Avian Influenza: Global Surveillance, CDC Updates, and World Map of Outbreaks

Introduction

Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype, particularly those belonging to clade 2.3.4.4b, have caused unprecedented global outbreaks in poultry, wild birds, and an expanding range of mammalian species [1, 2, 3]. The sustained circulation of these viruses necessitates robust surveillance systems that integrate molecular, serological, and epidemiological data across geographic scales [1, 4]. This article provides a technical review of global surveillance frameworks, updates from the United States Centers for Disease Control and Prevention (CDC) regarding animal surveillance, and the construction and interpretation of world outbreak maps. Emphasis is placed on veterinary and wildlife contexts, with reference to the underlying virological and diagnostic principles that inform outbreak detection and response.

Global Surveillance Networks

International surveillance for avian influenza is coordinated by the World Organisation for Animal Health (WOAH) and the Food and Agriculture Organization (FAO), with genomic data shared through platforms such as the Global Initiative on Sharing All Influenza Data (GISAID) [1, 3]. Multimodal data approaches that combine genomic, epidemiological, and environmental sampling have been employed to characterize the 2024-2025 HPAI outbreak in the United States [1]. Wastewater-based surveillance has emerged as a complementary tool for detecting influenza A virus RNA from both human and animal sources, as demonstrated in California [5]. In wild bird populations, rapid point-of-care molecular assays such as the GeneXpert platform have been deployed for early warning surveillance in seabirds and environmental samples in New Zealand [6]. Similarly, serological and molecular surveillance of influenza A virus in dogs and cats in central Chile has revealed spillover events into companion animals [7]. Predictive risk modeling using machine learning algorithms has been applied to optimize wild bird fecal surveillance sites for HPAI detection [8]. In Egypt, molecular surveillance combined with predictive risk modeling has identified high-risk zones for avian influenza virus circulation in wild birds [9]. Spatiotemporal evaluation tools such as EpiDCA have been used to assess the distribution of avian influenza outbreaks alongside other transboundary animal diseases [4].

Avian Influenza CDC: Reporting and Surveillance Systems

The CDC plays a central role in coordinating surveillance for influenza A viruses with pandemic potential in the United States, including those of avian origin. The agency's efforts are integrated with those of the U.S. Department of Agriculture (USDA) and state veterinary authorities. Multimodal data approaches have been used to examine the 2024-2025 HPAI outbreak, incorporating genomic epidemiology, case reporting, and environmental sampling [1]. Genomic wastewater surveillance has been applied to detect influenza A viruses in California, providing community-level data that complements traditional animal surveillance [5]. The CDC has also supported the development and validation of detection methods for H5N1 virus in dairy processing environments, reflecting the virus's expanded host range into cattle [10]. Comparative analysis of laboratory-based and portable quantitative PCR (qPCR) platforms, including the CFX, MIC, and Biomeme Franklin systems, has been conducted for African swine fever and avian influenza detection, informing field-deployable surveillance strategies [11]. The lower limit of detection of commercial respiratory virus reverse transcriptase-polymerase chain reaction (RT-PCR) panels for bovine influenza A(H5N1) has been evaluated, with implications for diagnostic sensitivity in cattle [12]. The CDC's surveillance framework also incorporates serological monitoring of domestic cats with outdoor access in the Netherlands, where exposure to H5 clade 2.3.4.4 and pandemic H1N1 viruses has been documented [13]. Associations between pre-existing bovine viral diarrhea virus, bovine leukemia virus, and Mycobacterium avium subspecies paratuberculosis exposure on H5N1 clinical signs and shedding in U.S. dairy cows have been investigated, highlighting the role of co-infections in modulating disease expression [14].

