GGCX promotes #Eurasian #avian-like #H1N1 #swine #influenza virus #adaption to interspecies #receptor binding

Abstract

The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic, owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor. Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells. Knocking out the enzyme gamma glutamyl carboxylase (GGCX) reduces virus replication in vitro and in vivo by inhibiting the carboxylation modification of viral haemagglutinin (HA) and the adhesion of progeny viruses, ultimately impeding the replication of EA H1N1 SIV. Furthermore, GGCX is revealed to be the determinant of the D225E substitution of EA H1N1 SIV, and GGCX-medicated carboxylation modification of HA 225E contributes to the receptor binding adaption of EA H1N1 SIV to the α-2,6 SA receptor. Taken together, our CRISPR screen has elucidated a novel function of GGCX in the support of EA H1N1 SIV adaption for binding to α-2,6 SA receptor. Consequently, GGCX emerges as a prospective antiviral target against the infection and transmission of EA H1N1 SIV.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-55903-0

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#Outbreak of suspected #Marburg Virus Disease - United Republic of #Tanzania

Description of the situation

Introduction

On 13 January 2025, WHO informed its Member States and IHR State Parties of an outbreak of suspected Marburg Virus Disease (MVD) in the Kagera region of the United Republic of Tanzania using our secure web-based platform—the Event Information Site (EIS). Under the International Health Regulations, the EIS is used to issue rapid alerts to Member States of acute and rapidly developing public health risks and events with possible international implications.

Summary of the situation

On 10 January 2025, WHO received reliable reports from in-country sources regarding suspected cases of MVD in the Kagera region of the United Republic of Tanzania. Six people were reported to have been affected, five of whom had died. The cases presented with similar symptoms of headache, high fever, back pain, diarrhoea, haematemesis (vomiting with blood), malaise (body weakness) and, at a later stage of disease, external haemorrhage (bleeding from orifices).

As of 11 January 2025, nine suspected cases were reported including eight deaths (case fatality ratio (CFR) of 89%) across two districts – Biharamulo and Muleba.  Samples from two patients have been collected and tested by the National Public Health Laboratory. Results are pending official confirmation. Contacts, including healthcare workers, are reported to have been identified and under follow-up in both districts.

The Bukoba district in Kagera region experienced its first MVD outbreak in March 2023, and zoonotic reservoirs, such as fruit bats, remain endemic to the area. The outbreak in March 2023 lasted for nearly two months with nine cases including six deaths.

Public health response

National rapid response teams have been deployed to support outbreak investigation and response; surveillance activities have been intensified with contact tracing ongoing; laboratory samples from recent cases have been sent for confirmation at the National Public Health Laboratory. A mobile laboratory is located in Kagera region and treatment units have reportedly been established.

WHO risk assessment

The risk of this suspected MVD outbreak is assessed as high at the national level due to several concerning factors. The suspected outbreak thus far involves at least nine suspected cases, including eight deaths, resulting in a high CFR of 89%. Healthcare workers are included among the suspected cases affected, highlighting the risk of nosocomial transmission. The source of the outbreak is currently unknown.

The reporting of suspected MVD cases from two districts suggests geographic spread. The delayed detection and isolation of cases, coupled with ongoing contact tracing, indicates lack of a full information of the current outbreak. More cases are expected to be identified.

The regional risk is considered high due to Kagera region's strategic location as a transit hub, with significant cross-border movement of the population to Rwanda, Uganda, Burundi and the Democratic Republic of the Congo. Reportedly, some of the suspected cases are in districts near international borders, highlighting the potential for spread into neighbouring countries.  MVD is not easily transmissible (i.e. in most instances, it requires contact with the body fluids of a sick patient presenting with symptoms or with surfaces contaminated with these fluids). However, it cannot be excluded that a person exposed to the virus may be travelling.

The global risk is currently assessed as low. There is no confirmed international spread at this stage, although there are concerns about potential risks. Kagera region, while not close to Tanzania's capital or major international airports, is well-connected through transportation networks, and has an airport that connects to Dar es Salaam for onward travel outside Tanzania by air. This highlights the need for enhanced surveillance and case management capacities at relevant points of entry and borders, and close coordination with neighbouring countries to strengthen readiness capacities.

WHO advice

Human-to-human transmission of Marburg virus is primarily associated with direct contact with the blood and/or other bodily fluids of infected people. WHO advises the following risk reduction measures be taken as an effective way to reduce MVD transmission and control an outbreak.

* Prevention: Protective measures individuals should take to reduce human exposure to the virus include:

-- Reduce the risk of human-to-human transmission in the community arising from direct or close contact with infected patients, particularly with their body fluids. Close physical contact with MVD patients should be avoided.

