Effect of Prior #Influenza #H1N1pdm09 Virus #Infection on #Pathogenesis and #Transmission of #Human Influenza A(#H5N1) Clade 2.3.4.4b Virus in #Ferret Model

Abstract

Reports of human infections with an influenza A(H5N1) clade 2.3.4.4b virus associated with outbreaks in dairy cows in the United States underscore the need to assess the potential cross-protection conferred by existing influenza immunity. We serologically evaluated ferrets previously infected with an influenza A(H1N1)pdm09 virus for cross-reactive antibodies and then challenged 3 months later with either highly pathogenic H5N1 clade 2.3.4.4b or low pathogenicity H7N9 virus. Our results showed that prior influenza A(H1N1)pdm09 virus infection more effectively reduced the replication and transmission of the H5N1 virus than did the H7N9 virus, a finding supported by the presence of group 1 hemagglutinin stalk and N1 neuraminidase antibodies in preimmune ferrets. Our findings suggest that prior influenza A(H1N1)pdm09 virus infection may confer some level of protection against influenza A(H5N1) clade 2.3.4.4.b virus.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/3/24-1489_article

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#Influenza A(#H5N1) Immune #Response among #Ferrets with Influenza #H1N1pdm09 #Immunity

Abstract

The emergence of highly pathogenic avian influenza A(H5N1) virus in dairy cattle herds across the United States in 2024 caused several human infections. Understanding the risk for spillover infections into humans is crucial for protecting public health. We investigated whether immunity from influenza A(H1N1)pdm09 (pH1N1) virus would provide protection from death and severe clinical disease among ferrets intranasally infected with H5N1 virus from dairy cows from the 2024 outbreak. We observed differential tissue tropism among pH1N1-immune ferrets. pH1N1-immune ferrets also had little H5N1 viral dissemination to organs outside the respiratory tract and much less H5N1 virus in nasal secretions and the respiratory tract than naive ferrets. In addition, ferrets with pH1N1 immunity produced antibodies that cross-reacted with H5N1 neuraminidase protein. Taken together, our results suggest that humans with immunity to human seasonal influenza viruses may experience milder disease from the 2024 influenza A(H5N1) virus strain.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/3/24-1485_article

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Urban #Coatis (Nasua nasua) Exposure to #Alphainfluenzavirus influenzae

Abstract

We detected neutralizing antibodies, viral RNA, and sialic acid receptors for Alphainfluenzavirus influenzae in urban coatis (Nasua nasua) in Brazil, suggesting exposure and susceptibility. We used hemagglutination inhibition, reverse transcription qualitative PCR, and immunohistochemistry for detection. Increased epidemiologic wildlife surveillance would improve influenza A emergency event response.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/3/23-1640_article

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#Human #Infection with Avian #Influenza A(#H9N2) Virus, #Vietnam, April 2024

Abstract

In April 2024, Vietnam confirmed its first human case of influenza A(H9N2) in a 37-year-old man, marking a critical point in regional infectious disease monitoring and response. This case underscores the importance of robust surveillance systems and One Health collaboration in managing emerging zoonotic threats.

Source: Emerging Infectious Diseases Journal, https://wwwnc.cdc.gov/eid/article/31/2/24-1146_article

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#Sudan virus #disease - #Uganda

{Excerpt}

Situation at a glance

As of 20 February 2025, a total of nine confirmed cases of Sudan virus disease, including one death have been reported from Uganda, since the outbreak was declared on 30 January 2025. Eight cases received care at treatment centres in the capital Kampala and in Mbale and were discharged on 18 February after two negative tests 72 hours apart. 

As of 20 February 2025, 58 contacts that have been identified are still under follow up in designated quarantine facilities located in Jinja, Kampala,and Mbale. 

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 ranging 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 detection, diagnosis, and optimized supportive care may increase the chance of survival.

Description of the situation

Since the first disease outbreak news on this event was published on 1 February 2025, additional eight laboratory-confirmed cases of Sudan virus disease (SVD) have been reported in Uganda. As of 20 February 2025, a total of nine confirmed cases, including one death have been reported with a case fatality ratio (CFR) of 11%. Cases ages range from 1.5 to 49 years, with a mean age of 27 years and males accounted for 56% of the total cases. The cases were reported from four districts in the country which include Jinja, Kampala, Mbale, and Wakiso.

The first reported case, who was a health worker, had symptom onset on 19 January in epidemiological week 3. The case initially self-medicated with antimalarials and sought care in different health facilities located in Wakiso, Kampala and Mbale districts, as well as a traditional healer in Mbale, before being referred to Mulago referral hospital, where he died on 29 January 2025. Following the detection and confirmation of SVD on 29 January, the case was accorded a safe and dignified burial on 31 January in Mbale.

