Yawning Man (disputed attribution), Pieter #Bruegel the Elder (c.1563)

 

Source: WikiArt, https://www.wikiart.org/en/pieter-bruegel-the-elder/yawning-man-disputed-attribution-1563

{Public Domain}

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#SARS-CoV-2 #Infection of the #CNS: A Case Report

Abstract

Central nervous system (CNS) infections caused by SARS-CoV-2 are uncommon. This case report describes the clinical progression of a 92-year-old female who developed a persistent neuroinfection associated with SARS-CoV-2. The patient initially presented with progressive fatigue, catarrhal symptoms, and a fever (38.6 °C). Initial laboratory findings revealed hypoxemia (O2 saturation 79.8%), acidosis (pH 7.3), an elevated C-reactive protein (CRP) level of 14.8 mg/L, and a high D-dimer level (2.15 µg/mL). Nasopharyngeal (NP) antigen and RT-PCR tests confirmed SARS-CoV-2 infection, and an NP swab also detected penicillin- and ampicillin-resistant Staphylococcus aureus. She was admitted for conservative management, including oxygen supplementation, IV fluids, and prophylactic anticoagulation. Subsequently, she developed neurological symptoms—lethargy, discoordination, and impaired communication—without signs of meningism. Cerebrospinal fluid (CSF) analysis identified SARS-CoV-2 RNA (Ct = 29) on RT-PCR, while bacterial cultures remained negative. Treatment was intensified to include 10% mannitol, dexamethasone, and empiric ceftriaxone. Despite these interventions, the patient remained somnolent, with a Glasgow Coma Scale (GCS) score of 10. Upon discharge, her GCS had improved to 14; however, she continued to experience lethargy and cognitive issues, commonly described as “brain fog”. Inflammatory markers remained elevated (CRP 23 mg/L) and repeat RT-PCR of CSF confirmed a persistent SARS-CoV-2 presence (Ct = 31). This case underscores the potential for SARS-CoV-2 to cause prolonged CNS involvement, leading to persistent neurological impairment despite standard therapy. Further research is essential to clarify the pathophysiology of and determine optimal management for SARS-CoV-2 neuroinfections.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1962

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#Risk #assessment of #zoonotic #viruses in #urban-adapted #wildlife

Abstract

The repeated emergence of pandemic viruses underscores the linkages between land-use change and wildlife disease, and urban-adapted wildlife are of special interest due to their close proximity to humans. However, viral diversity within urban-adapted species and their zoonotic potential remain largely unexplored. We compiled a large dataset on seven priority urban-adapted mammal species and their viruses covering over 115 countries from 1574 to 2023. These urban-adapted species host 286 virus species spanning 24 orders and 38 families, 14 of which are potentially high risk for human infection. Raccoons carried the most high-risk viruses, while raccoon dogs had increased viral positivity in urban habitats compared to raccoons, wild boars, and red foxes. Many viruses in urban-adapted species were phylogenetically related to those found in humans, and we also observed evidence of possible viral spillback. These results highlight zoonotic risks associated with urban-adapted species and suggest enhanced surveillance to mitigate future outbreaks.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.18.629064v1

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Intensive #transmission in wild, migratory #birds drove rapid geographic #dissemination and repeated #spillovers of #H5N1 into #agriculture in North #America

Abstract

Since late 2021, a panzootic of highly pathogenic H5N1 avian influenza virus has driven significant morbidity and mortality in wild birds, domestic poultry, and mammals. In North America, infections in novel avian and mammalian species suggest the potential for changing ecology and establishment of new animal reservoirs. Outbreaks among domestic birds have persisted despite aggressive culling, necessitating a re-examination of how these outbreaks were sparked and maintained. To recover how these viruses were introduced and disseminated in North America, we analyzed 1,818 Hemagglutinin (HA) gene sequences sampled from North American wild birds, domestic birds and mammals from November 2021-September 2023 using Bayesian phylodynamic approaches. Using HA, we infer that the North American panzootic was driven by ~8 independent introductions into North America via the Atlantic and Pacific Flyways, followed by rapid dissemination westward via wild, migratory birds. Transmission was primarily driven by Anseriformes, shorebirds, and Galliformes, while species such as songbirds, raptors, and owls mostly acted as dead-end hosts. Unlike the epizootic of 2015, outbreaks in domestic birds were driven by ~46-113 independent introductions from wild birds, with some onward transmission. Backyard birds were infected ~10 days earlier on average than birds in commercial poultry production settings, suggesting that they could act as early warning signals for transmission upticks in a given area. Our findings support wild birds as an emerging reservoir for HPAI transmission in North America and suggest continuous surveillance of wild Anseriformes and shorebirds as crucial for outbreak inference. Future prevention of agricultural outbreaks may require investment in strategies that reduce transmission at the wild bird/agriculture interface, and investigation of backyard birds as putative early warning signs.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.16.628739v1

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The crucial role of intercellular #calcium wave #propagation triggered by #influenza A virus in promoting #infection

Abstract

Influenza A viruses (IAVs) initially infect a few host cells, and the infection subsequently spreads to neighboring cells. However, the molecular mechanisms underlying this expansion remain unclear. Here, we show that IAV infection upregulates the frequency of intercellular calcium wave propagations (iCWPs) that mediate the spread of IAVs. ADP released from initially infected cells mediated iCWPs via the P2Y1 receptor. The generation of iCWPs and spread of viral infection were inhibited by a P2Y1 antagonist. Enhanced endocytosis in the surrounding cells that received ADP signaling upregulated viral entry. Expression of IAV matrix protein 2 (M2) in initially infected cells triggered iCWPs through ADP diffusion, thereby increasing infection, whereas an ion permeability-deficient mutation of M2 or inhibition of its ion channel activity suppressed iCWPs. Therefore, intercellular calcium signaling is essential for early expansion and potential establishment of IAV infection, which offers a promising target for IAV prophylaxis.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.20.629723v1

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#USA, #Iowa HHS Reports First #Human Case of Highly Pathogenic Avian #Influenza (#H5N1), #Risk Remains Very Low to Public

The Iowa Department of Health and Human Services (Iowa HHS) is reporting the first human case of avian influenza A(H5) in the state. 

The individual was exposed to infected poultry while working with a commercial flock in northwest Iowa. 

The individual reported mild symptoms, has received appropriate treatment and is recovering. 

The case was identified through testing at the State Hygienic Laboratory and confirmed by the Centers for Disease Control and Prevention (CDC).

As of December 20, 2024, the CDC has reported 64 confirmed human cases of H5 HPAI across nine states. The majority of the exposures are linked to infected poultry or dairy cows. 

There is no evidence that human-to-human transmission of influenza A(H5) is occurring in the U.S.

Although human infections are rare{!}, the virus is spread through prolonged exposure around infected flocks and herds, through the eyes, nose or mouth. Any individuals with direct contact who develop flu-like symptoms or an eye infection should contact their doctor. To reduce the risk of infection or spread, people in direct contact with exposed animals should wear proper PPE and avoid direct contact with sick or dead animals, including birds. 

“Iowa has monitored the spread of avian influenza closely since it was first detected in poultry in the state in 2022, and our state is prepared with the established knowledge, strong partnerships, and effective tools to mitigate its impact on our community,” said Iowa HHS State Medical Director Dr. Robert Kruse.

There is no concern {!!} about the safety of eggs and poultry products or pasteurized milk and dairy products. As a reminder, consumers should always properly handle and cook eggs and poultry products, including cooking to an internal temperature of 165˚F. Pasteurization has continually proven to successfully inactivate bacteria and viruses, like influenza, in milk.