-- People suspected or confirmed for MVD should immediately seek care in health facilities and be isolated in a designated treatment centre for early care and to avoid transmission at home. 

-- Community and family members should avoid caring for symptomatic individuals at home, and avoid touching bodies of people deceased with MVD symptoms. They should avoid touching other potentially contaminated items and surfaces. They should be encouraged to go to a health facility for assessment and treatment if they have symptoms.

-- Reduce the risk of bat-to-human transmission arising from prolonged exposure to mines or caves inhabited by fruit bat colonies. During work or research activities or tourist visits in mines or caves inhabited by fruit bat colonies, people should wear gloves and other appropriate protective clothing (including masks). During outbreaks, all animal products (blood and meat) should be thoroughly cooked before consumption.

* Coordination: Multisectoral coordination and pillar meetings at all levels and sharing of detailed situation reports is encouraged. Involvement of different stakeholders and partners in preparedness and response activities is also encouraged. To ensure an effective and sustained response, resource mobilization efforts within the government and with partners are recommended.

* Risk communication and community engagement: Raising public awareness and engaging with communities are important for successfully controlling MVD outbreaks. This includes raising awareness of symptoms, risk factors for infection, protective measures and the importance of seeking immediate care at a health facility. Sensitive and supportive information about safe and dignified burials is also crucial. This awareness should be increased through targeted campaigns and direct work with communities. Special attention should be given to high-risk groups, such as traditional healers, clergy, and community leaders, who may inadvertently facilitate disease spread, and who are important sources of information for the community. Misinformation and rumours should be addressed to foster trust and promote early symptom reporting.

* Surveillance: Active case detection, contact tracing, and alert management across affected and neighbouring regions should be intensified. Community-based surveillance systems should be strengthened to promptly identify and report new cases, particularly in high-risk areas. Close monitoring of healthcare workers, family members and individuals who have had contact with suspected cases or other high-exposure settings should be ensured. Surveillance capacities should also be intensified at relevant points of entry and borders to reduce the risk of further spread, including internationally.

* Infection prevention and control (IPC) measures: critical infection prevention and control measures should be implemented and/or strengthened in all health care facilities, per WHO’s Infection prevention and control guideline for Ebola and Marburg disease, which highlighted the importance of the rapid implementation of the IPC ring approach including but not limited to IPC rapid assessment, decontamination of the health facilities and household and early detection and identification of the cases through the screening and isolation of the suspected cases to minimize the transmission risk.

* Health workers caring for patients with confirmed or suspected MVD should apply transmission-based precautions in addition to: standard precautions, including appropriate use of personal protective equipment (PPE) and hand hygiene according to the WHO 5 moments to avoid contact with patient’s blood and other body fluids and with contaminated surfaces and objects. Waste generated in healthcare facilities must be safely segregated, safely collected, transported, stored, treated and finally disposed. Follow the national guidelines, rules and regulations for safe waste disposal or follow the WHO’s guidelines on safe waste management 

* Patient-care activities should be undertaken in a clean and hygienic environment that facilitates practices related to the prevention and control of health-care-associated infections (HAIs) as outlined in Essential environmental health standards in health care. Safe water, adequate sanitation and hygiene infrastructure and services should be provided in healthcare facilities. For details on recommendations and improvement, follow the WASH FIT implementation Package

* Laboratory testing: The processing and analysis of samples should be expedited, with results promptly shared with responders and clinicians to guide patient management, containment strategies and broader response efforts. This includes genomic sequencing on positive samples. International referral of samples to a regional reference laboratory should be considered for inter-laboratory comparison.

* Evaluation of candidate medical countermeasures: There are no licensed vaccines or therapeutics against MVD. Several candidate vaccines are in the pipeline and outbreaks offer an opportunity to assess their efficacy and safety. There are protocols available and a network of experts in filovirus ready to support national researchers. 

* Safe and dignified burials: Safe and dignified burial protocols should be implemented for people who have died to minimize community exposure. Additional training and equipment for healthcare workers and burial teams should be provided to ensure safe management of MVD-related fatalities. Thorough community engagement is required to ensure that affected communities are empowered to adhere to the protocol.

* Case management and mental health and psychosocial support: Isolation and treatment facilities should be adequately equipped to ensure the safety and efficacy of patient care, while simultaneously preventing the spread of the disease. Supportive care such as rehydration, symptom management, and psychological support for patients and their families is essential to improving survival rates and mitigating the outbreak's impact.

