#Risk #Assessment #Report using #TIPRA - 2nd edition For Avian #influenza clade 2.3.4.4b #H5N1 #B313 viruses - Executive Summary (#WHO)

{Excerpt}

1. Background 

A risk assessment exercise using the Tool for Influenza Pandemic Risk Assessment (TIPRA) was conducted for Clade 2.3.4.4b A(H5N1) genotype B3.13 virus in Aug – Oct 2024.  

From late 2023, unexplained illnesses were reported in dairy cattle across multiple states in the United States. 

Following those events, detection of avian influenza A(H5N1) in dairy cattle from Texas was confirmed on 25 March 2024. 

As of 9 December 2024, the virus has been detected in 720 dairy cattle herds across 15 states, according to the United States Department of Agriculture (USDA), with a total of 47 human infections from poultry and dairy cattle sources, excluding 11 human cases from Washington state, that might belong to genotype D1.1, also reported. 

Wild and domestic animals (e.g., cats, raccoons) near infected herds have been affected as well. 

The outbreak remains uncontrolled. 

Due to the unprecedented spread of the virus among dairy cattle and associated human cases, a pandemic risk assessment was warranted to evaluate its potential impact and identify research gaps. 

2. Objectives 

• Characterize the pandemic risk from Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses. 

• Identify knowledge gaps for Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses. 

• Recognize strengths, limitations, and room for improvement of the risk assessment protocol of TIPRA for further facilitation and standardization. 

• Engage international stakeholders in TIPRA to help facilitate information sharing for current and future assessments. 

3. Risk Question 

What is the overall public health risk of Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses, as compared to other viruses that were subject to previous TIPRA exercises? 

For this risk question, two components were assessed: 

-- the likelihood of the viruses acquiring the capacity for sustained human-to-human transmission and 

-- the public health impact if human-to-human transmission were to occur.  

4. Risk Assessment 

Method 

• Tool Applied 

The Tool for Influenza Pandemic Risk Assessment (TIPRA) was used to assess the above risk question. 

As per Step 1 in TIPRA, epidemiological and virological criteria triggered a risk assessment of Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses. 

The triggering was based on the following the internal epidemiological and experimental information provided from multiple stakeholders provided and literature review: 

• The first detection of avian A(H5N1) viruses from dairy cattle, 

• The sporadic but ongoing detection of human cases of avian A(H5N1) infection, 

• The multiple outbreaks and spread of avian influenza A(H5N1) viruses among dairy cattle,  

• Specific genotypes  of avian influenza A(H5N1) viruses isolated among dairy cattle, human, birds, and wild animals, 

• Molecular signatures associated with better replication in mammals. 

The risk was characterized using the statistical model described in TIPRA. 

Technical experts (TEs) scored risk elements based on evidence (a virus profile1) available about the virus at the time of assessment, and discussions based on the scores were used to characterize the risk and develop recommendations. 

Ten risk elements are described in the TIPRA guidance. The ten risk elements and their relevant weights per component (likelihood and impact) were then applied and risk scores generated.  

Summary of relative risk evaluation result of Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses 

-- Date of Assessment: Risk assessment teleconference date on 22 August and 10 October 2024 

-- Final risk scores: Likelihood: 5.62, Impact: 4.25 

-- Countries that have reported human infections: United States of America

Risk evaluation: 

- Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses have moderate likelihood of developing sustained human-to-human transmission capacity with low to moderate impact on the human population if the event occurs.  

- Confidence level: Moderate confidence for likelihood, moderate confidence for impact. Risk assessed was underpinned by the information available in October 2024 and the knowledge provided by TEs.  

(...)

Source: World Health Organization, https://cdn.who.int/media/docs/default-source/influenza/tipra/tipra-risk-assessment-reports/outcome-summaries/15.-oct-2024_h5n1-b3.13__summary-report.pdf?sfvrsn=65ed5a2a_3

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The Seven Deadly Sins and the Four Last Things, Hieronymus Bosch (1485)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/hieronymus-bosch/the-seven-deadly-sins-and-the-four-last-things-1485

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#Thermal #tolerance and #inactivation of #Ebola virus

{Summary}

HIGHLIGHTS

• The investigation demonstrated a high level of tolerance of EBOV to thermal disinfection.