Source: Department of Health, https://hhs.iowa.gov/news-release/2024-12-20/iowa-hhs-reports-first-human-case-highly-pathogenic-avian-influenza-hpai-iowa-risk-remains-very-low

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#USA, Confirmed #human #H5N1 #influenza case summary during 2024 #outbreak, by state and exposure source, as of Dec. 20 '24: 3 new cases, total now = 64

Exposure Source

[State - Exposure Associated with Commercial Agriculture and Related Operations: Dairy Herds (Cattle) - Poultry Farms and Culling Operations - Other Animal Exposure† - Exposure Source Unknown‡ - State Total]

1) California - 35 - 0 - 0 - 1 - 36 {+2}

2) Colorado - 1 - 9 - 0 - 0 - 10

3) Louisiana - 0 - 0 - 1 - 0 - 1 {+1} 

4) Michigan - 2 - 0 - 0 - 0 - 2

5) Missouri - 0 - 0 - 0 - 1 - 1

6) Oregon - 0 - 1 - 0 - 0 - 1

7) Texas - 1 - 0 - 0 - 0 - 1

8) Washington - 0 - 11 - 0 - 0 - 11

9) Wisconsin - 0 - 1 - 0 - 0 - 1 {+1}

-- Source Total - 39 - 22 - 1 - 2 - 64 {+3}

NOTE: One additional case was previously detected in a poultry worker in Colorado in 2022.

†Exposure was related to other animals such as backyard flocks, wild birds, or other mammals

‡Exposure source was not able to be identified

Probable human case summary during the 2024 outbreak, by state and exposure source

When a case tests positive for H5 at a public health laboratory but testing at CDC is not able to confirm H5 infection, per Council of State and Territorial Epidemiologists (CSTE) guidance, a case is reported as probable.

-- Probable cases with commercial poultry exposure (e.g., poultry farms or culling operations):

1) Washington (3)

2) Arizona (2)

-- Probable cases with commercial dairy (cattle) exposure:

1) California (1)

-- Probable cases with exposure source unknown:

1) Delaware (1)

Confirmed and probable cases are typically updated by 5 PM EST on Mondays (for cases confirmed by CDC on Friday, Saturday, or Sunday), Wednesdays (for cases confirmed by CDC on Monday or Tuesday), and Fridays (for cases confirmed by CDC on Wednesday and Thursday). Affected states may report cases more frequently.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/situation-summary/?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/avian-flu-summary.htm

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Highly Pathogenic Avian #Influenza A(#H5N1) Virus: Interim #Recommendations for #Prevention, #Monitoring, and Public Health #Investigations

Summary

The purpose of this guidance is to outline CDC's recommendations for preventing exposures to highly pathogenic avian influenza (HPAI) A(H5N1) viruses, infection prevention and control measures including the use of personal protective equipment, testing, antiviral treatment, patient investigations, monitoring of exposed persons (including persons exposed to sick or dead wild and domesticated animals and livestock with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) virus), and antiviral chemoprophylaxis of exposed persons. These recommendations are based on available information and will be updated as needed when new information becomes available.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html

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#Phylogenetic and #Pathogenic #Analysis of #H5N1 and #H5N6 High Pathogenicity Avian #Influenza Virus Isolated from #Poultry Farms (Layer and Broiler Chickens) in #Japan in the 2023/2024 Season

Abstract

During the 2023–2024 winter, 11 high pathogenicity avian influenza (HPAI) outbreaks caused by clade 2.3.4.4b H5N1 and H5N6 HPAI viruses were confirmed in Japanese domestic poultry among 10 prefectures (n = 10 and 1, respectively). In this study, we aimed to genetically and pathologically characterize these viruses. Phylogenetic analysis revealed that H5N1 viruses were classified into the G2d-0 genotype, whereas the H5N6 virus was a novel genotype in Japan, designated as G2c-12. The G2c-12 virus shared PB2, PB1, PA, HA, and M genes with previous G2c viruses, but had NP and NS genes originating from avian influenza viruses in wild birds abroad. The N6 NA gene was derived from an H5N6 HPAI virus that was different from the viruses responsible for the outbreaks in Japan in 2016–2017 and 2017–2018. Experimental infections in chickens infected with H5N1(G2d-0) and H5N6(G2c-12) HPAI viruses showed no significant differences in the 50% chicken lethal dose, mean death time, or virus shedding from the trachea and cloaca, or in the histopathological findings. Different genotypes of the viruses worldwide, their introduction into the country, and their stable lethality in chickens may have triggered the four consecutive seasons of HPAI outbreaks in Japan.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1956

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Structural basis of different #neutralization capabilities of #monoclonal #antibodies against #H7N9 virus

ABSTRACT

Neutralizing antibodies (nAbs) are important for the treatment of emerging viral diseases and for effective vaccine development. In this study, we generated and evaluated three nAbs (1H9, 2D7, and C4H4) against H7N9 influenza viruses and found that they differ in their ability to inhibit viral attachment, membrane fusion, and egress. We resolved the cryo-electron microscopy (cryo-EM) structures of H7N9 hemagglutinin (HA) alone and in complex with the nAb antigen-binding fragments (Fabs) and identified the HA head-located epitope for each nAb, thereby revealing the molecular basis and key residues that determine the differences in these nAbs in neutralizing H7N9 viruses. Moreover, we found that the humanized nAb CC4H4 provided complete protection in mice against death caused by a lethal H7N9 virus infection, even when nAb was given 3 days after the mice were infected. These findings provide new insights into the neutralizing mechanism and structural basis for the rational design of H7N9 virus vaccines and therapeutics.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01400-24?af=R

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#Marburg virus disease - #Rwanda

 {Summary}

Situation at a glance

On 20 December 2024, after two consecutive incubation periods (total of 42 days) since the second negative PCR test was conducted on 7 November for the last confirmed Marburg case, and without a new confirmed case reported, the Ministry of Health of Rwanda declared the end of the Marburg virus disease (MVD) outbreak, as per the WHO recommendations. 

The outbreak had been declared on 27 September 2024. 

As of 19 December 2024, 66 confirmed cases,15 deaths with a case fatality ratio (CFR) of 23%, and 51 recovered cases have been reported. 

The last confirmed case was reported on 30 October 2024. 

WHO through its country office and development partners provided technical and financial support to the government to contain this outbreak. 

The risk of re-emergence of MVD still remains even after the official declaration of the end of the outbreak, linked to viral persistence in body fluids (mostly semen) of recovered patients and the animal reservoir in the country. 

WHO encourages maintaining early case detection and care capacities in addition to sustaining the ability to quickly respond, also underscoring the importance of the recovered patient program, psychosocial support, and continued risk communication and community engagement.

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON548

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#Influenza at the #human - #animal #interface #summary and #assessment, 12 December 2024

 {Excerpt}

Influenza at the human-animal interface 

Summary and risk assessment, from 2 November to 12 December 2024 

• New human cases: From 2 November to 12 December 2024, the detection of influenza A(H5) virus in 16 humans and influenza A(H9N2) virus in nine humans were reported officially.  

• Circulation of influenza viruses with zoonotic potential in animals: High pathogenicity avian influenza (HPAI) events in poultry and non-poultry continue to be reported to the World Organisation for Animal Health (WOAH). The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.  

• Risk assessment: Based on information available at the time of the risk assessment, the overall public health risk from currently known influenza viruses at the human-animal interface has not changed remains low. Sustained human to human transmission has not been reported from these events and the occurrence of sustained human-to-human transmission of these viruses is currently considered unlikely. Although human infections with viruses of animal origin are infrequent, they are not unexpected at the human-animal interface.  

• IHR compliance: All human infections caused by a new influenza subtype are required to be reported under the International Health Regulations (IHR, 2005). This includes any influenza A virus that has demonstrated the capacity to infect a human and its haemagglutinin gene (or protein) is not a mutated form of those, i.e. A(H1) or A(H3), circulating widely in the human population. Information from these notifications is critical to inform risk assessments for influenza at the human-animal interface.  

(...)

Source: World Health Organization, https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment--12-december-2024

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Updated joint #FAO / #WHO / #WOAH public health #assessment of recent #influenza A(#H5) virus #events in animals and people (Dec. 20 '24)

Assessment based on data as of 18 November 2024 

12 December 2024 

Key points 

At the present time, based on available information, FAO-WHO-WOAH assess the global public health risk of influenza A(H5N1) viruses to be low, while the risk of infection for occupationally exposed persons is low to moderate depending on the risk mitigation measures in place and the local avian influenza epidemiological situation. 