* Border health and cross-border coordination: Surveillance and response capacities should be strengthened at relevant points of entry, onboard conveyances, and in border regions to prevent further spread, including internationally. Cases, contacts and individuals in affected areas who present signs and symptoms compatible with case definitions should be advised not to travel in line with WHO’s border health and points of entry technical guidance for filovirus disease outbreaks. Collaboration with neighbouring countries should be enhanced to harmonize reporting mechanisms, conduct joint investigations, and share critical data in real-time. Surrounding countries should enhance readiness activities to enable early case detection, isolation and treatment.

* Preparedness and Readiness: Readiness assessments in high-risk regions should be conducted to ensure response mechanisms, such as mobile labs and isolation units, are adequately equipped to manage new cases.

Based on the current risk assessment, WHO advises against any travel and trade restrictions with the United Republic of Tanzania.

Further information

-- WHO Factsheet- Marburg virus disease https://www.who.int/news-room/fact-sheets/detail/marburg-virus-disease

-- Infection prevention and control guidelines for Ebola and Marburg disease, August 2023.  https://www.who.int/publications/i/item/WHO-WPE-CRS-HCR-2023.1

- WHO Questions and Answers – Marburg virus disease.https://www.who.int/news-room/questions-and-answers/item/marburg-virus-disease  Risk communication and community engagement for Marburg virus disease outbreaks. Interim Guidance November 2024.  https://iris.who.int/bitstream/handle/10665/379761/B09185-eng.pdf?sequence=1

-- Steps to putting on PPE for Ebola/Marburg coverall.  https://www.who.int/multi-media/details/steps-to-put-on-ppe-for-ebola-marburg-disease-coverall

-- Steps to removing PPE for Ebola/Marburg disease coverall.  https://www.who.int/multi-media/details/steps-to-remove-ppe-for-ebola-marburg-disease-coverall

-- Steps to putting on PPE for Ebola/Marburg gown and headcover.  https://www.who.int/multi-media/details/steps-to-put-on-ppe-for-ebola-marburg-disease-gown-and-headcover

-- Steps to removing PPE for Ebola/Marburg gown and headcover.  https://www.who.int/multi-media/details/steps-to-remove-ppe-for-ebola-marburg-disease-gown-and-headcover

-- Standard precautions for the prevention and control of infections: aide-memoire.  https://www.who.int/publications/i/item/WHO-UHL-IHS-IPC-2022.1

-- Transmission-based precautions for the prevention and control of infections: aide-memoire.  https://www.who.int/publications/i/item/WHO-UHL-IHS-IPC-2022.2

-- Essential environmental health standards in healthcare facilities- https://www.who.int/publications/i/item/9789241547239 

-- WASH FIT implementation for WASH improvements in healthcare facilities WASH FIT Fact Sheets | WASH in Health Care Facilities (washinhcf.org) https://www.washinhcf.org/wash-fit-fact-sheets/

-- World Health Organization (March 2009). Hand hygiene technical reference manual: to be used by health-care workers, trainers and observers of hand hygiene practices.  https://www.who.int/publications/i/item/9789241598606

-- Ebola and Marburg diseases screening and treatment center design training.  https://openwho.org/courses/ebola-marburg-screen-treat-facilities

-- World Health Organization (2 June 2023). Disease Outbreak News; Marburg virus disease in the United Republic of Tanzania.  https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON471

-- Markotter W, Coertse J, DeVries M, et al.  Bat-borne viruses in Africa: a critical review. J of Zoology. 2020;311:77-98. doi:10.1111/jzo.12769.  https://zslpublications.onlinelibrary.wiley.com/doi/10.1111/jzo.12769(link is external)

-- Korine C Rousettus aegyptiacus. The IUCN Red List of Threatened Species 2016: e.T29730A22043105. https://www.iucnredlist.org/species/29730/22043105

-- Cross RW, Longini IM, Becker S, Bok K, Boucher D, Carroll MW, et al. (2022) An introduction to the Marburg virus vaccine consortium, MARVAC. PLoS Pathog 18(10): e1010805. https://doi.org/10.1371/journal.ppat.1010805

-- A WHO-Strategic Research Agenda for Filovirus Research and Monitoring (WHO-AFIRM). https://www.who.int/publications/m/item/a-who-strategic-research-agenda-for-filovirus-research-and-monitoring-----(who-afirm)

-- Building research readiness for a future filovirus outbreak, Workshop February 20 - 22, 2024, Uganda https://www.who.int/news-room/events/detail/2024/02/20/default-calendar/building-research-readiness-for-a-future-filovirus-outbreak-workshop-february-20-22-2024-uganda

