Pan-continental #spillover #risk: integrated spatiotemporal, transmissibility and #surveillance analysis of avian #influenza #H5N1 in #Africa

 

Abstract

Background: 

The HPAI H5N1 panzootic represents a critical threat to human health in Africa, where traditional poultry systems and dense human-animal interfaces facilitate frequent zoonotic spillover. While sporadic human cases raise pandemic concerns, continent-wide integration of spatial dynamics, transmissibility indicators, and surveillance performance has been lacking. This study quantifies avian influenza transmission over two decades across Africa, identifies geographical hotspots, and evaluates the responsiveness of current surveillance systems.

Methods: 

We analysed 8,037 avian influenza outbreak events and 369 laboratory-confirmed human cases, predominantly caused by HPAI H5N1 (2004–2025), using harmonised data from FAO (EMPRES-i+), WHO, and WOAH. A Bayesian Besag-York-Mollié (BYM) spatiotemporal model estimated residual transmission risks and Incidence Rate Ratios (IRR) by subtype. The basic reproduction number (R₀) was derived via an exponential growth model applied to human outbreak phases across infectious durations of 7–30 days. Surveillance responsiveness was assessed by quantifying notification delays between clinical observation and official reporting.

Results: 

Risk of infection in animals: HPAI H5N1 was the dominant strain, representing 87.8% of animal cases, with Egypt acting as the primary epidemiological epicentre (66% of total records). The spatiotemporal model revealed that H5N1 is associated with a significantly higher risk of animal infection (IRR = 8.37; 95% CI: 6.65–10.53). Although 71% of outbreaks were reported within 5 days of detection, significant delays (≥15 days) occurred in 12% of cases, with notable regional disparities. Risk of infection in human: H5N1 was associated with a 67-fold increase in the incidence of human cases compared to other subtypes (IRR = 66.78; 95% CI: 25.29–176.37). Sensitivity analyses yielded R0 estimates ranging from 1.05 (95% CI: 0.91–1.31) to 1.23 (95% CI: 0.60–2.33), indicating localised epidemic potential.

Conclusion: 

Our findings highlight a persistent and geographically heterogeneous H5N1 reservoir in Africa with high zoonotic affinity. Although sustained human-to-human transmission remains limited, the identification of dual poultry-human hotspots and localised R0 peaks underscores the urgent need for geographically targeted One Health interventions. Strengthening real-time reporting systems and improving biosecurity in high-risk poultry value chains are critical to mitigating future pandemic threats on the continent.

Source: 

Link: https://www.frontiersin.org/journals/epidemiology/articles/10.3389/fepid.2026.1813211/full

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#Camel #Prion Disease, Tataouine, #Tunisia, 2019–2021

 

Abstract

We report 6 cases of camel prion disease in dromedaries in Tunisia, confirming widespread occurrence in North Africa. Affected animals showed neurologic signs and scrape prion protein accumulation in brain and lymphoid tissues. These findings highlight the importance of active surveillance and investigation of the epidemiology, transmission, and public health implications.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1474_article

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Identification of #Contacts With High Rates of Missed and #Asymptomatic Infection Following an #Outbreak of #Ebola Virus Disease: A Seroepidemiological Study in Likati Health Zone, #DRC

 

Abstract

Background

Ebola virus disease (EVD) is often regarded as severe and highly fatal, but growing evidence suggests that subclinical or minimally symptomatic infections occur and frequently go undetected. During the 2017 outbreak in Likati Health Zone, only 8 cases were confirmed despite many reported exposures. We evaluated the extent of asymptomatic or unrecognized Ebola virus infection and associated factors among contacts of reported cases.

Methods

In November 2017, we conducted a cross-sectional community-based serosurvey among contacts originally identified through Ministry of Health records and newly identified through additional post-outbreak investigations. Participants provided blood samples and completed questionnaires on demographics, exposures, and symptoms within 4 weeks of symptom onset of the EVD case with whom contact was reported. Sera were tested for anti-EBOV nucleoprotein IgG by ELISA. Seropositive individuals were classified as asymptomatic (no symptoms) or unrecognized (≥1 symptom). Secondary attack rate (SAR) was estimated, and logistic regression assessed associations with sociodemographic factors, exposure level, and symptoms.