Transmission between animals continues to occur and, to date, a growing yet still limited number of human infections are being reported. 

Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, the overall public health impact of such infections at a global level, at the present time, is minor. 

This risk assessment from FAO, WHO, and WOAH updates the assessment of the risk of zoonotic transmission (for example, animal to human) considering additional information made available since the previous assessment of 14 August 2024. 

This update is limited to the inclusion of additional information being made available globally. 

Due to the potential risk to human health and the farreaching implications of the disease on the health of wild birds, poultry, livestock and other animal populations, the use of a One Health approach is essential to tackle avian influenza effectively, to monitor and characterize virus circulation, to prevent within species and to new species transmission, to reduce spread among animals, and to prevent human infections from exposure to animals. 

Infections in animals

In March 2024, influenza A(H5) clade 2.3.4.4b of subtype H5N1 virus was detected in unpasteurized milk samples and oropharyngeal swabs from dairy cattle for the first time in the USA.{1,2} 

Influenza A(H5N1) virus detections continue to be reported through testing of dairy cattle exhibiting clinical signs and with no apparent disease.{3,4} 

While H5N1 clade 2.3.4.4b virus was introduced into North America in late 2021, analyses of virus sequence data from infected dairy cows has suggested that the ongoing circulation in dairy herds is linked to a single bird-to-dairy cow transmission event of a B3.13 genotype A(H5N1) virus that occurred in late 2023 or early 2024.{5} 

Thus far, this genotype has not been detected in cattle outside of the USA under field conditions.{6} 

As of 18 November 2024, 599 dairy cattle herds in 15 states of the USA have tested positive for A(H5N1), with a significant surge of confirmed outbreaks in dairy cattle in the State of California reaching 383 herds since the first detection in late August 2024.{7} 

The average incidence of clinical disease on affected farms ranges between 10 and 20% with main clinical signs including decreased milk production with abnormal milk, decreased feed intake, fever, dehydration, altered faecal consistency, respiratory distress, and abortions.{8,9,10} 

Studies have shown that commercial milk pasteurization inactivates the virus making it safe for human consumption.{11,12,13} 

The routes and modes of transmission between cattle, the duration of virus shedding as well as the infectious period are under investigation, and while there have been advancements in our understanding, this is still not well understood. 

Transmission between states in the USA has been linked to cattle movements or possibly through feed and manure handling equipment, or on clothing or footwear of people working or visiting farms.{10} 

Experimental studies of lactating dairy cattle and non-lactating heifers have been published and have provided some insight into receptor distribution, viral replication kinetics, and infection routes. 

Studies have indicated that alpha 2,3 sialic acid receptors (avian virus-type) are abundant in dairy cattle mammary tissue, consistent with the observation of high viral load in raw milk, and such receptors have also been detected in the respiratory tract of dairy cattle.{14,15} 

However, one study addressing the receptor binding specificity of the mammary gland and respiratory tract of cows to influenza A viruses (IAV) indicated that the upper respiratory tract of cows is devoid of receptors for IAV.{16} 

The same study demonstrated that the mammary gland of cows abundantly displays aviantype receptors for circulating H5 viruses while lacking human-type receptors. 

The lack of human-type receptors in mammary tissue contradicts a previous study that solely relied on plant-derived lectins to identify receptors.{15} 

Experimental inoculations of calves, heifers, and lactating cows demonstrated greater potential of A(H5N1) viruses to infect and replicate in the mammary gland than in the respiratory tract. 

In calves, intranasal inoculation with A(H5N1) B3.13 genotype virus resulted in poor nasal replication and viral shedding and the observed clinical signs were mild and there was no reported transmission to sentinel calves. 

While in lactating dairy cows, intramammary inoculation with high doses of A(H5N1) viruses (B3.13 or a representative European wild bird isolate) resulted in severe mammary gland infection with necrotizing mastitis, drastically reduced milk production, with no nasal replication nor systemic infection.{17, 18} 

On 29 October 2024, the USDA National Veterinary Services Laboratories confirmed A(H5N1) virus detection in swine from a backyard farm in Oregon State where A(H5N1) virus was also confirmed in poultry on 25 October. 

The farming operation had a mix of poultry and livestock (including five swine, sheep and goats) that had been in close contact and sharing water sources, housing, and equipment. 

Although the swine did not express any clinical signs, they were euthanized for further diagnostic analysis.{19} 

Two of the five swine tested positive for A(H5N1) virus by polymerase chain reaction (PCR). 

Partial genome sequencing indicated the A(H5N1) belonged to the D1.2 genotype, similarly to the infected poultry on the same farm, and not the B3.13 genotype.{20} 

The detection of H5N1 virus in two pigs in Oregon State was not unexpected given the close contact between infected poultry and pigs on the farm likely enabling a poultry-to-swine transmission event. 

Nonetheless, avian influenza detections in pigs warrant attention as they can act as "mixing vessels" for genetic reassortment of avian and human influenza viruses, potentially creating new strains with pandemic potential. 

The mechanisms underlying A(H5N1) virus adaptation to pigs and the potential for efficient and sustained transmissibility among pigs are yet to be understood. 

Several experimental infections studies conducted in pigs with A(H5N1) clade 2.3.4.4b viruses showed that mammalian-derived A(H5N1) virus strains demonstrated higher potential for replication, pathogenicity, and transmissibility as compared to avian-derived A(H5N1) virus strains.{21,22} 

Nonetheless, avian-derived A(H5N1) virus isolated in the USA in 2022 replicated successfully in the lungs of pigs with pulmonary lesions consistent with IAV infection and A(H5N1) virus transmission to at least one naive pig through direct contact was observed using mammalian isolates (racoon and red fox) from the USA.{23}  

Detections of A(H5) in mammals, other than dairy cattle, and wild and domestic birds continue to be reported in the USA and in other countries worldwide. 

Since 2021, clade 2.3.4.4b H5 virus circulation in wild and migratory birds and poultry resulted in numerous separate infections of wild carnivorous and scavenging mammals, domestic cats and dogs, marine mammals, and seabirds in various countries and territories. 

Clade 2.3.4.4b virus infections in mammals in the Americas, Asia and Europe have often resulted in severe disease with neurological signs in some species.{24} 

Notably, the wild marine mammal populations along the Atlantic and Pacific coastlines of the Americas weathered an important H5N1 epizootic leading to mass mortality events, particularly in Argentina, Chile, and Peru.{25} 

Amino acid changes potentially associated with increased virulence, transmission, or adaptation to mammalian hosts have been identified in H5N1 viruses responsible for the spillover events in marine mammals, and scientific publications suggested the occurrence of mammal-to-mammal transmission events supported by epidemiological, ecological, and phylogenetic data.{26, 27} 

Between August and September 2024, avian influenza outbreaks were reported in captive wild felines in two zoos in southern Viet Nam. These led to the death of at least 47 tigers, three lions and a leopard, and were confirmed to be caused by a reassortant clade 2.3.2.1c A(H5N1) virus containing clade 2.3.4.4b gene segments. 

None of the zoo staff members in close contact with the infected animals experienced any respiratory symptoms.{28, 29} 

Previous influenza A(H5N1) outbreaks in felines, characterized by severe pneumonia and high mortality, have been associated with the feeding of infected poultry and likely tiger-to-tiger transmission.{30,31}  

For the latest information on avian influenza situation in animals worldwide, see the FAO Global Avian Influenza Viruses with Zoonotic Potential situation update and the WOAH situation reports on HPAI, as well as WOAH’s World Animal Health Information System. 

Detections in humans 

Since the last joint assessment of August 2024 and as of 27 November 2024, an additional 49 human cases of infection with A(H5) viruses have been reported. 

Of these, 45 were reported from the USA: 28 in persons with exposure to A(H5N1)-infected dairy cattle in California, 15 in persons with exposure while involved in depopulation of A(H5N1)-infected commercial poultry farms, and two in persons with unknown exposure at the time of reporting. 

