Safety outcomes for adverse events were assessed 90 days following the first dose and for serious adverse events throughout the study in the safety analysis set (ie, all participants who received at least one injection of sipavibart or comparator). This study is registered with ClinicalTrials.gov, NCT05648110.

Findings

Participants were screened from March 31 to Oct 27, 2023; 3349 participants (56·8% female) were randomly assigned: 1674 to the sipavibart group (five no first dose; 1669 sipavibart) and 1675 to the comparator group (nine no first dose; 1105 tixagevimab–cilgavimab and 561 placebo). Within 181 days of dosing, 122 (7·4%) of 1649 participants in the sipavibart group and 178 (10·9%) of 1631 participants in the comparator group had symptomatic COVID-19 due to any variant (relative risk reduction [RRR] 34·9% [97·5% CI 15·0 to 50·1]; p=0·0006), 54 (3·3%) participants in the sipavibart group and 90 (5·5%) participants in the comparator group had symptomatic COVID-19 due to non-Phe456Leu-containing variants (RRR 42·9% [95% CI 19·9 to 59·3]; p=0·0012), and 47 (2·9%) participants in the sipavibart group and 64 (3·9%) participants in the comparator group had symptomatic COVID-19 due to Phe456Leu-containing variants (30·4% [–1·8 to 52·5]). Adverse events occurred in 833 (49·9%) of 1671 participants in the sipavibart group and 857 (51·5%) of 1663 participants in the comparator group within 3 months of the first dose. One COVID-19-related death occurred in the comparator group. Serious adverse events considered related to trial intervention occurred in two (0·1%) of 1671 participants in the sipavibart group and seven (0·4%) of 1663 participants in the comparator group (none fatal). No serious cardiovascular or thrombotic events were considered to be related to sipavibart.

Interpretation

The primary analysis showed efficacy and safety of sipavibart in preventing symptomatic COVID-19 in participants who are immunocompromised when susceptible (ie, non-Phe456Leu-containing) variants dominated, although no efficacy was shown against resistant (ie, Phe456Leu-containing) variants that dominate as of November, 2024.

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00804-1/fulltext?rss=yes

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#Exposure and #survival of wild #raptors during the 2022–2023 highly pathogenic #influenza a virus #outbreak

Abstract

The global outbreak of clade 2.3.4.4b H5N1 highly pathogenic influenza A virus (HP H5N1) has had an unprecedented impact on wild birds including raptors, but long-term population impacts have not been addressed. To determine if raptors survive infections with HP H5N1, raptors from the upper Midwest United States were serologically tested for antibodies to influenza A virus (IAV), H5 and N1. Raptors were sampled at The Raptor Center’s (University of Minnesota) wildlife rehabilitation hospital and at Hawk Ridge Bird Observatory. Samples were tested for IAV antibodies using a commercially available blocking ELISA, with positive samples tested for antibodies to H5 and N1. Antibodies to IAV were detected in 86 out of 316 individuals representing 7 species. Antibodies to H5 and N1 were detected in 60 individuals representing 6 species. Bald eagles had the highest seroprevalence with 67/97 (69.1%) seropositive for IAV and 52 of these 67 (77.6%) testing positive for antibodies to both H5 and N1. Prevalence of antibodies to IAV observed in this study was higher than reported from raptors sampled in this same region in 2012. The high prevalence of antibodies to H5 and N1 indicates a higher survival rate post-HP H5N1 infection in raptors than previously believed.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-90806-6

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#Monkeypox Virus Occurrence in #Wastewater #Environment and Its Correlation with Incidence Cases of #Mpox: A Systematic Review and Meta-Analytic Study

