Friday, March 7, 2025

#UK, #England: #Lassa #fever contact #tracing underway

The UK Health Security Agency has been informed under the International Health Regulations that an individual travelled to England from Nigeria while they were unwell with Lassa fever at the end of February. The individual returned to Nigeria where they were diagnosed.

We are now working to identify people who were in contact with the affected individual while they were in the country.

Lassa fever does not spread easily between people and the overall risk to the public is very low. If you have not been contacted by UKHSA then you are very unlikely to have had any exposure to Lassa fever and do not need to take action.

Lassa fever causes acute infections which can range from very mild symptoms through to a severe viral haemorrhagic fever. People usually become infected with Lassa virus through exposure to food or household items contaminated with urine or faeces of infected rats – present in some West African countries where the disease is endemic. The virus can also be spread between people through contact with infectious bodily fluids.

Dr Meera Chand, Deputy Director at the UK Health Security Agency, said:

''Our Health Protection Teams are working at pace to get in touch with people who were in contact with this individual while they were in England, to ensure they seek appropriate medical care and testing should they develop any symptoms. The infection does not spread easily between people, and the overall risk to the UK population is very low.''

Source: UK Health Security Agency, https://www.gov.uk/government/news/lassa-fever-contact-tracing-underway

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

 A wild Carrion Crow in Khabarovsk Region.

Source: https://wahis.woah.org/#/in-review/6304

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#UK - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

{England} Commercial turkey fattening unit with 27,658 turkeys. Increased mortality and other clinical signs of HPAI reported. The samples were positive for HPAI H5N1.

Source: WOAH, https://wahis.woah.org/#/in-review/6314

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

 This event will collect the detections made by sampling carried out in 2025. Peregrine falcon, adult male, transmitted to a Centre for the protection of endangered species on 05/02/2025 with nervous symptoms, that died on 06/02/2025. The necropsy was performed at the Wildlife Center for Analysis and Diagnosis.

Source: WOAH, https://wahis.woah.org/#/in-review/6316

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Variable #DPP4 #expression in multiciliated cells of the #human #nasal #epithelium as a determinant for #MERS-CoV tropism

Significance

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic coronavirus that continues to cause periodic outbreaks in humans with a case-fatality rate of approximately 35%. MERS-CoV generally transmits poorly, but superspreading events are well documented. Efficient human-to-human transmission of respiratory viruses generally correlates with a tropism for the upper respiratory tract, but this tropism for MERS-CoV remains poorly understood. Characterizing the MERS-CoV tropism in the human upper respiratory tract is of critical importance to understand its epidemiology and pandemic potential of future MERS-CoV variants and other dipeptidyl peptidase 4 (DPP4)-utilizing coronaviruses present in animal reservoirs.


Abstract

Transmissibility of respiratory viruses is a complex viral trait that is intricately linked to tropism. Several highly transmissible viruses, including severe acute respiratory syndrome coronavirus 2 and Influenza viruses, specifically target multiciliated cells in the upper respiratory tract to facilitate efficient human-to-human transmission. In contrast, the zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) generally transmits poorly between humans, which is largely attributed to the absence of its receptor dipeptidyl peptidase 4 (DPP4) in the upper respiratory tract. At the same time, MERS-CoV epidemiology is characterized by occasional superspreading events, suggesting that some individuals can disseminate this virus effectively. Here, we utilized well-differentiated human pulmonary and nasal airway organoid-derived cultures to further delineate the respiratory tropism of MERS-CoV. We find that MERS-CoV replicated to high titers in both pulmonary and nasal airway cultures. Using single-cell messenger-RNA sequencing, immunofluorescence, and immunohistochemistry, we show that MERS-CoV preferentially targeted multiciliated cells, leading to loss of ciliary coverage. MERS-CoV cellular tropism was dependent on the differentiation of the organoid-derived cultures, and replication efficiency varied considerably between donors. Similarly, variable and focal expression of DPP4 was revealed in human nose tissues. This study indicates that the upper respiratory tract tropism of MERS-CoV may vary between individuals due to differences in DPP4 expression, providing an explanation for the unpredictable transmission pattern of MERS-CoV.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2410630122

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A #human-infecting #H10N5 avian #influenza virus: #clinical features, virus #reassortment, #receptor-binding affinity, and possible #transmission routes

Abstract

Background

In late 2023, the first human case caused by an H10N5 avian influenza virus (AIV) was diagnosed in China. H10Ny AIVs have been identified in various poultry and wild birds in Eurasia, the Americas, and Oceania.

Methods

We analyzed the clinical data of the H10N5 AIV-infected patient, isolated the virus, and evaluated the virus receptor-binding properties together with the H10N8 and H10N3 AIVs identified in humans and poultry. The genomic data of the human-infecting H10N5 strain and avian H10Ny AIVs (n = 48, including 16 strains of H10N3 and 2 strains of H10N8) from live poultry markets in China, during 2019–2021, were sequenced. We inferred the genetic origin and spread pattern of the H10N5 AIV using the phylodynamic methods. In addition, given all available nucleotide sequences, the spatial-temporal dynamics, host distribution, and the maximum-likelihood phylogenies of global H10 AIVs were reconstructed.

