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

 A wild cygnus species birds in Sachsen-Anhalt Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6234

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

Forty Mute Swans in Lviv Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6232

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The Emergence of #Coxsackievirus A16 Subgenotype B1c: A Key Driver of the #HFMD #Epidemic in #Guangdong, #China

Abstract

Background: 

In 2024, mainland China witnessed a significant upsurge in Hand, Foot, and Mouth Disease (HFMD) cases. Coxsackievirus A16 (CVA16) is one of the primary causative agents of HFMD. Long-term monitoring of theCVA16 infection rate and genotype changes is crucial for the prevention and control of HFMD. 

Methods: 

A total of 40,673 clinical specimens were collected from suspected HFMD cases in Guangdong province from 2018 to 2024, including rectal swabs (n = 27,954), throat swabs (n = 6791), stool (n = 5923), cerebrospinal fluid (n = 3), and herpes fluid (n = 2). A total of 24,410 samples were detected as EV-positive and further typed by RT-PCR. A total of 872 CVA16-positive samples were isolated and further sequenced to obtain the full-length VP1 sequence. Phylogenetic analysis was performed based on viral protein 1 gene (VP1). 

Results: 

In the first 25 weeks of 2024, reported cases of HFMD were 1.36 times higher than the mean rates of 2023. In 2024, CVA16 predominated at 75.42%, contrasting with the past etiological pattern in which the CVA6 was predominant with the detection rate ranging from 32.85 to 77.61% from 2019 to 2023. Phylogenetic analysis based on the VP1 gene revealed that the B1a and B1b subtypes co-circulated in Guangdong from 2018 to 2022. The B1c outbreak clade, detected in Guangdong in 2023, constituted 68.24% of the 148 strains of CVA16 collected in 2024, suggesting a subtype shift in the CVA16 virus. There were three specific amino acid variations (P3S, I235V, and T240A) in the VP1 sequence of B1c. 

Conclusions: 

The new emergence of the CVA16 B1c outbreak clade in Guangdong during 2023–2024 highlights the necessity for the enhanced surveillance of the virus evolution epidemiological dynamic in this region. Furthermore, it is imperative to closely monitor the etiological pattern changes in Hand, Foot, and Mouth Disease (HFMD) in other regions as well. Such vigilance will be instrumental in guiding future vaccination strategies for HFMD.

Source: Viruses, https://www.mdpi.com/1999-4915/17/2/219

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The Madonna of the Pesaro Family, Titian (1519-26)

 Public Domain.

Source: WikiArt, https://www.wikiart.org/en/titian/pesaros-madonna-1526

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Distal #protein-protein #interactions contribute to #nirmatrelvir #resistance

Abstract

SARS-CoV-2 main protease, Mpro, is responsible for processing the viral polyproteins into individual proteins, including the protease itself. Mpro is a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component of Paxlovid). Resistance mutants identified clinically and in viral passage assays contain a combination of active site mutations (e.g., E166V, E166A, L167F), which reduce inhibitor binding and enzymatic activity, and non-active site mutations (e.g., P252L, T21I, L50F), which restore the fitness of viral replication. To probe the role of the non-active site mutations in fitness rescue, here we use an Mpro triple mutant (L50F/E166A/L167F) that confers nirmatrelvir drug resistance with a viral fitness level similar to the wild-type. By comparing peptide and full-length Mpro protein as substrates, we demonstrate that the binding of Mpro substrate involves more than residues in the active site. Particularly, L50F and other non-active site mutations can enhance the Mpro dimer-dimer interactions and help place the nsp5-6 substrate at the enzyme catalytic center. The structural and enzymatic activity data of Mpro L50F, L50F/E166A/L167F, and others underscore the importance of considering the whole substrate protein in studying Mpro and substrate interactions, and offers important insights into Mpro function, resistance development, and inhibitor design.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-56651-x

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#Pandemic #preparedness: analyzing national #plans for respiratory #pathogen pandemics in the #Americas region

Abstract

Background

The International Health Regulations (2005) (IHR), requires that States Parties develop their capacities to detect, assess, and respond to public health threats and report to the World Health Assembly through the States Parties Annual Report (SPAR). The National Pandemic Preparedness and Response Plans (PPRP) contribute to countries capacities however there are some discrepancies between both tools. To identify gaps and define priority actions to strengthen pandemic plans, we assessed the concordance between national pandemic preparedness and response plans for respiratory pathogens against the pandemic checklist published in 2023 and the SPAR.