-- WHO Technical Advisory Group – candidate vaccine prioritization.  Summary of the evaluations and recommendations on the four Marburg vaccines.   https://www.who.int/publications/m/item/who-technical-advisory-group---candidate-vaccine-prioritization.--summary-of-the-evaluations-and-recommendations-on-the-four-marburg-vaccines

-- Marburg virus vaccine landscape  https://www.who.int/publications/m/item/marburg-virus-vaccine-landscape

-- Marburgvirus therapeutics landscape https://www.who.int/publications/m/item/marburg-virus-therapeutics-landscape

-- Considerations for border health and points of entry for filovirus disease outbreaks: https://www.who.int/publications/m/item/considerations-for-border-health-and-points-of-entry-for-filovirus-disease-outbreaks

Citable reference: World Health Organization (14 January 2024). Disease Outbreak News; Outbreak of suspected Marburg Virus Disease in the United Republic of Tanzania. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON552

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON552

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#Influenza A virus in dairy #cattle: #infection #biology and potential mammary #gland-targeted #vaccines

Abstract

Influenza, a major “One Health” threat, has gained heightened attention following recent reports of highly pathogenic avian influenza in dairy cattle and cow-to-human transmission in the USA. This review explores general aspects of influenza A virus (IAV) biology, its interactions with mammalian hosts, and discusses the key considerations for developing vaccines to prevent or curtail IAV infection in the bovine mammary gland and its spread through milk.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01063-7

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#USDA Confirms Highly Pathogenic Avian #H5N1 #Influenza in Backyard #Poultry Flock in #PuertoRico

WASHINGTON, January 13, 2025 – The United States Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) has confirmed the presence of highly pathogenic avian influenza (HPAI) in a backyard poultry flock in Puerto Rico.  

This is the first case of HPAI in domestic birds in Puerto Rico during this outbreak, which began in February 2022.

Samples from the flock were tested and confirmed at the APHIS National Veterinary Services Laboratories in Ames, Iowa.

APHIS is working closely with animal health officials in Puerto Rico on a joint incident response and will provide appropriate support as requested. 

According to the U.S. Centers for Disease Control and Prevention (CDC), the public health risk associated with these avian influenza detections in birds remains low.  As a reminder, the proper handling and cooking of all poultry and eggs to an internal temperature of 165˚F is recommended as a general food safety precaution.

As part of existing avian influenza response plans, APHIS and the Puerto Rico Department of Agriculture are conducting additional surveillance and testing in areas around the affected flock. The United States has the strongest AI surveillance program in the world, and USDA is working with its partners to actively look for the disease in commercial poultry operations, live bird markets and in migratory wild bird populations. 

Anyone involved with poultry production from the small backyard to the large commercial producer should review their biosecurity activities to assure the health of their birds. Visit APHIS’ Defend the Flock Resource Center for materials about biosecurity, including videos, checklists, and a toolkit.

USDA will report these findings to the World Organisation for Animal Health (WOAH) as well as international trading partners. USDA also continues to communicate with trading partners to encourage adherence to WOAH standards and minimize trade impacts. WOAH trade guidelines call on countries to base trade restrictions on sound science and, whenever possible, limit restrictions to those animals and animal products within a defined region that pose a risk of spreading disease of concern. WOAH trade guidelines also call on member countries to not impose bans on the international trade of poultry commodities in response to notifications in non-poultry.

All cases in commercial and backyard flocks are listed on the APHIS website.

In addition to practicing good biosecurity, all bird owners should prevent contact between their birds and wild birds and report sick birds or unusual bird deaths to State/Federal officials, either through their state veterinarian or through APHIS’ toll-free number at 1-866-536-7593. APHIS urges producers to consider bringing birds indoors, when possible, to further prevent exposures. The Animal Health Protection Act authorizes APHIS to provide indemnity payments to producers for birds and eggs that must be depopulated during a disease response. APHIS also provides compensation for disposal activities and virus elimination activities. Additional information on biosecurity for backyard flocks can be found on APHIS’ Defend the Flock webpage.

Source: US Department of Agriculture, https://www.aphis.usda.gov/news/agency-announcements/usda-confirms-highly-pathogenic-avian-influenza-backyard-poultry-flock

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

{Scotland} Backyard flock with 6 hens, approximately 5 months old. Increased mortality and other clinical signs reported. Official samples were H5N1 HPAI positive.

Source: WOAH, https://wahis.woah.org/#/in-review/6186

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#China reported two new #human #infections with #H9N2 avian #influenza virus and one with #H10N3 virus

 {Excerpt}

-- Avian influenza A(H9N2):

-- 1) Chongqing Municipality: An one-year-old girl with onset on December 13, 2024. 

