#Germany - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 A poultry farm in Bayern Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6131

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High Pathogenicity Avian #Influenza Virus (HPAIV) #H5N1 clade 2.3.4.4b recovered from a kelp #gull (Larus dominicanus) in the South Shetland Islands, #Antarctica

Abstract

Whole-genome analysis of the earliest-detected High Pathogenicity Avian Influenza Virus (HPAIV) H5N1 clade 2.3.4.4b detected in Hannah Point, Antarctica (January 2024) reveals close relatedness to strains that circulated in pinnipeds and seabirds along the Atlantic coast of South America during the second half of 2023.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.29.630510v1?rss=1

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Dona Antonia de Ipenarrieta y Galdos and her Son, Diego Velazquez (c.1631)

 

Credits: Public Domain.

Source: WikiArt, https://www.wikiart.org/en/diego-velazquez/dona-antonia-de-ipenarrieta-y-galdos-and-her-son

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The #PA-X #host shutoff site 100 V exerts a contrary effect on viral #fitness of the highly pathogenic #H7N9 #influenza A virus in mice and chickens

ABSTRACT

Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed “host shutoff.” Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery. IAV PA-X is one of these factors that selectively shuts off the global host genes. However, the specific role of PA-X host shutoff activity in viral fitness of IAV remains poorly understood. Herein, we successfully mapped PA-X 100 V as a novel site important for host shutoff of the H7N9 and H5N1 viruses. By analysing the polymorphism of this residue in various subtype viruses, we found that PA-X 100 was highly variable in H7N9 viruses. Structural analysis revealed that 100 V was generally close to the PA-X endonuclease active site, which may account for its host shutoff activity. By generating the corresponding mutant viruses derived from the parental H7N9 virus and the PA-X-deficient H7N9 virus, we determined that PA-X 100 V significantly enhanced viral fitness in mice while diminishing viral virulence in chickens. Mechanistically, PA-X 100 V significantly increased viral polymerase activity and viral replication in mammalian cells. Furthermore, PA-X 100 V highly blunted the global host response in 293T cells, particularly restraining genes involved in energy metabolism and inflammatory response. Collectively, our data provided information about the intricate role of the PA-X host shutoff site in regulating the viral fitness of the H7N9 influenza virus, which furthers our understanding of the complicated pathogenesis of the influenza A virus.

Source: Virulence, https://www.tandfonline.com/doi/full/10.1080/21505594.2024.2445238

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#USA, Snow #Geese Test Presumptive Positive for Avian #H5 #Influenza; #Delaware #poultry producers encouraged to take precautions

 {Excerpt}

DOVER, Del. (Dec. 28, 2024) – The Delaware Department of Natural Resources and Environmental Control (DNREC) and the Delaware Department of Agriculture (DDA) announced today that laboratory testing conducted by the University of Delaware’s Allen Laboratory, part of the National Animal Health Laboratory Network, has returned presumptive positive findings of H5 avian influenza in sick and dead snow geese collected on December 27, 2024, in coastal Sussex County. 

In response to the findings, the state of Delaware has established a Joint Information Center with DNREC, DDA, the Delaware Division of Public Health (DPH) and the Delaware Emergency Management Agency (DEMA).

The detections mark the Delmarva region’s most recent confirmation of H5 avian influenza in wild birds since May 2022, when the virus was found through wildlife surveillance in black vultures in Harford County, Md. Avian influenza is known to be carried by wild birds, especially waterfowl, raptors, and vultures.

Avian influenza is a highly contagious airborne respiratory virus that spreads quickly among birds through nasal and eye secretions and manure. Snow geese, which are waterfowl, are known to migrate from the Arctic and form large flocks in Delaware each winter. Due to close contact with thousands of other snow geese while feeding and roosting, they can get sick and die. It is unknown when or where the snow geese may have acquired the virus given their highly migratory nature and association with other waterfowl and waterbirds throughout the Atlantic Flyway through which they travel into Delaware and more southern states.

People should not touch or handle injured, sick, or dead birds. Special attention should be paid to keep pets and children away from these wild birds and bird droppings.

Even with the ongoing detections of HPAI in wild birds, poultry, and dairy cattle in North America, continuing testing of people who are in close contact with infected animals indicates a low risk to the general public’s health. The H5N1 virus has infected very few people and has not been documented to be transmitted between people. 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.

(...)

Source: Department of Health, https://news.delaware.gov/2024/12/28/snow-geese-test-presumptive-positive-for-avian-influenza-delaware-poultry-producers-encouraged-to-take-precautions/

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Molecular #Evolution of the #H5 and #H7 Highly Pathogenic Avian #Influenza Virus #Haemagglutinin Cleavage Site Motif

ABSTRACT

Avian influenza viruses are ubiquitous in the Anatinae subfamily of aquatic birds and occasionally spill over to poultry. Infection with low pathogenicity avian influenza viruses generally leads to subclinical or mild clinical disease. In contrast, highly pathogenic avian influenza viruses emerge from low pathogenic forms and can cause severe disease associated with extraordinarily high mortality rates. Here, we describe the natural history of avian influenza virus, with a focus on H5Nx and H7Nx subtypes, and the emergence of highly pathogenic forms; we review the biology of AIV; we examine cleavage of haemagglutinin by host cell enzymes with a particular emphasis on the biochemical properties of the proprotein convertases, and trypsin and trypsin-like proteases; we describe mechanisms implicated in the functional evolution of the haemagglutinin cleavage site motif that leads to emergence of HPAIVs; and finally, we discuss the diversity of H5 and H7 haemagglutinin cleavage site sequence motifs. It is crucial to understand the molecular attributes that drive the emergence and evolution of HPAIVs with pandemic potential to inform risk assessments and mitigate the threat of HPAIVs to poultry and human populations.