• A water-bath is recommended and the tubes should be fully submerged during the process.

• The established inactivation guidelines should be followed very strictly.

Dear Editor,

Viruses of the genus Orthoebolavirus cause sporadic outbreaks of severe haemorrhagic fever, with case fatality rates ranging from 25% to 90% (Mahanty and Bray, 2004). Six species of the virus (Orthoebolavirus zairense, sudanense, bundibugyoense, taiense, restonense, and bombaliense) have so far been identified (Biedenkopf et al., 2023). Among these, Orthoebolavirus zairense, commonly known as Ebola virus (EBOV), stands out as the most virulent. Given its high contagiousness and lethality, EBOV must be manipulated under biosafety level 4 (BSL-4) conditions, as stipulated by the National Health Commission of the People's Republic of China's list of human pathogenic microorganisms. Prior to being removed from a BSL-4 laboratory, it is imperative that infectious EBOV undergoes complete inactivation. Here we systematically evaluate viral thermostability under BSL-4 containment conditions, demonstrating EBOV’s marked thermotolerance.

(...)

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000975

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A live attenuated NS1-deficient #vaccine candidate for #cattle-origin #influenza #H5N1 clade 2.3.4.4.b viruses

Abstract

Avian Influenza viruses (AIVs) present a public health risk, especially with seasonal vaccines offering limited protection. AIV H5N1 clade 2.3.4.4b has caused a multi-state outbreaks in the United States (US) poultry and cattle since March 2024, raising pandemic concerns. We developed a nonstructural protein 1 (NS1)-deficient mutant of a low pathogenic version of the cattle-origin human influenza A/Texas/37/2024 H5N1, namely LPhTXdNS1, and assessed its safety, immunogenicity, and protection efficacy. LPhTXdNS1 is attenuated in vitro, showing reduced replication efficiency in Vero cells and inability to control IFNβ promoter activation. The LPhTXdNS1-immunized C57BL/6 J mice exhibit significantly reduced viral replication and pathogenicity compared to those infected with the low pathogenic version expressing NS1, namely LPhTX. Notably, a single intranasal dose of LPhTXdNS1 elicited protective immune responses, providing robust protection against lethal wild-type H5N1 challenge. These results demonstrate that LPhTXdNS1 is safe and able to induce protective immune responses against H5N1.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01207-9

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History of Mass Transportation: the FS D341 Diesel-Electric Locomotive

 

Di Bruno Cividini - https://www.ilportaledeitreni.it/2018/06/07/d-341-1025-san-candido-febbraio-1975/, Pubblico dominio, https://commons.wikimedia.org/w/index.php?curid=78316787

Source: Wikipedia, https://it.wikipedia.org/wiki/Locomotiva_FS_D.341#/media/File:FS_D.341.1025-2.1975-S.Candido.jpg

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Considerations for use of avian #influenza #H5 #vaccines during the #interpandemic and emergence periods

Report of a WHO virtual scientific consultation, September 2024

© World Health Organization 2025 Some rights reserved. This work is available under the Creative Commons AttributionNonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).  

Executive summary 

Avian influenza viruses – particularly A(H5) – pose a significant risk for potential pandemics as they can infect humans and other mammals. 

The high mutation rate of influenza viruses raises concerns about their potential to adapt for efficient human-to-human transmission. 

Influenza vaccines are crucial tools in mitigating the impact of influenza epidemics and pandemics. 

Given the global circulation of A(H5) viruses – especially the spillover to dairy cattle since early 2024 – and the rapidly evolving vaccine landscape, the World Health Organization (WHO) held a virtual scientific consultation on 12–13 September 2024 to review: 

-- the current global A(H5) epidemiological situation; 

-- the availability and landscape of A(H5) vaccines and their characteristics; 

-- updated evidence on A(H5) vaccine immunogenicity, safety and other characteristics; 

and 

-- considerations for the use of A(H5) vaccines, based on expert opinions. 

The consultation did not discuss: 

-- A(H5) vaccine stockpiles; 

-- A(H5) vaccine regulatory approvals or access issues; 

-- mathematical modelling to inform options for use of A(H5) vaccines in the context of other public health measures and stockpiles; 

-- acceptance, cost, cost–effectiveness, risk–benefit ratios or other programmatic considerations; 

or 

-- strategies for animal A(H5) vaccination. 

