Avian Influenza in 2025: Low Pathogenic Strains, Global Distribution, and Notifiable Disease Status

Introduction

Avian influenza (AI) is a viral disease of global significance in poultry and wild bird populations. The causative agent, influenza A virus, is classified within the family Orthomyxoviridae and possesses a segmented, single-stranded negative-sense RNA genome. The scientific name for the virus is Influenza A virus, with subtype designation based on the antigenic properties of the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). For avian hosts, 16 HA subtypes (H1 through H16) and 9 NA subtypes (N1 through N9) have been identified in wild aquatic birds, which serve as the primary natural reservoir [1].

The pathogenicity of avian influenza viruses in gallinaceous poultry, particularly chickens (Gallus gallus domesticus), is a critical determinant of disease classification and regulatory response. Viruses are categorized as either highly pathogenic avian influenza (HPAI) or low pathogenic avian influenza (LPAI). This distinction is based on the intravenous pathogenicity index (IVPI) in six-week-old specific-pathogen-free (SPF) chickens and on the presence of a multibasic cleavage site (MBCS) in the HA0 precursor protein. LPAI viruses possess a monobasic cleavage site that is cleaved only by trypsin-like proteases present in the respiratory and intestinal tracts, resulting in localized infection. In contrast, HPAI viruses contain a MBCS that is cleaved by ubiquitous furin-like proteases, enabling systemic replication and high mortality [2].

This article provides a detailed veterinary reference on LPAI in 2025, focusing on strain classification, global distribution, clinical impact on chickens, and the regulatory framework of notifiable disease status. The content is structured for veterinary virologists, molecular diagnosticians, and computational biologists engaged in poultry health surveillance.

Classification of Low Pathogenic Strains

Molecular Basis of Pathogenicity

The molecular determinant of pathogenicity in avian influenza viruses resides in the HA0 cleavage site. LPAI viruses are characterized by a monobasic cleavage site motif, typically consisting of a single arginine residue at the cleavage position (e.g., PQ--R or P--R). This motif is cleaved exclusively by host proteases such as trypsin-like serine proteases, which are expressed in the epithelial cells of the respiratory and intestinal mucosae. Consequently, LPAI replication is confined to these mucosal surfaces, producing mild or subclinical disease in immunocompetent birds.

The IVPI for LPAI viruses is less than 1.2, and typically below 0.5, in SPF chickens. In contrast, HPAI viruses exhibit an IVPI of 1.2 or greater and possess a MBCS containing multiple basic amino acids (e.g., R-X-R/K-R). The presence of the MBCS is the primary molecular marker used for rapid genotypic classification via sequencing of the HA gene.

Subtype Diversity

LPAI viruses encompass a broad range of HA and NA subtypes. The most frequently isolated LPAI subtypes in domestic poultry include H5, H7, and H9, although other subtypes such as H3, H4, H6, and H10 are also detected in wild birds and occasionally spill over into poultry. It is critical to note that LPAI viruses of the H5 and H7 subtypes have the potential to mutate into HPAI viruses following introduction into poultry populations. This mutation occurs through the acquisition of a MBCS, often via non-homologous recombination or polymerase slippage during replication. Therefore, all H5 and H7 LPAI detections are subject to immediate regulatory action and are classified as notifiable diseases by the World Organisation for Animal Health (WOAH).

Table 1: Comparison of LPAI and HPAI Characteristics

Global Distribution in 2025

Epidemiological Situation as of June 2025

The global distribution of LPAI in 2025 reflects ongoing circulation in wild bird reservoirs and recurrent spillover events into commercial poultry operations. Surveillance data from WOAH and national veterinary authorities indicate that LPAI viruses are endemic in wild waterfowl populations across all continents except Antarctica. The primary wild reservoirs are Anseriformes (ducks, geese, swans) and Charadriiformes (gulls, terns, shorebirds). These birds typically exhibit asymptomatic infection and shed virus via the fecal-oral route, contaminating aquatic environments.