Samples from three cases related to poultry depopulation in the State of Colorado were confirmed to contain A(H5N1) clade 2.3.4.4b, genotype B3.13, virus while cases related to poultry depopulation in the State of Washington contained viruses belonging to the D1.1 genotype.   

Intensive epidemiological investigation of the case with unknown exposure in the State of Missouri could not identify any animal or animal product exposure. 

Five health care workers in contact with the case were shown to be A(H5N1) seronegative, the case and one household contact who reported symptoms with the same onset date were weakly A(H5N1) seropositive. 

The timing of symptom onsets supports a single common exposure, which at present remains unknown, rather than human-to-human transmission.{32}  

All but one of the detected cases in the USA have reported mild symptoms, including conjunctivitis and mild respiratory symptoms, and recovered without hospitalization. 

The one exception who had comorbidities reported gastrointestinal symptoms and was hospitalized.{33,34}  

A recent sero-study in 115 persons in Colorado and Michigan working on dairy farms during A(H5N1) outbreaks among dairy cattle found that eight (7.0%) had serologic evidence of recent infection (seropositive, ≥40 antibody titres to H5 2.3.4.4b by both micro-neutralization and hemagglutination inhibition assays). 

These seropositive individuals reporting working with dairy cattle or in the milking parlour, and four reported being ill when A(H5) was detected among the dairy cattle.{35} 

Three human cases of clade 2.3.2.1c A(H5N1) virus infection were reported from Cambodia since the last update of August 2024. 

All were hospitalized; two recovered and the other died. 

All three cases had exposure to sick or dead backyard poultry. 

On 13 November, one human case of domestically acquired A(H5N1) infection was confirmed by Canadian authorities in a young person without underlying conditions. The condition of the case was reported as critical. There are several ongoing investigations to better understand the exposures of this case, and so far investigations have not been able to identify the source of exposure. 

The virus from the case belonged to clade 2.3.4.4b, specifically the D1.1 genotype, which was similar to viruses concurrently affecting poultry in the region.{36} 

Virus characteristics

Regular monitoring and screening of viral sequences from birds has rarely found markers of mammalian adaptation in clade 2.3.4.4b viruses; those that have been detected are mainly in the polymerase proteins of the virus. 

These polymerase markers have been more frequently detected in viruses from mammals. 

As of 4 November 2024, none of the virus sequences from dairy cattle in the USA have well-recognized markers in the HA gene associated with a switch in receptor preference despite continued circulation of the virus. 

Additional studies on some B3.13 A(H5N1) viruses indicate no differences in receptor binding, pH fusion or thermostability compared to other non-B3.13 avian A(H5N1) viruses, and that these viruses retain their avian influenza virus phenotype.{37}

Available virus sequences from human cases have shown some genetic markers that may reduce susceptibility to neuraminidase inhibitors (antiviral medicines such as oseltamivir) or endonuclease inhibitors (such as baloxavir marboxil). 

While these changes may reduce antiviral susceptibility in laboratory testing the clinical impact of these genetic changes requires further studies.{38}  

Experimental studies with A(H5N1) clade 2.3.4.4b viruses, including a B3.13 virus from the human case in Texas, have shown variable transmission between ferrets by direct contact, but no or inefficient transmission via respiratory droplets in most studies. {39, 40 , 41, 42, 43, 44} 

Ferrets infected with a non-B3.13 A(H5N1) clade 2.3.4.4b virus via the ocular route did experience severe disease and were able to transmit the virus to other ferrets via direct contact; these contact animals also developed severe disease.{45} 

Currently circulating A(H5N1) viruses would need further genetic changes to gain the ability to spread efficiently among humans via respiratory droplets, consistent with the current level of risk to public health, which is low.{39} 

Other A(H5) virus clades such as 2.3.2.1c46 and 2.3.2.1a continue to circulate and evolve in poultry in geographically restricted regions. 

Three A(H5N1) human cases have been detected in Cambodia since the previous assessment. 

The detected viruses were identified as reassortant influenza A(H5N1) viruses that were also detected in poultry in Cambodia, Lao People’s Democratic Republic{47} and Viet Nam, and previously detected in human cases reported from Cambodia since late 2023 and Viet Nam in 2024. This reassortant virus has HA and NA genes from clade 2.3.2.1c viruses, while its internal genes belong to clade 2.3.4.4b viruses.{48,49} 

The viruses were similar to those detected in captive tigers and leopards in Viet Nam.{50}  

Based on limited seroprevalence information available on A(H5) viruses, human population immunity against the HA of H5 viruses is expected to be minimal; human population immunity targeting the N1 neuraminidase is found to be present although the impact of this immunity is yet to be understood.{51}  

Candidate vaccine viruses (CVV) 

The WHO Global Influenza Surveillance and Response System (GISRS), in collaboration with animal health partners (FAO, WOAH, OFFLU (Joint WOAH-FAO network of expertise on animal influenza) and others), continue to evaluate candidate vaccine viruses for pandemic preparedness purposes both bi-annually and on an ad hoc basis. 

Regular genetic and antigenic characterization of contemporary zoonotic influenza viruses are published here with the most recent update on A(H5) CVVs published in September following the WHO Consultation on the Composition of Influenza Virus Vaccines for Use in the 2025 Southern Hemisphere Influenza Season.  

While the majority of circulating clade 2.3.4.4b viruses reacted well to at least one of the postinfection ferret antisera raised against the existing CVVs, an increasing proportion of clade 2.3.2.1c viruses from Cambodia and Viet Nam had reduced reactivity with post-infection ferret antiserum raised against an existing CVV. 

Thus, a new CVV from clade 2.3.2.1c was proposed. 

The list of available zoonotic influenza candidate vaccine viruses (CVVs) which include A(H5N1) viruses and potency testing reagents is updated on the WHO website. 

Assessment of current public health risk posed by influenza A(H5N1) viruses {52} 

(1). What is the global public health risk of additional human cases of infection with avian influenza A(H5) viruses? 

Despite the high and increasing number of A(H5) clade 2.3.4.4b outbreaks and detections in animals and increasing human exposures to the virus at the human-animal-environment interface, there have been relatively few human infections reported to date.  Of the human cases of A(H5) detections reported since the beginning of 2021, the majority were infections in people associated with exposure to A(H5) viruses through direct or indirect contact with infected animals, or contaminated environments, such as live poultry markets or other premises with infected animals. Severity of illness has ranged from mild to fatal, with the majority of recent cases reporting mild illness. The exception is the recent case reported from Canada, in a young person with no underlying conditions, reported as critical. Thus far, among these cases, there has been no reported or identified human-to-human transmission through follow up epidemiologic, virologic and serologic investigations. Investigations for some of the cases continue. Current virologic and epidemiologic information indicates that these viruses remain avian influenza viruses without established adaptations to mammalian hosts and have not acquired the capacity for sustained transmission between humans.  The epidemiological situation has changed with the ongoing spread of A(H5) virus in the USA dairy cattle population. Persons exposed to affected dairy cattle and other infected animals may be in prolonged and close contact with potentially contaminated surfaces and animal products. As long as A(H5) viruses continue to be detected in wild and domestic birds and mammals, including dairy cattle, and related environments, including in unpasteurized/raw milk, further human cases are expected, particularly amongst exposed individuals not wearing appropriate personal protective equipment and/or in environments where mitigation measures are not in place. Further studies on the detection of A(H5N1) in two pigs in the USA is needed in order to better understand the risk posed by this finding. Based on currently available information, FAO-WHO-WOAH assesses the global public health risk of influenza A(H5) viruses as low. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, they remain limited in the general population and the overall current public health impact of such infections at a global level is minor, considering the surveillance, response, mitigation and control measures in place.  However, while the risk of infection to the general public is low, among persons with exposure to infected birds or mammals or contaminated environments, the risk of infection can range from low to moderate, depending on nature of the exposure, the duration of exposure, the consistent and appropriate use of personal protective equipment, and the use of other response, mitigation and control measures particularly in environments where animals are kept.  The pandemic potential of these viruses requires enhanced vigilance, especially in animal populations where animal to animal transmission is known to occur (poultry and dairy cattle), and close monitoring in animals and humans. It remains essential that, while farmers enhance biosecurity on their farms, governments focus efforts on strengthening surveillance in susceptible animal populations and in persons exposure to infected animals, to prevention and mitigation efforts to reduce and/or stop animal to animal transmission and reduce environmental contamination, to prevention efforts to stop animals to human transmission and to improve communication with at risk persons and provide occupationally exposed persons with and train in the use of personal protective equipment. 