Following the prompt declaration of the outbreak by the Ministry of Health on 30 January, a detailed case investigation was conducted on the first case including comprehensive contact listing in all the districts where the case travelled. Contacts were quarantined in a designated facility and monitored for 21 days. 

The other eight reported confirmed cases were among the listed contacts and include family members (five cases) and health workers (three) who had direct contact with the first case as they provided care during his illness.  The secondary cases had symptom onset between 29 January to 6 February. All were detected at early onset of their disease by contact tracing team while in quarantine. They were referred to Mulago National Referral Hospital (seven cases) and Mbale Regional Referral Hospital (one case) for optimized supportive care and received Remdesivir under the Monitored emergency use of unregistered and experimental interventions (MEURI) protocol. All eight cases were discharged on 18 February 2025 after two negative tests carried out 72 hours apart.

(...)

Based on the WHO criteria to declare the end of a filovirus outbreak, a countdown to the end of the human-to-human transmission can be started from the day after the last possible exposure, in this case, the day following negative tests. Should no additional cases be reported, the outbreak will be declared over in 42 days, that is two incubation periods. Several activities including heightened surveillance for a period of 42 days is recommended to ensure that there are no missed chains of transmission. 

As of 20 February, a cumulative of 299 contacts have been listed from affected districts in the country since the start of the outbreak. Over 75% of contacts have completed the 21-day follow-up period. However, 58 are still being monitored in institutional quarantine facilities to complete a 21-day since the last contact with a confirmed case.  

Alert levels both from the community and the health facilities have been low. Several activities, including training and active case search are ongoing during the 42-day countdown to strengthen surveillance with integrated approach and increase the number of alerts and suspected cases reported, investigated and tested. Mortality surveillance has also been set up since the declaration of the outbreak and will continue in Jinja, Kampala and Mbale.

In addition, retrospective investigations are ongoing to find the source of the outbreak through active case search in and around the community and health facilities where the first case was residing and working. 

This is the sixth outbreak of SVD in Uganda, the most recent outbreak was reported in September 2022 with 164 cases and 55 deaths. 

Epidemiology

Sudan virus disease is a severe disease, belonging to the same family as Ebola virus disease. It is caused by Sudan virus (SUDV) and can result in 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 haemorrhagic 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:

-- Coordination:

- The Ministry of Health (MoH) has activated the coordination structures at national and subnational levels, including the Incident Management Team and dispatched Rapid Response Teams to the affected districts. Regional Emergency Operation Centers are being activated in Kampala and Mbale districts. In addition, the country has developed a National Response Plan (February - April 2025). The response plan builds on lessons learned from previous outbreaks and deploys the basic minimum packages of activities across the districts according to risk.

-- Surveillance and contract tracing:

- MoH with support from WHO and partners are conducting alert management including the setup of an alert desk with toll free numbers to detect and verify alerts from all over the country that meet the case definition. Since 30 January, 138 alerts have been reported and discarded following negative laboratory testing.

- MoH with support from partners has allocated teams to conduct detailed case investigations around the first reported case and the eight additional cases to identify the source of the outbreak and the chains of transmission.

- MoH has allocated teams to conduct contact listing of confirmed cases with overall daily contact follow-up rates in the last seven days improving to 100%. Following the declaration of the outbreak, MoH with support from WHO has established mortality surveillance with over 400 non-trauma deaths tested in communities and health facilities located in the affected districts and all have tested negative.

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

- MoH is conducting exit screening of SVD signs and symptoms among travelers at Uganda’s 13 high volume points of entry (POE) including Entebbe International Airport.

-- Case Management:

- MoH with support from WHO and partners have set up three designated isolation and treatment units in Jinja, Kampala and Mbale where the confirmed cases received optimized supportive care and Remdesivir under the Monitored emergency use of unregistered and experimental interventions (MEURI) protocol.

- Suspected SVD cases are also isolated and receiving care at the isolation units while awaiting test results.

- Patients who recovered from the disease will be included in survivor care programme for support and care.

-- Laboratory:

- MoH and partners have strengthened laboratory capacities and deployed a mobile laboratory to Mbale to reduce turnaround time for laboratory results. MoH has performed a full genome sequencing on the sample of the first confirmed case and findings indicating the outbreak is most likely the result of a spillover event.

-- Infection prevention and control:

- MoH organized a safe and dignified burial of the first reported case. 