Avian Influenza World Map: Spatial Epidemiology and Outbreak Mapping

The construction of a global avian influenza world map relies on the integration of case data from national veterinary authorities, genomic sequences, and environmental surveillance. Spatiotemporal evaluation tools such as EpiDCA have been applied to avian influenza outbreaks to assess clustering and spread patterns [4]. In Italy, host species contribution to the spatiotemporal dynamics of the 2024-2025 H5N1 epidemic has been analyzed, revealing differential roles of poultry, wild birds, and mammals in virus dissemination [2]. Germany has been identified as a key transit hub for the emergence and spread of H5 clade 2.3.4.4b reassortants in Europe, based on genomic and epidemiological data [3]. Risk prediction models for HPAI outbreaks have been developed for Kuwait using environmental and demographic variables [15]. In Egypt, molecular surveillance and predictive risk modeling have been used to map avian influenza virus circulation in wild birds [9]. Machine learning algorithms have been employed to optimize wild bird fecal surveillance sites, improving the efficiency of outbreak detection [8]. The spatial distribution of H5N1 in dairy cattle in the United States has been mapped, with receptor binding studies providing a mechanistic basis for the unusual tissue tropism observed in bovine mammary glands [16]. These mapping efforts are critical for identifying high-risk areas and informing targeted surveillance and control measures.

Molecular Diagnostics and Detection Methods

Accurate and timely detection of avian influenza viruses is fundamental to surveillance and outbreak response. A range of molecular diagnostic platforms are available, each with distinct performance characteristics. Laboratory-based qPCR systems (e.g., CFX) and portable devices (e.g., MIC, Biomeme Franklin) have been compared for the detection of avian influenza virus, with portable platforms offering field-deployable options without substantial loss of sensitivity [11]. The GeneXpert platform has been used for rapid surveillance of influenza A virus in seabirds and environmental samples in New Zealand [6]. A microfluidic non-competitive fluorescence polarization immunoassay has been developed for the detection of H5 subtype avian influenza virus in avian oropharyngeal swab samples, providing a rapid, antibody-based alternative to nucleic acid amplification [17]. CRISPR-Cas12a-based multimodal biosensing platforms have been engineered for point-of-care detection of H5N1, offering triplex readout capabilities [18]. Methods for detecting H5N1 virus in dairy processing environments have been validated, including swab-based sampling and RT-PCR [10]. The lower limit of detection of commercial respiratory virus RT-PCR panels for bovine influenza A(H5N1) has been characterized, with some panels showing reduced sensitivity for the bovine-adapted virus [12]. Environmental detection using bacteriophage Phi6 as a surrogate for H5N1 has been employed to evaluate inactivation methods such as ultraviolet light and advanced oxidative processes in raw bovine milk [19].

Host Range and Receptor Binding

The expanding host range of H5N1 clade 2.3.4.4b viruses is underpinned by changes in receptor binding specificity. The receptor basis of unusual tissue tropism in cattle has been elucidated, with the virus showing preferential binding to sialic acid receptors expressed in bovine mammary gland epithelium [16]. A hemagglutinin double mutation has been shown to enhance binding of human-infecting avian influenza virus clade 2.3.4.4b H5Ny to human and sialyl Lewis X (SLeX) receptors, indicating a potential for increased zoonotic risk [20]. The N-terminal region of the PA protein from pandemic H1N1 virus synergizes with its cognate NP to enhance mammalian adaptation of avian-origin H9N2 canine influenza virus [21]. Dominant HA motif 131/132-NT shapes the phenotype of avian H9N2 influenza virus by modulating agglutination property, receptor specificity, and infectivity in animals [22]. These molecular determinants are critical for assessing the pandemic potential of circulating avian influenza viruses.