In June 2025, several notable LPAI outbreaks were reported in poultry flocks across Europe, Asia, and North America. In Europe, LPAI H9N2 was detected in layer flocks in France and Poland, causing a transient drop in egg production without significant mortality. In Asia, LPAI H5N2 was identified in duck flocks in Vietnam and China, with subsequent culling to prevent mutation to HPAI. In North America, LPAI H7N3 was isolated from turkey flocks in the Midwestern United States, prompting quarantine and depopulation measures. These events underscore the continuous threat LPAI poses to commercial poultry.

Geographic Hotspots

The geographic distribution of LPAI is influenced by migratory bird flyways. The four major flyways are the African-Eurasian, the East Asian-Australasian, the Central Asian, and the Americas flyways. Regions with high densities of domestic poultry and overlapping wild bird habitats are at elevated risk. Key LPAI hotspots in 2025 include:

• East and Southeast Asia: High prevalence of LPAI H9N2 in China, Vietnam, and Indonesia. This subtype is endemic in many Asian poultry populations and is associated with mild respiratory disease and secondary bacterial infections.
• Europe: Recurrent incursions of LPAI H5 and H7 subtypes via migratory waterfowl. The Netherlands, Germany, and France have experienced multiple LPAI H7N7 and H5N2 events in free-range layer flocks.
• North America: LPAI H7 and H5 subtypes are detected annually in wild bird surveillance programs. Spillover into commercial turkeys and chickens occurs sporadically, particularly in the Mississippi and Pacific flyways.
• Africa: LPAI H5N2 and H9N2 are reported in Egypt, Nigeria, and South Africa. Surveillance capacity remains limited, leading to underreporting.

Table 2: Selected LPAI Subtypes and Geographic Distribution (2025)

Impact on Chickens: Mortality and Clinical Signs

Pathogenesis in Chickens

LPAI viruses replicate primarily in the epithelial cells of the upper respiratory tract and the intestinal crypts. In chickens, the virus targets ciliated epithelial cells in the trachea and nasal passages, as well as enterocytes in the intestinal mucosa. Replication is cytolytic, leading to loss of ciliary function, mucus accumulation, and focal necrosis. The host immune response, including interferon induction and inflammatory cytokine release, contributes to clinical signs.

Clinical Manifestations

The clinical presentation of LPAI in chickens is highly variable and depends on viral subtype, host age, immune status, and the presence of secondary pathogens. Common clinical signs include:

• Mild to moderate respiratory distress: sneezing, coughing, rales, and ocular discharge.
• Decreased feed and water intake.
• Drop in egg production, often by 10% to 30%, with eggs showing shell thinning, loss of pigment, and misshapen forms.
• Mild diarrhea.
• Sinusitis and facial edema in some cases.

Mortality in uncomplicated LPAI infections is typically low, ranging from 0% to 5%. However, mortality can increase substantially when LPAI is complicated by secondary bacterial infections, such as Escherichia coli (see Escherichia coli in Chickens and Poultry Products) or Avibacterium paragallinarum (see Infectious Coryza in Chickens and Quail). In such cases, mortality may reach 15% to 30%, particularly in broiler flocks with compromised respiratory barriers.

Differential Diagnosis

LPAI must be differentiated from other respiratory and egg-drop causing diseases in poultry. Key differentials include:

• Infectious bronchitis virus (IBV): causes similar respiratory signs and egg production drops but is distinguished by virus isolation and molecular typing.
• Newcastle disease virus (NDV): lentogenic strains cause mild respiratory signs; differentiation requires hemagglutination inhibition (HI) and real-time RT-PCR.
• Infectious coryza: caused by Avibacterium paragallinarum; presents with facial edema and sinusitis; bacterial culture and PCR are diagnostic.
• Mycoplasmosis: Mycoplasma gallisepticum causes chronic respiratory disease; serology and PCR are used for differentiation.
• Egg drop syndrome (EDS): caused by duck adenovirus A; characterized by egg shell abnormalities without respiratory signs.

For a detailed comparison with a bacterial respiratory pathogen, refer to Infectious Coryza in Poultry and Ducks: Etiology, Clinical Signs in Chickens, Differential Diagnosis from Avian Influenza, and Prevention Strategies.