Abstract

The COVID-19 pandemic has increased the interest in the use of wastewater-based surveillance (WBS) strategy for infectious disease monitoring, especially when clinical cases are underreported. The excretion of monkey virus (MPXV) in the feces of both symptomatic and preclinical individuals has further driven the interest in WBS applicability to MPXV monitoring in wastewater to support its mitigation efforts. We performed a systematic review with meta-analysis, using six databases to assess MPXV detection in wastewater. We performed a random-effects model meta-analysis to calculate the pooled prevalence at a 95% confidence interval (95% CI). Also, we carried out a subgroup analysis according to the country regions and a sensitivity analysis excluding studies classified as having a high risk of bias. The overall MPXV positivity rate in wastewater was estimated at 22% (95% CI: 14−30%; I2 = 94.8%), with more detection rate in North America (26%, 95% CI: 8–43%) compared to Europe and Asia (22%, 95% CI: 12–31%). The MPXV detection rate was significantly higher in 2022 studies (22%, 95% CI: 13–31%) compared to 2023 (19%, 95% CI: 14–25%). The real-time PCR platform significantly detected more MPXV (24%, 95% CI: 14–34%) than the digital droplet PCR-based studies (17%, 95% CI: 4–31%), which was used less frequently. Viral concentration with centrifugation procedure indicated higher detection rates (21%, 95% CI: 10–33%) than other known sample concentration protocols. Generally, MPXV detection rates in wastewater samples strongly correlate with incidence cases of mpox (range of R = 0.78–0.94; p < 0.05). Findings from this study suggest that WBS of MPXV could be employed as an epidemiological early warning tool for disease monitoring and mpox outbreak prediction similar to the clinical case-based surveillance strategies.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/308

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The #Impact of Highly Pathogenic Avian #Influenza #H5N1 in the #USA: A Scoping #Review of Past #Detections and Present #Outbreaks

Abstract

Highly Pathogenic Avian Influenza H5N1 (HPAI H5N1) was first detected in chickens in Scottland in 1959 and has since circulated globally, causing regular outbreaks among different animal species, as well as incidental infections in humans. In this scoping review, the epidemiology and impact of HPAI H5N1 among migratory birds, poultry, and cattle in the United States were analyzed, with a particular focus on outbreaks since January 2022. Following PRISMA guidelines, a total of 27 articles were identified for this review. Publicly available data and reports from the USDA and CDC were also evaluated and summarized. The identified articles primarily included epidemiological studies of detections in wild birds, mammals, and case reports on H5N1 and transmission dynamics among cattle, with a notable absence of poultry-focused reports. Wild birds, especially migratory species, have played an important role in virus dissemination. Studies among mammals, including seals, bears, and domestic cats, along with the emerging outbreak among cattle, highlight the virus’s ability to adapt to diverse hosts, with the possibility of mammal-to-mammal transmission. Despite the low number of human infections, the zoonotic risk of the disease and the possibility of a human outbreak remain significant. The complexity and risks associated with the virus, in comparison with the limited current scientific studies in the United States, demand further investigations to mitigate its impact on animals, ecosystems, and human health.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/307

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Highly Pathogenic Avian #Influenza A (#H5N1) Clade 2.3.2.1a virus #infection in domestic #cats, #India, 2025

Abstract

In January 2025, the highly pathogenic avian influenza A(H5N1) virus clade 2.3.2.1a infection was detected in domestic cats and whole-genome sequencing of two cat H5N1 isolates was performed using the Oxford Nanopore MinION sequencing platform. Phylogenetic analysis revealed the circulation of triple reassortant viruses in cats. Although cat viruses lacked classic mammalian adaptation markers they carried mutations associated with enhanced polymerase activity in mammalian cells and increased affinity for α2-6 sialic acid receptor suggesting their potential role in facilitating infection in cats. The identification of reassortant HPAI H5N1 clade 2.3.2.1a viruses in domestic cats in India highlights the urgent need for enhanced surveillance in domestic poultry, wild birds, and mammals, including humans, to track genomic diversity and molecular evolution of circulating strains.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.23.638954v1

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In-hospital #outcomes and 6-month follow-up results of #patients supported with #ECMO for #COVID19 from the 2nd wave to end of pandemic (EuroECMO-COVID)...