Vaccine Strategies and Immune Responses

Vaccination of poultry is a key component of avian influenza control in endemic regions. Several novel vaccine platforms have been evaluated in experimental settings. A cGAMP-loaded M2e nanovaccine elicits cross-reactive immunity and mitigates H6N1 avian influenza infection in chickens [23]. A bivalent mRNA-lipid nanoparticle (LNP) vaccine confers broad-spectrum protection against both homologous and heterologous H5/H7 HPAI viruses in specific-pathogen-free (SPF) chickens [24]. Engineered Bacillus subtilis has been used to deliver double-stranded RNA via extracellular vesicles against the H9N2 avian influenza virus, representing a probiotic-based vaccine approach [25]. A vesicular stomatitis virus (VSV)-vectored vaccine simultaneously targeting H5N1 hemagglutinin and matrix protein 2 induces robust neutralizing and antibody-dependent cellular cytotoxicity (ADCC) responses and provides full protection against lethal H5N1 infection in a mouse model [26]. An oral vaccine strategy utilizing a plasmid with a CAG promoter-driven alphavirus replicase for co-expression of NA epitope and adjuvant in attenuated Salmonella has been shown to boost immune responses against H9N2 in mice [27]. A neutralizing nanobody targeting a conserved lateral patch on HA1 confers protection against multiple H7 avian influenza viruses [28]. A trimeric hemagglutinin vaccine provides chickens complete protection against lethal H5 subtype avian influenza virus from clade 2.3.4.4b [29]. Pigeon interferon lambda (piIFN-λ) has been molecularly cloned and shown to possess antiviral function against influenza virus, suggesting potential as a therapeutic or adjuvant [30]. The role of microRNAs in antiviral immunity has been explored, with gga-miR-92-targeted TNFRSF1B inhibiting influenza A virus replication by degrading TRAF3 [31].

Antiviral Resistance and Treatment

Antiviral resistance remains a concern for the management of influenza infections, including those caused by avian influenza viruses. A comprehensive review of antiviral resistance in influenza has highlighted the clinical and public health implications of resistance to neuraminidase inhibitors and other classes [32]. In the veterinary context, treatment options are limited, and control relies primarily on biosecurity, stamping out, and vaccination. Inactivation methods for H5N1 in food matrices have been studied, including the use of ultraviolet light (254 nm), advanced oxidative processes, and the endogenous lactoperoxidase system in raw bovine milk, using bacteriophage Phi6 as a surrogate [19].

One Health Implications and Future Directions

The spillover of H5N1 clade 2.3.4.4b viruses into mammals, including cattle, cats, dogs, and other species, underscores the need for a One Health approach to surveillance [7, 16, 13, 14]. Serological and molecular surveillance of influenza A virus in dogs and cats in central Chile has documented exposure to avian influenza viruses [7]. Domestic cats with outdoor access in the Netherlands have been exposed to H5 clade 2.3.4.4 and pandemic H1N1 viruses [13]. In dairy cattle, associations between pre-existing viral and bacterial infections and H5N1 clinical signs and shedding have been identified [14]. Co-infections between avian pathogenic Escherichia coli (APEC) and H9N2 avian influenza virus promote bacterial adhesion during their infections, highlighting synergistic interactions between viral and bacterial pathogens [33]. The influence of infectious bursal disease virus (IBDV) on influenza A virus transmission in chickens has been evaluated, with immunosuppression potentially enhancing viral shedding [34]. Comparative analysis of virus-host interactions between diverse influenza A viruses and the human innate immune system has been performed to predict pandemic potential [35]. These findings emphasize the importance of integrated surveillance across species and the need for continued genomic and epidemiological monitoring.

References

[1] Sopko J, Han AR, Powers J et al. Multimodal Data Approaches for Examining the 2024-2025 Highly Pathogenic Avian Influenza Outbreak in the United States: Descriptive Study. JMIR Public Health Surveill. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42330167/

[2] Savegnago E, Cavicchio L, Dianati M et al. Host Species Contribution to the Spatiotemporal Dynamics of the 2024-2025 H5N1 Epidemic in Italy. Influenza Other Respir Viruses. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42299833/

[3] Ahrens AK, Grund C, Beer M et al. Germany as a key transit hub for the emergence and spread of high pathogenicity avian influenza H5 clade 2.3.4.4b reassortants in Europe. Front Microbiol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42293551/