Source: Reviews in Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/rmv.70012

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#Coronavirus Disease Research #References (by AMEDEO, December 28 2024)

 

Ann Intern Med

1. 
   Annals Video Summary - Anticoagulation Among Patients Hospitalized for COVID-19.
   Ann Intern Med. 2024 Dec 24:e2403257VS. doi: 10.7326/ANNALS-24-03257.
   PubMed        
   
   
2. VALE CL, Godolphin PJ, Fisher DJ, Higgins JPT, et al
   Anticoagulation Among Patients Hospitalized for COVID-19 : A Systematic Review and Prospective Meta-analysis.
   Ann Intern Med. 2024 Dec 24. doi: 10.7326/ANNALS-24-00800.
   PubMed         Abstract available
   
   
3. SHAPPELL CN, Anesi GL
   Anticoagulation for COVID-19: Seeking Clarity and Finding Yet More Gray.
   Ann Intern Med. 2024 Dec 24. doi: 10.7326/ANNALS-24-03244.
   PubMed        
   
   

   
   Clin Chem

4. FALAK S, O'Sullivan DM, Cleveland MH, Cowen S, et al
   The Application of Digital PCR as a Reference Measurement Procedure to Support the Accuracy of Quality Assurance for Infectious Disease Molecular Diagnostic Testing.
   Clin Chem. 2024 Dec 26:hvae187. doi: 10.1093.
   PubMed         Abstract available
   
   

   
   Emerg Infect Dis

5. KITI MC, Sacoor C, Aguolu OG, Zelaya A, et al
   Social Contact Patterns in Rural and Urban Settings, Mozambique, 2021-2022.
   Emerg Infect Dis. 2025;31:94-103.
   PubMed         Abstract available
   
   
6. ENGELI V, Roussos S, Demiris N, Hatzakis A, et al
   Social Contact Patterns and Age Mixing before and during COVID-19 Pandemic, Greece, January 2020-October 2021.
   Emerg Infect Dis. 2025;31:75-85.
   PubMed         Abstract available
   
   
7. MA J, Yang Y, Huang Y
   Research and Development of Medical Countermeasures for Emerging Infectious Diseases, China, 1990-2022.
   Emerg Infect Dis. 2025;31:14-21.
   PubMed         Abstract available
   
   

   
   Int J Infect Dis

8. CHEN X, Chen H, Tao F, Chen Y, et al
   Global analysis of influenza epidemic characteristics in the first two seasons after lifting the non-pharmaceutical interventions for COVID-19.
   Int J Infect Dis. 2024 Dec 20:107372. doi: 10.1016/j.ijid.2024.107372.
   PubMed         Abstract available
   
   

   
   J Med Virol

9. WANG C, Yang Y, Wu K, Wang C, et al
   An Outbreak of Human Adenovirus Infection Among Children Post COVID-19 Pandemic in Southern China.
   J Med Virol. 2024;96:e70139.
   PubMed         Abstract available
   
   
10. LI K, Wu Y, Zhang H, Chen S, et al
    A Novel Circular Delta-XBB15 RBD Dimeric Protein Subunit Vaccine Mediated by Split Intein Elicits an Immune Response and Protection Against Multiple SARS-CoV-2 Variants in Mice.
    J Med Virol. 2024;96:e70134.
    PubMed         Abstract available
    
    
11. GOSERT R, Koller R, Meyer J, Drager S, et al
    Multicenter Evaluation of the QIAstat-Dx and the BioFire Multiplex Panel Tests for the Detection of Respiratory Pathogens.
    J Med Virol. 2024;96:e70129.
    PubMed         Abstract available
    
    

    
    Radiology

12. FINNIGAN LEM, Cassar MP, Jafarpour M, Sultana A, et al
    (1)H and (31)P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID.
    Radiology. 2024;313:e233173.
    PubMed         Abstract available

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Dec. 28 ' 24)

 

Antiviral Res

1. WANG B, Xia H, Peng BH, Choi EJ, et al
   Pellino-1, a therapeutic target for control of SARS-CoV-2 infection and disease severity.
   Antiviral Res. 2024;233:106059.
   PubMed         Abstract available
   
   
2. SCHRELL L, Fuchs HL, Dickmanns A, Scheibner D, et al
   Inhibitors of dihydroorotate dehydrogenase synergize with the broad antiviral activity of 4'-fluorouridine.
   Antiviral Res. 2024 Dec 3:106046. doi: 10.1016/j.antiviral.2024.106046.
   PubMed         Abstract available
   
   

   
   Epidemiol Infect

3. SUTER J, Devos I, Matthes KL, Staub K, et al
   The health and demographic impacts of the "Russian flu" pandemic in Switzerland in 1889/1890 and in the years thereafter.
   Epidemiol Infect. 2024;152:e174.
   PubMed         Abstract available
   
   

   
   JAMA

4. ANDERER S
   CDC Calls Attention to Underuse of Antiviral Treatment in Higher-Risk Youth With Influenza.
   JAMA. 2024 Dec 27. doi: 10.1001/jama.2024.25515.
   PubMed        
   
   

   
   PLoS Comput Biol

5. CALMON L, Colosi E, Bassignana G, Barrat A, et al
   Preserving friendships in school contacts: An algorithm to construct synthetic temporal networks for epidemic modelling.
   PLoS Comput Biol. 2024;20:e1012661.
   PubMed         Abstract available
   
   

   
   PLoS One

6. BAGALA I, Namuganga JF, Nayebare P, Cuu G, et al
   Seroprevalence of SARS-CoV-2 and risk factors for infection among children in Uganda: A serial cross-sectional study.
   PLoS One. 2024;19:e0312554.
   PubMed         Abstract available
   
   
7. ZHANG Y, Guo X, Su Y
   Spatiotemporal dynamic and regional differences of public attention to vaccination: An empirical study in China.
   PLoS One. 2024;19:e0312488.
   PubMed         Abstract available
   
   
8. KIM S, Aum T, Lee DG
   Depression in the COVID-19 endemic era: Analysis of online self-disclosures by young South Koreans.
   PLoS One. 2024;19:e0314881.
   PubMed         Abstract available
   
   
9. OPOKU-BOATENG YN, Opoku-Asante E, Lagarde M, Nketiah-Amponsah E, et al
   Effect of Covid-19 on maternal and child health services utilization in Ghana. Evidence from the National Health Insurance Scheme (NHIS).
   PLoS One. 2024;19:e0311277.
   PubMed         Abstract available
   
   
10. TARIGAN S, Sekarmila G, Apas, Sumarningsih, et al
    Challenges and strategies in the soluble expression of CTA1-(S14P5)4-DD and CTA1-(S21P2)4-DD fusion proteins as candidates for COVID-19 intranasal vaccines.
    PLoS One. 2024;19:e0306153.
    PubMed         Abstract available
    