(2). What is the likelihood of human-to-human transmission of avian influenza A(H5) viruses?  

There has been no reported human-to-human transmission of A(H5) viruses since 2007, although there may be knowledge gaps in investigations around identified human infections. In 2007 and the years prior, small clusters of A(H5) virus infections in humans were reported, including limited human to human transmission from patients to health care workers. At the present time sustained human-to-human transmission has not been reported of A(H5) viruses.{53}  The A(H5) viruses currently detected in mammals, including in human cases, largely retain genomic and biological characteristics of avian influenza viruses and remain well-adapted to spread among birds. Except for in-host obtained amino acid mutations in polymerase proteins, there is still limited evidence for adaptation to mammals and humans even when transmission in mammals has been suspected.{54} No changes in receptor binding tropism have been consistently observed that would increase binding to receptors in the human upper respiratory tract which would increase the probability of transmission to and among people. In addition, available preliminary sero-studies and sero-investigations have not identified human-to-human transmission of A(H5N1) in the USA. Therefore, sustained human-to-human transmission of the currently circulating A(H5N1) viruses is considered unlikely without further genetic changes in the virus. This is actively being assessed by agencies in affected Member States, FAO, WHO, WOAH and partners. WHO, together with FAO and WOAH, continues to evaluate A(H5) viruses closely and will reassess the risk associated with the currently circulating A(H5) viruses as more information becomes available.  Further antigenic characterization of A(H5) viruses, including in relation to the existing CVVs, and development of specific reagents are being prioritized at the WHO Collaborating Centres and Essential Regulatory Laboratories of GISRS in collaboration with public health, animal health, and veterinary sector colleagues.  

Recommended actions  

It is recommended that Member States and national authorities: 

• increase surveillance and vigilance, in human populations, especially amongst occupationally exposed persons, for the possibility of zoonotic infections, particularly through National Influenza Centres (NICs) and other influenza laboratories associated with GISRS; 

• assess and reduce the risk among occupationally exposed persons using methods such as active case finding and molecular and serologic methods, reducing environmental exposures, providing adequate and appropriate personal protective equipment; 

• conduct active case finding around suspected and confirmed human cases to determine if there are additional cases or indications of human-to-human transmission; and   

• work with national agencies and partners to better understand the exposure to and risk from raw/unpasteurized milk and milk products.  

Under the International Health Regulations (IHR) (2005),{55} States Parties are required to notify WHO within 24 hours of any laboratory-confirmed case of human influenza caused by a new subtype according to the WHO case definition.{56} WHO has published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005).{57}  

Member States and national authorities are also recommended to: 

• increase surveillance and timely reporting efforts for the early detection of A(H5) influenza viruses in domestic birds, wild birds and mammals{58}; 

• include infection with an A(H5) influenza virus as a differential diagnosis, in non-avian species, including cattle, swine and other livestock and farmed domestic and wild animal populations, with high likelihood of exposure to A(H5) viruses; 

• Implement preventive and early response measures to break the chain of infection among domestic animals (for example, poultry and dairy cattle)    

• promptly report high pathogenicity avian influenza (HPAI) events in all animal species, including domestic and wild mammals, to WOAH and other international organizations such as FAO; 

• conduct genetic sequencing and share genetic sequences of influenza viruses and associated metadata in publicly available databases; 

• mitigate the risk of introduction and spread of the disease in animals by implementing and/or strengthening biosecurity in livestock holdings/premises and along the value chain;  

• employ good production and hygiene practices when handling animals and animal products, and protect persons in contact with suspected/infected animals with appropriate personal protective equipment, information and access to testing; and 

• strengthen communication and education on the importance and proper use of personal protective equipment to individuals at risk of exposure to animal influenza viruses. 

Additional sets of recommendations related to avian influenza viruses with zoonotic potential can be found in: • WOAH Statement on High Pathogenicity Avian Influenza in Cattle, Updated 6 December 2024. • FAO Recommendations for the surveillance of influenza A(H5N1) in cattle with broader application to other farmed mammals, published 27 November 2024 • FAO alert on avian influenza: Risk of upsurge and regional spread through wild birds in Latin America and the Caribbean in English and Spanish • FAO recommendations for Global Avian Influenza Viruses with Zoonotic Potential. • FAO EMPRES Watch entitled ‘A(H5N1) influenza in dairy cattle in the United States of America’. • WHO Practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses • CDC Information for Workers Exposed to H5N1 Bird Flu 

Additional studies/surveillance, applying One Health principles are warranted, which could provide information to enhance confidence in the risk assessment. These may include serological studies in high-risk animal populations, in high-risk human populations, and epidemiological investigations.  Anyone who may have been exposed to infected or potentially infected animals or contaminated environments should be advised to promptly seek health care if they feel unwell, and to inform their health care provider of their possible exposure. Following prompt testing, early and appropriate clinical management should be initiated, and precautionary measures put in place to assess and prevent potential further spread among humans and animals.  Clinicians should also be alerted to potential zoonotic infection in patients with an exposure history to birds or animals especially in areas where A(H5N1) viruses are known or suspected to be circulating in animals but also in areas where surveillance in animals may be limited.  

Routine epidemiologic and virologic surveillance for influenza should be conducted ideally yearround using a standard case definition in healthcare facilities according to WHO guidance.{59}  Timely sharing of information and sequence data from both the human and animal health sectors from all regions should continue to be strongly recommended and is critical for rapid and robust joint risk assessment. The rapid sharing of virus materials with WHO Collaborating Centres of GISRS continues to be essential to conduct a thorough risk assessment and develop or adjust targeted response measures. 

The Tool for Influenza Pandemic Risk Assessment (TIPRA) provides an in-depth assessment of risk associated with some zoonotic influenza viruses – notably the likelihood of the virus gaining human-to-human transmissibility, and the impact should the virus gain such transmissibility. TIPRA maps relative risk amongst viruses assessed using multiple elements.{60} 

Data pertaining to the risk elements within TIPRA should be generated and shared with WHO.  

Efforts to reduce human exposure to birds, livestock, and other mammals infected with or potentially infected with avian and other animal influenza viruses should be implemented and enhanced to minimize the risk of zoonotic infections. Individuals with activities that involve exposure to infected animals and/or contaminated environments are at higher risk and should take necessary precautions to prevent infection.{61} 

Those who are exposed to potentially infected animals should have access to, be trained in their use under different environmental conditions, and wear personal protective equipment including eye protection.{62} 

If they develop respiratory symptoms or conjunctivitis, they should be rapidly tested, and precautionary infection control measures should be put in place to prevent potential further spread among humans and to animals. 

For detailed guidance on treatment, refer to relevant global and national guidance.{63} 

Some manufacturers have initiated production of an A(H5) human vaccine that matches current circulating strains. Although a few countries are procuring vaccine to vaccinate occupationally exposed persons, this is not currently being recommended as a global strategy considering the limited number of human infections with A(H5N1) 2.3.4.4b viruses.  

Investigations are ongoing to understand the risk to humans from consuming raw/unpasteurized milk contaminated with A(H5N1) virus. FAO, WHO and WOAH advise consuming pasteurized milk. Due to the potential health risks from many dangerous zoonotic pathogens, raw/unpasteurized milk consumption should be avoided. 