[4] Boudoua B, Roche M, Teisseire M et al. Spatio-temporal evaluation of EpiDCA: Case studies on avian influenza, African swine fever, and West Nile virus disease. Spat Spatiotemporal Epidemiol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42285614/

[5] Wang AL, Lamtyugina A, Jiang M et al. Genomic wastewater surveillance of human and animal influenza A viruses in California during the 2024-2025 flu season. medRxiv. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42326814/

[6] Heremia L, Langsbury H, Treece J et al. Rapid GeneXpert surveillance of influenza A virus in seabirds and the environment provides early warning for wildlife health in Aotearoa New Zealand. Virology. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42322875/

[7] Baumberger C, Di Pillo F, Sanchez F et al. Serological and Molecular Surveillance of Influenza A Virus in Dogs and Cats in Central Chile. Zoonoses Public Health. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42324577/

[8] Kim S, Cho H, Jeong H et al. Optimizing wild bird fecal surveillance sites for HPAI through risk estimation using machine learning algorithms. One Health. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42294012/

[9] Nabil NM, Tawakol MM, Hagag N et al. Molecular surveillance and predictive risk modelling of avian influenza virus in wild birds in Egypt. J Gen Virol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42301748/

[10] Puchades-Colera P, Girón-Guzmán I, Pérez-Cataluña A et al. Methods for detecting highly pathogenic avian influenza H5N1 virus in dairy processing environments. Front Microbiol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42326402/

[11] Auer A, Settypalli TBK, Rozstalnyy A et al. Comparative analysis of laboratory-based and portable qPCR platforms: CFX, MIC, and Biomeme Franklin for African swine fever and avian influenza detection. BMC Vet Res. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42321793/

[12] Higerd-Rusli GP, Hoffman SA, Karan A et al. Lower limit of detection of commercial respiratory virus reverse transcriptase-polymerase chain reaction panels for bovine influenza A(H5N1). Am J Clin Pathol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42308142/

[13] Duijvestijn MBHM, Broens EM, Schuurman NNMPNMP et al. EXPRESS: Highly pathogenic avian influenza H5 clade 2.3.4.4 and human new pandemic H1N1 virus exposure in domestic cats with outdoor access in the Netherlands in 2024. J Feline Med Surg. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42265865/

[14] Urie N, Stenkamp-Strahm C, Wagner B et al. Associations between bovine viral diarrhea virus, bovine leukemia virus, and Mycobacterium avium subspecies paratuberculosis exposure on H5N1 clinical signs and shedding in US dairy cows. J Dairy Sci. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42264359/

[15] Alshatti M, Al-Hemoud A, Othman A et al. A risk prediction model for HPAI outbreaks in Kuwait. Front Vet Sci. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42290772/

[16] Srinivas S, Chothe SK, Ramasamy S et al. Receptor basis of unusual tissue tropism of avian influenza H5N1 clade 2.3.4.4b virus in cattle. Sci Adv. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42319934/

[17] Takahashi K, Takeda Y, Nishiyama K et al. Detection of H5 subtype avian influenza virus in avian oropharyngeal swab samples using a microfluidic non-competitive fluorescence polarization immunoassay. Analyst. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42306856/

[18] Guo B, Li Y, Shi M et al. A triplex-readout CRISPR-Cas12a multimodal biosensing platform for point-of-care detection of avian influenza H5N1. J Hazard Mater. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42263439/

[19] Chiappe C, Jarvie E, Marotta S et al. Inactivation of Pseudomonas Enveloped Bacteriophage Phi6 (H5N1 Surrogate) in Raw Bovine Milk using a Combination of Ultraviolet light (254 nm), Advanced Oxidative Process, and Endogenous Lactoperoxidase System. J Food Prot. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42263941/