Findings

The first H10N5 AIV-infected human case co-infected with seasonal influenza H3N2 virus was identified. Unfortunately, the patient died after systematic treatments. The H10N5 virus predominantly bound avian-type receptor, without any known mammalian-adapted mutations. Phylodynamic inference indicated that the H10N5 AIV was generated by multiple reassortments among viruses from Korea and Japan, central Asia, and China in late 2022, acquiring the seven gene segments from H10N7 or other low pathogenic AIVs in wild Anseriformes, except for the PA gene from H5N2 AIVs in Domestic Anseriformes. The HA gene of the H10N5 virus belongs to the North American lineage, which was probably introduced into Asia by migratory birds, subsequently forming local circulation.

Interpretation

Unlike the human-infecting H10N3 and H10N8 AIVs acquiring six internal protein-coding genes from H9N2 AIVs in domestic poultry, the human-infecting H10N5 AIV was generated through multiple reassortments among viruses mainly carried by wild Anseriformes. Furthermore, worldwide distribution, inter-continental transmission, and genetic exchanges between Eurasian and North American lineages call for more concerns about influenza surveillance on H10Ny AIVs, especially in the flyway overlapping areas.

Source: Journal of Infection, https://www.journalofinfection.com/article/S0163-4453(25)00050-7/fulltext

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#Belgium - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Follow up report 8

Two wild cats, two European Polecats, Forty-four Domestic Mustelidae, Twenty-two foxes in various Regions.

Source: WOAH, https://wahis.woah.org/#/in-review/4971?reportId=172740&fromPage=event-dashboard-url

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#Risk to People in #USA from Highly Pathogenic Avian #Influenza A(#H5N1) Viruses {as of Feb. 28 '25}



As of February 28, 2025

CDC assessed the risk from H5N1 viruses to the U.S. general population and to populations in the United States with contact with potentially infected animals, including through contaminated surfaces or fluids. Risk describes the potential public health implications and significance of an outbreak for populations assessed. See definitions below for more detail.


{Risk posed by H5N1 viruses to the United States. Please see methods section for further information on definitions of terms.}

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The purpose of this assessment is to evaluate the current public health risk of H5N1 viruses to the general U.S. population and to those in contact with potentially infected animals or contaminated surfaces or fluids, and to inform public health preparedness efforts.

CDC assessed risk by considering both likelihood and impact of infection in each population (...). Both the likelihood and impact of infection are assessed at a population level. Likelihood of infection refers to the probability of infection occurring in the population of interest and considers factors such as the likelihood of transmission to or within the population, the number of people exposed and/or infected, population immunity against infection, and effectiveness or capacity of public health measures to limit spread. Impact of infection considers factors such as the severity of disease, level of population immunity against severe disease, availability of resources to limit impact, and necessary public health response resources.

This assessment outlines the current risk posed by H5N1 viruses to populations in the United States based on currently available data; however, this risk could change. H5N1 viruses are of public health concern because of their pandemic potential. If an H5N1 virus acquires the ability through genetic mutation or reassortment to cause sustained human-to-human transmission, it could cause a pandemic. Because influenza viruses constantly change, CDC monitors these viruses routinely, works to prevent further spread of H5N1 viruses between animals and people, and coordinates H5N1 preparedness activities. CDC will update this risk assessment as needed.


Risk assessment for general U.S. population


{Risk posed by H5N1 viruses to the general U.S. population. Please see methods section for further information on definitions of terms.}

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Risk

CDC assesses the overall risk to the general U.S. population as low, with moderate confidence. Of note, for any individual in this population, risk will vary depending on nature of, frequency, and time spent in contact with infected or potentially infected animals or contaminated surfaces or fluids. We also include a section below on factors that could change our assessment.

Likelihood

CDC assesses the likelihood of infection for the general U.S. population as very low. Factors that informed our assessment of likelihood include the following:

- To date, there has been no evidence of human-to-human spread of H5N1 viruses in the United States, and there have been very few reported cases among people in the general population to date. The majority of confirmed human H5N1 cases in the United States since 2024 (67 of 70) were associated with exposure to infected animals, including poultry and dairy cows. Three U.S. cases in humans with no known exposure to infected animals have been identified.

- The likelihood of exposure is higher among people in settings where infected birds or dairy cows have been identified, including occupational settings. See our risk assessment for populations in contact with potentially infected animals below.

- To date, there has been little evidence of genetic changes that suggest adaptation to humans.

- Genetic analysis of samples from the fatal Louisiana case detected low frequency changes that may result in the increased ability of these viruses to infect the human upper respiratory tract. These or similar changes or mutations may be needed for H5N1 viruses to be able to spread more easily to and among humans.

- The observed genetic changes in the patient's H5N1 virus, when compared with the virus identified from the patient's backyard poultry (the presumed source of human infection), suggest that the changes were likely generated by virus replication in this patient after hospital admission for advanced disease and were not present at the time of infection.

- Genetic analysis of samples from the Wyoming and Nevada cases found mutations that have previously been associated with more efficient H5N1 virus replication in mammalian cells and in people.

- The likelihood of exposure is higher among people consuming raw (unpasteurized) milk from infected animals, although the chance of people acquiring H5N1 virus infection from consuming raw milk is not clear at this time.

- Consumption of raw milk can lead to other serious health outcomes, especially for certain populations. CDC and FDA recommend against consuming raw milk.

- Raw milk sold commercially in California has tested positive for H5N1 virus. While USDA's National Milk Testing Strategy tests milk samples from across the country before pasteurization, raw milk in many states can be purchased directly from the farms where it is produced, and may not be captured in these testing protocols.