If pasteurized milk is not available, heating raw milk until it boils makes it safer for consumption.{64}  

More information will be available as investigations are actively ongoing in the USA and elsewhere. WHO and GISRS, jointly with FAO, WOAH and OFFLU are working closely together to continuously assess the avian influenza situation. This includes increased surveillance and testing to monitor the evolution and geographic spread of avian influenza viruses, including A(H5N1) viruses, to provide timely and updated joint risk assessments.  

References 

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Source: World Health Organization, https://www.who.int/publications/m/item/updated-joint-fao-who-woah-assessment-of-recent-influenza-a(h5n1)-virus-events-in-animals-and-people_dec2024

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#USA, #Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (Dec. 20 '24)

 {Excerpt}

Time Period: December 08 - December 14, 2024

H5 Detection: 49 sites (14.5%)

No Detection: 288 sites (85.5%)

No samples in last week: 35 sites

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Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html

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#USA, Novel Influenza A #H5N1 Virus, four new cases detected in week 50/2024 {2 in #California, 1 in #Louisiana, 1 in #Delaware} (US #CDC FluView)

{Excerpt}

Three confirmed cases and one probable influenza A(H5) case were reported to CDC this week. 

To date, human-to-human transmission of influenza A(H5) virus has not been identified in the United States.

Two of these confirmed cases were reported by the California Department of Public Health. The cases occurred in a workers aged ≥18 years at a commercial dairy cattle farm in an area where highly pathogenic avian influenza (HPAI) A(H5N1) viruses had been detected in cows. The individuals had mild symptoms, which they reported to local health department officials. There have now been 34 total confirmed cases and one probable case in California.

The other confirmed case was reported by the Louisiana Department of Health. This case occurred in an individual aged ≥18 years. This individual developed respiratory symptoms during week 48 and was hospitalized with their illness. A respiratory specimen was collected at the healthcare facility and tested positive for influenza A, but negative for seasonal virus subtypes. The specimen was sent to the Louisiana Public Health Laboratory for further testing, where it tested presumptive positive for influenza A(H5) virus using the CDC influenza A(H5) assay. Influenza A(H5) virus was confirmed at CDC. The investigation by public health officials identified exposure to backyard poultry prior to the patient's illness onset. The patient remains hospitalized. This is the first influenza A(H5) case in Louisiana and the first instance of severe illness from influenza A(H5) virus infection in the United States.

The probable case was reported by the Delaware Division of Public Health. The case occurred in an individual aged ≥18 years. This individual developed respiratory symptoms during week 48 and sought healthcare for their illness. A respiratory specimen was collected at the healthcare facility and tested positive for influenza A. The specimen was sent to the Delaware Public Health Laboratory for routine surveillance, where it tested presumptive positive for influenza A(H5) virus using the CDC influenza A(H5) assay. The specimen was negative for influenza A(H5) virus using diagnostic RT-PCR at CDC. The investigation by public health officials did not find any exposure to poultry or cows or consumption of raw dairy products prior to the patient's illness onset. The patient has since recovered. This is the first probable case in Delaware.

Notification of the case reported by the Louisiana Department of Health to WHO was initiated per International Health Regulations (IHR). More information regarding IHR can be found at http://www.who.int/topics/international_health_regulations/en/. 

No additional notification to WHO of the probable case or confirmed cases exposed to dairy cows in California is required per International Health Regulations (IHR).

The CSTE position statement, which includes updated case definitions for confirmed, probable, and suspected cases is available at http://www.cste.org/resource/resmgr/position_statements_files_2023/24-ID-09_Novel_Influenza_A.pdf

An up-to-date human case summary during the 2024 outbreak by state and exposure source is available at www.cdc.gov/bird-flu/situation-summary/index.html

Information about avian influenza is available at https://www.cdc.gov/flu/avianflu/index.htm.

Interim recommendations for Prevention, Monitoring, and Public Health Investigations are available at https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html.

The latest case reports on avian influenza outbreaks in wild birds, commercial poultry, backyard or hobbyist flocks, and mammals in the United States are available from the USDA at https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/avian/avian-influenza/2022-hpai.

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Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/fluview/surveillance/2024-week-50.html

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#Norway - #Influenza A #H5N5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 A wild Eurasian Lynx in Troms Og Finnmark.

Source: WOAH, https://wahis.woah.org/#/in-review/6117

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

 Forty Southern elephant seal (WILD), Sealion Island.

Source: WOAH, https://wahis.woah.org/#/in-review/6118

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

 A wild red fox in Podravska Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6119

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#Influenza Virus #Surveillance from the 1918 Influenza #Pandemic to the 2020 #Coronavirus Pandemic in #NewYork State, #USA

Abstract

A historical perspective of more than one hundred years of influenza surveillance in New York State demonstrates the progression from anecdotes and case counts to next-generation sequencing and electronic database management, greatly improving pandemic preparedness and response. Here, we determined if influenza virologic surveillance at the New York State public health laboratory (NYS PHL) tests sufficient specimen numbers within preferred confidence limits to assess situational awareness and detect novel viruses that pose a pandemic risk. To this end, we analyzed retrospective electronic data on laboratory test results for the influenza seasons 1997–1998 to 2021–2022 according to sample sizes recommended in the Influenza Virologic Surveillance Right Size Roadmap issued by the Association of Public Health Laboratories and Centers for Disease Control and Prevention. Although data solely from specimens submitted to the NYS PHL were insufficient to meet surveillance goals, when supplemented with testing data from clinical laboratories participating in surveillance programs, the recommended surveillance goals were achieved. Despite the sudden decline in influenza cases in 2020–2021, impacted by the COVID-19 mitigation measures, the dramatic increases in influenza cases surrounding the coronavirus pandemic reveal that influenza remains a national and international public health threat. Sample submissions to public health laboratories must be encouraged to facilitate monitoring for emerging viruses and preparedness for another pandemic.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1952

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#Persistence of #Oropouche virus in #body #fluids among imported cases in #France, 2024

{Extract}

Since late 2023, more than 10 000 locally acquired cases of Oropouche virus have been reported in the Americas.1 Here, we describe the first cluster of Oropouche virus imported into France from Cuba, where transmission has been ongoing since at least May, 2024.2 Oropouche virus infection was documented in a group of five women (patients 1–5, confirmed cases) travelling to Cuba with two infants (patients 6–7, suspect cases) between July 28 and Aug 14, 2024. During their stay, patients 1–5 developed a dengue-like syndrome lasting 2–11 days, presenting symptoms similar to those described in the literature for Oropouche virus infection (appendix p 8).3 After recovery, patients 1, 2, and 5 experienced symptom relapse upon their return to France; the observed relapse rate aligns with recent estimates suggesting that 60% of patients with Oropouche virus experience a biphasic illness (appendix pp 7–8).4 During relapse, patient 1 sought medical advice, becoming the first diagnosed Oropouche virus case in this series and leading to the investigation of the cluster.

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Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00815-6/fulltext?rss=yes

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Use of #equine #H3N8 #hemagglutinin as a broadly protective #influenza #vaccine immunogen

Abstract

Development of an efficacious universal influenza vaccines remains a long-sought goal. Current vaccines have shortfalls such as mid/low efficacy and needing yearly strain revisions to account for viral drift/shift. Horses undergo bi-annual vaccines for the H3N8 equine influenza virus, and surveillance of sera from vaccinees demonstrated very broad reactivity and neutralization to many influenza strains. Subsequently, vaccinating mice using the equine A/Kentucky/1/1991 strain or recombinant hemagglutinin (HA) induced similar broadly reactive and neutralizing antibodies to seasonal and high pathogenicity avian influenza strains. Challenge of vaccinated mice protected from lethal virus challenges across H1N1 and H3N2 strains. This protection correlated with neutralizing antibodies to the HA head, esterase, and stem regions. Vaccinated ferrets were also protected after challenge with H1N1 influenza A/07/2009 virus using whole viral or HA. These data suggest that equine H3N8 induces broad protection against multiple influenzas using a unique antigen that diverges from other universal vaccine approaches.