Results

Among 180 participants (79 originally identified; 101 newly identified), 33 (18.3%) were seropositive. Of these, 19 (58%) reported symptoms, and 14 (42%) were asymptomatic. Any EVD-related symptom was associated with higher odds of seropositivity (OR 2.48, P = .021), though no specific symptom was significant. Asymptomatic individuals had higher antibody titers than symptomatic seropositive contacts (P = .009). The overall SAR was 19.1% (95% CI: 15.9–23.0). High exposure level strongly predicted seropositivity (OR 11.2, 95% CI: 3.8–33.3).

Conclusions

Asymptomatic infections occurred, including among contacts missed during the response, highlighting the need for exposure-based serologic assessments in EVD investigations and raising questions about immune responses and the true disease burden in outbreak-affected settings.

Source: 

Link: https://academic.oup.com/ofid/article/13/7/ofag397/8725922

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#Screening and #monitoring of #travellers returning from countries affected by #Bundibugyo virus: an overview of #European approaches, July 2026

 

Abstract

The 2026 Ebola outbreak caused by Bundibugyo virus in the Democratic Republic of the Congo and Uganda has prompted European countries and the United States to revise measures for travellers, healthcare workers and humanitarian personnel returning from affected areas. We compare current procedures and protocols with those implemented during the 2013–2016 Ebola outbreak. Despite some national differences, policies have largely converged towards risk-based management, early case detection, rapid isolation, exposure-based monitoring and healthcare preparedness, rather than routine border screening.

Source: 

Link: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2026.31.28.2600578?emailalert=true#abstract_content

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Occupationally Exposed and General #Population #Antibody #Profiles to #Influenza A Viruses Circulating in #Swine as Indication of Zoonotic #Risk

 

Abstract

Persons with occupational exposure to swine might be at disproportionate risk for zoonotic swine influenza A virus. To evaluate human antibody responses, we tested serum or plasma from swine veterinarian, farm employee, and general population cohorts by hemagglutination inhibition assays against representative swine and human seasonal influenza vaccine strains. We analyzed hemagglutination inhibition data by antigenic cartography to assess strain relationships and reproduction number modeling to evaluate pandemic potential using age-stratified immunity profiles. Occupationally exposed groups had lower human seasonal vaccine uptake (45.5% vs. 70%) and lower odds of seropositivity to several H1 and H3 strains from swine than did general population cohorts. One swine strain exhibited significant antigenic drift (3.62 antigenic units) from its nearest vaccine strain. Multiple strains required lower reproduction number thresholds for pandemic spread (1.09–1.35) than recorded pandemic strains (1.46–1.80), demonstrating that population immunity gaps heighten zoonotic risk to circulating swine H1 and H3 strains.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1995_article

____

First nationwide full- #genome characterisation of #human-derived #Andes virus in #Chile: a retrospective genomic #epidemiology study

Summary

Background

Andes virus (ANDV) is the only hantavirus known to transmit between humans and causes hantavirus cardiopulmonary syndrome in Chile and Argentina. In Chile, ANDV genomic diversity remains incompletely characterised. This study aimed to characterise the genetic diversity, geographical structure, and molecular signatures of ANDV using human clinical samples collected over a 13-year period (2011–24).

Methods

We conducted a retrospective genomic epidemiology study of ANDV infections in Chile. Clinical samples from patients with confirmed ANDV, collected between March 9, 2011, and June 27, 2024, were analysed and sequenced. Clinical and epidemiological data were obtained from diagnostic laboratories and surveillance programmes. Consensus sequences for the S, M, and L segments were generated, and genetic clustering and divergence were assessed using phylogenetic inference and variant calling.