    
11. VALDERRAMA-BELTRAN SL, Cuervo-Rojas J, Rondon M, Montealegre-Diaz JS, et al
    Development of a diagnostic multivariable prediction model of a positive SARS-CoV-2 RT-PCR result in healthcare workers with suspected SARS-CoV-2 infection in hospital settings.
    PLoS One. 2024;19:e0316207.
    PubMed         Abstract available
    
    
12. JIMENEZ-CAMPOS AG, Maestas LI, Velappan N, Beck B, et al
    A cell-based Papain-like Protease (PLpro) activity assay for rapid detection of active SARS-CoV-2 infections and antivirals.
    PLoS One. 2024;19:e0309305.
    PubMed         Abstract available
    
    
13. FENTA EH, Tassew B, Abera A, Wolde FB, et al
    Maintaining essential healthcare services in Addis Ababa during COVID-19: A qualitative study.
    PLoS One. 2024;19:e0308534.
    PubMed         Abstract available
    
    
14. HUI CY, Condon K, Kolekar S, Roberts N, et al
    Implementing digital respiratory technologies for people with respiratory conditions: A protocol for a scoping review.
    PLoS One. 2024;19:e0314914.
    PubMed         Abstract available
    
    
15. SCHICK RC, Bast H, Frank M, Urban T, et al
    Simulated low-dose dark-field radiography for detection of COVID-19 pneumonia.
    PLoS One. 2024;19:e0316104.
    PubMed         Abstract available
    
    
16. ROMASZKO-WOJTOWICZ A, Doboszynska A, Piechnik A, Kuziemski K, et al
    Impact of the COVID-19 pandemic on lung cancer diagnosis in northern Poland-addressing the COVID-19 debt.
    PLoS One. 2024;19:e0316261.
    PubMed         Abstract available
    
    
17. ALI MA, Shaker OG, Ezzat EM, Ali ESG, et al
    Peripheral lncRNA NEAT-1, miR374b-5p, and IL6 panel to guide in COVID-19 patients' diagnosis and prognosis.
    PLoS One. 2024;19:e0313042.
    PubMed         Abstract available
    
    
18. HADID D, Correia RH, McDonald SD, Darling EK, et al
    Assessing the impact of the COVID-19 pandemic on uptake and experiences of gestational diabetes mellitus screening in Ontario: A parallel convergent mixed-methods study.
    PLoS One. 2024;19:e0315983.
    PubMed         Abstract available
    
    

    
    Vaccine

19. WANG J, Tonnies T, Brinks R
    Seasonal influenza vaccination coverage and the social determinants of influenza vaccination among people over 50 with diabetes in Europe: Analyzing population-based SHARE data for the 2019-2020 and 2021-2022 influenza seasons.
    Vaccine. 2024;45:126646.
    PubMed         Abstract available
    
    
20. FRAIHA ALS, da Silva Santos BSA, Aguilar NR, Gallinari GC, et al
    Immunization and challenge trials in a murine model using different inactivated recombinant vaccines against H1N1 swine influenza virus circulating in Brazil.
    Vaccine. 2024;45:126638.
    PubMed         Abstract available
    
    
21. WERTHNER Q, Faehrmann L, Och K, Bragazzi NL, et al
    Client satisfaction, safety, and insights from a three-season survey on influenza vaccinations delivered at community pharmacies in Germany.
    Vaccine. 2024;45:126650.
    PubMed         Abstract available
    

Virological and #antigenic characteristics of #SARS-CoV-2 #variants #LF721, #NP1, and #LP81

Abstract

XEC and KP.3.1.1 have surpassed KP.3 to become the globally dominant lineages due to their unique NTD mutations. However, several emerging JN.1 sublineages, such as LF.7.2.1, MC.10.1, NP.1, and, especially, LP.8.1, have demonstrated superior growth advantages compared to XEC. It is critical to access the virological and antigenic characteristics of these emerging SARS-CoV-2 variants. Here, we found that LF.7.2.1 is significantly more immune invasive than XEC, primarily due to the A475V mutation, which enabled the evasion of Class 1 neutralizing antibodies. However, LF.7.2.1's weak ACE2 binding affinity substantially impaired its fitness. Likewise, MC.10.1 and NP.1 exhibited strong antibody immune evasion due to the A435S mutation, but their limited ACE2 engagement efficiency restricted their growth advantage, suggesting that A435S may regulate the Spike conformation, similar to the NTD glycosylation mutations found in KP.3.1.1 and XEC. Most importantly, we found that LP.8.1 showed comparable humoral immune evasion to XEC but demonstrated much increased ACE2 engagement efficiency, supporting its rapid growth. These findings highlight the trade-off between immune evasion and ACE2 engagement efficiency in SARS-CoV-2 evolution, and underscore the importance of monitoring LP.8.1 These findings highlight the trade-off between immune evasion and ACE2 engagement efficiency in SARS-CoV-2 evolution, and underscore the importance of monitoring LP.8.1 and its descend lineages.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.27.630350v1?rss=1

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#USA, Confirmed #H5N1 #influenza #human case summary during 2024 #outbreak, by state and exposure source {as of Dec. 27 '24: 1 new case, total = 66}

 {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 - 1 - 37 {+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 - 2 - 66 {+1}

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

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

{‡} Exposure source was not able to be identified

Probable human case summary during the 2024 outbreak, by state and exposure source {Seven Cases}

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):

- Washington (3)

- Arizona (2)

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

- California (1)

-- Probable cases with exposure source unknown:

- 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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Acute #respiratory #infections complicated by #malaria (previously undiagnosed disease) - #DRC

{Excerpts}

27 December 2024

Situation at a glance

This is an update to the Disease Outbreak News on Undiagnosed disease in the Democratic Republic of the Congo published on 8 December 2024 (now named acute respiratory infections complicated by malaria). 

It includes updated epidemiological investigation information and preliminary laboratory results. 

On 29 November, an alert was raised by local health zone authorities of Panzi health zone in Kwango province after an increase in deaths, particularly among children under five years of age, following febrile illness. 

Enhanced epidemiological surveillance was rapidly implemented, which in the absence of a clear diagnosis was based on the detection of syndromic cases of febrile illnesses with cough, body weakness, with one of a number of other symptoms compatible with acute respiratory and febrile illnesses. 

This resulted in a rapid increase in the number of cases meeting the definition, with a total of 891 cases reported as of 16 December. 

However, the weekly number of reported deaths (48 deaths reported over the period) has remained relatively stable. 