- 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. 

- 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. A total of US$ 3.4 million was released from the Contingency Fund for Emergency for the three levels of WHO to support the government-led SVD response.

- Supporting the national laboratory system to implement sample collection, transport and diagnostic testing.

- Facilitating access to candidate vaccines and therapeutics and supporting launch of the vaccine trial. Rings have been defined around all confirmed cases and their contacts have been invited to consent in the trial.  As part of this support, the "TOKEMEZA SVD" vaccine trial was launched on 3rd February 2025.

- Providing technical and operation assistance for the setup of isolation centers for suspected cases and two Ebola treatment units in Kampala and Mbale.

- Mobilizing logistics to complement government supplies, including IPC supplies, drugs, resuscitation and monitoring equipment, admission packages, and mattresses.

- Deploying a team of 47 experts to Mbale, Kampala, Wakiso and Jinja districts to support across different response pillars including coordination, surveillance, laboratory, logistics, IPC, RCCE, and case management pillars.

- Supporting RCCE efforts to counter misinformation and enhance community engagement through the deployment of two anthropologists.

- Intensified and integrated risk communication and community engagement, including sensitization and training of Village Health Teams, traditional healers, religious leaders and teachers. 

- Collecting social and behavioural data and using evidence to respond to communities’ anxieties and concern, rumours, misinformation and disinformation.

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 55 deaths were reported in nine districts.

Uganda has experience in Ebola disease outbreaks including SVD, and in the ongoing outbreak, necessary actions have been initiated and implemented quickly for effective control.

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 source and the scope of the outbreak and the possibility of spread from the capital city, Kampala, to other districts. Exit screening has been set up at different points of entry to reduce the risk of potential exportation of cases to neighbouring countries.

WHO advice

Effective Ebola disease outbreak, including SVD, control relies on applying a package of interventions, including case management, surveillance and contact tracing, a strong laboratory system, implementation of infection prevention and control measures in health care and community settings, safe and dignified burials and community engagement and social mobilization.

Risk communication and community engagement is crucial to successfully controlling SVD 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. Awareness should be built through targeted campaigns and direct work with affected and proximate communities, with special attention to engage with traditional healers, clergy, and community leaders, who are important sources of information for the community. Rapid qualitative assessments should be implemented to collect socio-behavioural data, which can then be utilized to guide the response.  Misinformation and rumours should be addressed to foster trust and promote early symptom reporting. 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.

WHO encourages countries to implement a comprehensive care programme to support people who recovered from Ebola disease with any subsequent sequelae and to enable them to access body fluid testing and to mitigate the risk of transmission through infected body fluids by adequate practices.

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. Since 2020, WHO has convened scientific deliberations and set up an independent process to review candidate MCMS prioritization and clinical trial designs. One candidate vaccine and two candidate therapeutics (a monoclonal antibody and an antiviral) have been recommended and are available in country and are being assessed (clinical efficacy and safety) through randomized clinical trial protocols.

Thanks to preparedness measures that the government took after the previous outbreak in 2022, and a global research collaboration led by WHO (first MARVAC now FILOVIRUS CORC), a trial of a candidate vaccine was launched just four days after the outbreak was declared. A therapeutics trial will start as soon as national authorities provide approval.

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. 

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON556

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Human #monoclonal #antibodies that target clade 2.3.4.4b #H5N1 #hemagglutinin

Abstract

The highly pathogenic avian influenza H5N1 virus clade 2.3.4.4b has been spreading globally since 2022, causing mortality and morbidity in domestic and wild birds and mammals, including infection in humans, raising concerns about its pandemic potential. We aimed to generate a panel of anti-hemagglutinin (HA) human monoclonal antibodies (mAbs) against the H5 protein of clade 2.3.4.4b. H2L2 Harbour Mice, which express human immunoglobulin germline genes, were immunized with H5 and N1 recombinant proteins from A/mallard/New York/22-008760-007-original/2022 H5N1 virus, enabling the generation of human chimeric antibodies. Through hybridoma technology, sixteen full human mAbs were generated, most of which showed cross-reactivity against H5 proteins from different virus variants. The functionality of the sixteen mAbs was assessed in vitro using hemagglutination inhibition and microneutralization assays with viruses containing a clade 2.3.4.4b HA. Fourteen out of the sixteen mAbs neutralized the virus in vitro. The mAbs with the strongest hemagglutination inhibition activity also demonstrated greater neutralizing capacity and showed increased protective effects in vivo when administered prophylactically or therapeutically in a murine H5N1 challenge model. Using cryo-electron microscopy, we identified a cross-clonotype conserved motif that bound a hydrophobic groove on the head domain of H5 HA. Akin to mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus 2019 (COVID-19) pandemic, these mAbs could serve as important treatments in case of a widespread H5N1 epidemic or pandemic.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.21.639446v1