- There are no confirmed cases of human H5N1 virus infection associated with consuming contaminated raw milk. However, animals such as mice and cats have been infected following consumption of milk contaminated with H5N1 virus, and the possibility of human infection with H5N1 virus through ingestion of raw milk cannot be ruled out.

- The United States has resources to detect symptomatic human cases of H5N1 and can implement measures to reduce opportunities for onward spread, at the current rate of infection (on average, approximately six to seven cases per month since April 2024).

- Human cases of H5N1 are nationally notifiable, meaning every identified case is investigated by local and state public health and reported to CDC.

- CDC and a wide range of public health and healthcare partners conduct regular monitoring for influenza viruses and illness activity, reviewing data from case reporting, public health laboratory monitoring, clinical laboratory trends, ED visits, and wastewater surveillance.

- As of February 2025, more than 136,000 specimens have been tested using a protocol that would have detected A(H5) virus, and more than 15,000 people have been monitored after exposure to animals infected with H5N1 virus.

- CDC now recommends subtyping of all influenza A virus-positive specimens from hospitalized patients on an accelerated basis.

- CDC has also provided interim recommendations for prevention, monitoring, and public health investigations that indicate, where feasible, an expansion of testing to include an offer of testing to asymptomatic individuals with high likelihood of unprotected exposure to H5N1 virus.

- Three commercial testing laboratories (Quest Diagnostics, Labcorp, and ARUP) in the United States now offer A(H5) testing, significantly increasing testing access and diagnostic capacity.


Impact

CDC assesses the impact of infection for the general U.S. population as moderate. Factors that informed the assessment of impact include the following:

- The majority of reported U.S. cases have had mild illness characterized by conjunctivitis and/or upper respiratory symptoms, irrespective of the genotype. Of the three confirmed cases of H5N1 in humans in 2025, one was in a dairy worker, and two people had exposure to poultry and experienced severe illness requiring hospitalization.

- On December 13, 2024, CDC confirmed a severe case of H5N1 in an individual in Louisiana. The patient was infected with a genotype of H5N1 virus closely related to viruses recently detected in wild birds and poultry in the United States and in recent human cases in British Columbia, Canada, Iowa, and Washington State. The patient in Louisiana died, and the patient in British Columbia was critically ill.

- Historically, there has been a wide clinical spectrum of H5N1 illness (mild to severe), and deaths have occurred. Prior to the current U.S. outbreak, most reported human H5N1 cases since 1997 were identified late in the course of illness after hospital admission and with severe disease (e.g., pneumonia).

- The general population is not known to have specific immunity against H5N1 virus.

- Medical countermeasures are available to help limit the severity of disease should a member of the general U.S. population become infected.

- Genetic analysis suggests that that H5N1 viruses currently circulating among wild birds, poultry, and dairy cattle in the United States are susceptible to available FDA-approved influenza antiviral medications. Antiviral treatment is currently recommended for patients with confirmed or suspected H5N1 virus infection.

- Antiviral post-exposure prophylaxis can be used to help prevent infection or illness and could be used specifically in those who had unprotected exposure to infected animals.

- Additionally, prompt treatment has been shown to attenuate severe seasonal influenza disease.

- No FDA-authorized or approved vaccines for prevention of H5N1 virus infection are currently commercially available for the general population in the United States.

- However, under the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) program, the Department of Health and Human Services routinely develops vaccines against a wide range of novel influenza A viruses, including H5N1 viruses, and efforts are under way to accelerate the availability of a well-matched vaccine and increase inventory.

- The animal and public health response to outbreaks in poultry and dairy cows has societal and economic impacts for the U.S. general population, including the rise of egg prices, a decrease in milk production, and food recalls.


Confidence

CDC has moderate confidence in this assessment. This degree of uncertainty is due to several factors, including variability in levels of testing among different animal populations and by geography, as well as the role of wild bird exposure in causing human infections, as the prevalence of H5N1 virus infections in wild birds is difficult to assess. There is additional uncertainty on likelihood of human exposures from other infected animals, including exposure to infected cats (house cats or big cats in zoo and animal sanctuary settings). CDC also recognizes uncertainty in impact, as the effects of transmission route and virus genotype in human infection are unclear.


Risk to populations in contact with potentially infected animals or contaminated surfaces or fluids


{Risk posed by H5N1 viruses to populations in contact with potentially infected animals or contaminated surfaces or fluids. Please see methods section for further information on definitions of terms.}


Risk

The risk posed by H5N1 viruses to humans in contact with potentially infected animals or contaminated surfaces or fluids is moderate to high. Of note, for any individual in this population, risk will vary depending on use of workplace controls including personal protective equipment (PPE), nature and frequency of exposure, and time spent in contact with infected or potentially infected animals or contaminated surfaces or fluids. We also include a section below on factors that could change our assessment.


Likelihood

CDC assesses the likelihood of infection for populations in contact with potentially infected animals or contaminated surfaces or fluids as low to high. Individual risk will vary depending on the frequency, duration, and nature of contact with potentially infected animals. The likelihood of exposure from important classes of animals are outlined below:

- The likelihood of exposure to H5N1 viruses from infected commercial poultry and dairy cows is moderate to high.