As of 16 December, laboratory results from a total of 430 samples indicated positive results for malaria, common respiratory viruses (Influenza A (H1N1, pdm09), rhinoviruses, SARS-COV-2, Human coronaviruses, parainfluenza viruses, and Human Adenovirus). 

While further laboratory tests are ongoing, together these findings suggest that a combination of common and seasonal viral respiratory infections and falciparum malaria, compounded by acute malnutrition led to an increase in severe infections and deaths, disproportionally affecting children under five years of age. 

Multidisciplinary rapid response teams have been deployed to investigate the event and strengthen the response. 

Efforts are ongoing to address the health needs in Panzi health zone. 

Enhanced surveillance in the community and within health facilities continues. 

The teams have also been providing support for diagnosis, the treatment of patients as well as with risk communication and community engagement. 

This event highlights the severe burden from common infectious diseases (acute respiratory infections and malaria) in a context of vulnerable populations facing food insecurity. It emphasizes the need to strengthen access to health care and address underlying causes of vulnerability, particularly malnutrition, given the worsening food insecurity.

Description of the situation

Since the last Disease Outbreak News on this event was published on 8 December 2024, 485 additional suspected cases and 17 additional deaths have been reported from Panzi health zone in Kwango Province, Democratic Republic of the Congo, across 25 out of the 30 health areas in Panzi. These cases were identified as a result of enhanced surveillance put in place following the report of deaths in the context of febrile illness with acute respiratory symptoms and anaemia, first reported on 29 November. While the number of reported cases was not deemed particularly unusual in a context of high burden of pneumonia, malaria and acute respiratory infections, particularly at the start of the rainy season, it is the increase in the number of deaths that triggered the alert on 29 November.

In the absence of diagnosis, a broad surveillance case definition was used, with the resulting case numbers reflecting the detection of any febrile illness occurring in Panzi and thus representing a range of diseases and clinical syndromes. The case definition includes: any person living in the Panzi health zone from September 2024 to date, presenting with fever, cough, body weakness, runny nose, with or without one of the following symptoms and signs: chills, headache, difficulty breathing, malnutrition, body aches. This was done to better understand the epidemiology and characteristics of deaths and to collect a range of clinical samples for laboratory testing.

Between 24 October and 16 December 2024, 48 deaths and a total of 891 cases across 25/30 health areas of Panzi health zone met the case definition. Children under five years of age are disproportionally affected, representing 47% of all cases and 54% of all deaths, while they represent around 18% of the population, likely reflecting the vulnerability of young children to severe disease and death in this context. The main symptoms associated with death include difficulty in breathing, anaemia, and signs of acute malnutrition.

A total of 430 samples including blood samples, oropharyngeal and nasopharyngeal swabs, urine and breastmilk samples were collected from suspected cases in Panzi health zone and transported to the laboratory at the INRB. 

Out of 88 rapid diagnostics tests for malaria performed in the field, 55 (62%) samples tested positive. In addition, out of 26 samples analyzed by PCR BioFire Global Fever Panel test (which tests 18 different pathogens including some of the viral hemorrhagic fevers), 17 (65%) samples tested positive for Plasmodium falciparum.  In addition, a total of 89 samples were tested at INRB Respiratory Disease Surveillance Laboratory. Of the 89 samples, 64 samples were positive for common respiratory viruses including Influenza A (H1N1, pdm09) (n=25), rhinoviruses (n=18), SARS-COV-2 (n=15), Human coronaviruses (n=3), parainfluenza viruses (n=2), and Human adenovirus (n=1).

Other laboratory tests on the collected samples, including virological and bacterial analysis, are still ongoing. The ongoing investigations and preliminary laboratory findings suggest that a combination of common viral respiratory infections and falciparum malaria, compounded by acute malnutrition led to an increase in severe infections and deaths.

Enhanced surveillance will continue, alongside response activities. The number of weekly reported suspected cases has remained steady with the exception of an increase in epidemiological week 50 (week ending 15 December 2024, Figure 1). While this may partly reflect an increase in transmission of respiratory viruses and malaria with the rainy season, it is driven by an increase in surveillance and case finding following the deployment of the rapid response teams. Notably, the increase in cases is not matched with a comparable increase in deaths.

(...)

There are proportionally more cases reported among females (58%, 514/889), particularly among adults (66% female, 173/262). While data is lacking to better understand this difference, it may stem from contact patterns of respiratory virus transmission within households, particularly a close interaction between mothers and children during acute respiratory illnesses. 

(...)

The affected area experienced deterioration in food security in recent months, with increasing levels of acute malnutrition. Between July and December 2024, which coincides with a drop in acute malnutrition, Kwango province was in Integrated Food Security Phase Classification (IPC) Acute Malnutrition (AMN) Phase 3 (Serious). Between January and June 2025, an increase in cases of malnutrition is projected in the province with a significant deterioration in the nutritional situation expected, moving to IPC AMN Phase 4 (Critical). Between July 2024 and June 2025, nearly 4.5 million children aged 6 to 59 months in the DRC are facing or expected to face acute malnutrition, including approximately 1.4 million cases of severe acute malnutrition and 3.1 million cases of moderate acute malnutrition. It is also estimated that 3.7 million pregnant and breastfeeding women are facing or expected to face acute malnutrition over the same period.[1]

Severe acute malnutrition is a life-threatening condition that requires medical treatment. In addition, disease and malnutrition combine to worsen each other. The area has low routine vaccination coverage. There is also very limited access to diagnostics and quality case management, and a lack of supplies and transportation, shortage of health staff in the area, as well as financial and geographical barriers to access to health care. Increasing malaria trends are expected with the start of the rainy season, however, malaria control measures in the area are very limited. Together, these factors may increase the severity of malaria, and common respiratory infections.

Overall, this event highlights the severe burden from common infectious diseases (acute respiratory infections and malaria) in a context of vulnerable populations facing food insecurity and emphasizes the need to strengthen access and quality of health care.

Public health response

1. Leadership and coordination:

Daily coordination meetings are being held at the national level, with provincial teams actively participating in ongoing planning and response.

National rapid response team (RRT) composed of experts from Ministry of Health (MoH), INRB and WHO deployed from Kinshasa on 7 December and arrived in Panzi on 10 December. Following the departure of the national team, a joint MoH-Africa CDC rapid response team has been deployed with support from WHO.

2. Surveillance:

A case definition has been developed based on clinical symptoms observed, guiding surveillance and reporting efforts.  

Active case search is continuing in health facilities and the community. 