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#USA: #Situation #summary of confirmed and probable #human cases of #H5N1 #influenza since 2024 {#Ohio case reclassified from probable to confirmed}

{Excerpt}

[Confirmed cases: State, Dairy  Herds, Poultry Farms and Culling Operations, Other Animal Exposure, Exposure Source Unknown, State Total]

-- National, 41, 24, 2, 3, 70 {+1}

1) California, 36, 0, 0, 2, 38

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) Nevada, 1, 0, 0, 0, 1

8) Ohio, 0, 1, 0, 0, 1 {+1}

9) Oregon, 0, 1, 0, 0, 1

10) Texas, 1, 0, 0, 0, 1

11) Washington, 0, 11, 0, 0, 11

12) Wisconsin, 0, 1, 0, 0, 1

13) Wyoming, 0, 0, 1, 0, 1

[Probable Cases: States, Dairy Herds, Poultry Farms and Culling Operations, Other Animal Exposure, Exposure Source Unknown, State Total]

-- National, 1, 5, 0, 1, 7 {-1}

1) Arizona, 0, 2, 0, 0, 2

2) California, 1, 0, 0, 0, 1

3) Delaware, 0, 0, 0, 1, 1

4) Washington, 0, 3, 0, 0, 3

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 Associated with Commercial Agriculture and Related Operations

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

{‡} Exposure source was not able to be identified

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/situation-summary/?CDC_AAref_Val=https%3A%2F%2Fwww.cdc.gov%2Fflu%2Favianflu%2Favian-flu-summary.htm&cove-tab=1

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#USA, #Ohio DH Urges #Parents to Protect Their #Kids Following State’s First #Pediatric #Flu #Death of Season

(COLUMBUS, Ohio) — The Ohio Department of Health (ODH) today is reporting the state’s first flu-associated pediatric death of the 2024-25 flu season, a teenager under the age of 18 from Allen County.

“Sadly, this tragic death reminds us that influenza, though common, is a serious health threat,” said ODH Director Bruce Vanderhoff, MD, MBA. 

“We urge parents to protect their kids. It’s not too late for parents and kids to get a flu vaccine. It may very well prevent you or your loved ones from getting seriously ill. And, especially during flu season, it’s important to maintain good hand hygiene and to stay home if you are sick.”

Flu activity usually peaks between December and February. In Ohio, flu activity has been increasing since early December and has increased more rapidly since the beginning of the year. Current activity is very high.

Since the start of the season, more than 9,000 influenza-associated hospitalizations have been reported in Ohio, which is well above the five-year average for this time in the season.

Ohio generally reports between one and six influenza-associated pediatric deaths each season.

Flu vaccines are available at most healthcare providers’ offices, local health departments, and retail pharmacies.

Other effective ways to avoid getting or spreading the flu include washing hands frequently or using alcohol-based hand sanitizer, covering coughs and sneezes with tissues or coughing or sneezing into elbows, and avoiding touching your eyes, nose, and mouth.

More information about flu and flu activity in Ohio is available at www.flu.ohio.gov.

###

Source: Department of Health, https://odh.ohio.gov/media-center/ODH-News-Releases/odh-urges-parents-to-protect-their-kids

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#Equine #Influenza: #Epidemiology, #Pathogenesis, and Strategies for #Prevention and Control

Abstract

Equine influenza (EI) is a highly contagious respiratory disease caused by the equine influenza virus (EIV), posing a significant threat to equine populations worldwide. EIV exhibits considerable antigenic variability due to its segmented genome, complicating long-term disease control efforts. Although infections are rarely fatal, EIV’s high transmissibility results in widespread outbreaks, leading to substantial morbidity and considerable economic impacts on veterinary care, quarantine, and equestrian activities. The H3N8 subtype has undergone significant antigenic evolution, resulting in the emergence of distinct lineages, including Eurasian and American, with the Florida sublineage being particularly prevalent. Continuous genetic surveillance and regular updates to vaccine formulations are necessary to address antigenic drift and maintain vaccination efficacy. Additionally, rare cross-species transmissions have raised concerns regarding the zoonotic potential of EIV. This review provides a comprehensive overview of the epidemiology, pathogenesis, and prevention of EI, emphasizing vaccination strategies and addressing the socio-economic consequences of the disease in regions where the equine industry is vital.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/302

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {Feb. 21 '25}

{Excerpt}

(...)