Topics such as equity were also not discussed, as the Pandemic Influenza Preparedness Framework has enabled WHO to make significant progress in preparing for equitable access to vaccines. 

The primary objective of the virtual scientific consultation was to update WHO’s Options for the use of human H5N1 influenza vaccines and the WHO H5N1 vaccine stockpile, which was developed during a previous scientific consultation on A(H5N1) held in October 2007. 

The participants in the 2024 consultation included: 

-- experts from research academia, WHO collaborating centres and essential regulatory laboratories of the Global Influenza Surveillance and Response System, 

-- experts from countries, 

-- the WHO Strategic Advisory Group of Experts (SAGE) Secretariat, 

-- industry associations and other partners. 

This report summarizes the outcomes of the virtual scientific consultation, and is expected to be used during the potential update of SAGE recommendations on the use of licensed H5N1 vaccines. 

The A(H5) vaccine landscape included in this report is up to date as of 31 March 2025. 

A(H5) viruses pose a threat to human and animal health globally. National, regional and global preparedness is needed urgently. 

Countries should remain vigilant in conducting surveillance for emerging influenza viruses with pandemic potential. 

WHO will continue to monitor the situation and provide updated risk assessments, guidance and technical support, where needed. 

(...)

Source: World Health Organization, https://www.who.int/publications/i/item/9789240111462

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#Mpox Multi-country, external #situation #report no. 55 published 11 July 2025 (#WHO, Summary)

 

Highlights

• All clades of monkeypox virus (MPXV) continue to circulate in several countries. When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, they continue to pose a risk of sustained community transmission.  

• Since the last edition of this report, no new countries have reported cases of clade Ib MPXV for the first time.  

• Nineteen countries in Africa have reported ongoing mpox transmission in the past six weeks. Clade IIb MPXV continues to be reported in West Africa, while Central African countries report both clade Ia and clade Ib MPXV, and East African countries report clade Ib MPXV. 

• The recent overall downward trend of confirmed cases across the continent is driven by the decrease in cases in Sierra Leone, the Democratic Republic of the Congo, and some reporting delays. Challenges with access to testing continue in the Democratic Republic of the Congo.  

• An upward trend has been observed in West Africa, particularly in Guinea, Liberia, and Togo, where growing outbreaks of clade IIb MPXV have been reported in recent weeks. This report contains a summary of the epidemiological situation in these three countries.  

• China has reported nine additional cases of mpox due to clade Ib MPXV since the last situation report. Epidemiological investigations for some of them are ongoing, and the transmission status of clade Ib MPXV in China is classified as "Unknown" pending further information. 

• Türkiye has retrospectively notified WHO of a case of mpox due to clade Ia MPXV, detected in October 2024 in a traveler from the Democratic Republic of the Congo. No secondary cases were reported among the contacts of the case who underwent monitoring.  

• This report includes a summary of the fourth meeting of the International Health Regulations (2005) Emergency Committee regarding the upsurge of mpox, held on 5 June 2025. 

(...)

Source: World Health Organization, https://www.who.int/publications/m/item/multi-country-outbreak-of-mpox--external-situation-report--55---11-july-2025

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#USA, #Wastewater Data for Avian #Influenza #H5 (US #CDC, July 11 '25)

 

{Excerpt}

Time Period: June 29, 2025 - July 05, 2025

-- H5 Detection: 2 sites (0.6%)

-- No Detection: 330 sites (99.4%)

-- No samples in last week: 77 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/nwss/rv/wwd-h5.html

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The mutational landscape of #SARS-CoV-2 provides new insight into viral #evolution and #fitness

Abstract

Although vaccines and treatments have strengthened our ability to combat the COVID-19 pandemic, new variants of SARS-CoV-2 continue to emerge in human populations. Because the evolution of SARS-CoV-2 is driven by mutation, a better understanding of its mutation rate and spectrum could improve our ability to forecast the trajectory of the pandemic. Here, we use circular RNA consensus sequencing (CirSeq) to determine the mutation rate of six SARS-CoV-2 variants and perform a short-term evolution experiment to determine the impact of these mutations on viral fitness. Our analyses indicate that the SARS-CoV-2 genome mutates at a rate of ∼1.5 × 10−6/base per viral passage and that the spectrum is dominated by C → U transitions. Moreover, we find that the mutation rate is significantly reduced in regions that form base-pairing interactions and that mutations that affect these secondary structures are especially harmful to viral fitness. In this work, we show that the biased mutation spectrum of SARS-CoV-2 is likely a result of frequent cytidine deamination and that the secondary structure of the virus plays an important role in this process, providing new insight into the parameters that guide viral evolution and highlighting fundamental weaknesses of the virus that may be exploited for therapeutic purposes.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61555-x