Findings

We analysed clinical samples from 58 infected individuals and identified two major genomic variants of ANDV with distinct geographical distributions, defined by regionally structured patterns of nucleotide and amino acid substitutions across the S, M, and L segments: ANDV Chi-North (central Chile) and ANDV-South (southern Chile). No consistent clustering by clinical severity was observed, and no recurrent non-synonymous substitutions were uniquely associated with severe disease. Substitutions previously associated with person-to-person transmission in outbreaks in Argentina were not consistently observed in Chilean sequences, including in four person-to-person transmission cases. Although some substitutions described in ANDV-like viruses were present in the Chi-North lineage, this lineage remained phylogenetically distinct and geographically restricted to central Chile.

Interpretation

To our knowledge, this study provides the first nationwide genomic characterisation of human-derived ANDV in Chile. The identification of geographically structured variants indicates that ANDV diversity in Chile is driven by regional diversification rather than clinical outcome. The absence of consistent amino acid signatures associated with disease severity or person-to-person transmission suggests that these phenotypes are unlikely to be explained by viral genetic variation alone. These findings refine current understanding of ANDV evolution and highlight the need for continued integrated genomic surveillance in endemic regions.

Funding

Agencia Nacional de Investigación y Desarrollo de Chile and National Institutes of Health.

Source: 

Link: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(26)00109-6/fulltext

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#Bundibugyo #ebolavirus from the 2026 Ebola #outbreak in #Uganda and #DRC: a new #variant

 

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In conclusion, we show that the BDBV variant identified in Uganda from a travel-related case linked to the ongoing outbreak in Ituri represents a new clade of BDBV. These findings underscore the diversity of the BDBV ecosystem and the urgent need for antiviral and vaccine countermeasures to reduce fatalities and for public health measures to limit the spread of the virus. Global efforts are immediately needed in this region. Continued genomic surveillance is required for in-depth monitoring to track emerging BDBV variants and adjust and employ BDBV countermeasures in a timely manner.

Source: 

Link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01079-2/fulltext

____

#Andes Virus — A #Clinical #Review

 

Summary

Andes virus (ANDV) is the sole orthohantavirus with documented human-to-human transmission. We summarize the epidemiology and clinical features of ANDV infection and review best practices in clinical management, as based on published expert consensus guidelines, field experience, and clinical trials. We also evaluate currently available and investigational treatments (including the use of antiviral agents), assess emerging monoclonal antibody therapies, and outline prospects for vaccine development. Finally, we discuss important infection prevention and control measures.

Source: 

Link: https://www.nejm.org/doi/full/10.1056/NEJMra2606651?query=TOC

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Detection of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype #D1.2 Virus in #Swine after Experimental Inoculation

 

Abstract

Highly pathogenic avian influenza H5NX clade 2.3.4.4b viruses continue to circulate globally. Reintroduction of Eurasian lineage viruses into North America and reassortment with endemic low pathogenicity strains have resulted in new genotypes, including D1.2. To assess pathogenicity and cellular tropism, we intranasally inoculated genotype D1.2 virus into pigs. We isolated virus from nasal secretions from most inoculated animals for multiple days. At 5 days postinoculation, PCR and immunohistochemistry detected virus in musculoskeletal, respiratory, digestive, lymphatic, and nervous systems and isolates from meat juice. At 35 days postinoculation, we detected viral antigen and low levels of RNA in the brain of an animal with lesions consistent with a viral etiology and found viral antigen in the ethmoid of 2 animals. Consistent detection in nasal swab specimens, combined with subclinical respiratory infection, systemic distribution, and protracted detection of clade 2.3.4.4b virus in swine, suggest identifying infection in commercial swine without overt respiratory signs could be difficult.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1765_article

____

A systematic #review of #Nipah virus disease epidemiological #parameters, #outbreaks, and mathematical #models

 