- H5N1 viruses are widespread in U.S. poultry and dairy cows, with detections in more than 160,000,000 birds in all 50 states since January 2022 and more than 970 dairy herds in 17 states since January 2024.

- The majority of individuals with confirmed H5N1 virus infection (67 of 70) had exposures associated with commercial agriculture or backyard poultry.

- Of these, 41 were exposed to dairy herds (cows) and 24 were exposed to poultry farms and culling operations.

- Some workers were identified as cases before any animals on the farm had tested positive for H5N1.

- Among dairy workers (including veterinarians), the likelihood of exposure may be particularly high among those working in milking parlors and other environments with contaminated surfaces and fluids.

- Use of PPE is low among this population, and increased availability and use can decrease the likelihood of exposure, especially for workers in direct contact with animals or their secretions.

- Several serosurveys have been conducted to identify recent infections that may not have been detected. For example, in a serosurvey of bovine practitioners, evidence of infection was found in three individuals who were asymptomatic, including two without exposures to animals with known or suspected H5N1 virus infection and one who did not practice in a state with known infected cattle. In a serosurvey of dairy workers in Michigan and Colorado, 7% of those tested had serologic evidence of infection.

- The likelihood of exposure to H5N1 viruses from infected non-commercial poultry and wild birds is moderate.

- H5N1 viruses also circulate among non-commercial poultry and wild birds, and among some other wild animals. H5N1 viruses have been detected in more than 12,000 wild birds across 52 jurisdictions in the United States since January 2022.

- Exposure to sick or dying birds infected with H5N1 viruses, including potentially through contaminated fluids or surfaces, raises the likelihood of human infection. Exposure risk may be elevated in populations with animal contact, such as backyard poultry farmers and wild bird or waterfowl hunters.

- The likelihood of exposure to H5N1 viruses from recreational animal activities, such as visiting agricultural fairs, livestock shows, or petting zoos, is low to moderate.

- None of the reported cases had a known exposure to an animal involved in a recreational animal activity.

- Animal monitoring and infection control measures have the potential to reduce the likelihood of exposure to H5N1 viruses for people.

- USDA Federal Orders require mandatory testing of lactating dairy cows prior to interstate movement, and require herd owners with positive cows to provide epidemiological information to facilitate contact tracing and disease monitoring. Additionally, national testing programs are in place for monitoring wild birds and poultry.

- Extensive monitoring of exposed persons and public health control efforts are in place. CDC has interim recommendations for prevention, monitoring, and public health investigations of human cases of H5N1. CDC also has recommendations for worker protection and use of personal protective equipment (PPE) to reduce the risk of exposure.

- People with job-related or recreational exposures to birds or infected mammals can reduce their chance of infection using appropriate precautions to protect against H5N1.


Impact

CDC assesses the impact of human infection via exposure to potentially infected animals as moderate. In addition to the factors outlined in the Impact section for the general population, CDC notes economic and policy impacts, including the financial loss associated with population culling, product disposal, and loss of production. As of November 2024, more than $1.4 billion has been spent on response to ongoing H5N1 outbreaks in animals, and egg demand continues to exceed supply.


Confidence

CDC has moderate confidence in this assessment. This degree of uncertainty is due to factors including variability in levels of A(H5) testing among different animal populations and by geography, as well as the role of wild bird exposure in human infection, as the true prevalence of infection in animal populations is difficult to assess. There is additional uncertainty on likelihood of exposure to other infected animals, including exposure to infected cats (house cats or big cats in zoo and animal sanctuary settings). CDC also notes uncertainty in impact due to limited evidence on whether illness severity differs by transmission route and virus genotype.


Future Risk

This assessment outlines the risk posed to the United States by H5N1 viruses as of February 28, 2025, but CDC stresses this risk could change, as influenza A viruses can mutate quickly, and therefore have the potential to cause pandemics.

The viral changes needed to cause a pandemic are unpredictable. However, the high prevalence of H5N1 virus infections among animals in close contact with humans increases opportunities for mutation or reassortment that could lead to sustained person-to-person spread, causing a pandemic. It is possible that co-infections with seasonal influenza A and H5N1 viruses in the same person or animal provide opportunities for reassortment of genes between two influenza A viruses, potentially resulting in an influenza A virus with characteristics of both seasonal influenza A and H5N1 viruses that is more efficiently transmitted among people than current H5N1 viruses circulating among birds, cows, and other animals.

H5N1 virus infection can cause severe illness in people; H5N1 viruses historically have caused severe cases in humans. CDC has developed H5 candidate vaccine viruses (CVVs) that are expected to be effective against H5N1 viruses now circulating among wild birds, poultry, and cows in the United States. These H5 CVVs could be used to produce a vaccine for people, if needed, thereby reducing the risk for severe disease among humans. Access to antivirals for treatment or post-exposure prophylaxis could also decrease future risk of severe illness or transmission.

(...)