Methods

In this retrospective, semi-quantitative study, conducted in August 2024, we reviewed the most recent respiratory pandemic plans for 35 PAHO member states and assessed their concordance with (1) actionable guidelines in the World Health Organization pandemic checklist and (2) IHR (2005) core capacities using the latest SPAR tool. We developed 25 tracking questions to identify gaps, strengths, and opportunities for improvement in the pandemic plans, using the pandemic checklist built on the capacities and capabilities described in the WHO’s Preparedness and Resilience for Emerging Threats (PRET) Module 1. We used a five-point scale (from 1, when the subcomponent was not mentioned, to 5, when the subcomponent was described at all levels), and we calculated the average pandemic plans score (PP score) for each component. Data from pandemic plans (2005–2024) were compiled, selected, analyzed, and scored. We compared the average SPAR score and the PP score to assess areas of convergence and variance between preparedness and capacities. The analysis was carried out using R and Excel.

Results

We analyzed 35 respiratory pandemic plans: 29 were influenza-specific, five were COVID-19-specific, and one was not pathogen-specific. Most current national plans showed limited alignment with the content recommended in the PRET pandemic checklist. At regional level, the lowest concordance between plans and pandemic checklist was in the following subcomponents Public Health and Social Measures (80% of the plans had a score of 1); Emergency, Logistics and Supply Chain Management (74%); and Research and Development (71%). Conversely, the strongest subcomponents (≥40% of plans with a score of 4 or 5) were: Policy, Legal, and Normative Instruments (45%); Coordination (46%); and Surveillance: early detection and assessment (43%). In most countries, the SPAR scores tended to be higher than PP scores, except for Argentina (the newest plan reviewed) for which the pattern was reversed, and the PP scores exceeded the SPAR scores.

Conclusion

Given the gaps identified between current plans and the global standards espoused by the PRET Module 1 initiative, it is recommended that countries build on the strengths of their national pandemic preparedness and response plans and update them using PRET module 1. This will support countries advance the capacities required by the IHR.

Source: Journal of Infectious Diseases, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaf047/7994597

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Structurally convergent #antibodies derived from different #vaccine #strategies target the #influenza virus HA anchor epitope with a subset of VH3 and VK3 genes

Abstract

H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their VH and VK genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-56496-4

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#Sudan virus disease - #Uganda

Situation at a glance

On 30 January 2025, the Ministry of Health of Uganda declared an outbreak of Sudan virus disease (SVD) following confirmation from three national reference laboratories. 

The case presented with signs and symptoms between 20 and 21 January and died on 29 January at the National Referral Hospital in Kampala. 

As of 30 January 2025, 45 contacts have been identified, including 34 healthcare workers and 11 family members. 

Sudan virus disease belongs to the same family as Ebola virus disease. It is caused by Sudan virus (SUDV). It is a severe disease with high case fatality from 41% to 70% in past outbreaks. 

In the absence of licensed vaccines and therapeutics for the prevention and treatment of SVD, the risk of potential serious public health impact is high. 

Early supportive patient care and treatment may increase the chance of survival from severe disease.

Description of the situation

On 30 January 2025, the Ministry of Health of Uganda declared an outbreak of Sudan virus disease (SVD) following confirmation from three national reference laboratories.

The confirmed case was an adult male nurse who initially developed fever-like symptoms and sought treatment from a traditional healer as well as at multiple health facilities.

The patient presented with a history of high fever, chest pain, and difficulty in breathing with symptoms onset between 20 and 21 January, which later progressed to unexplained bleeding from multiple body sites. The patient experienced multi-organ failure and died at the National Referral Hospital on 29 January.

Samples taken post-mortem were confirmed for Sudan virus (SUDV).

Forty-five contacts have so far been identified, including 34 healthcare workers and 11 family members.

Epidemiology

Sudan virus disease is a viral hemorrhagic fever disease, belonging to the same family as Ebola virus disease. It is caused by Sudan virus (SUDV). It is a severe disease with high case fatality. 