Data collection is ongoing, focusing on preparing a line list and detailed epidemiological analysis.  

Community deaths are being investigated to better understand the context of deaths and vulnerability factors.

WHO is deploying a senior epidemiologist and a data manager to support the ongoing surveillance activities and improve data collection.

3. Case Management:

Provincial and national RRTs, including WHO, UNICEF and Médecins Sans Frontières, have been deployed to the affected areas and are strengthening case management in health facilities as well as providing medical supplies including medication. The teams carried medication and medical equipment to support case management and prevent more deaths.

Efforts are underway to strengthen the capacity of healthcare providers to ensure the best possible care for patients. 

Six oxygen concentrators are being installed at the Panzi General Referral Hospital and three hotspot health centers to support patient care.

4. Laboratory:

Laboratory equipment was transported to collect samples from cases and send samples for testing at the INRB in Kinshasa. Additionally, RDTs for malaria and COVID-19 have been provided to assist in diagnosis. 

Laboratory reagents have been procured to continue facilitating the ongoing testing at INRB.

5. Risk communication and community engagement:

Key messages were developed to enhance public awareness and encourage general preventive behaviors. These messages are being disseminated through community engagement, with sensitization campaigns underway. 

6. Infection prevention and control:

Infection prevention and control measures are being reinforced. Health workers have been briefed on key practices, including the proper use of masks, hand washing, and gloves, to reduce the risk of transmission of respiratory and other pathogens. 

7. Logistics

Logistical support is being provided for effective case management, including the transportation of samples to INRB Kinshasa for laboratory testing. Health facilities and hospitals in the most affected health areas are being supplied with appropriate medications and sampling kits to support the response. 

Medical kits for malaria, IPC kits, blood transfusion kits as well as additional medical supplies to support treatment efforts have been provided.

A mobile internet kit is being deployed to address some of the telecommunication challenges in the affected health zone. 

WHO risk assessment

Symptoms such as fever, cough, headache, and body aches have been observed since 24 October, primarily through health worker reports, and an uptick in deaths was observed in epi week 47, which triggered the signal. Since the alert was reported, there has not been any significant increase in reported deaths.

The epidemiological information together with the early laboratory result indicate an event triggered by an increase in acute respiratory virus cases associated with malaria, with a background of a worsening of the nutritional situation in Panzi, disproportionally affecting young children. 

The WHO African Region accounts for about 94% of all malaria cases and 95% of deaths globally (World Malaria Report 2024). Children under five account for about 76% of all malaria deaths in the Region. Over half of these deaths occurred in four countries: Nigeria (30.9%), the Democratic Republic of the Congo (11.3%), Niger (5.9%) and United Republic of Tanzania (4.3%). Support is being provided for laboratory diagnosis and strengthening case management including the treatment of malaria cases with appropriate medication.

An increase in common respiratory viruses and malaria is expected at this time of year in Panzi with the rainy season, however it is the increase in deaths that triggered the initial signal. There has been an increase in influenza and SARS-CoV-2 activity reported from Kinshasa through sentinel sites since mid-October. WHO and UNICEF estimates of national immunization coverage for 2023 show DTP3 and PCV3 coverage at 60% and 59%, respectively, however, no data is currently available for the affected health zone, leading to uncertainties about vaccine-derived population immunity.

The Integrated Food Security Phase Classification (IPC) for acute food insecurity levels in Kwango province increased from IPC 1 (acceptable) in April 2024 to IPC 3 (Crisis Level) in September 2024. This suggests a significant phase of increase in food insecurity and risk of severe acute malnutrition. In Addition, the IPC acute malnutrition classification currently classifies Panzi health zone as IPC acute malnutrition phase 3 (serious), projected to move to phase 4 (critical) from January 2025.

While mortality from common infectious diseases is expected to increase as transmission increases, this event highlights that mortality from known and expected infectious diseases can be high in a context of vulnerability and malnutrition, emphasizing the need to strengthen malaria control, clinical management, improve access to care and reduce the prevalence of malnutrition.

Gaps in case management have also been identified. Stock-outs of medications for treating common diseases frequently occur, and care is not provided free of charge, which could limit access to treatment for vulnerable populations and increase severity and mortality of known and treatable infections.

The affected area’s remoteness and logistical barriers, including a two-day or longer road journey from Kinshasa due to the rainy season affecting the roads and limited telecommunication network coverage across the health areas, have hampered the rapid deployment of response teams and resources. Furthermore, there is no functional laboratory in the health zone or province, requiring the collection and shipment of samples to Kinshasa for analysis. This has delayed diagnosis and can continue to impact the ongoing response efforts. 

Insecurity in the region adds another layer of complexity to the response. The potential for attacks by armed groups poses a direct risk to response teams and communities, which could further disrupt the response. 

Based on the above rationale, the overall public health risk level to the affected communities is assessed as high, and requires an integrated public health approach to reduce mortality from infections, improve nutritional status and strengthen malaria control, among others.

At the national level, the risk is considered low due to the localized nature of the event and that it is caused by a range of illnesses whose severity is compounded by the vulnerability of the population in the local context. However, many other areas of DRC are seeing increasing levels of malnutrition, and what has been witnessed in Panzi could also happen elsewhere in the country.

As such, efforts need to continue to prevent similar situation in other vulnerable parts of the country.  At the regional and global levels, the risk remains low at this time.  

WHO advice

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

-- Strengthening coordination mechanisms at all levels—national, provincial, zonal, and local—is critical for a unified response. Enhanced communication infrastructure, such as satellite phones, is required to overcome the limited network coverage in affected areas.

-- Improving surveillance efforts is a priority to better understand disease trends and mortality. Active case searches should continue in both health facilities and communities, with a particular focus on areas reporting deaths and family clusters. Community-based surveillance must be strengthened to ensure early case detection and rapid response.

-- Careful characterization of the clinical syndrome and outcomes and an improved case definition based on the information collected will be necessary to understand the situation. In particular, data which clarify possibility of coinfection and multiple pathologies, and uncertainties in outcomes among vulnerable groups should be collected. The WHO has established the Global Clinical Platform to provide rapid turnaround of structured data analysis using anonymized case records; its use is recommended in the detailed capture of patient syndromes and outcomes. 