Summary

Our systematic review, based on PRISMA guidelines (PROSPERO CRD42023393345), characterised the epidemiology, outbreaks, and mathematical models of Nipah virus, an important public health threat in south and southeast Asia. We searched PubMed and Web of Science from database inception to March 14, 2025, and extracted 243 parameters, 89 risk factors, 39 models, and 23 distinct outbreaks from 119 papers. IgG seroprevalence estimates in the general population ranged from 0% to 12·5%. Nipah virus causes severe disease, with pooled case–fatality ratio estimates ranging widely from 9·1% (95% CI 0·2–41·3) in Singapore to 81·9% (95% CI 71·9–88·9) in Bangladesh. The infection timeline and clinical course of Nipah virus remain poorly characterised; we estimated a median incubation period of 8·77 days (165, 95% CI 7·53–10·02) from eight estimates in seven articles with sufficient information. Transmission parameter estimates were scarce, and all but one of five central estimates of the basic reproduction number were less than one. Nipah virus mathematical models (39) were rarely fitted to data (eight). All extracted information is accessible via our R package, epireview.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00239-2/abstract?rss=yes

____

#Neurological Manifestations of #Hantavirus Infection - A Review

 

Abstract

Importance  

Hantaviruses have caused several recent human disease outbreaks. They carry a high mortality rate, and some species can spread from person to person although they are typically spread from rodents to humans. Neurological complications have been documented but are poorly understood.

Observations

Broadly, 2 types of syndromes have been associated with hantaviruses. The pulmonary syndrome carries a high mortality rate and can result in pulmonary and cardiac failure. Neurological involvement is typically secondary to hypoxic and ischemic injury or metabolic dysfunction. Another manifestation of the infection that is associated with some species of the virus is termed hemorrhagic fever with renal syndrome. Some patients may develop a meningoencephalitis or pituitary apoplexy resulting in sudden visual loss and pituitary dysfunction. Rarely, seizures, myelitis, and peripheral neuropathy may occur. Although there are no specific antiviral drugs approved for treatment of hantavirus, there are several that showed efficacy in preclinical trials. Management is supportive care and treatment of symptoms.

Conclusions and Relevance  

Neurological manifestations of hantavirus infection are uncommon but can be severe. Prospective studies and experimental models are needed to better characterize these manifestations, understand pathophysiology, identify therapeutic targets, and develop guidelines for management.

Source: 

Link: https://jamanetwork.com/journals/jamaneurology/fullarticle/2851731

____

Rapid #Expansion of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype #D1.1 Virus across #Flyway Regions, North #America, Fall 2024

 

Abstract

Highly pathogenic avian influenza clade 2.3.4.4b virus continues to circulate in North America and has caused severe human disease. That clade includes genotype D1.1, which became dominant in birds in late 2024. Recent phylodynamic reconstructions place D1.1 emergence in mid-2024 but differ on its inferred origin and early dissemination pathways. We combined targeted surveillance of wild birds in Arizona with publicly available US clade 2.3.4.4b hemagglutinin sequences to estimate when D1.1 genotype emerged and to infer its diffusion among the 4 major US flyways. Phylodynamic analyses showed transitions concentrated among adjacent flyways regions, consistent with stepwise dissemination during fall 2024 and limited support for long-distance Pacific–Atlantic exchange. The Pacific Flyway showed patterns consistent with an early source and the Central Flyway with a secondary hub linked to onward spread. Our findings support coordinated genomic surveillance across adjacent flyways to reduce detection delays and improve situational awareness during rapid viral expansion.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/26-0205_article

____

Highly Pathogenic Avian #Influenza #H5N1 in South #America, 2022–2025: Spread, Affected Species, and Southward Expansion into the #Antarctic Region

 

Abstract

The H5N1 highly pathogenic avian influenza (HPAI) virus has caused severe global losses, reaching South America in 2022 and Antarctica in 2024. Here, we synthesize outbreak reports submitted to the World Organization for Animal Health by South American countries and overseas territories in this continent, and document the virus’s unprecedented expansion into Antarctica, affecting wild birds, wild mammals, and domestic poultry. Phylogenetic and time-calibrated Bayesian analyses were performed on available genomic sequences. Over 6 million domestic birds were lost, mostly from commercial operations. Of the 11 South American countries and overseas territories that reported H5N1 to WOAH, 10 reported infections in wild birds, spanning 104 species, 59.62% of which are migratory and predominantly non-trans-equatorial. Marine mammal outbreaks followed wild bird detections, with the South American sea lion (Otaria flavescens) being the most reported species. Several Antarctic bird species with migratory behavior were also reported in South America. Genomic analyses revealed multiple introduction events, regional viral diversification, and patterns consistent with repeated cross-species spillover events. These findings highlight H5N1’s extensive ecological reach in the Southern Hemisphere and underscore the urgent need for a One Health approach that strengthens wildlife and backyard-poultry surveillance, alongside coordinated regional action to control and prevent further HPAI spread.