Source: npj Vaccines, https://www.nature.com/articles/s41541-024-01037-1

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Respiratory Virus-Specific and #Time-Dependent #Interference of #Adenovirus Type 2, #SARS-CoV-2 and #Influenza Virus #H1N1pdm09 During Viral Dual Co-Infection and Superinfection In Vitro

Abstract

Background. 

Understanding the interference patterns of respiratory viruses could be important for shedding light on potential strategies to combat these human infectious agents. 

Objective. 

To investigate the possible interactions between adenovirus type 2 (AdV2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/H1N1 pandemic (H1N1pdm09) using the A549 cell line. 

Methods. 

Single infections, co-infections, and superinfections (at 3 and 24 h after the first virus infection) were performed by varying the multiplicity of infection (MOI). Virus replication kinetics and the mRNA expression of IFN-α, IL-1α and IL-6 were assessed by real-time qPCR. 

Results. 

Co-infection experiments showed different growth dynamics, depending on the presence of the specific virus and time. AdV2 replication remained stable or possibly enhanced in the presence of co-infection with each of the two H1N1pdm09 and SARS-CoV-2 viruses used. In contrast, SARS-CoV-2 replication was facilitated by H1N1pdm09 but hindered by AdV2, indicating possible different interactions. Finally, H1N1pdm09 replication exhibited variably effectiveness in the presence of AdV2 and SARS-CoV-2. Superinfection experiments showed that the replication of all viruses was affected by time and MOI. The mRNA expression of IFN-α, IL-1α and IL-6 showed divergent results depending on the virus used and the time of infection. 

Conclusions. 

Further investigation of co-infection or superinfection may be helpful in understanding the potential relationship involved in the outcome of viral respiratory infection in the human population.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1947

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Are we cultivating the perfect #storm for a #human avian #influenza #pandemic?

Abstract

The emergence of highly pathogenic avian influenza (HPAI) A H5N1 virus in dairy cattle marks a troubling new chapter in the ongoing battle against zoonotic diseases. Since its initial detection in 1955, the H5N1 virus has primarily been associated with poultry, posing significant threats to both animal and human health. However, recent outbreaks in U.S. dairy herds across nine states have revealed an alarming expansion of the virus, with over 190 herds affected as of September 2024. This unprecedented spread in cattle has sparked intense concern among scientists and health officials, especially with reports indicating that up to 20% of dairy products may contain traces of the virus. The implications of the H5N1 virus establishing itself in cattle populations are profound. This potential endemic presence could transform dairy farms into reservoirs of the virus, facilitating its evolution and increasing the risk of human transmission. Mutations enhancing viral replication in mammals have already been identified, including the notorious PB2 E627K mutation linked to increased virulence. Moreover, the detection of the virus in the central nervous system of infected animals, including cats, underscores the broad tissue tropism and severe pathogenic potential of the H5N1 virus. Current containment efforts include stringent biosecurity measures and financial incentives for enhanced testing and personal protective equipment (PPE) for farmers. Yet, gaps in testing infrastructure and the resurgence of raw milk consumption pose significant challenges. The U.S. Department of Agriculture (USDA) and the Centers for Disease Control and Prevention (CDC) emphasize the critical need for comprehensive testing and pasteurization to mitigate the risk of human infection. As the scientific community races to adapt existing antiviral treatments and develop effective vaccines, the concept of a One Health approach becomes increasingly vital. This holistic strategy calls for coordinated actions across human, animal, and environmental health sectors to preemptively tackle emerging zoonotic threats. Strengthening surveillance, fostering international cooperation, and investing in research are essential steps to prevent the H5N1 virus from igniting the next global health crisis. The current avian influenza outbreak serves as a stark reminder of the delicate balance between human activities and viral evolution. Our collective ability to respond effectively and proactively will determine whether we can avert the perfect storm brewing on the horizon.

Source: Biological Research, https://biolres.biomedcentral.com/articles/10.1186/s40659-024-00570-6

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Revealing novel #CD8+ T-cell #epitopes from the #H5N1 avian #influenza virus in HBW/B1 haplotype #ducks

Abstract

The duck CD8+ T-cell response effectively defends against H5N1 highly pathogenic avian influenza virus (HPAIV) infection, but the recognized peptide is rarely identified. Here, we found that the ratio of CD8+ T cells and the expression of IFN-γ and cytotoxicity-associated genes, including granzyme A/K, perforin and IL2, at 7 days post-infection in peripheral blood mononuclear cells (PBMCs) from B1 haplotype ducks significantly increased in the context of defending against H5N1 AIV infection in vivo. Moreover, similar results were observed in cultured and sorted H5N1 AIV-stimulated duck CD8+ T cells in vitro. Next, we selected 109 epitopes as candidate epitopes on the basis of the MHC-I restriction binding peptide prediction website database and further identified twelve CD8+ T-cell epitopes that significantly increased IFN-γ gene expression after stimulating B1 haplotype duck memory PBMCs. In particular, NP338−346, NP473−481, M2−10, PB1540−548 and PA80−88 were highly conserved in H5N1, H5N6, H5N8, H7N9, and H9N2 AIVs. These findings provide directions for the development of universal T-cell epitope vaccines for AIV in ducks.

Source: Veterinary Research, https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-024-01415-6

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An #influenza #mRNA #vaccine protects #ferrets from lethal #infection with highly pathogenic avian #influenza A(#H5N1) virus

Abstract

The global spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus poses a serious pandemic threat, necessitating the swift development of effective vaccines. The success of messenger RNA (mRNA) vaccine technology in the COVID-19 pandemic, marked by its rapid development and scalability, demonstrates its potential for addressing other infectious threats, such as HPAI A(H5N1). We therefore evaluated mRNA vaccine candidates targeting panzootic influenza A(H5) clade 2.3.4.4b viruses, which have been shown to infect a range of mammalian species, including most recently being detected in dairy cattle. Ferrets were immunized with mRNA vaccines encoding either hemagglutinin alone or hemagglutinin and neuraminidase, derived from a 2.3.4.4b prototype vaccine virus recommended by the World Health Organization. Kinetics of the immune responses, as well as protection against a lethal challenge dose of A(H5N1) virus, were assessed. Two doses of mRNA vaccination elicited robust neutralizing antibody titers against a 2022 avian isolate and a 2024 human isolate. Further, mRNA vaccination conferred protection from lethal challenge, whereas all unvaccinated ferrets succumbed to infection. It also reduced viral titers in the upper and lower respiratory tracts of infected ferrets. These results underscore the effectiveness of mRNA vaccines against HPAI A(H5N1), showcasing their potential as a vaccine platform for future influenza pandemics.

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#Surveillance #Strategy in #Duck Flocks Vaccinated against Highly Pathogenic Avian #Influenza Virus

Abstract

Since 2016, epizootics of highly pathogenic avian influenza (HPAI) virus have threatened the poultry sector in Europe. Because conventional prevention and control measures alone were insufficient in some contexts, the European Commission authorized poultry vaccination in 2023. Subsequently, France launched a nationwide duck vaccination campaign combined with a comprehensive surveillance plan. We used a mathematical model to simulate the transmission of HPAI viruses in vaccinated duck flocks and assess the effectiveness of a wide range of surveillance strategies. Sampling and testing dead ducks every week (enhanced passive surveillance) was the most sensitive (≈90%) and the most timely strategy. Active surveillance through monthly testing of a cross-sectional sample of live ducks was the least sensitive and timely strategy. Thus, we advise focusing HPAI surveillance efforts on enhanced passive surveillance and reducing active surveillance of live ducks.

Source: Emerging Infectious Diseases Journal, https://wwwnc.cdc.gov/eid/article/31/1/24-1140_article

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#USA confirms its first severe case of #H5N1 #flu - #California declares state of #emergency - #UN agencies warn: This epidemic "is increasingly crossing species barriers"

According to CCTV News, on December 18 local time, California Governor Gavin Newsom declared a state of emergency in California to deal with the increasingly serious avian influenza epidemic.