-- Effective case management requires ensuring an adequate supply of essential medications, access to oxygen therapy, and training of healthcare workers including basic emergency and critical care to support treatment and prevent more deaths. RDTs for malaria should be distributed to facilitate early diagnosis and prompt treatment. Long-term laboratory capacity strengthening, and decentralization will be important in provision of diagnostic capability in the affected health zone and detect cause of deaths early.  

-- Infection prevention and control measures must be reinforced across all health facilities. Healthcare workers should receive training on best practices, including the proper use of personal protective equipment such as masks and gloves, as well as strict hand hygiene protocols. These measures will reduce transmission risks within health facilities and improve the safety of healthcare delivery.  

-- The role and added value of the health sector during food crises is crucial to prevent, reduce and reverse the causal relationship between poor nutrition, disease and death – before, during and after the onset of severe food shortages. As needs and vulnerabilities during food crises are complex, interlinked and multidimensional, intersectoral coordination and collaboration, especially between the health, nutrition, water, sanitation and hygiene (WASH) and food security clusters, should be stepped up as part of the overall humanitarian response. Data collection and analysis should be strengthened to inform the overall response.

-- Risk communication and community engagement are essential to raising public awareness. Targeted messages should be disseminated to educate the public on respiratory illness symptoms, preventive measures, and the importance of seeking care early. Community leaders must be engaged to build trust and encourage adherence to public health guidance. Addressing misinformation and fears within the community is critical to ensuring effective collaboration in the response.  

-- Logistical and security challenges also require attention. Strengthening logistical support for the deployment of teams and supplies will ensure timely access to affected areas. Contingency plans should be developed to address potential insecurity posed by armed groups, safeguarding response personnel and maintaining continuity in response activities.  

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Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON547

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#USA, Novel #Influenza A #H5N1 Virus: Five New Cases reported in Week 51/2024 {3 in #California, 1 in #Wisconsin, 1 in #Iowa}

{Excerpts}

-- Five confirmed cases of influenza A(H5) were reported to CDC this week. 

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

Three of these cases were reported by the California Department of Public Health. The cases occurred in workers aged ≥18 years at commercial dairy cattle farms in an area where highly pathogenic avian influenza (HPAI) A(H5N1) viruses had been detected in cows. The individuals had mild symptoms, which they reported to local health department officials. There have now been 37 total confirmed cases and one probable case in California during the 2024-2025 influenza season.

One case was reported by the Wisconsin Department of Health. This case occurred in an individual aged ≥18 years who worked at a poultry facility where HPAI A(H5N1) virus had been identified in birds. This individual developed respiratory symptoms during Week 50. Specimens were collected from the individual and initially tested at the state public health laboratories using the CDC influenza A(H5) assay before being sent to CDC for further testing. Influenza A(H5) virus was confirmed at CDC. This is the first influenza A(H5) case in Wisconsin.

One case was reported by the Iowa Department of Health and Human Services. This case occurred in an individual aged ≥18 years who worked at a poultry facility where HPAI A(H5N1) virus had been identified in birds. This individual developed conjunctivitis and respiratory symptoms during Week 50. Specimens were collected from the individual and initially tested at the State Hygienic Laboratory at the University of Iowa using the CDC influenza A(H5) assay before being sent to CDC for further testing. Influenza A(H5) virus was confirmed at CDC. This is the first influenza A(H5) case in Iowa.

Notification to WHO of the cases reported by the Wisconsin and Iowa departments of health was initiated per International Health Regulations (IHR). More information regarding IHR can be found at http://www.who.int/topics/international_health_regulations/en/. 

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

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

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

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

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

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

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/fluview/surveillance/2024-week-51.html

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Highly Pathogenic Avian #Influenza Contributes to the #Population Decline of the Peregrine #Falcon (Falco peregrinus) in the #Netherlands

Abstract

Highly pathogenic avian influenza (HPAI) epizootics have caused repeated mass mortality events among wild birds. The effect of the infection is potentially detrimental for a variety of bird species, including the Peregrine Falcon (Falco peregrinus). The numbers of wintering and breeding Peregrine Falcons in the Netherlands have recently declined. We investigated the changes in population trends in relation to HPAI H5 virus outbreaks. For this purpose, we analyzed variations in annual numbers of wintering and breeding birds, the virology of reported dead birds, and the presence of the HPAI H5 virus in unhatched eggs. We showed that significant mortalities of Peregrine Falcons had occurred in 2016–2017 and 2020–2023, years of major HPAI H5 virus outbreaks. In particular, the highest rates of bird mortality and HPAI virus infection were reported in 2023. In this year, over 80% (28/32) of the tested birds were positive for HPAI H5 virus. No HPAI H5 virus was present in the eggs. Based on these findings, we concluded that HPAI represents a serious threat to the Peregrine Falcon population in the Netherlands, and, in combination with anthropogenic factors, may contribute to the decline of this species. Targeted HPAI surveillance and disease mitigation measures are necessary for the conservation of this species.

Source: Viruses, https://www.mdpi.com/1999-4915/17/1/24

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#USA, #Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (Dec. 27 '24)

{Excerpt}

Time Period: December 15 - December 21, 2024

-- H5 Detection: 52 sites (17.4%)

-- No Detection:  246 sites (82.6%)

-- No samples in last week:  87 sites

(...)

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

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Evidence of an emerging triple- #reassortant #H3N3 avian #influenza virus in #China

Abstract

The H3 subtype of avian influenza virus (AIV) stands out as one of the most prevalent subtypes, posing a significant threat to public health. In this study, a novel triple-reassortant H3N3 AIV designated A/chicken/China/16/2023 (H3N3), was isolated from a sick chicken in northern China. The complete genome of the isolate was determined using next-generation sequencing, and the AIV-like particles were confirmed via transmission electron microscopy. Subsequent phylogenetic analyses revealed that HA and NA genes of the H3N3 isolate clustered within the Eurasian lineage of AIVs, exhibiting the closest genetic relationship with other H3N3 AIVs identified in China during 2023. Interestingly, the HA and NA genes of the nove H3N3 isolate were originated from H3N8 and H10N3 AIVs, respectively, and the six internal genes originated from prevalent H9N2 AIVs. These findings indicated the novel H3N3 isolate possesses a complex genetic constellation, likely arising from multiple reassortment events involving H3N8, H9N2, and H10N3 subtype influenza viruses. Additionally, the presence of Q226 and T228 in the HA protein suggests the H3N3 virus preferentially binds to α-2,3-linked sialic acid receptors. The HA cleavage site motif (PEKQTR/GIF) and the absence of E627K and D701N mutations in PB2 protein classify the virus as a characteristic low pathogenicity AIV. However, several mutations in internal genes raise concerns about potential increases in viral resistance, virulence, and transmission in mammalian hosts. Overall, this study provides valuable insights into the molecular and genetic characterization of the emerging triple-reassortant H3N3 AIVs, and continued surveillance of domestic poultry is essential for monitoring the H3N3 subtype evolution and potential spread.