Summary

Background

Extracorporeal membrane oxygenation (ECMO) for COVID-19 was thoroughly assessed during the first pandemic wave, but data on subsequent waves are limited. We aimed to investigate in-hospital and 6-month survival of patients with COVID-19 supported with ECMO from the second pandemic wave (Sept 15, 2020) until the end of the pandemic (March 21, 2023, announced by WHO).

Methods

EuroECMO-COVID is a prospective, observational study including adults (aged ≥16 years) requiring ECMO respiratory support for COVID-19 from 98 centres in 21 countries. We compared patient characteristics and outcomes between in-hospital survivors and non-survivors. Mixed-effects multivariable logistic regressions were used to investigate factors linked to in-hospital mortality. 6-month survival and overall patient status were determined via patient contact or chart review. This study is registered with ClinicalTrials.gov, NCT04366921, and is complete.

Findings

We included 3860 patients (2687 [69·7%] were male and 1169 [30·3%] were female; median age 51 years [SD 11]) from 98 centres in 21 countries. In-hospital mortality was 55·9% (n=2158), with 81·2% (n=1752) deaths occurring during ECMO support. More non-survivors had diabetes, hypertension, cardiovascular disease, and renal failure, and required more pre-ECMO inotropes and vasopressors compared with survivors. Median support duration was 18 days (IQR 10–31) for both groups. Factors linked to in-hospital mortality included older age, pre-ECMO renal failure, pre-ECMO vasopressors use, longer time from intubation to ECMO initiation, and complications, including neurological events, sepsis, bowel ischaemia, renal failure, and bleeding. Of the 1702 (44·1%) in-hospital survivors, 99·7% (n=1697) were alive at 6 months follow-up. Many patients at 6 months follow-up had dyspnoea (501 [32·0%] of 1568 patients), cardiac (122 [7·8%] of 1568 patients), or neurocognitive (168 [10·7%] of 1567 patients) symptoms.

Interpretation

Our data for patients undergoing ECMO support for respiratory distress from the second COVID-19 wave onwards confirmed most findings from the first wave regarding patient characteristics and factors correlated to in-hospital mortality. Nevertheless, in-hospital mortality was higher than during the initial pandemic wave while 6-month post-discharge survival remained favourable (99·7%). Persisting post-discharge symptoms confirmed the need for post-ECMO patient follow-up programmes.

Source: Lancet Respiratory Medicine, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(24)00369-2/abstract?rss=yes

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Structure-based #Design of Chimeric #Influenza #Hemagglutinins to Elicit Cross-group #Immunity

Abstract

Antigenic variability among influenza virus strains poses a significant challenge to developing broadly protective, long-lasting vaccines. Current annual vaccines target specific strains, requiring accurate prediction for effective neutralization. Despite sequence diversity across phylogenetic groups, the hemagglutinin (HA) head domain's structure remains highly conserved. Utilizing this conservation, we designed cross-group chimeric HAs that combine antigenic surfaces from distant strains. By structure-guided transplantation of receptor-binding site (RBS) residues, we displayed an H3 RBS on an H1 HA scaffold. These chimeric immunogens elicit cross-group polyclonal responses capable of neutralizing both base and distal strains. Additionally, the chimeras integrate heterotrimeric immunogens, enhancing modular vaccine design. This approach enables the inclusion of diverse strain segments to generate broad polyclonal responses. In the future, such modular immunogens may serve as tools for evaluating immunodominance and refining immunization strategies, offering potential to bridge and enhance immune responses in individuals with pre-existing immunity. This strategy holds promise for advancing universal influenza vaccine development.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.17.628867v2

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A Vestal Virgin Crowned With Flowers, Jacques-Louis David (1783)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/jacques-louis-david/a-vestal-virgin-crowned-with-flowers

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