Although there have been no cases of human-to-human transmission in California, 61 people have been infected with avian influenza in the United States, 34 of which are from California. Newsom emphasized that although the risk is low, the government will continue to take necessary measures to prevent the spread of the virus and open funds to support the emergency response of relevant agencies.

According to Xinhua News Agency, the U.S. Centers for Disease Control and Prevention issued a statement on the 18th saying that the United States reported the first severe case of human infection with the H5N1 avian influenza virus . The patient was hospitalized and his infection may be related to contact with sick and dead poultry raised in private backyard farms.

The CDC said in a statement that the patient was from Louisiana, and was diagnosed with the H5N1 avian influenza virus on the 13th. The investigation into the source of infection is still ongoing, but it can be confirmed that the patient had contact with sick and dead poultry raised in a private backyard farm. This is also the first case of human infection with the H5N1 avian influenza virus in the United States related to a private backyard farm.

Preliminary genetic analysis results show that the avian influenza virus that infected the patient belongs to the D1.1 type. The CDC is conducting further genome sequencing on the virus samples.

According to the data from the US Centers for Disease Control and Prevention, since April this year, a total of 61 cases of human infection with the H5 avian influenza virus have been reported in the United States. The agency said that it is not surprising that some people have been seriously ill with the H5N1 avian influenza. Previously, other countries have reported cases of severe illness or death from human infection with the H5N1 avian influenza. So far, no human-to-human transmission of the H5 avian influenza virus has been found. The direct risk to public health posed by the H5N1 avian influenza is still low.

The CDC reminds the public to avoid contact with sick or dead animals, especially wild birds and poultry, as much as possible. Individuals who have direct or close contact with wild birds or sick, dead poultry and other animals need to wear protective equipment.

According to a report by Xinhua News Agency on November 7, a new study conducted by researchers from the US Centers for Disease Control and Prevention and other institutions showed that the actual number of US dairy farm workers infected with the highly pathogenic H5N1 avian influenza virus may far exceed official statistics. The relevant research report was published in the US Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Journal.

From June to August 2024, researchers collected and tested blood samples from workers on dairy farms in Michigan and Colorado, where outbreaks of highly pathogenic H5N1 avian influenza had occurred. They found that 8 of the 115 workers tested had recently been infected with the H5N1 avian influenza virus, with an infection rate of 7%.

Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security in the United States, said that thousands of dairy workers may have been exposed to infected dairy cows, and the new study shows that many cases have been missed. She believes that it is likely that most or all states with H5N1 avian influenza outbreaks have human cases.

Since March this year, the H5N1 avian influenza virus has continued to spread in the United States. According to the latest statistics from the U.S. Department of Agriculture, the H5N1 avian influenza virus has been detected in more than 440 dairy cow herds in 15 states in the United States.

In response to the latest findings, the CDC is expanding testing of affected dairy farm workers. The agency is also recommending that workers who have had high-risk contact with infected animals take antiviral drugs.

According to Cankaoxiaoxi.com, Reuters reported on October 31 that bird flu has spread rapidly among poultry in many EU countries this season, raising concerns about a repeat of the crisis. Previous bird flu outbreaks have killed tens of millions of poultry in many EU countries, and people are also worried that bird flu could be transmitted to humans.

The UK Department for Environment, Food and Rural Affairs announced on December 17 that cases of highly pathogenic avian influenza were confirmed in two breeding farms in Norfolk. The animal health department decided to kill the poultry in the farms and designate protection and monitoring areas.

The Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health and other organizations warned at a briefing at the United Nations Office in Geneva on the 17th that the avian influenza epidemic sweeping the world "is increasingly crossing species barriers . "

Gregorio Torres, director of the Scientific Department of the World Organization for Animal Health, said that since October 2021, the avian influenza epidemic has killed more than 300 million poultry worldwide. The virus is increasingly crossing species barriers, infecting poultry and wild mammals, causing serious impacts on the ecosystem.

FAO official Madhur Dingra also pointed out that the impact of the highly pathogenic avian influenza virus has spread to wild animals, infecting more than 500 species of birds and more than 70 species of mammals, including endangered animals such as polar bears.

Source: SINA, https://news.sina.com.cn/w/2024-12-19/doc-inczynpw0156337.shtml

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#USA, DHS Reports Presumptive Positive #Human Case of Highly Pathogenic Avian #Influenza (#H5N1) in #Wisconsin

{Excerpt}

The Wisconsin Department of Health Services (DHS) has detected the first presumptive positive human case of Highly Pathogenic Avian Influenza A (H5N1), also known as bird flu, in Barron County. The human case follows an infected flock of commercial poultry identified in Barron County. The person had exposure to the infected flock. The case was identified through testing at the Wisconsin State Lab of Hygiene (WSLH) and is pending confirmation at CDC (Centers for Disease Control and Prevention).

DHS, in coordination with Barron County Health and Human Services, is monitoring farm workers who may have been exposed to the virus and has provided them with information to protect their health. The risk to the general public in Wisconsin remains low. People who work with infected animals, or have recreational exposure to them, are at higher risk.

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Source: Department of Health, https://www.dhs.wisconsin.gov/news/releases/121824.htm

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#USA, #CDC Confirms First Severe Case of #H5N1 #Birdflu in the United States

December 18, 2024-- A patient has been hospitalized with a severe case of avian influenza A(H5N1) virus ("H5N1 bird flu") infection in Louisiana. 

This marks the first instance of severe illness linked to the virus in the United States. The case was confirmed by the Centers for Disease Control and Prevention (CDC) on Friday, December 13. 

Since April 2024, there have been a total of 61 reported human cases of H5 bird flu reported in the United States.

Partial viral genome data of the H5N1 avian influenza virus that infected the patient in Louisiana indicates that the virus belongs to the D1.1 genotype related to other D1.1 viruses recently detected in wild birds and poultry in the United States and in recent human cases in British Columbia, Canada, and Washington state. This H5N1 bird flu genotype is different than the B3.13 genotype detected in dairy cows, sporadic human cases in multiple states, and some poultry outbreaks in the United States. Additional genomic sequencing and efforts to isolate virus from clinical specimens from the patient in Louisiana are underway at CDC.

While an investigation into the source of the infection in Louisiana is ongoing, it has been determined that the patient had exposure to sick and dead birds in backyard flocks. This is the first case of H5N1 bird flu in the U.S. that has been linked to exposure to a backyard flock. A sporadic case of severe H5N1 bird flu illness in a person is not unexpected; avian influenza A(H5N1) virus infection has previously been associated with severe human illness in other countries during 2024 and prior years, including illness resulting in death. No person-to-person spread of H5 bird flu has been detected. This case does not change CDC's overall assessment of the immediate risk to the public's health from H5N1 bird flu, which remains low.

This case underscores that, in addition to affected commercial poultry and dairy operations, wild birds and backyard flocks also can be a source of exposure. People with work or recreational exposures to infected animals are at higher risk of infection and should follow CDC's recommended precautions when around animals that are infected or potentially infected with H5N1 avian influenza virus. This means that backyard flock owners, hunters and other bird enthusiasts should also take precautions.

The best way to prevent H5 bird flu is to avoid exposure whenever possible. Infected birds shed avian influenza A viruses in their saliva, mucous, and feces. Other infected animals may shed avian influenza A viruses in respiratory secretions and other bodily fluids (e.g., in unpasteurized cow milk or 'raw milk').

As a general precaution, whenever possible, people should avoid contact with sick or dead animals, in particular wild birds, and poultry.

For individuals with direct/close contact with wild birds or sick or dead poultry or other animals, wear recommended personal protective equipment (PPE). Wild birds can be infected with avian influenza A viruses even if they don't look sick.

-- Do not touch surfaces or materials (e.g., animal litter or bedding material) contaminated with saliva, mucous, or animal feces from wild or domestic birds or other animals with confirmed or suspected avian influenza A virus infection.

For more information on H5 bird flu in the U.S. and CDC's response, including regularly updated case counts, visit the H5 Bird Flu: Current Situation page.

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/media/releases/2024/m1218-h5n1-flu.html

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