-- 2) Hubei An eight-year-old girl with onset on November 27, 2024. 

-- Avian influenza A(H10N3): 

-- 1) Guangxi Zhuang Autonomous Region: A 23-year-old woman with onset on December 12, 2024. 

Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk02.pdf

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The #Haemagglutinin #Gene of #Bovine-Origin #H5N1 #Influenza Viruses Currently Retains #Receptor-binding and pH-fusion Characteristics of #Avian #Host Phenotype

Abstract

Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) has caused a panzootic affecting all continents except Australia, expanding its host range to several mammalian species. In March 2024, H5N1 HPAIV was first detected in dairy cattle and goats in the United States. Over 891 dairy farms across 16 states have tested positive until 25th December 2024, with zoonotic infections reported among dairy workers. This raises concerns about the virus undergoing evolutionary changes in cattle that could enhance its zoonotic potential. The Influenza glycoprotein haemagglutinin (HA) facilitates entry into host cells through receptor binding and pH-induced fusion with cellular membranes. Adaptive changes in HA modulate virus-host cell interactions. This study compared the HA genes of cattle and goat H5N1 viruses with the dominant avian-origin clade 2.3.4.4b H5N1 in the United Kingdom, focusing on receptor binding, pH fusion, and thermostability. All the tested H5N1 viruses showed binding exclusively to avian-like receptors, with a pH fusion of 5.9, outside the pH range associated with efficient human airborne transmissibility (pH 5.0 to 5.5). We further investigated the impact of emerging HA substitutions seen in the ongoing cattle outbreaks, but saw little phenotypic difference, with continued exclusive binding to avian-like receptor analogues and pHs of fusion above 5.8. This suggests that the HA genes from the cattle and goat outbreaks do not pose an enhanced threat compared to circulating avian viruses. However, given the rapid evolution of H5 viruses, continuous monitoring and updated risk assessments remain essential to understanding virus zoonotic and pandemic risks.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2451052

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#USA, #California: Presumptive {#Human #H5N1} #Birdflu Case Identified In #SanFrancisco Resident

FOR IMMEDIATE RELEASE: Friday, January 10, 2025 

*** PRESS RELEASE *** 

Contact: SFDPH Media Desk: DPH.Press@sfdph.org 

SAN FRANCISCO – The San Francisco Department of Public Health (SFDPH) announced today that a presumptive case of H5N1 bird flu has been identified in a San Francisco resident. 

The individual is a child who experienced symptoms of fever and conjunctivitis but did not need to be hospitalized and has since fully recovered. 

The risk to the general public remains low as there is currently no evidence of person-to-person transmission. 

SFDPH is encouraging people to avoid direct contact with sick or dead birds, especially wild birds and poultry. 

Wild birds can be infected with bird flu even if they do not look sick. 

If you have found a dead bird, please contact 311. 

In addition, as bird flu continues to spread among U.S. dairy cows, SFDPH strongly recommends that individuals not consume raw milk or raw milk products, including raw cheese. 

“I want to assure everyone in our city that the risk to the general public is low, and there is no current evidence that the virus can be transmitted between people,” said Dr. Grant Colfax, Director of Health. 

“We will continue to investigate this presumptive case, and I am urging all San Franciscans to avoid direct contact with sick or dead birds, especially wild birds and poultry. Also, please avoid unpasteurized dairy products.” 

The presumptive case tested positive for H5N1 at the SFDPH Public Health Laboratory, which performed this testing as part of enhanced surveillance efforts. 

Confirmatory testing will be performed at the Centers for Disease Control and Prevention (CDC). 

The child initially tested for COVID-19, influenza, and RSV based on symptoms and tested positive for influenza A. As part of SFDPH enhanced surveillance, the specimen was subsequently tested for H5N1. 

An initial investigation by SFDPH has not revealed how the child may have contracted H5N1 bird flu. 

The Department is continuing to investigate, including assessing all close contacts. 

Again, the risk to the general public remains low as there is currently no evidence of person-to-person transmission. 

(...) Human infections with bird flu viruses are rare, and no person-to-person transmission has been detected to date in the United States. Symptoms of bird flu in humans include eye redness, coughing, fatigue, fever, and headaches. If you are experiencing these symptoms, please contact your health care provider. 

At this time, bird flu cases in California have been mild without any hospitalizations. 

Additional case information can be found at the California Department of Public Health and CDC websites.