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/764

____

#MHC-II acts as a #fusion-triggering #receptor for #bat #influenza virus

 

Abstract

Influenza A virus hemagglutinin is a prototypical class I viral fusion protein that binds sialylated glycans and is activated by low pH in endosomes. In contrast, bat-derived IAV subtypes H17N10 and H18N11 use major histocompatibility complex class II (MHC-II) as an entry receptor, but how this receptor contributes to membrane fusion remains unknown. We find that MHC-II-dependent hemagglutinin subtypes H17, H18, and H19 possess an increased negative net charge relative to canonical HAs. Using cryo-electron tomography, we demonstrate that H18N11 morphology remains stable and H18 is in prefusion conformation at strongly acidic pH. Remarkably, H18 undergoes fusion-relevant conformational changes only when both MHC-II binding and low pH are present. By reconstitution of H18N11 fusion with liposomes and purified MHC-II, we show that receptor engagement is required to trigger the fusion activity of H18. These findings identify MHC-II as a receptor that directly triggers membrane fusion and reveal a previously unrecognized receptor-dependent mechanism of influenza virus entry.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, 240245660 – P19, 537227910

European Research Council, 882631—Bat Flu

Excellence Initiative of the German Research Foundation, GSC-4, Spemann Graduate School

Hans A. Krebs Medical Scientist Programme

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.08.737388v1

____

Lactylation of #Influenza Virus #Polymerase Acidic Protein Promotes Viral #Replication and #Pathogenicity

 

Abstract

Influenza virus poses a potential risk of triggering the next global pandemic. In-depth investigation into the mechanisms underlying influenza virus replication and pathogenicity will provide robust support for controlling influenza virus infection. Although post-translational modifications are known to regulate viral infection, the role of lactylation in influenza virus replication remains elusive. In this study, influenza virus ribonucleoprotein complex subunits are found to be lactylated. Specifically, ATAT1 promotes viral polymerase acidic protein (PA) lactylation and enhances viral replication. In contrast, SIRT1 mediates de-lactylation of PA and exerts an inhibitory effect on viral replication. Further investigations reveal lactylation of PA at residues K605 and K609 is essential for viral replication and pathogenicity. Mechanistically, PA K605/609 residues are localized at the interaction interface of the ANP32-mediated polymerase asymmetric dimer; mutation at these residues inhibits polymerase asymmetric dimerization, thereby impairing RNA production during viral genome replication. Collectively, this study uncovers a novel mechanism by which influenza virus hijacks host enzymes to mediate PA lactylation, and expands the molecular regulatory network of influenza virus infection.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.10.737663v1

____

Long-Term #Monitoring of #Influenza A Viruses in Wild #Waterfowl: Evidence from the Lake #Baikal Basin (2018–2024)

 