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Isolation, characterization and phylogenetic analyses of avian #influenza A #H9N2 viruses isolated from #poultry between 2019 and 2023 in #Egypt

Abstract

The current study aimed to investigate the genetic characterization and evolution of low pathogenic avian influenza virus H9N2 in Egypt. Ten H9N2 viruses were recently isolated from samples collected between 2019 and 2023. Phylogenetic analysis of the haemagglutinin (HA) gene segment of the H9N2 isolates showed a relatedness with G1 H9 4.2 lineage and clustered within genotype III of the Egyptian strains identified earlier in 2018. The majority of H9N2 strains had seven and eight glycosylation sites in HA and neuraminidase (NA) respectively. All strains carried H191 and L234 residues in their hemagglutinin which are markers facilitating avian-to-human cross species barrier transmission. No stalk deletions were detected in NA gene. In addition, genetic analysis of the NA and M encoding proteins revealed the absence of substitutions associated with resistance to oseltamivir and amantadine. The NA showed S372A and R403W substitutions which were previously detected in H3N2 and H1N2 viruses that were reported in previous influenza pandemics in 1975 and 2001 respectively. Many mutations associated with virulence and mammalian infection were detected in internal proteins such as PB2(V504), PB1-F2(N66), PA (V127, L672, and L550), M2(S64), and NS1(42S). Analysis showed the presence of full-length PB1-F2 with 227PDZ230 motif which is associated with virus virulence and pathogenesis. Mammalian associated mutations such as PB2 (I 667, T64), PB1-P13, PB1-F2-S82, NP-K214, NP-Q398 and M1-I15 were detected. The HA gene was under positive selection pressure especially at sites 198 and 235 of RBS, while other internal genes were under negative selection pressure. The study highlights the importance of continuous monitoring of H9N2 virus to enable timely implementation of control measures in poultry populations in Egypt.

Source: BMC Veterinary Research, https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-025-04514-4

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Fourth #meeting of #IHR (2005) Emergency #Committee regarding the upsurge of #mpox 2024 (#WHO, July 10 '25)

 

{Summary}

The Director-General of the World Health Organization (WHO) is hereby transmitting the report of the fourth meeting of the International Health Regulations (2005) (IHR) Emergency Committee (Committee) regarding the upsurge of mpox 2024, held on Thursday, 5 June 2025, from 12:00 to 17:00 CEST.

Concurring with the advice unanimously expressed by the Committee during the meeting, the WHO Director-General determined that the upsurge of mpox 2024 continues to meet the criteria of a public health emergency of international concern (PHEIC) and, accordingly, on 9 June 2025, issued temporary recommendations to States Parties, available here.  

The WHO Director-General expresses his most sincere gratitude to the Chair, Members, and Advisors of the Committee.

(...)

Source: World Health Organization, https://www.who.int/news/item/10-07-2025-fourth-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-upsurge-of-mpox-2024

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#Portugal - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

By Alexis Lours - Own work, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=138694692

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A Yellow-legged Gull in Leiria Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6609

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A #nanobody-based #therapeutic targeting #Nipah virus limits viral escape

Abstract

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an anti-fusion glycoprotein nanobody with an anti-receptor-binding glycoprotein (RBP) antibody to deliver a dual-targeting biologic that is resistant to viral escape. We show that the nanobody, DS90, engages a unique, conserved site within the fusion glycoprotein of NiV and HeV and provides neutralization and complete protection from NiV disease. Bispecific engineering of DS90 with the anti-RBP monoclonal antibody m102.4 results in neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. These findings carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants.