Source: San Francisco Department of Health, https://www.sf.gov/news/presumptive-bird-flu-case-identified-san-francisco-resident

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Molecular #diagnosis and phylogenetic #analysis of a #MERS #coronavirus #human case in #Jordan

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is an important zoonotic pathogen. The aim of this paper is to report one polymerase chain reaction (PCR)-positive case of MERS-CoV in a 27-year-old man who was involved in a nationwide longitudinal surveillance study of certain zoonotic diseases in Jordan including MERS-CoV. Whole-blood and nasal swab samples were collected from the man and five camels in the vicinity of his living area. The samples were subjected to enzyme-linked immunosorbent assay (ELISA) and real-time reverse-transcription PCR (RT-PCR) to detect MERS-CoV-specific antibodies and MERS-CoV genetic material, respectively. Genomic sequencing and phylogenetic analysis were also performed to detect similarities with known strains of the virus in the region. In January 2021, an ongoing surveillance study detected a MERS-CoV-positive nasal swab sample from an asymptomatic male and camels using RT-PCR. Phylogenetically, the MERS-CoV isolated in this case belonged to clade B and is clustered with other strains originating in the Arabian Peninsula. The case report represents the first PCR-positive case of MERS-CoV in an asymptomatic individual in Jordan, indicating active circulation of the virus within the population.

Source: European Journal of Public Health, https://academic.oup.com/eurpub/article/35/Supplement_1/i55/7951904

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#USA, #Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {Week 52/24, 01/25}

{Excerpt}

Time Period: December 29, 2024 - January 04, 2025

H5 Detection: 51 sites (17.0%)

No Detection: 249 sites (83.0%)

No samples in last week:  93 sites

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

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#Safety and #immunogenicity of ascending doses of #influenza A(#H7N9) inactivated #vaccine with or without MF59®

Abstract

Introduction

While it remains impossible to predict the timing of the next influenza pandemic, novel avian influenza A viruses continue to be considered a significant threat.

Methods

A Phase II study was conducted in healthy adults aged 18–64 years to assess the safety and immunogenicity of two intramuscular doses of pre-pandemic 2017 influenza A(H7N9) inactivated vaccine administered 21 days apart. Participants were randomized (n = 105 in each of Arms 1–3) to receive 3.75 μg, 7.5 μg or 15 μg of hemagglutinin (HA) with MF59® adjuvant, or 15 μg of HA unadjuvanted vaccine (n = 57, Arm 4).

Results

The three MF59 adjuvanted vaccines and the 15 μg unadjuvanted vaccine were safe and well-tolerated.

Little antibody activity was detected against the A(H7N9) vaccine antigen after the first vaccination across study Arms. After second vaccination, the three adjuvanted Arms showed increases in hemagglutination inhibition (HAI), neutralizing (Neut), and neuraminidase inhibition (NAI) geometric mean titers (GMT), peaking at 21 days post second vaccination. The percentage of participants with titer ≥1:40 and seroconversion rates for HAI were 30–43 % and 0 for the adjuvanted Arms and the unadjuvanted Arm, respectively. Antibody responses against antigenically drifted A(H7N9) strains A/Shanghai/2/2013 and A/Guangdong/17SF003/2016 showed similar trends.

Exploratory linear modeling of HAI and Neut responses post second vaccination revealed significantly lower log antibody titers among older participants (aged 35–49 and 50–64 years) compared to participants aged 18–34 years after adjusting for study vaccination, BMI, sex, and prior seasonal influenza vaccination. Post second vaccination, participants who received seasonal influenza vaccination in at least one of the two previous seasons had significantly lower log antibody titers than participants who did not.

Conclusion

Adjuvanted doses of vaccine provided higher antibody responses, on average, than the 15 μg unadjuvanted vaccine. Proportion of participants achieving seroconversion and antibody titers ≥40 remained below 50 % in all study Arm.

Source: Vaccine, https://www.sciencedirect.com/science/article/abs/pii/S0264410X24013847?via%3Dihub

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Development of avian #influenza A(#H5) virus #datasets for #Nextclade enables rapid and accurate #clade assignment