[20] Jin X, Han P, Wang Y et al. Hemagglutinin double-mutation enhances binding of human-infecting avian influenza virus clade 2.3.4.4b H5Ny to human and SLe(X) receptors. EMBO Rep. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42303811/

[21] Zhou Y, Wang P, Li S et al. The N-terminal region of pdm09/H1N1 PA synergizes with its cognate NP to enhance mammalian adaptation of avian-origin H9N2 canine influenza virus. Vet Microbiol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42302523/

[22] Chen X, Dong J, Zhao C et al. Dominant HA motif 131/132-NT shapes the phenotype of avian H9N2 influenza virus by modulating agglutination property, receptor specificity and infectivity in animals. Virol Sin. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42288138/

[23] Chen LY, Tsai HH, Peng L et al. cGAMP-Loaded M2e Nanovaccine Elicits Cross-Reactive Immunity and Mitigates H6N1 Avian Influenza Infection in Chickens. Int J Nanomedicine. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42325400/

[24] Wei D, Pan Y, Zhang X et al. A bivalent mRNA-LNP vaccine confers broad-spectrum protection against both homologous and heterologous H5/H7 highly pathogenic avian influenza viruses in SPF chickens. Vet Res. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42316313/

[25] Liu J, Yang Y, Ma Y et al. Engineered Bacillus subtilis to deliver dsRNA via extracellular vesicles against the H9N2 avian influenza virus. Trends Biotechnol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42315362/

[26] Ao Z, Vendramelli R, Buyu M et al. A VSV-vector vaccine simultaneously targeting H5N1 hemagglutinin and matrix protein 2 induces robust neutralizing and ADCC antibody responses and provides full protection against lethal H5N1 infection in a mouse model. J Virol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42300735/

[27] Wang M, Gao Y, Zhang Y et al. A novel oral vaccine strategy utilizing a plasmid with CAG promoter-driven alphavirus RdRp for Co-expression of NA epitope and adjuvant in attenuated Salmonella boosts immune responses against H9N2 in mice. Microb Pathog. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42297223/

[28] Xu S, Zhang Q, Xie X et al. A neutralizing nanobody targeting a conserved lateral patch on HA1 confers protection against multiple H7 avian influenza viruses. J Virol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42274212/

[29] Chen T, Huang Q, Chen X et al. Trimeric hemagglutinin vaccine provides chickens complete protection against lethal H5 subtype avian influenza virus from clade 2.3.4.4b. Emerg Microbes Infect. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42269026/

[30] Huang Q, Yang F, Wu S et al. Molecular cloning and antiviral function analysis of pigeon interferon lambda(piIFN-λ). Poult Sci. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42302606/

[31] Liu Z, Fan M, Zeng Y et al. Gga-miR-92-targeted TNFRSF1B inhibits the replication of influenza A virus by degrading TRAF3. J Virol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42283462/

[32] Ngiam JN, Koh MCY, Hayden FG. Antiviral Resistance in Influenza: Clinical and Public Health Implications. Influenza Other Respir Viruses. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42306964/

[33] Li Y, Xue Y, Quan Y et al. Direct interaction between avian pathogenic Escherichia coli and H9N2 avian influenza virus promotes bacterial adhesion during their infections. Microbiol Spectr. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42294695/

[34] Bonney P, Culhane M, Broadbent A et al. Evaluating how infectious bursal disease virus influences influenza A virus transmission in chickens. Can J Microbiol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42263279/ *** Disclaimer: This article is for educational and informational purposes only. It is not intended to substitute for professional veterinary advice, diagnosis, treatment, or regulatory guidance. Always consult a licensed veterinarian or qualified specialist regarding animal health, disease diagnosis, and therapeutic decisions.

[35] Gerodez A, Dos Santos M, Attia M et al. Toward Predicting Pandemic Potential: A Comparative Analysis of Virus-Host Interactions Between Diverse Influenza A Viruses and the Human Innate Immune System. Proteomics. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42319249/