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Thursday, March 6, 2025

Examining the #Survival of A #H5N1 #Influenza Virus in Thermised Whole #Cow #Milk

Abstract

The recent spillover events of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b to dairy cattle, and high viral shedding in the milk from infected animals, has created concern that milk and dairy products could be a route for human infection. It has been demonstrated that pasteurization is effective in inactivating A(H5N1) in milk. However, multiple dairy products are made with unpasteurized but thermised milk. The aim of this study was to examine whether some conditions commonly used for thermisation are effective against inactivation of A(H5N1) in whole milk. For this purpose, we artificially inoculated whole raw cow milk with 6.5 log10 EID50 A(H5N1) and heated for 15 seconds at 60°C, 63°C and 66°C, the viral infectivity was tested using embryonated chicken eggs. We observed over 4 and 5 log10 reduction in viral infectivity at 60°C and 63°C, respectively. The viral infectivity was reduced to below the detection limit at 66°C. We also calculated the D-values, the time required to reduce the viral titer by one log10, for each treatment and as expected, we observed a decrease in D-values with increasing thermisation temperature. These data demonstrate that thermisation is effective in reducing the viral load and thus they allow for informed risk assessment of A(H5N1) contaminated dairy products made from thermized milk.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.05.641644v1

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Cross-species and #mammal-to-mammal #transmission of clade 2.3.4.4b highly pathogenic avian #influenza A #H5N1 with #PB2 adaptations

Abstract

Highly pathogenic H5N1 avian influenza viruses (HPAIV) belonging to lineage 2.3.4.4b emerged in Chile in December 2022, leading to mass mortality events in wild birds, poultry, and marine mammals and one human case. We detected HPAIV in 7,33% (714/9745) of cases between December 2022–April 2023 and sequenced 177 H5N1 virus genomes from poultry, marine mammals, a human, and wild birds spanning >3800 km of Chilean coastline. Chilean viruses were closely related to Peru’s H5N1 outbreak, consistent with north-to-south spread down the Pacific coastline. One human virus and nine marine mammal viruses in Chile had the rare PB2 D701N mammalian-adaptation mutation and clustered phylogenetically despite being sampled 5 weeks and hundreds of kilometers apart. These viruses shared additional genetic signatures, including another mammalian PB2 adaptation (Q591K, n = 6), synonymous mutations, and minor variants. Several mutations were detected months later in sealions in the Atlantic coast, indicating that the pinniped outbreaks on the west and east coasts of South America are genetically linked. These data support sustained mammal-to-mammal transmission of HPAIV in marine mammals over thousands of kilometers of Chile’s Pacific coastline, which subsequently continued through the Atlantic coastline.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-57338-z

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#XBB.1.5 monovalent #vaccine induces lasting cross-reactive responses to #SARS-CoV-2 #variants such as HV.1 and #JN1, as well as SARS-CoV-1, but elicits limited XBB.1.5 specific #antibodies

ABSTRACT

The evolution of the antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacted by the nature and number of antigenic exposures. First-generation coronavirus disease 2019 (COVID-19) vaccines encoded an ancestral spike protein. Updated bivalent vaccines and breakthrough infections have shaped the intricate diversity of the polyclonal antibody response and specificity of individual antibody clones. We and others previously showed that bivalent vaccines containing the ancestral and Omicron (BA.5) spikes induce high levels of cross-reactive antibodies but undetectable BA.5-specific antibodies in serum. Here, we assessed sera collected before as well as 1 and 3 months following administration of an updated XBB.1.5 monovalent vaccine to individuals with diverse infection and vaccination histories. Vaccination increased neutralization against recent variants of concern, including HV.1, JN.1, and the vaccine-homologous XBB.1.5. Antibody binding and avidity against ancestral and XBB.1.5 antigens significantly increased after vaccination. However, antibody depletion experiments showed that most of the response was cross-reactive to the ancestral spike, and only low levels of XBB.1.5-specific antibodies to the spike or the receptor-binding domain were detected. Importantly, increased antibody levels were still detectable in circulation 3 months post-vaccination and cross-reacted with severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) as measured by pseudovirus neutralization and binding assays. Overall, our data suggest that the XBB.1.5 monovalent vaccine predominantly elicits a cross-reactive response imprinted by viral spike antigens encountered early during the pandemic.


IMPORTANCE

Updated COVID-19 vaccine formulations and SARS-CoV-2 exposure history affect the antibody response to SARS-CoV-2. High titers of antibodies are induced in serum by XBB.1.5 monovalent vaccination. Antibody depletion experiments reveal that the majority of the antibody response is cross-reactive to the ancestral spike, despite vaccination increasing neutralization against recently circulating Omicron variants. Vaccine-induced SARS-CoV-2 antibodies cross-react with SARS-CoV-1 and remain in the bloodstream for at least 3 months after immunization.

Source: mSphere, https://journals.asm.org/doi/10.1128/mbio.03607-24

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Wednesday, March 5, 2025

Impact of highly pathogenic avian #influenza virus on Black-headed #Gulls Chroicocephalus ridibundus population in #Poland in 2023

ABSTRACT

The highly pathogenic avian influenza virus (HPAIV) A(H5N1) has caused the most extensive and severe epizootic event affecting both poultry and wild birds globally. This study investigated the impact of HPAIV on the breeding population of the Black-headed Gull Chroicocephalus ridibundus, the most abundant gull species in Poland. During the 2023 outbreak, this species was reported as the most frequently infected in the country. A higher-than-natural adult mortality rate (greater than 1.5% of the breeding individuals) was observed in 114 surveyed colonies across all regions of Poland. Laboratory tests confirmed the presence of HPAIV in all 17 colonies sampled, with average adult mortality estimated at 26.1%, and ranging from 1.7% to 77.8%. The estimated mortality rate across all surveyed colonies was 22.2%. Extrapolations across the entire Polish breeding population (at least 115,000 pairs according to the national census) indicated that approximately 51,000 adult Black-headed Gulls might have perished due to HPAIV in 2023. The number of adults found dead was positively correlated with colony size (r = 0.733, P < 0.001). The deaths were associated with a single HPAIV genotype (BB) across all confirmed cases. Understanding the spread and severity of HPAIV in colonially breeding waterbirds, such as gulls, is essential for assessing the full extent of the threats this virus poses to wild bird populations.