Source: Nature Structural and Molecular Biology, https://www.nature.com/articles/s41594-025-01598-2

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#Genetic Characterization of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b, #Antarctica, 2024

Abstract

In 2024, we sequenced highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b genomes isolated from 5 brown skuas from James Ross Island, Antarctica. Phylogenetic analysis suggested the virus reached Antarctica through South America. Continued genetic surveillance will be critical to elucidate H5N1 virus transmission dynamics within Antarctica and surrounding areas.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0186_article

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#Transmission Dynamics of Highly Pathogenic Avian #Influenza #H5N1 and #H5N6 Viruses in Wild #Birds, South #Korea, 2023–2024

Abstract

We analyzed 15 cases of highly pathogenic avian influenza (HPAI) clade 2.3.4.4b virus infections detected in wild birds in South Korea during September 2023–March 2024. We isolated and sequenced 8 H5N1 and 7 H5N6 viruses. We investigated spatiotemporal transmission dynamics by using a Bayesian discrete trait phylodynamic model that incorporated geographic and host species information. Our source–sink dynamics support introductions of H5N1 viruses from northern Japan to South Korea and subsequent spread through multiple regions in South Korea. The H5N6 viruses were most likely introduced into southwestern South Korea and spread northeastward. Wild waterfowl, especially wild ducks, played a key role in transmission of both H5N1 and H5N6 viruses. Our data showed multiple introductions and extensive spread of HPAI clade 2.3.4.4b viruses and bidirectional transmission between Japan and South Korea. Our results highlight the value of enhanced active surveillance for monitoring HPAI viruses, which can provide insight into preventing future outbreaks.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0373_article

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Susceptibility and shedding in Mx1+ and Mx1− female #mice experimentally infected with dairy #cattle #H5N1 #influenza viruses

Summary

Background

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses have spread prolifically in dairy cattle in the US, resulting in dozens of human infections, some without well-established links to animal contacts. Many wild mammals have also been affected, including peridomestic house mice.

Methods

Here, we evaluated susceptibility, tissue tropism, and shedding in female PWK/PhJ and BALB/cJ mice, two laboratory strains derived from house mice that differ in expression of the antiviral restriction factor Mx1. PWK/PhJ mice, which were selected for their natural expression of Mx1, better reflect the antiviral capacity of most wild house mice, whereas BALB/cJ mice lack functional Mx1.

Findings

We found that, regardless of Mx1 expression status, mice are susceptible to infection by dairy cattle HPAI H5N1 viruses, that infection leads to systemic spread to non-respiratory sites, and that infected animals shed virus into the environment via urine. Shed virus remained infectious in urine for at least 24 h at room temperature.

Interpretation

These findings suggest that wild house mice could contribute to HPAI H5N1 environmental contamination and may play a role in transmission to other hosts.

Funding

This work was supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Response (contract 75N93021C00014) and by grants from the Japan Agency for Medical Research and Development (JP25wm0125002, JP253fa627001, and JP24fk0108626, to Y.K.).

Source: EBioMedicine, https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00286-5/fulltext

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Spatiotemporal #reconstruction of the North #American #H5N1 #outbreak reveals successive #lineage #replacements by descendant reassortants

Abstract

The November 2021 introduction of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b into North America triggered a devastating outbreak, affecting more than 180 million domestic birds and spreading to more than 80 wildlife species across Canada and the US. From this outbreak, we have sequenced 2955 complete A(H5N1) viral genomes from samples collected in Canada and, in conjunction with previously published data, performed multifaceted phylodynamic analyses. These analyses reveal extensive diversification of A(H5N1) viruses via reassortment with low-pathogenic avian influenza viruses. We find evidence of repeated ancestral strain replacement by direct descendants, indicative of compounding viral fitness increases. Spatiotemporal modeling identified critical geographic areas facilitating transcontinental spread and demonstrated genotype-specific host dynamics, offering essential data for ongoing control and prevention strategies.

Source: Science Advances, https://www.science.org/doi/10.1126/sciadv.adu4909

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#Wastewater #Parvovirus B19 #Signal Amid Rising #Maternal Cases

Abstract

We report widespread detection of parvovirus B19 in Texas Wastewater using hybrid-capture virome sequencing across 43 sites. Wastewater signal correlated with clinical cases at institutional, county, and state levels and preceded case surges by one month. Full-genome coverage enabled real-time mutation tracking, highlighting wastewater's utility for epidemiologic surveillance.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.07.25331044v1

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