It is typically characterized by acute onset of fever with non-specific symptoms/signs (e.g., abdominal pain, anorexia, fatigue, malaise, myalgia, sore throat) usually followed several days later by nausea, vomiting, diarrhoea, and occasionally a variable rash. 

Hiccups may occur. Severe illness may include hemorrhagic manifestations (e.g., bleeding from puncture sites, ecchymoses, petechiae, visceral effusions), encephalopathy, shock/hypotension, multi-organ failure, spontaneous abortion in infected pregnant women. 

Individuals who recover may experience prolonged sequelae (e.g., arthralgia, neurocognitive dysfunction, uveitis sometimes followed by cataract formation), and clinical and subclinical persistent infection may occur in immune-privileged compartments (e.g., CNS, eyes, testes). 

Person-to-person transmission occurs by direct contact with blood, other bodily fluids, organs, or contaminated surfaces and materials with risk beginning at the onset of clinical signs and increasing with disease severity. 

Family members, healthcare providers, and participants in burial ceremonies with direct contact with the deceased are at particular risk. 

The incubation period ranges from 2 to 21 days, but typically is 7–11 days. 

Public health response

Health authorities are implementing public health measures, including but not limited to the following:

-- The Ministry of Health (MoH) has activated the Incident Management Team and dispatched Rapid Response Teams to the affected district. The MoH team has also listed contacts at the National Reference Hospital.

-- Regional Emergency Operation Centers are being activated in Kampala and the affected district.

-- Facilities have been identified for quarantine of all listed contacts.

-- MoH is organizing to carry out a safe and dignified burial of the patient. 

-- In their official press statement, the MoH provided recommendations to health workers, district leaders, and the public to strengthen detection of suspected cases and implement appropriate infection, prevention and control measures.

-- MoH set up a hotline for notification of suspected cases.

WHO is supporting the national authorities, including through:

-- Risk assessment and investigation.

-- Providing operational, financial and technical support to the Ministry of Health to ensure swift response.  

-- Facilitating access to candidate vaccines and therapeutics

WHO risk assessment

Sudan virus disease (SVD) is a severe, often fatal illness affecting humans. Sudan virus (SUDV) was first identified in southern Sudan in June 1976. Since then, the virus has emerged periodically and up to now and prior to this current one, eight outbreaks caused by SUDV have been reported, five in Uganda and three in Sudan. The case fatality rates of SVD have varied from 41% to 70% in past outbreaks.

SUDV is enzootic and present in animal reservoirs in the region. Uganda reported five SVD outbreaks (one in 2000, one in 2011, two in 2012, and one in 2022).  The current outbreak is the sixth SVD outbreak in Uganda. Uganda also reported a Bundibugyo virus disease outbreak in 2007 and an Ebola virus disease outbreak exported from the Democratic Republic of the Congo in 2019. The latest SVD outbreak in Uganda was declared over on 11 January 2023. A total of 164 cases with 77 deaths were reported in nine districts.

Uganda has experience in Ebola disease outbreaks including SVD, and necessary action has been initiated quickly.

In the absence of licensed vaccines and therapeutics for the prevention and treatment of SVD, the risk of potential serious public health impact is high. Community deaths, care of patients in private facilities and hospitals and other community health services as well as at traditional healers with limited protection and infection prevention and control measures entail a high risk of many transmission chains. 

An investigation is ongoing to determine the scope of the outbreak and the possibility of spread to other districts and potential exportation of cases to neighbouring countries cannot be ruled out at this stage.

WHO advice

Effective Ebola disease outbreak, including SVD, control relies on applying a package of interventions, including case management, surveillance and contact tracing, a good laboratory service, implementation of infection prevention and control measures in health care and community settings, safe and dignified burials and community engagement and social mobilization. Community engagement is key to successfully controlling outbreaks. Raising awareness of risk factors for infection and prevention measures that individuals can take is an effective way to reduce human transmission.

Early initiation of intensive supportive treatment increases the chances of survival. All above-mentioned interventions need to be thoroughly implemented in affected areas to stop chains of transmission and decrease disease mortality. Cases, contacts and individuals in affected areas who present signs and symptoms compatible with case definitions should be advised not to travel and seek early care at designated facilities to improve their chances of survival and limit transmission.

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.

A range of candidate vaccines and therapeutics are under different stage of development. In 2022, WHO convened expert deliberations to review candidate products prioritization and trial designs. 