Source: Avian Pathology, https://www.tandfonline.com/doi/full/10.1080/03079457.2025.2467122

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Real-time #epidemiological #surveillance #data: tracking the occurrences of avian #influenza #outbreaks around the world

Abstract

Objectives

This study aims to provide real-time surveillance of epidemiological outbreaks of avian influenza in humans and mammals. The primary objective is to understand and track the dynamics of outbreaks as they develop, facilitating timely interventions and informed public health decisions. The data collection is part of a broader initiative focused on improving preparedness and response capabilities to emerging health threats.

Data description

The dataset includes comprehensive and up-to-date information on epidemiological patterns, including geographic spread, incidence rates, and demographic factors. Collected through systematic monitoring and reporting systems, this dataset is invaluable to researchers seeking to understand the evolving nature of avian influenza outbreaks in the global context. By sharing these data, we aim to contribute to the collective knowledge base by supporting evidence-based strategies for effective public health management and intervention.

Source: BMC Research Notes, https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-024-07042-w

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Defining transmissible dose 50%, donor #inoculation dose that results in #airborne #transmission to 50% of contacts, for 2 #pandemic #influenza viruses in ferrets

Abstract

Ferrets are widely used to model airborne transmission of influenza viruses in humans. Airborne transmission is evaluated by infecting donor ferrets with a high virus dose (106 infectious units) and monitoring transmission to contact animals sharing the same airspace. However, humans can be infected with a broad range of influenza virus doses. Therefore, we evaluated the relationship between virus inoculation dose and transmission for two pandemic influenza viruses in ferrets. Donor ferrets were inoculated with 100 to 106 tissue culture infectious dose 50 (TCID50) of the 2009 pandemic H1N1 or 1968 H3N2 pandemic virus, and were then paired with respiratory contacts. Using the proportion of donors that became infected across virus doses, we calculated the infectious dose 50 (ID50). Subsequently, by comparing the proportion of respiratory contacts that became infected, we calculated the transmissible dose 50% (TD50): the donor inoculation dose that resulted in transmission to 50% of contacts. For the 2009 H1N1 virus, the ID50 and TD50 were equivalent at <1 TCID50. However, for the 1968 H3N2 virus, the ID50 and TD50 were <4 and 103.49 TCID50, respectively. The increased TD50 for the H3N2 virus was associated with reductions in peak viral titers and viral shedding in donors over decreasing virus inoculation doses. Collectively, these studies define a new measure of transmission that permits comparisons of transmissibility over a log scale. Using this metric, we show the 1968 pandemic H3N2 virus has reduced transmissibility in ferrets relative to the 2009 pandemic H1N1 virus.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.04.641289v1

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#Pathogenicity and #transmissibility of #bovine-derived HPAI #H5N1 #B3.13 virus in #pigs

Abstract

Since the first emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses in dairy cattle, the virus has continued to spread, reaching at least 16 states and at least 950 dairy herds in the United States. Subsequently, spillovers of the virus from dairy cattle to humans have been reported. Pigs are an important reservoir in influenza ecology because they serve as a mixing vessel in which novel reassortant viruses with pandemic potential can be generated. Here, we show that oro-respiratory infection of pigs resulted in productive replication of a bovine-derived HPAI H5N1 B3.13 virus. Infectious viruses were mainly identified in the lower respiratory tract of principal infected pigs, and sero-conversion was observed in most of the principal pigs at later time points. In one animal, we detected the emergence of a mutation in hemagglutinin (HA) previously associated with increased affinity for mammalian-type alpha 2,6-linked sialic acid receptors, but this mutation did not reach consensus levels. Sentinel contact pigs remained sero-negative throughout the study, indicating lack of transmission. The results support that pigs are susceptible to a bovine-derived HPAI H5N1 B3.13 virus, but this virus did not replicate as robustly in pigs as mink-derived HPAI H5N1 and swine-adapted influenza viruses.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.04.641414v1

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Evolutionary Studies on the #Coxsackievirus A24 #Variants Causing Acute #Hemorrhagic #Conjunctivitis with Emphasis on the Recent #Outbreak of 2023 in #India

Abstract

Acute Hemorrhagic Conjunctivitis (AHC) is primarily caused by viral infections, with Coxsackievirus A-24v (CV-A24v) being a significant culprit. Enteroviruses, including CV-A24v, are responsible for global AHC outbreaks. Over time, CV-A24v has evolved, and genotype IV (GIV) has become the dominant strain. This study focused on examining the genetic features and evolutionary trends of CV-A24v responsible for the recent AHC outbreak of 2023 in India. Researchers isolated viral strains from ocular swabs and confirmed the presence of CV-A24v using reverse transcriptase quantitative PCR (RT-qPCR) and whole-genome sequencing. Genomic comparisons between isolates of 2023 and those from a previous outbreak in 2009 were conducted. Phylogenetic analysis revealed that the 2023 isolates formed a distinct cluster within GIV-5 and were related to recent strains from China and Pakistan. The older Indian isolates from 2009 grouped with GIV-3. New subclades, GIV-6 and GIV-7, were also identified in this study, indicating the diversification of CV-A24. Molecular clock and phylogeographic analysis traced the virus’s circulation back to the 1960s, with the common ancestor likely to have originated in Singapore in 1968. The 2023 Indian strains probably originated from Thailand around 2014, with subsequent spread to China and Pakistan. This study concluded that the 2023 outbreak was caused by a genetically distinct CV-A24v strain with nine mutations, underlining the virus’s ongoing evolution and adaptations and offering valuable insights for future outbreak control.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/371