Abstract

Wild waterfowl constitute the primary natural reservoir of influenza A viruses, and wetlands at the convergence of major migratory flyways serve as critical hubs for viral genetic exchange. Baikal Siberia, situated at the intersection of the East African–West Asian, Central Asian, and East Asian–Australasian flyways, represents a unique yet understudied region in this context. Here we report the results of long-term virological surveillance of wild birds in the Lake Baikal basin conducted between 2018 and 2024. A total of 1036 cloacal swab samples from 28 bird species were screened, yielding 42 influenza A virus isolates belonging to 12 HA/NA subtype combinations: H1N1, H3N1, H3N2, H3N5, H3N6, H3N8, H4N6, H6N1, H6N2, H6N3, H6N8, and H12N5. Among the detected subtypes, H6 viruses—identified with four distinct neuraminidase combinations (N1, N2, N3, N8)—are of particular public health relevance owing to their documented capacity for dual-receptor binding and potential for zoonotic transmission to mammals, including humans. Full-genome sequencing followed by cluster analysis of internal gene segments identified 16 distinct segment constellations, indicating extensive reassortment. BLAST searches against the GISAID database revealed closest genetic relatives in Mongolia, South Korea, Japan, China, and Western Siberia, with more distant links to Bangladesh, Europe, and a possible intercontinental connection via the Pacific flyway. Maximum-likelihood phylogenetic analysis of the HA and NA segments confirmed that all isolates belong to the Eurasian genetic lineage, yet they are distributed across multiple clades rather than forming a single monophyletic group, reflecting the role of Buryatia as a mixing zone for genetically diverse viral populations. These findings substantially expand the understanding of influenza A virus ecology in the Lake Baikal basin and underscore the importance of continued surveillance at this key migratory crossroads in Northern Asia.

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/761

____

Preparing for the Next #Pandemic: Learning From #COVID19 to Build What Comes Next

 

Abstract

WHO's efforts to strengthen pandemic preparedness—grounded in what the world learned during COVID-19 and what today's outbreaks of avian influenza, Hantavirus and Ebola are teaching us.

Source: 

Link: https://academic.oup.com/ofid/article/13/7/ofag348/8728458

____

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Isolation and characterization of a clade 2.3.4.4b genotype #D1.1 #H5N1 virus from dairy #cattle in #Wisconsin

 

ABSTRACT

Highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses of clade 2.3.4.4b have recently been detected in U.S. dairy cattle following multiple spillover events from avian reservoirs. In December 2025, HPAI H5N1 virus was identified in a dairy herd in Wisconsin through the National Milk Testing Strategy. Here, we report the isolation of a clade 2.3.4.4b, genotype D1.1 H5N1 virus, A/dairy cow/Wisconsin/25G05743-001/2025 (WI5743-H5N1), from bulk milk associated with the affected herd, describe its phylogenetic relationships, and assess its pathogenicity in mice. Infectious virus was recovered following blind passage in embryonated chicken eggs. Phylogenetic analysis demonstrated that WI5743-H5N1 is distinct from previously reported D1.1 viruses detected in dairy cattle in Nevada and Arizona, supporting an independent introduction into cattle, and indicating a likely local avian source. Compared with closely related avian viruses, WI5743-H5N1 encoded the mammalian-adapting substitution PB2-E627K and additional amino acid differences in HA, PB1-F2, and NS1. In mice, WI5743-H5N1 replicated efficiently in respiratory tissues and was detectable in the brain but exhibited lower lethality relative to other recent clade 2.3.4.4b, genotype B3.13 viruses. Together, these findings highlight the genetic and phenotypic diversity of HPAI H5N1 viruses infecting dairy cattle and underscore the importance of continued surveillance and functional characterization of emerging strains.

IMPORTANCE

Highly pathogenic avian influenza A(H5N1) viruses have recently entered U.S. dairy cattle through multiple spillover events from avian reservoirs, creating new opportunities for viral adaptation in mammals. Here, we describe the isolation and characterization of a clade 2.3.4.4b, genotype D1.1 H5N1 virus from bulk milk collected during a spillover event in Wisconsin in December 2025. Phylogenetic analyses demonstrated that this virus represents an independent introduction into dairy cattle distinct from previously reported D1.1 viruses identified in Nevada and Arizona. Although the virus encoded the mammalian-adapting PB2-E627K substitution, it exhibited comparatively low lethality in mice, highlighting the complexity of mammalian adaptation and pathogenicity in H5N1 viruses. These findings expand current understanding of the genetic and phenotypic diversity of H5N1 viruses infecting dairy cattle and emphasize the importance of continued surveillance and functional characterization of emerging strains.

Source: 

Link: https://journals.asm.org/doi/10.1128/jvi.00761-26

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