Time Period: February 09 - February 15, 2025

-- H5 Detection: 12 sites (3.3%)

-- No Detection: 348 sites (96.7%)

-- No samples in last week: 94 sites

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

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

{Northern Ireland} About 63,000 68 and 78-week-old layers across four houses. Increased mortality, feed drop and egg abnormalities. The samples taken were positive for HPAI H5N1.

Source: WOAH, https://wahis.woah.org/#/in-review/6288

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Prevalence, clinical #management, and #outcomes of #adults hospitalised with endemic #arbovirus illness in southeast #Europe (MERMAIDS-ARBO): a prospective observational study

Summary

Background

Arboviruses have expanded into new regions in Europe, yet data indicate gaps in disease notifications and a risk of further spread. We aimed to report on prevalence, clinical management, and outcomes of endemic arbovirus infections in southeast Europe.

Methods

In this prospective observational study (MERMAIDS-ARBO), we enrolled adults (age ≥18 years) hospitalised with an arbovirus-compatible disease syndrome within 21 days of symptom onset across 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (May 1–Oct 31, during 2016–19). We obtained data from case report forms completed by site investigators on admission and discharge. Participants were excluded if they had non-infectious CNS disorders, symptoms of another confirmed cause, an identified focal source of infection, or symptoms caused by recurrence of a pre-existing condition. The primary outcome was the proportion of participants with confirmed or probable acute infections with West Nile virus (WNV), tick-borne encephalitis virus (TBEV), Crimean–Congo haemorrhagic fever virus (CCHFV), or Toscana virus (TOSV), per reference laboratory criteria. Secondary outcomes were the proportions of patients treated with antivirals, antibiotics, or corticosteroids; the proportion of patients requiring intensive care; hospital length of stay; and mortality.

Findings

Of 2896 adults screened for eligibility, 929 were recruited and 913 met protocol-defined eligibility criteria (median age 43·1 years [IQR 29·5–59·7]; 550 [60%] men, 361 [40%] women, and two [<1%] with missing data). 530 (58%) participants presented with suspected meningitis, encephalitis, or both, and 318 (35%) with fever plus myalgia, fever plus arthralgia, or both. 820 (90%) reported no international travel within 21 days before symptom onset. 727 (80%) were administered antibiotics, 379 (42%) corticosteroids, and 222 (24%) antivirals. The median length of hospital stay was 9 days (IQR 6–14), and 113 (12%) required intensive care. Of 847 participants with a reference laboratory sample who met full eligibility criteria for analysis, 110 (13%) were diagnosed with 114 confirmed or probable acute arbovirus infections (four had coinfections or cross-reactivity): one (<1%) with CCHFV, 16 (2%) with TBEV, 44 (5%) with TOSV, and 53 (6%) with WNV. There was one death (<1%) of an individual with WNV. Of the 110 participants, 49 (45%) had a local clinician-attributed arbovirus discharge diagnosis.

Interpretation

Our data highlight the need to strengthen arbovirus surveillance systems for the early detection of emerging and re-emerging outbreaks, including investments to increase awareness of arbovirus infections among clinicians, to improve access to specialist diagnostics, and to develop effective and accessible vaccines and treatments to protect populations and health systems in southeast Europe.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00655-8/fulltext?rss=yes

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

Note 20/02/2025: this immediate notification is linked to the avian influenza cases detected in cats and reported in event 6276.

HPAI - H5N1 virus was detected in poultry droppings, poultry waste swab, meat cutting table swab, and knife swab collected from the live bird market {in Madhya Pradesh}.

Source: WOAH, https://wahis.woah.org/#/in-review/6277

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

A wild Barnacle Goose. The animal was found weakened on Middelkerke beach. It showed severe neurological symptoms. It was culled on suspicion of avian influenza.