Source: BMC Genomics, https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-024-11152-x

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The #evolution of #hemagglutinin-158 and #neuraminidase-88 #glycosylation sites modulates antigenicity and #pathogenicity of clade 2.3.2.1 #H5N1 avian #influenza viruses

Abstract

Clade 2.3.2.1 of the H5N1 avian influenza virus (AIV) evolved into several subclades. However, the effect of glycosylation on the biological characteristics of hemagglutinin (HA) and/or neuraminidase (NA) from H5N1 AIVs remains unclear. Here, we determined that the global prevalence of clade 2.3.2.1 H5N1 AIVs with deglycosylated residue 158 on HA (HA158-) and glycosylated residue 88 on NA (NA88+) were predominant via multiple sequence analysis. The deglycosylation of residue on NA 88 (NA88-) was observed in clade 2.3.2.1a (new) and clade 2.3.2.1e H5N1 AIVs. Interestingly, NA88- was coupled with the acquisition of 158 glycosylation sites on HA (HA158+) in clade 2.3.2.1e H5N1 AIVs from China, and clade 2.3.2.1a (new) H5N1 AIVs exhibiting the HA158-NA88- pattern were predominant in Bangladesh. Meanwhile, the temporal distribution of strain HA158+ NA88- was highly consistent with the implementation of Re-6 vaccine in China. The recombinant H5N1 AIVs constructed using a reverse genetic system showed that the acquisition of the HA158 glycosylation site facilitated viral evasion from Re-6 antisera, and the virus lacking glycosylation sites at HA158 and NA88 resulted in reduced NA activity, replication in mammalian cells, and pathogenicity in both chickens and mice compared to that of the viruses with alternative glycosylation patterns. Therefore, the acquisition of HA158+ in clade 2.3.2.1e H5N1 AIVs enables evasion of Re-6 vaccination pressure, and the virulence of clade 2.3.2.1 H5N1 AIVs is modulated by the absence of glycosylation sites at HA158 and NA88. Our finding highlighted the importance of epidemiological surveillance and timely updating vaccines of H5 AIVs.

Source: Veterinary Microbiology, https://www.sciencedirect.com/science/article/abs/pii/S0378113524003559?via%3Dihub

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#DRC, #Kwango province affected by #influenza {A #H1N1} virus in #Panzi health zone

The flu caused by the Influenza virus, associated with malaria on a ground of malnutrition, is the unknown disease that has been decimating the population in the health zone of Panzi, in the province of Kwango, for more than a month.

This is what the diagnosis made by the INRB reveals after in-depth analyses. 

The governor of Kwango province, Willy Bitwisila, officially declared on Wednesday night, December 5, this epidemic which has caused around thirty deaths and more than 400 cases in this part of the Kasongolunda territory.

"This is the epidemic that is causing deaths in the previously unidentified Panzi health zone. 

''After a rigorous investigation, the results from the INRB laboratory have just confirmed that it is influenza caused by the Influenza AH1N1 virus, {rhinovirus, SARS-CoV-2, edited, in the article the terms are unreadable}, associated with malaria on the ground of malnutrition. 

''An epidemic that I am now officially declaring. I would therefore like to reassure each and every one of you that all necessary measures are being taken to slow the spread of this virus," said Willy Bitwisila.  

Source: Radio Okapi, https://www.radiookapi.net/2024/12/26/actualite/sante/la-province-du-kwango-affectee-par-le-virus-influenza-dans-la-zone-de

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Avian #Influenza Virus #Infections in #Felines: A Systematic Review of Two Decades of Literature

Abstract

As an avian influenza virus (AIV) panzootic is underway, the threat of a human pandemic is emerging. Infections among mammalian species in frequent contact with humans should be closely monitored. One mammalian family, the Felidae, is of particular concern. Domestic cats are susceptible to AIV infection and provide a potential pathway for zoonotic spillover to humans. Here, we provide a systematic review of the scientific literature to describe the epidemiology and global distribution of AIV infections in felines reported from 2004 – 2024. We identified 607 AIV infections in felines, including 302 associated deaths, comprising 18 countries and 12 felid species. We observed a drastic flux in the number of AIV infections among domestic cats in 2023 and 2024, commensurate with the emergence of H5N1 clade 2.3.4.4b. We estimate that this phenomenon is underreported in the scientific literature and argue that increased surveillance among domestic cats is urgently needed.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.04.30.24306585v2

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

{Summary as of December 26 '24}

What to know

-- This guidance outlines CDC’s recommendations for preventing human exposures to highly pathogenic avian influenza (HPAI) A(H5N1) viruses and infection prevention and control measures, including the use of personal protective equipment, testing, antiviral treatment, patient investigations, monitoring of exposed persons, and antiviral chemoprophylaxis of exposed persons.

Summary

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

(...)

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

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#Genetic #Sequences of Highly Pathogenic Avian #Influenza A(#H5N1) Viruses Identified in a Person in #Louisiana

What to know

-- CDC has sequenced the influenza viruses in specimens collected from the patient in Louisiana who was infected with, and became severely ill from HPAI A(H5N1) virus. 

-- The genomic sequences were compared to other HPAI A(H5N1) sequences from dairy cows, wild birds and poultry, as well as previous human cases and were identified as the D1.1 genotype. 

-- The analysis identified low frequency mutations in the hemagglutinin gene of a sample sequenced from the patient, which were not found in virus sequences from poultry samples collected on the patient’s property, suggesting the changes emerged in the patient after infection.

Background

This is a technical summary of an analysis of the genomic sequences of the viruses identified in two upper respiratory tract specimens from the patient who was severely ill from an infection with highly pathogenic avian influenza (HPAI) A(H5N1) virus in Louisiana. 

The patient was infected with A(H5N1) virus of the D1.1 genotype virus that is closely related to other D1.1 viruses recently detected in wild birds and poultry in the United States and in recent human cases in British Columbia, Canada, and Washington State. 

