Wednesday, January 15, 2025

#USA, US #CDC: #H5 #Birdflu #Response: Focus Areas for Ongoing Public Health #Risk #Assessment



{Edited}

Current H5N1 bird flu risk

People who are at increased risk include:

-- Farmers and workers who work with infected animals or their byproducts

-- Backyard bird flock owners

-- Animal care workers (e.g., veterinarians, wild animal facility workers)

-- Animal health and public health responders.

But what factors would influence a change to CDC’s current risk assessment for the general public? What follows is a description of the epidemiological and virologic characteristics of the avian influenza situation that CDC scientists are tracking to formulate the agency’s immediate avian flu risk assessment and further calibrating the avian flu response to protect the public’s health:

-- Virus transmission: How is virus spreading and how efficiently does it spread?

-- Disease severity: How ill do people with H5N1 bird flu infections become?

-- Case distribution: How widespread are cases?

-- Effects of genetic changes in the virus: What is the impact of genetic changes to the virus on infectivity or transmissibility, the accuracy of diagnostic tests, and effectiveness of antiviral drugs and vaccines?


Virus transmission

What is CDC on the lookout for? 

Sustained human-to-human transmission outside of a household increases the likelihood of significant public health impact.

Influenza A(H5N1) has been spreading in wild birds globally since the mid-1990s and in the United States since 2014. The virus initially spread to commercial and backyard poultry and has also infected mammals, including minks, sea lions and now dairy cattle. 

There have been sporadic human cases both in the United States and in other countries, and limited human-to-human transmission of avian influenza has been occasionally reported globally. 

To date, there is no evidence of human-to-human transmission associated with the current avian influenza situation in the United States

Transmission identified outside of a household would be of greater concern than within a household when assessing immediate public health risk.

Beyond looking out for human-to-human transmission through case investigation, CDC continues to rapidly analyze and share genetic sequences of samples from human cases and, alongside information gained from viral samples from infected animals, is monitoring for changes that would allow the virus to spread more easily—particularly to humans and other mammals.


Disease severity

What is CDC on the lookout for? 

CDC is concerned about all people who become infected with avian flu and is particularly concerned if we begin seeing people who quickly become severely ill and require hospitalization or who die of the infection. 

Severe disease may indicate the virus has changed and is now better able to make people severely ill. 

This degree of severity could have a greater public health impact, straining the healthcare system and may have other societal and economic impacts (e.g., if people cannot work).

Most cases of H5N1 bird flu associated with the ongoing outbreak in the United States have resulted in mild symptoms

CDC experts and other scientists continue to work to understand why some infections, including an infection reported in Canada and one reported in Louisiana, resulted in serious illness. 

Severity of illness can be impacted by a number of factors, including acquired genetic changes of the virus, the amount of virus to which the infected people were exposed, the route of transmission, underlying health conditions, how long the person was sick and the timeliness of medical care/treatment, or some combination of all these factors.


Case distribution

What is CDC on the lookout for? 

Indication that that virus may have broad dissemination among humans within specific populations or to the general population, or increasing numbers of people who are becoming infected without clear exposure to infected animals.

Human cases associated with the ongoing outbreak have been sporadic, and nearly all have followed identifiable exposures to dairy cows, poultry, and/or other animals.

Broad dissemination of cases would be evident if all of the following were to occur:

-- Numerous sporadic (i.e., occurring at irregular intervals or infrequently as isolated events) human cases unrelated to expected shared/common animal exposures

-- Cases occurring in multiple geographic locations

-- Cases occurring close together in time


Effects of genetic changes in the virus

What is CDC on the lookout for? 

Genetic changes known to be associated with increased severity or transmissibility or other viral changes seen at the same time as increased transmissibility and increasing severity of infection.

CDC conducts routine assessment of the sequences of the viruses from humans and animals for changes that might impact infectivity or transmissibility in humans, the accuracy of diagnostic tests and the effectiveness of vaccines or antivirals. 

To date, genetic analysis has not identified changes in viruses compared to available clade 2.3.4.4b candidate vaccine viruses (CVVs) that would be predicted to impact cross-protection if A(H5) vaccines were needed for use in humans. 

Nor have changes been identified in the receptor binding domain of viruses except for low frequency changes in the fatal case from Louisiana and the severe case from Canada

These changes were believed to have occurred after the individuals were infected rather than acquired from their infecting exposure. 

There is no evidence that viruses with these changes spread beyond these patients.

Collectively, these data indicate that A(H5N1) viruses circulating in animals retain avian receptor binding properties with no significant changes that would impact infectivity or transmissibility in humans

Additionally, there have been only a few sporadic changes identified in viruses detected in animals or humans associated with mammalian adaptation or slightly reduced susceptibility to commercially available antiviral drugs. 

Finally, no changes have been identified in viruses that impact the performance of H5 influenza diagnostic tests that are used for testing across all U.S. states and at CDC.

These factors are all important considerations that inform what public health actions should be implemented in the H5 avian flu public health response. 

Should we see concerning changes in these factors, additional actions may be necessary to protect the health and safety of people with potential animal exposures as well as the general public. 

Additional actions may include but are not limited to:

-- Updating guidance to better protect those who may be exposed to H5 avian flu, such as who should receive pre- or post-exposure prophylaxis, testing strategy, and how to best use personal protective equipment.

-- Procuring additional treatments and vaccines, to ensure we have sufficient supply for those who would benefit from their use.

-- Initiating a voluntary H5 vaccination program focused on people with predictable exposure to the virus.

-- Initiating a broader voluntary H5 vaccination program if the possibility of widespread transmission or increasing disease severity is found.