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Tuesday, March 4, 2025

#Albania - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

 A poultry farm in DurrĂ«s Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6305

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Role of #antiviral #CD8+ T cell #immunity to #SARS-CoV-2 #infection and #vaccination

ABSTRACT

The COVID-19 pandemic has greatly enhanced our understanding of CD8+ T cell immunity and their role in natural infection and vaccine-induced protection. Rapid and early SARS-CoV-2-specific CD8+ T cell responses have been associated with efficient viral clearance and mild disease. Virus-specific CD8+ T cell responses can compensate for waning, morbidity-related, and iatrogenic reduction of humoral immunity. After infection or vaccination, SARS-CoV-2-specific memory CD8+ T cells are formed, which mount an efficient recall response in the event of breakthrough infection and help to protect from severe disease. Due to their breadth and ability to target mainly highly conserved epitopes, SARS-CoV-2-specific CD8+ T cells are also able to cross-recognize epitopes of viral variants, thus maintaining immunity even after the emergence of viral evolution. In some cases, however, CD8+ T cells may contribute to the pathogenesis of severe COVID-19. In particular, delayed and uncontrolled, e.g., nonspecific and hyperactivated, cytotoxic CD8+ T cell responses have been linked to poor COVID-19 outcomes. In this minireview, we summarize the tremendous knowledge about CD8+ T cell responses to SARS-CoV-2 infection and COVID-19 vaccination that has been gained over the past 5 years, while also highlighting the critical knowledge gaps that remain.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01350-24?af=R

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#Cluster of #community #deaths in Basankusu, Equateur- #DRC

Situation at a glance

On 9 February 2025, officials in the Democratic Republic of the Congo reported to regional health authorities a cluster of 24 unexplained community deaths in a single village in Ekoto health area, Basankusu health zone, Equateur province

As of 25 February, a total of 53 deaths have been reported, with the last death occurring on 22 February. 

Deaths have occurred in all age groups, but adolescents and young adults, particularly males, appeared to be disproportionately affected in the initial cluster reported. 

Disease progression appeared to be fast, with a median time from onset of symptoms to death of one day

Given the rapid decline in the incidence of reported deaths, their geographic clustering, the age profile of deaths and the rapid disease progression in the initial cluster, working hypotheses include chemical poisoning or a rapid onset bacterial meningitis cluster, on a background of malaria and other infectious illnesses endemic in the region. 

The definitive cause of illness remains undetermined, with initial samples testing negative for Ebola and Marburg viruses. 

Field investigations and additional laboratory testing are ongoing including but not limited to the cerebrospinal fluid testing and the toxicological analysis of environmental samples, including water and other samples to explore chemical causes. 

Local authorities began surveillance with a broad case definition including any individual with fever and at least one other symptom, to better understand disease patterns. 

A total of 1318 patients had symptoms meeting the working suspected case definition as of 25 February 2025. Approximately 50% of malaria tests performed on these cases tested positive for malaria, the cases identified through this enhanced surveillance therefore likely reflect the various febrile illnesses in the area. 

With the available information, WHO assesses the local public health risk as moderate, and the national and global public health risk as low.


Description of the situation

On 9 February 2025, an initial cluster of 24 community deaths of unknown origin were reported from a single village in Ekoto Health Area, Basankusu Health Zone, Equateur province, in the Democratic Republic of Congo. This triggered an investigation by the Ministry of Health, supported by WHO.

Enhanced surveillance was implemented shortly after, using a broad working case definition given the limited details on the clinical presentation, disease progression, demographic and other characteristics of the initial cluster. 

As of 25 February, a total of 53 deaths were reported. Deaths occurred across all age groups, but compared to the age and sex distribution of the population, appeared to disproportionately affect adolescents and young adult males, particularly in the initial cluster. This further pointed to an unusual event, as mortality from common causes in the area is usually highest among the elderly, and among young children (under five years) in a context of a high burden from infectious diseases, including malaria. The majority of deaths (50) occurred in the same village. Furthermore, the incidence of death rapidly declined following the initial cluster, suggesting this is not an event spreading in time or place.

The preliminary findings of the in-depth analysis revealed that the median time from symptom onset to death in the initial cluster was one day, with a mean time of two days. Symptoms reported include fever, chills, headaches, muscle aches, abdominal pains, diarrhea, sweating, dizziness, shortness of breath, agitation, and others.

(...)

Since the initiation of enhanced surveillance,1318 people reported symptoms meeting the working suspected case definition. However, given the broad nature of the case definition (fever and one other symptom from a range of general respiratory, gastrointestinal, or neurological symptoms), the trends in cases are difficult to interpret, and most likely reflect the prevalence of a range of febrile illnesses in the community. This is further suggested by the age distribution broadly mirroring that of the population, and the high malaria positivity among cases that were tested (approximately 50% positive on rapid diagnostic tests), which is not deemed unusual in an area where malaria is hyperendemic.