This avian influenza A(H5N1) virus genotype is different from the B3.13 genotype spreading widely and causing outbreaks in dairy cows, poultry, and other animals, with sporadic human cases in the United States. 

Deep sequencing of the genetic sequences from two clinical specimens from the patient in Louisiana was performed to look for changes associated with adaptation to mammals. 

There were some low frequency changes in the hemagglutinin (HA) gene segment of one of the specimens that are rare in people but have been reported in previous cases of A(H5N1) in other countries and most often during severe infections. 

One of the changes found was also identified in a specimen collected from the human case with severe illness detected in British Columbia, Canada, suggesting they emerged during the clinical course as the virus replicated in the patient. 

Analysis of the N1 neuraminidase (NA), matrix (M) and polymerase acid (PA) genes from the specimens showed no changes associated with known or suspected markers of reduced susceptibility to antiviral drugs.

CDC Update

December 26, 2024 – CDC has sequenced the HPAI A(H5N1) avian influenza viruses in two respiratory specimens collected from the patient in Louisiana who was severely ill from an A(H5N1) virus infection. 

CDC received two specimens collected at the same time from the patient while they were hospitalized for severe respiratory illness: a nasopharyngeal (NP) and combined NP/oropharyngeal (OP) swab specimens. 

Initial attempts to sequence the virus from the patient's clinical respiratory specimens using standard RNA extraction and multisegment-RTPCR (M-RTPCR)1 techniques yielded only partial genomic data and virus isolation was not successful. 

Nucleic acid enrichment was needed to sequence complete genomes with sufficient coverage depth to meet quality thresholds. 

CDC compared the influenza gene segments from each specimen with A(H5N1) virus sequences from dairy cows, wild birds, poultry and other human cases in the U.S. and Canada. 

The genomes of the virus (A/Louisiana/12/2024) from each clinical specimen are publicly posted in GISAID (EPI_ISL_19634827 and EPI_ISL_19634828) and GenBank (PQ809549-PQ809564).

Summary of amino acid mixtures identified in the hemagglutinin (HA) of clinical specimens from the patient.

Overall, the hemagglutinin (HA) sequences from the two clinical specimens were closely related to HA sequences detected in other D1.1 genotype viruses, including viruses sequenced from samples collected in November and December 2024 in wild birds and poultry in Louisiana. 

The HA genes of these viruses also were closely related to the A/Ezo red fox/Hokkaido/1/2022 candidate vaccine virus (CVV) with 2 or 3 amino acid changes detected. 

These viruses have, on average, 3 or 4 amino acid changes in the HA when compared directly to the A/Astrakhan/3212/2020 CVV sequence. 

These data indicate the viruses detected in respiratory specimens from this patient are closely related to existing HPAI A(H5N1) CVVs that are already available to manufacturers, and which could be used to make vaccines if needed.

There were some differences detected between the NP/OP and the NP specimens. 

Despite the very close similarity of the D1.1 sequences from the Louisiana human case to bird viruses, deep sequence analysis of the HA gene segment from the combined NP/OP sample detected low frequency mixed nucleotides corresponding to notable amino acid residues (using mature HA sequence numbering):

-- A134A/V [Alanine 88%, Valine 12%];

- N182N/K [Asparagine 65%, Lysine 35%]; and

- E186E/D [Glutamic acid 92%, Aspartic Acid 8%].

The NP specimen, notably, did not have these low frequency changes indicating they may have been detected from swabbing the oropharyngeal cavity of the patient. 

While these low frequency changes are rare in humans, they have been reported in previous cases of A(H5N1) in other countries and most often during severe disease2345. 

The E186E/D mixture, for example, was also identified in a specimen collected from the severe human case detected in British Columbia, Canada67.

This summary analysis focuses on mixed nucleotide detections at residues A134V, N182K, E186D as these changes may result in increased virus binding to α2-6 cell receptors found in the upper respiratory tract of humans. 

It is important to note that these changes represent a small proportion of the total virus population identified in the sample analyzed (i.e., the virus still maintains a majority of 'avian' amino acids at the residues associated with receptor binding). 

The changes observed were likely generated by replication of this virus in the patient with advanced disease rather than primarily transmitted at the time of infection. 

Comparison of influenza A(H5) sequence data from viruses identified in wild birds and poultry in Louisiana, including poultry identified on the property of the patient, and other regions of the United States did not identify these changes. 

Of note, virus sequences from poultry sampled on the patient's property were nearly identical to the virus sequences from the patient but did not have the mixed nucleotides identified in the patient's clinical sample, strongly suggesting that the changes emerged during infection as virus replicated in the patient. 

Although concerning, and a reminder that A(H5N1) viruses can develop changes during the clinical course of a human infection, these changes would be more concerning if found in animal hosts or in early stages of infection (e.g., within a few days of symptom onset) when these changes might be more likely to facilitate spread to close contacts. 

Notably, in this case, no transmission from the patient in Louisiana to other persons has been identified. 

The Louisiana Department of Public Health and CDC are collaborating to generate additional sequence data from sequential patient specimens to facilitate further genetic and virologic analysis.

Additional genomic analysis

The genetic sequences of the A(H5N1) viruses from the patient in Louisiana did not have the PB2 E627K change or other changes in polymerase genes associated with adaptation to mammals and no evidence of low frequency changes at critical positions. 

And, like other D1.1 genotype viruses found in birds, the sequences lack PB2 M631L, which is associated with viral adaptation to mammalian hosts, and which has been detected in >99% of dairy cow sequences but is only sporadically found in birds. 

Analysis of the N1 neuraminidase (NA), matrix (M) and polymerase acid (PA) genes from the specimens showed no changes associated with known or suspected markers of reduced susceptibility to antiviral drugs. 

The remainder of the genetic sequences of A/Louisiana/12/2024 were closely related to sequences detected in wild bird and poultry D1.1 genotype viruses, including poultry identified on the property of the patient, providing further evidence that the human case was most likely infected following exposure to birds infected with D1.1 genotype virus.

Follow Up Actions

Overall, CDC considers the risk to the general public associated with the ongoing U.S. HPAI A(H5N1) outbreak has not changed and remains low. 

The detection of a severe human case with genetic changes in a clinical specimen underscores the importance of ongoing genomic surveillance in people and animals, containment of avian influenza A(H5) outbreaks in dairy cattle and poultry, and prevention measures among people with exposure to infected animals or environments.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/spotlights/h5n1-response-12232024.html

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