Such escalation will likely require additional resources.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/spotlights/h5n1-response-01142025.html

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#USA, Confirmed #H5N1 #influenza #human case summary since 2024, by state and exposure source: 1 new case in CA, total now = 67



{Excerpt}

Exposure Source

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

1) California - 36 - 0 - 0 - 2 - 38 {+1}

2) Colorado - 1 - 9 - 0 - 0 - 10

3) Iowa - 0 - 1 - 0 - 0 - 1

4) Louisiana - 0 - 0 - 1 - 0 - 1

5) Michigan - 2 - 0 - 0 - 0 - 2

6) Missouri - 0 - 0 - 0 - 1 - 1

7) Oregon - 0 - 1 - 0 - 0 - 1

8) Texas - 1  - 0 - 0 - 0 - 1

9) Washington - 0 - 11 - 0 - 0 - 11

10) Wisconsin - 0 - 1 - 0 - 0 - 1

-- Source Total - 40 - 23 - 1 - 3 - 67 {+1}

NOTE: One additional case was previously detected in a poultry worker in Colorado in 2022. Louisiana reported the first H5 bird flu death in the U.S.

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

{‡} Exposure source was not able to be identified


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

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

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

1) Washington (3)

2) Arizona (2)

Probable cases with commercial dairy (cattle) exposure:

1) California (1)

Probable cases with exposure source unknown:

1) Delaware (1)

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

(...)

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

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#Pathogenesis of #bovine #H5N1 clade 2.3.4.4b #infection in #Macaques

Abstract

Since early 2022 highly pathogenic avian influenza (HPAI) H5N1 virus infections have been reported in wild aquatic birds and poultry throughout the United States (US) with spillover into several mammalian species1-6. In March 2024, HPAIV H5N1 clade 2.3.4.4b was first detected in dairy cows in Texas, US and continues to circulate on dairy farms in multiple states7,8. Milk production and quality are diminished in infected dairy cows, with high virus titers in milk raising concerns of exposure to mammals including humans through consumption9-12. Here we investigated routes of infection with bovine HPAIV H5N1 clade 2.3.4.4b in cynomolgus macaques, a surrogate model for human infection13. We show that intranasal or intratracheal inoculation of macaques could cause systemic infection resulting in mild and severe respiratory disease, respectively. In contrast, infection by the orogastric route resulted in limited infection and seroconversion of macaques which remained subclinical.

Source: Nature, https://www.nature.com/articles/s41586-025-08609-8

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Clinical #Features of #Human #Parvovirus B19-Associated #Encephalitis Identified in the #Dakar Region, #Senegal, and Viral Genome Characterization

Abstract

Neurological manifestations associated with human parvovirus B19 (B19V) infections are rare and varied. Acute encephalitis and encephalopathy are the most common, accounting for 38.8% of all neurological manifestations associated with human B19V. Herein, we report on the clinical features of 13 laboratory-confirmed human cases of B19V-associated encephalitis in Senegal in the framework of a hospital-based surveillance of acute viral encephalitis conducted from 2021 to 2023. Overall, B19V was detected from 13 cerebrospinal fluid samples using specific real time PCR. The mean age was 16.7 years among B19V-positive patients, with a higher prevalence in 0–5-year-old children and the sex ratio (male/female) was 2.25. The B19V-positive patients mainly exhibited hypoleukocytosis, normal glycorrhachia, and normal proteinorrachia in the cerebrospinal fluid. While the main neurological symptoms included meningeal and infectious syndromes. Furthermore, three complete B19V genome sequences were successfully characterized using next-generation sequencing. The newly characterized sequences belonged to the genotype 1a and represent, to date, the first complete B19V genome sequences from Senegal. These sequences could be useful not only in future phylodynamic studies of B19V but also in the development of prevention or treatment countermeasures. Our study is noteworthy for the identification of acute B19V-associated encephalitis in Senegal More investigations on the risk factors associated with B19V transmission in Africa are warranted.

Source: Viruses, https://www.mdpi.com/1999-4915/17/1/111

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

 A fattening turkeys farm in Baden-WĂ¼rttemberg Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6188

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Clade 2.3.4.4b but not historical clade 1 #HA replicating #RNA #vaccine protects against #bovine #H5N1 challenge in #mice

Abstract

The ongoing circulation of influenza A H5N1 in the United States has raised concerns of a pandemic caused by highly pathogenic avian influenza. Although the United States has stockpiled and is prepared to produce millions of vaccine doses to address an H5N1 pandemic, currently circulating H5N1 viruses contain multiple mutations within the immunodominant head domain of hemagglutinin (HA) compared to the antigens used in stockpiled vaccines. It is unclear if these stockpiled vaccines will need to be updated to match the contemporary H5N1 strains. Here we show that a replicating RNA vaccine expressing the HA of an H5N1 isolated from a US dairy cow confers complete protection against homologous lethal challenge in mice. A repRNA encoding the HA of a clade 1 H5 from 2004 (A/Vietnam/1203/2004) as utilized by some stockpiled vaccines, confers only partial protection. Our data highlight the utility of nucleic acid vaccines to be rapidly updated to match emergent viruses of concern while demonstrating that contemporary bovine H5N1 viruses can evade immunity elicited by historical HA antigens.

Source: Nature Communication, https://www.nature.com/articles/s41467-024-55546-7

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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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Tuesday, January 14, 2025

#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

_____

#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

_____

Monday, January 13, 2025

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

_____

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 week93 sites



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

______

#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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Sunday, January 12, 2025

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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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