Source: WOAH, https://wahis.woah.org/#/in-review/6284

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Isolation of a novel #human #prion #strain from a PRNP codon 129 heterozygous #vCJD #patient

Abstract

The epizootic prion disease of cattle, bovine spongiform encephalopathy (BSE), caused variant Creutzfeldt-Jakob disease (vCJD) in humans following dietary exposure. Codon 129 polymorphism of the human prion protein gene (PRNP), encoding either methionine (M) or valine (V), dictates the propagation of distinct human prion strains and up to now all but one neuropathologically confirmed vCJD patients have had a 129MM genotype. Concordant with this genetic association, transgenic modelling has established that human PrP 129V is incompatible with the vCJD prion strain and that depending on codon 129 genotype, primary human infection with BSE prions may, in addition to vCJD, result in sporadic CJD-like or novel phenotypes. In 2016 we saw the first neuropathologically confirmed case of vCJD in a patient with a codon 129MV genotype. This patient’s neuropathology and molecular strain type were pathognomonic of vCJD but their clinical presentation and neuroradiological features were more typical of sporadic CJD, suggestive of possible co-propagation of another prion strain. Here we report the transmission properties of prions from the brain and lymphoreticular tissues of the 129MV vCJD patient. Primary transmissions into transgenic mice expressing human PrP with different codon 129 genotypes mainly produced neuropathological and molecular phenotypes congruent to those observed in the same lines of mice challenged with prions from 129MM vCJD patient brain, indicative that the vCJD prion strain was the dominant propagating prion strain in the patient’s brain. Remarkably however, some transgenic mice challenged with 129MV vCJD patient brain propagated a novel prion strain type which at secondary passage was uniformly lethal in mice of all three PRNP codon 129 genotypes after similar short mean incubation periods. These findings establish that cattle BSE prions can trigger the co-propagation of distinct prion strains in humans.

Source: PLoS Pathogens, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012904

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Highly Pathogenic Avian #Influenza A(#H5N1) Virus #Infection of Indoor Domestic #Cats Within #Dairy Industry #Worker #Households — #Michigan, May 2024

Summary

-- What is already known about this topic?

- Outdoor cats on U.S. dairy farms have been infected with highly pathogenic avian influenza (HPAI) A(H5N1) virus; infection has not been reported in indoor cats.

-- What is added by this report?

- HPAI A(H5N1) virus was detected in two indoor domestic cats with respiratory and neurologic illness that lived in homes of dairy workers but had no known direct exposure to HPAI A(H5N1)–affected farms. Both dairy workers declined testing; other household members received negative test results for influenza A.

-- What are the implications for public health practice?

- Veterinarians in states with confirmed HPAI A(H5N1) in livestock should consider obtaining household occupational information, testing for influenza A viruses, and wearing personal protective equipment when evaluating companion cats with respiratory or neurologic illness. Suspected cases should be reported to public and animal health officials.

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) virus, clade 2.3.4.4b, genotype B3.13 infection has been documented in cats on U.S. dairy cattle farms. In May 2024, the detection of HPAI A(H5N1) virus infection in two cats that were reported to be exclusively indoor, and that had respiratory and neurologic illness in different households, prompted an investigation by the Michigan Department of Health and Human Services and Mid-Michigan District Health Department (MDHHS/MMDHD). The cats’ owners and household members were interviewed and offered testing for influenza A(H5) virus. The owner of one cat worked on a dairy farm but declined A(H5) testing; three other household members received negative A(H5) test results. The owner of the other cat lived alone and worked on multiple dairy farms transporting unpasteurized milk; this worker also reported getting splashed in the face and eyes by unpasteurized milk but declined A(H5) testing. Both workers were employed in a county known by MDHHS/MMDHD to have HPAI A(H5N1) virus, clade 2.3.4.4b, genotype B3.13–positive dairy cattle. In states with confirmed HPAI A(H5N1) in livestock, veterinary care can be aided if veterinarians obtain household members’ occupational information, especially when evaluating cats with signs of respiratory or neurologic illness. If occupational exposure to HPAI A(H5N1)-infected livestock is identified among cat owners, and their companion cats are suspected to have HPAI A(H5N1) virus infection, it is important that veterinarians contact state and federal public health and animal health officials to collaborate on joint One Health investigations and testing to protect human and animal health.

Source: US Centers for Disease Control and Prevention, MMWR Morbidity and Mortality Weekly Report, https://www.cdc.gov/mmwr/volumes/74/wr/mm7405a2.htm?s_cid=mm7405a2_e&ACSTrackingID=USCDC_921-DM145231&ACSTrackingLabel=This%20Week%20in%20MMWR%3A%20Vol.%2074%2C%20February%2020%2C%202025&deliveryName=USCDC_921-DM145231

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#Russia health authority is conducting additional #monitoring of #birdflu in #livestock #farms with #cows

{Automatic Translation}

Since 2020, the world has seen an increase in the number of outbreaks of avian influenza caused by the highly pathogenic avian influenza A (H5N1) virus and an expansion of the geography of circulation of this virus.