One candidate vaccine and two candidate therapeutics (a monoclonal antibody and an antiviral) are available in country and will be made available through clinical trial protocol.

The two vaccines licensed against Ebola virus disease will not provide cross protection against SVD and cannot be used in this outbreak.

WHO advises against any restrictions on travel and/or trade to Uganda based on available information for the current outbreak. 

Further information

-- WHO African Region press release: WHO accelerates efforts to support response to Sudan virus disease outbreak in Uganda. https://www.afro.who.int/countries/uganda/news/who-accelerates-efforts-support-response-sudan-virus-disease-outbreak-uganda

-- The Ministry of Health Uganda confirms the outbreak of Sudan virus disease: https://www.health.go.ug/cause/uganda-confirms-outbreak-of-sudan-ebola-virus-disease/

-- Ebola virus disease fact sheet: http://www.who.int/en/news-room/fact-sheets/detail/ebola-virus-disease

-- Optimized Supportive Care for Ebola Virus Disease. Clinical management standard operating procedures. WHO. 2019. https://www.who.int/publications/i/item/9789241515894#:s 

-- Ebola: technical guidance documents for medical staff (2014-2016). https://www.who.int/teams/health-care-readiness/ebola-clinical-management 

-- Safety of two Ebola virus vaccines: https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/ebola-virus-vaccines

-- Personal protective equipment for use in a filovirus disease outbreak: rapid advice guideline: https://apps.who.int/iris/handle/10665/251426

-- Framework and toolkit for infection prevention and control in outbreak preparedness, readiness and response at the national level: https://www.who.int/publications/i/item/framework-and-toolkit-for-infection-prevention-and-control-in-outbreak-preparedness--readiness-and-response-at-the-health-care-facility-level

-- ICD-11 2022 release: https://www.who.int/news/item/11-02-2022-icd-11-2022-release

-- New filovirus disease classification and nomenclature: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637750/#SD1

-- Sudan Ebolavirus – Experts deliberations Candidate treatments prioritization and trial design discussions, 2022: https://www.who.int/publications/m/item/sudan-ebolavirus---experts-deliberations.--candidate-treatments-prioritization-and-trial-design-discussions

-- 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 (1 February 2025). Disease Outbreak News; Sudan virus disease in Uganda. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON555

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Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON555

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#Coronavirus Disease Research #References (by AMEDEO, February 1 '25)

 

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2. HANKINS RJ, Handke L, Fey PD, Cavalieri RJ, et al
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   BMC Pediatr

2. ZHANG P, Xin M, Bai Y, Ren X, et al
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3. BEDNARSKA NG, Smith S, Bardsley M, Loveridge P, et al
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   J Virol

4. KIRKPATRICK ROUBIDOUX E, Meliopoulos V, Livingston B, Brigleb PH, et al
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5. SADLER HL, Rijal P, Tan TK, Townsend ARM, et al
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Emergence of a novel #reassortant highly pathogenic avian #influenza clade 2.3.4.4b A(#H5N2) Virus, 2024

ABSTRACT

Reassortant highly pathogenic avian influenza A(H5N2) clade 2.3.4.4.b viruses were detected from ducks and environmental samples in Egypt, June 2024. Genomic and phylogenetic analyses revealed a novel genotype produced by the reassortment of an A(H5N1) clade 2.3.3.4b virus with an A(H9N2) G1-like virus. Monitoring the spread of this virus is important.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2455601#abstract

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No #Evidence of Anti - #influenza #Nucleoprotein #Antibodies in Retail #Milk from Across #Canada (April to July 2024)

Abstract

Following reports of HPAI H5N1 infections of dairy cattle in the United States (US) in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies, as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the US has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.01.31.25321461v1

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Intraductal #infection with #H5N1 clade 2.3.4.4b #influenza virus

LETTER

In March 2024, highly pathogenic avian influenza (HPAI) H5N1 of the clade 2.3.4.4b was detected in dairy cows in Texas and has since been detected in several other U.S. states (1). Virus has been detected within cow’s milk, indicating that the mammary epithelium may support viral replication (2). Virus has also been detected on milking machines, leading to a hypothesis that influenza is spreading through fomites from udder to udder instead of the intranasal route (3, 4). There have been studies using cows to better understand mammary infections; however, the cow model is costly and limited (1, 5). We sought to establish a model for intramammary infections of H5N1 and H1N1 influenza virus in mice.