Abstract

The ongoing panzootic of highly pathogenic avian influenza (HPAI) A(H5) viruses is the largest in history, with unprecedented transmission to multiple mammalian species. Avian influenza A viruses of the H5 subtype circulate globally among birds and are classified into distinct clades based on their hemagglutinin (HA) genetic sequences. Thus, the ability to accurately and rapidly assign clades to newly sequenced isolates is key to surveillance and outbreak response. Co-circulation of endemic, low pathogenic avian influenza (LPAI) A(H5) lineages in North American and European wild birds necessitates the ability to rapidly and accurately distinguish between infections arising from these lineages and epizootic HPAI A(H5) viruses. However, currently available clade assignment tools are limited and often require command line expertise, hindering their utility for public health surveillance labs. To address this gap, we have developed datasets to enable A(H5) clade assignments with Nextclade, a drag-and-drop tool originally developed for SARS-CoV-2 genetic clade classification. Using annotated reference datasets for all historical A(H5) clades, clade 2.3.2.1 descendants, and clade 2.3.4.4 descendants provided by the Food and Agriculture Organization/World Health Organization/World Organisation for Animal Health (FAO/WHO/WOAH) H5 Working Group, we identified clade-defining mutations for every established clade to enable tree-based clade assignment. We then created three Nextclade datasets which can be used to assign clades to A(H5) HA sequences and call mutations relative to reference strains through a drag-and-drop interface. Nextclade assignments were benchmarked with 19,834 unique sequences not in the reference set using a pre-released version of LABEL, a well-validated and widely used command line software. Prospective assignment of new sequences with Nextclade and LABEL produced very well-matched assignments (match rates of 97.8% and 99.1% for the 2.3.2.1 and 2.3.4.4 datasets, respectively). The all-clades dataset also performed well (94.8% match rate) and correctly distinguished between all HPAI and LPAI strains. This tool additionally allows for the identification of polybasic cleavage site sequences and potential N-linked glycosylation sites. These datasets therefore provide an alternative, rapid method to accurately assign clades to new A(H5) HA sequences, with the benefit of an easy-to-use browser interface.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.07.631789v1

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Comprehensive #Infectome #Analysis Reveals Diverse Infectious Agents with #Zoonotic #Potential in #Wildlife

Abstract

Understanding wildlife-pathogen interactions is crucial for mitigating zoonotic risk. Through meta-transcriptomic sequencing we profiled the infectomes of 1,922 samples from 67 mammalian species across China, uncovering a remarkable diversity of viral, bacterial, fungal, and parasitic pathogens. Of the 195 pathogens identified, 62 were novel, including a bi- segmented coronavirus in diseased lesser pandas, which we propose represents a new genus – Zetacoronavirus. The orders Carnivora and Rodentia exhibited the highest pathogen diversity and were implicated in numerous host-jumping events. Comparative analysis of diseased versus healthy animals revealed a trend of higher pathogen loads in the former, with possible differences in tissue tropisms. In total, 48 zoonotic and 17 epizootic pathogens were identified, with frequent cross-species transmission, emphasizing the potential for emerging public health threats. This study highlights the urgent need for wildlife pathogen surveillance to inform proactive disease management strategies.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.09.632079v1

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The Channel of Gravelines, Petit Fort - Philippe Georges Seurat (1890)

 Source: WikiArt, https://www.wikiart.org/en/georges-seurat/the-channel-of-gravelines-petit-fort-philippe-1890

Public Domain.

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Respiratory #Shedding of Infectious #SARS-CoV-2 #Omicron #XBB.1.41.1 Lineage among Captive White-Tailed #Deer, #Texas, #USA

Abstract

White-tailed deer (Odocoileus virginianus) have high value for research, conservation, agriculture, and recreation and might be key SARS-CoV-2 reservoirs. In November 2023, we sampled 15 female deer in a captive facility in Texas, USA. All deer had neutralizing antibodies to SARS-CoV-2; respiratory swab samples from 11 deer were SARS-CoV-2–positive by quantitative reverse transcription PCR, and 1 deer also had a positive rectal swab sample. Six of the 11 respiratory swab samples yielded infectious virus; replication kinetics of most samples displayed lower growth 24–48 hours postinfection in vitro than Omicron lineages isolated from humans in Texas in the same period. Virus growth was similar between groups by 72 hours, suggesting no strong attenuation of deer-derived virus. All deer viruses clustered in XBB Omicron clade and demonstrated more mutations than expected compared with contemporaneous viruses in humans, suggesting that crossing the species barrier was accompanied by a high substitution rate.

Source: Emerging Infectious Diseases Journal, https://wwwnc.cdc.gov/eid/article/31/2/24-1458_article

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An intranasal, NLC-delivered self-amplifying #RNA #vaccine establishes protective #immunity against pre-pandemic #H5N1 and #H7N9 #influenza

Abstract

Seasonal and pandemic influenzas are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. New RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent self-amplifying RNA (saRNA) vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/2013 H7N9. These saRNA vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The saRNA-NLC vaccines provided complete protection against morbidity and mortality in ferret challenge models, establishing this intranasally-administered saRNA-NLC vaccine platform as a potential pandemic response tool.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.07.631792v1?rss=1

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The Q226L #mutation can convert a highly pathogenic #H5 2.3.4.4e virus to #bind #human-type #receptors