In 2024, more than 1.2 thousand outbreaks of influenza A (H5N1) among wild birds and about 2 thousand outbreaks among poultry were registered in the world. The infection affected 68 countries in Asia, Europe, Africa, North and South America, and also reached Antarctica.

In addition, in 2024, a large number of cases of detection of the influenza A (H5N1) virus among wild and domestic mammals were recorded, including with subsequent infection of people. These include outbreaks among cattle on US dairy farms, which by the end of the year affected more than 900 dairy farms in 16 states. The avian influenza A (H5N1) virus, isolated from cows, also caused illness in 40 people - farm workers. At the same time, the influenza A(H5N1) viruses detected in cows and humans contained mutations of adaptation to mammals.

High activity of A(H5N1) virus circulation, including among mammals, accumulation of mutations of adaptation to mammals, growth in the number of cases of human infection indicate an increasing risk of interspecies transition of this virus from mammals to humans.

Since 2013, Rospotrebnadzor has created and is operating a system for monitoring the circulation of highly pathogenic avian influenza in the Russian Federation. The system includes regular studies of biomaterial samples taken from birds and animals in Russian regions located in bird migration zones, as well as studies of biomaterial samples obtained from foci of highly pathogenic avian influenza, both from the birds themselves and from people caring for them. In addition, monitoring of the avian influenza situation in foreign countries is carried out.

Primary studies of biomaterial samples are carried out in Rospotrebnadzor laboratories in the regions of Russia. In-depth molecular genetic studies of viruses are carried out at the reference center for zoonotic avian influenza caused by highly pathogenic strains, operating on the basis of the Federal Budgetary Institution of Science State Research Center of Virology and Biotechnology Vector of Rospotrebnadzor, which is also a Collaborating Center of the World Health Organization for the Study of Influenza at the Intersection Points of Human and Animal Ecosystems.

As part of the monitoring carried out in 2024, more than 15 thousand samples of biomaterial from wild and domestic birds and pigs, as well as 7.8 thousand samples of material from people who, due to the nature of their work, come into contact with wild or domestic birds, were studied. All viruses isolated in 2024 belong to clade 2.3.4.4b, do not contain mutations of increased pathogenicity and drug resistance, with the exception of the avian influenza virus A (H5N1), isolated from birds in the Sakhalin Oblast - a mutation was identified that can increase virulence and ensure adaptation of the virus to mammalian cells.

Due to the registration of a significant number of outbreaks of avian influenza A (H5N1) on dairy farms in the United States, Rospotrebnadzor has also introduced additional monitoring of avian influenza in livestock farms containing cows in the Russian Federation since December 2024. 

Since December 2024, 11.6 thousand samples of material from cattle, including 5 thousand samples of milk, have been collected and tested in 84 regions; as well as more than 4.2 thousand samples of material from people caring for animals. More than 14.7 thousand samples of material have already been tested, including more than 11.3 thousand samples of material from cattle. No genetic material of avian influenza viruses was found in the tested samples.

The situation is under the control of Rospotrebnadzor.

Source: Ministry of Health, https://rospotrebnadzor.ru/about/info/news/news_details.php?ELEMENT_ID=29425

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#Pathogenicity of Novel #H3 Avian #Influenza Viruses in #Chickens and Development of a Promising #Vaccine

Abstract

Since 2022, three cases of human infections of novel H3N8 avian influenza viruses (AIVs) have been confirmed in China. Given the potential for significant public health implications, the prompt detection and containment of the virus is particularly important. Comprehensive analyses were conducted of the complete viral gene sequences of five H3 subtype AIVs that were isolated from chickens, pigeons, and geese in live poultry markets in China in 2023. Four strains exhibited a high degree of homology with the H3N8 viruses responsible for human infections in 2022 and 2023. A subsequent study was conducted to investigate the pathogenicity differences among multiple subtypes of the H3 AIVs in chickens. The study revealed that all infected chickens exhibited clinical signs and viral shedding. Notably, two H3N8 viruses, which were highly homologous to human strains, demonstrated significant differences in adaptability to chickens. The goose-derived H3N5 strain displayed high adaptability to chickens and could replicate in multiple organs, with the highest titer in the cloaca. Additionally, a potential vaccine strain, designated CK/NT308/H3N3, was successfully developed that provided complete clinical protection and effectively prevented viral shedding against both H3N3 and H3N8 viruses. In conclusion, CK/NT308/H3N3 presents a promising vaccine candidate.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/288

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#Mycoplasma pneumoniae #infection in #adult inpatients during the 2023–24 #outbreak in #France (MYCADO): a national, retrospective, observational study

Summary

Background

An epidemic of Mycoplasma pneumoniae infection has been observed in France since September, 2023. We aimed to describe the characteristics of adults hospitalised for M pneumoniae infection and identify factors associated with severe outcomes of infection.