(...)

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01927-24?af=R

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Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater, January 19-25 2025

{Excerpt}

Time Period: January 19 - January 25, 2025

-- H5 Detection: 33 sites (10.1%)

-- No Detection: 295 sites (89.9%)

-- No samples in last week: 61 sites

(...)

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

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

The laboratory diagnosed type H5 on Thursday, January 23 in one of the sick birds that was sampled in the framework of passive surveillance, on January 24 all birds were culled, on January 29 the laboratory confirmed the detection of Neuraminidase 1 and identification of hemagglutinin genes found in the cleavage site of avian influenza virus type A lineage Goose/Guangdong (Gs/GD) subtype H5, clade 2.3.4.4. highly pathogenic.

Out of the 408 backyard birds, one died and two became sick in Chiriquí Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6225

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#Hungary - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification, 2nd

A  foie gras goose holding in Heves Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6227

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

 A breeding goose holding in Pest Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6228

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

 A wild Eurasian Jackdaw in Lounais-Suomen aluehallintovirasto Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6229

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#Mexico’s Laboratory-Confirmed #Human Case of #Infection with the #Influenza A(#H5N2) Virus

Abstract

In April 2024, the Instituto Nacional de Enfermedades Respiratorias of Mexico City identified a case of unsubtypeable Influenza A in a 58-year-old immunocompromised patient with renal failure due to diabetic nephropathy and bacterial peritonitis. Through sequencing the M, NS, NA, NP, and HA complete segments, we identified an H5N2 influenza virus with identity of 99% with avian influenza A(H5N2) from Texcoco, Mexico, in 2024. This case is the first reported with direct evidence of human infection caused by the H5N2 influenza virus; the relationship of the virus with the severity of his condition remains unknown.

Source: Viruses, https://www.mdpi.com/1999-4915/17/2/205

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Suspected and confirmed #mpox cases in #DRC: a retrospective #analysis of national epidemiological and laboratory #surveillance data, 2010–23

Summary

Background

DR Congo has the highest global burden of mpox, a disease caused by infection with the monkeypox virus. The incidence has risen since 1980, but recent analyses of epidemiological trends are lacking. We aimed to describe trends in suspected and confirmed mpox cases in DR Congo using epidemiological and laboratory mpox surveillance data collected from 2010 to 2023, and provide insights that can better inform the targeting and monitoring of control strategies.

Methods

We analysed aggregated national epidemiological surveillance data and individual-level laboratory data from 2010 to 2023. We calculated incidence based on suspected cases, case-fatality ratios, and percentage of laboratory-confirmed cases and assessed geospatial trends. Demographic and seasonal trends were investigated using generalised additive mixed models.

Findings

Between Jan 1, 2010, and Dec 31, 2023, a total of 60 967 suspected cases and 1798 suspected deaths from mpox were reported in DR Congo (case-fatality ratio 2·9%). The number of reporting provinces increased from 18 of 26 provinces in 2010 to 24 of 26 provinces in 2023. The annual incidence increased from 2·97 per 100 000 in 2010 to 11·46 per 100 000 in 2023. The highest incidence (46·38 per 100 000) and case-fatality ratio (6·0%) were observed in children younger than 5 years. Incidence was higher in rural compared with urban areas. PCR testing was performed for 7438 suspected cases (12·2%), with 4248 (57·1%) of 7438 samples testing positive. Median age of confirmed cases (13·0 years [IQR 6·0–25·0]) remained stable, although the 95th percentile of age increased over time.

Interpretation

The incidence and geographical distribution of suspected mpox cases have increased substantially since 2010. Improvements in surveillance and decentralised testing are essential to monitor mpox trends and direct interventions effectively, to address the public health emergency declarations issued in August, 2024.

Funding

Belgian Directorate-General Development Cooperation and Humanitarian Aid; European and Developing Countries Clinical Trials Partnership; Research Foundation–Flanders; European Civil Protection and Humanitarian Aid Operations; Department of Economy, Science, and Innovation of the Flemish Government; Canadian Institutes of Health Research; and the International Development Research Centre.

Source: Lancet, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02669-2/abstract?rss=yes

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