Abstract

H5Nx viruses continue to wreak havoc in avian and mammalian species worldwide. The virus distinguishes itself by the ability to replicate to high titers and transmit efficiently in a wide variety of hosts in diverse climatic environments. Fortunately, transmission to and between humans is scarce. Yet, if such an event were to occur, it could spark a pandemic as humans are immunologically naive to H5 viruses. A significant determinant of transmission to and between humans is the ability of the influenza A virus hemagglutinin (HA) protein to shift from an avian-type to a human-type receptor specificity. Here, we demonstrate that a 2016 2.3.4.4e virus HA can convert to human-type receptor binding via a single Q226L mutation, in contrast to a cleavage-modified 2016 2.3.4.4b virus HA. Using glycan arrays, x-ray structural analyses, tissue- and direct glycan binding, we show that L133adelta and 227Q are vital for this phenotype. Thus, whereas the 2.3.4.4e virus HA only needs a single amino acid mutation, the modified 2.3.4.4b HA was not easily converted to human-type receptor specificity.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.10.632119v1?rss=1

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#USA, #Michigan: {Oakland County} Health Division: 11 people under health #surveillance after contact with #H5N1 #birdflu infected #poultry

Waterford Township, Mich. – The Oakland County Health Division is monitoring a situation involving highly pathogenic avian influenza (HPAI), commonly known as bird flu, identified in animals at the farm at Hess-Hathaway Park in Waterford Township. 

|--     Eleven individuals who had direct contact with the animals are being         monitored    for 10 days, beginning yesterday. --|

Initially, it was reported that two of the 11 are experiencing flu-like symptoms. Since then, the Health Division has learned that only one individual has symptoms. That person’s influenza test has been collected and results from the state lab are pending.

“The risk of contracting bird flu is very low for the general public, but it’s important to be aware of the disease in the community,” said Oakland County Director of Health and Human Services Leigh-Anne Stafford. “Protect yourself and prevent bird flu by avoiding direct contact with sick or dead birds and wash your hands thoroughly if you come into contact with them.

In response to the discovery of HPAI at the farm at Hess-Hathaway Park, Waterford Township has taken proactive measures. Supervisor Anthony Bartolotta emphasized the township’s commitment to safety.

“Until further notice, portions of the farm will be closed to protect our animals, staff and visitors. However, the rest of Hess-Hathaway Park remains open for community enjoyment,” Bartolotta said. “We appreciate the community’s cooperation, patience and understanding as we work to return our farm to regular operations. We look forward to reopening in the Spring of 2025.”

Residents are encouraged to follow these prevention tips:

-- Avoid direct contact with sick or dead birds and animals.

-- Use recommended personal protective equipment (PPE) if contact is necessary.

-- Refrain from touching surfaces contaminated by bird droppings or bodily fluids.

-- Avoid consuming raw milk or raw milk products.

-- If bird flu is suspected in a domestic flock, contact Michigan Department of Agriculture and Rural Development (MDARD) immediately at 800-292-3939 (daytime) or 517-373-0440 (after hours). Additionally, report cases of unusual or unexplained deaths among wild bird populations by contacting the Michigan Department of Natural Resources at 517-336-5030.

MDARD is closely monitoring and responding to reports of sick domestic birds and HPAI throughout the state.

Contact your health care provider if you’ve had close contact with domestic fowl or wild bird and have bird flu symptoms. 

Bird flu symptoms range from no symptoms to severe disease. Signs and symptoms of bird flu in people may include:

-- Eye redness and irritation (conjunctivitis)

-- Mild fever (100 degrees Fahrenheit or greater) or feeling feverish (fever may not always be present)

-- Cough

-- Sore throat

-- Runny or stuffy nose

-- Muscle or body aches

-- Headaches

-- Fatigue

-- Shortness of breath or difficulty breathing

-- Less common symptoms include diarrhea, nausea or vomiting.

HPAI virus is widespread in wild birds worldwide and detected in domestic poultry and other animals. It can spread in various ways from flock to flock, including by wild birds, through contact with infected animals, by equipment, and on the clothing and shoes of caretakers. 

More information about bird flu can be found on the Health Division’s website at oakgov.com/health or by contacting Nurse on Call at 800-848-5533 or noc@oakgov.com. Nurse on Call is available 8:30 a.m. to 5:00 p.m., Monday through Friday. For up-to-date public health information, follow @publichealthOC on Facebook and X.  

Read the initial alert from MDARD here. For additional bird flu information from the state, click on michigan.gov/birdflu.  

Source: Oakland County Department of Health, https://www.oakgov.com/Home/Components/News/News/1751/591

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