(...)

Although the cases were initially identified using a broad (i.e. non-specific) case definition, given the localized nature of the cluster of deaths, the steady decline in incidence of deaths, the demographic profile of deaths, and the rapid disease progression in the initial cluster, working hypotheses are that of a contamination by a chemical poisoning–be it accidental or deliberate—or possibly a rapid onset bacterial meningitis cluster.

Initial laboratory test results released on 13 February 2025 were negative for both Marburg and Ebola. Additional samples (blood, urine, oral, nasal) have been collected for further testing and investigations are ongoing. In addition, environmental samples–including water and other samples–are being collected to explore chemical causes, such as contamination by organophosphates.

The definitive cause of illness remains undetermined. Further testing and field investigations are ongoing to better characterize the cases and deaths.

Of note, this event in Basankusu follows a recent cluster of community deaths in the Bolomba Health Zone, which occurred from 10 to 27 January 2025. The epidemiological investigation documented 12 cases with eight deaths. Laboratory testing excluded Ebola and Marburg virus diseases and suggested that severe malaria could be the cause. While both Bolomba and Basankusu are located within Equateur Province, these health zones are separated by approximately 175 kilometers of difficult terrain including dense forests and poor road infrastructure; epidemiological investigation has found no evidence linking these distinct events.


Public health response

-- Coordination: A provincial rapid response team deployed to Basankusu and arrived on 16 February. The team was further supported by a WHO-MoH team from Kinshasa which arrived on 23 February.

-- Surveillance: WHO is supporting the MoH teams with field investigations, including the development of a structured epidemiological investigation protocol and the collection of additional samples for testing. As surveillance is being scaled up, the focus is on better understanding the characteristics of deaths. WHO is supporting health teams in their case investigations and active case search in the affected areas, including in communities, churches, and health facilities.

-- Laboratory: WHO is providing laboratory support to guide proper collection, storage, and transport of collected specimens to the National Institute of Biomedical Research (INRB) in Kinshasa, the biggest and most equipped laboratory in the country.

-- Logistics: WHO has provided essential medical supplies for management of usual infectious diseases and their symptoms, laboratory testing and infection prevention and control (IPC).

-- Risk communication and community engagement: Community engagement efforts are ongoing. Training sessions for community health workers are being conducted on how to identify people who meet the case definition and perform disease surveillance reporting. Awareness activities include community briefings and local radio broadcasts, as well as targeted discussion in villages on care-seeking behavior. 

-- Infection prevention and control: Systematic decontamination of isolation rooms at the General Hospital in Basankusu and Ekoto Health Center have been performed. On-site training of IPC supervisors and hygienists on chlorine solution preparation for decontamination have been conducted.


WHO risk assessment

Since the initial cluster of deaths was reported on 9 February 2025, there has been an overall downward trend in deaths. The most recent death was reported on 22 February 2025. Current epidemiological information suggests a localized event with a steady decline in incidence, not expanding in time and place. Given the clinical presentation of deaths and the speed from symptom onset to death in this unusual cluster, current differentials include a rapid onset bacterial meningitis cluster or a contamination by a chemical poisoning as key hypotheses in a context of high incidence of other common infectious diseases in the areas, particularly malaria.

Operational challenges related to this event involve the isolation of Basankusu and resulting logistical barriers, as it is located in a forested region, approximately 450 kilometers from the nearest major city of Mbandaka and has poor infrastructure. The remoteness of Basankusu has hindered the timeliness of the initial investigation and response activities and poses challenges to laboratory testing. Samples must be collected, stored, and shipped long distances to a larger city with laboratory testing capacity (either Mbandaka or Kinshasa), introducing delays in diagnosis. Access to care is another key challenge, as the region lacks robust healthcare services, and the region’s poor infrastructure makes travel to neighboring health zones difficult, leading to delays in treatment.  

The province faces a severe urban water crisis with only 5% of its urban population having access to drinking water. The water network suffers frequent leaks and has never been rehabilitated. Many households rely on unregulated private water sources such as wells, springs and streams which pose contamination risks.

With ongoing investigations and given that the causative agent of the cluster is not yet determined, there remains a level of risk attributed to the event. As such, the overall public health risk level to the affected communities is assessed as moderate.

At the national level, however, the risk is considered low due to the localized nature of the event and apparent decreasing incidence. Similarly, at the regional and global levels, the risk is low at this time. 


WHO advice

To reduce the impact of the event in the Basankusu health zone, WHO advises the following measures:  

-- Careful characterization of the clinical syndrome and outcomes as well as an improved case definition based on collected information to better understand the outbreak.

-- Enhanced surveillance focusing specifically on deaths, and severe febrile cases or severe cases of unexplained illness, with better clinical characterization to reinforce early case detection and reporting.

-- Continued laboratory testing and environmental assessments (including water sources) to evaluate the current hypotheses of meningitis and/or a toxin/poisoning event, particularly among severe cases and deaths.

-- Risk communication and community engagement to increase public awareness about the event, explaining symptoms and the importance of seeking immediate care. It is also critical to address any potential misinformation about the outbreak circulating in the community.

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON557

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Monday, March 3, 2025

#Germany - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

 A poultry farm in Sachsen Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6301

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