Methods

MYCADO is a retrospective observational study including adults hospitalised for 24 h or more in 76 hospitals in France for a M pneumoniae infection between Sept 1, 2023, and Feb 29, 2024. Clinical, laboratory, and imaging data were collected from medical records. We identified factors associated with severe outcomes of infection, defined as a composite of intensive care unit (ICU) admission or in-hospital death, using multivariable logistic regression.

Findings

1309 patients with M pneumoniae infection were included: 718 (54·9%) were men and 591 (45·1%) were women; median age was 43 years (IQR 31–63); 288 (22·0%) had chronic respiratory failure; 423 (32·3%) had cardiovascular comorbidities; and 105 (8·0%) had immunosuppression. The most common symptoms were cough (1098 [83·9%]), fever (1023 [78·2%]), dyspnoea (948 [72·4%]), fatigue (550 [42·0%]), expectorations (473 [36·1%]), headache (211 [16·1%]), arthromyalgia (253 [19·3%]), ear, nose, and throat symptoms (202 [15·4%]), diarrhoea (138 [10·5%]), and vomiting (132 [10·1%]). 156 (11·9%) of 1309 patients had extra-respiratory manifestations, including 36 (2·8%) with erythema multiforme, 19 (1·5%) with meningoencephalitis, 44 (3·4%) with autoimmune haemolytic anaemia, and 17 (1·3%) with myocarditis. The median hospital stay was 8 days (IQR 6–11). 424 (32·4%) patients had a severe outcome of infection, including 415 (31·7%) who were admitted to the ICU and 28 (2·1%) who died in hospital. Those more likely to present with severe outcomes of infection were patients with hypertension, obesity, chronic liver failure, extra-respiratory manifestations, pulmonary alveolar consolidation or bilateral involvement on CT scan, as well as elevated inflammatory markers, lymphopenia or neutrophilic polynucleosis, and those who did not versus did receive any antibiotic active against M pneumoniae before admission.

Interpretation

This national, observational study highlighted unexpected, atypical radiological presentations, a high proportion of transfers to the ICU, and an association between severity and delayed administration of effective antibiotics. This should remind clinicians that no radiological presentation can rule out M pneumoniae infection, and encourage them to reassess patients early after prescribing a β-lactam, or even to discuss prescribing macrolides as first-line treatment in the context of an epidemic.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00805-3/abstract?rss=yes

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#Global #production #capacity of seasonal and #pandemic #influenza #vaccines in 2023

Abstract

Introduction

Vaccination is a critical part of the response to an influenza pandemic. Future influenza pandemics will likely leverage existing production processes and manufacturing facilities for seasonal influenza to make pandemic vaccines. Therefore, pandemic influenza vaccine response is heavily dependent on seasonal influenza vaccine production capacity.

Methods

WHO monitors global vaccine production to inform pandemic preparedness by regularly surveying influenza vaccine manufacturers to estimate both seasonal and potential pandemic vaccine production capacity overall and by region, vaccine type, and manufacturing process. The last survey estimates were for 2019; here, we report updated estimates based on data from the 2023 survey and compare to estimates from previous surveys.

Results

Our analysis estimates that annual seasonal influenza vaccine production capacity has remained relatively stable since 2019 at 1.53 billion doses and pandemic vaccine capacity at 4.13 and 8.26 billion doses for moderate and best case scenarios, respectively. Over 80 % of seasonal and pandemic vaccine production capacity relies on embryonated eggs, and inactivated influenza virus vaccines comprise the majority of vaccine supply. There is influenza vaccine manufacturing capacity in all WHO regions, except for the African Region, though influenza vaccine production is concentrated in high and upper-middle income countries. The ability to achieve maximum production capacity could be hindered by access to eggs and other ancillary supplies.

Conclusions

While influenza vaccine production capacity has been sustained since 2019, significant gaps persist in its distribution, especially in low and lower-middle income countries, and most notably in the African region. This imbalance in production could result in unequal access to vaccines in the event of a pandemic. Strengthening local vaccine manufacturing, promoting seasonal vaccination programmes, and investing in research and development of next-generation influenza vaccines or improved production platforms are essential to improve pandemic preparedness, sustain the influenza vaccine market, and enable more robust local responses.

Source: Vaccine, https://www.sciencedirect.com/science/article/pii/S0264410X25001367?via%3Dihub

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