Notifiable Disease Status

Regulatory Framework

Avian influenza is classified as a notifiable disease by WOAH under the Terrestrial Animal Health Code. The notifiable status applies to all HPAI viruses and to LPAI viruses of the H5 and H7 subtypes. This classification mandates immediate reporting of suspected or confirmed cases to national veterinary authorities and to WOAH. The rationale for notifying LPAI H5 and H7 detections is their potential to mutate into HPAI, posing a significant threat to poultry health and international trade.

In 2025, the regulatory landscape for LPAI remains consistent with WOAH guidelines. Member countries are required to implement surveillance programs for early detection of LPAI H5 and H7 in poultry. Detection triggers a series of control measures, including:

• Quarantine of the affected premises.
• Epidemiological investigation to trace contacts and identify the source.
• Depopulation of infected and contact flocks.
• Enhanced biosecurity and disinfection protocols.
• Movement restrictions on poultry and poultry products within a defined control zone.
• Surveillance of wild birds in the vicinity.

National Variations

Individual countries may extend notifiable status to additional LPAI subtypes based on local risk assessments. For example, some European Union member states classify LPAI H9N2 as notifiable due to its endemicity and economic impact. In the United States, the National Poultry Improvement Plan (NPIP) includes surveillance for LPAI H5 and H7, and detection results in a quarantine and depopulation policy. In contrast, LPAI subtypes other than H5 and H7 are generally not subject to mandatory reporting in many jurisdictions, although voluntary reporting is encouraged.

Implications for Poultry Producers

The notifiable disease status of LPAI H5 and H7 has profound implications for poultry producers. A confirmed outbreak can lead to the culling of entire flocks, trade restrictions, and significant economic losses. Producers must maintain rigorous biosecurity measures, including:

• Preventing contact between domestic poultry and wild birds.
• Implementing all-in/all-out production systems.
• Using dedicated footwear and clothing for personnel.
• Regular cleaning and disinfection of facilities and equipment.
• Monitoring flock health and submitting samples for diagnostic testing when clinical signs are observed.

Diagnostic Approaches

Laboratory Diagnosis

Definitive diagnosis of LPAI requires laboratory confirmation. The gold standard methods include virus isolation in embryonated chicken eggs followed by hemagglutination inhibition (HI) and neuraminidase inhibition (NI) assays for subtype identification. However, molecular diagnostics have largely replaced virus isolation for routine surveillance due to their speed and sensitivity.

Real-time reverse transcription polymerase chain reaction (rRT-PCR) targeting the matrix (M) gene is the primary screening tool. Positive samples are further subtyped using HA and NA gene-specific rRT-PCR assays. Sequencing of the HA cleavage site is performed to differentiate LPAI from HPAI. For a discussion of molecular diagnostic platforms, see Point-of-Care Molecular Diagnostics for Feline Upper Respiratory Pathogens: FHV-1, FCV, and Bordetella.

Serological detection of antibodies against the nucleoprotein (NP) or matrix protein can be performed using commercial ELISA kits. However, serology cannot differentiate between LPAI and HPAI and is primarily used for surveillance in unvaccinated populations.

Mermaid Diagram: LPAI Diagnostic Workflow

flowchart TD
    A[Clinical suspicion: respiratory signs, egg drop], > B[Sample collection: tracheal swabs, cloacal swabs, or tissues]
    B, > C[RNA extraction and rRT-PCR for M gene]
    C, > D{M gene positive?}
    D, Yes, > E[HA and NA subtyping rRT-PCR]
    D, No, > F[Report as negative for AI]
    E, > G{HA subtype H5 or H7?}
    G, Yes, > H[Sequence HA cleavage site]
    G, No, > I[Report as LPAI non-H5/H7; no regulatory action]
    H, > J{Multibasic cleavage site present?}
    J, Yes, > K[Classify as HPAI; notify WOAH]
    J, No, > L[Classify as LPAI H5/H7; notify WOAH]
    L, > M[Implement quarantine, depopulation, and surveillance]
    K, > M

Latest Epidemiological Situation

June 2025 Update

As of June 2025, the global LPAI situation is characterized by sustained circulation in wild birds and sporadic outbreaks in poultry. The most significant developments include:

• Europe: An LPAI H7N7 outbreak in free-range layer flocks in the Netherlands resulted in the culling of approximately 200,000 birds. The source was traced to wild waterfowl using a nearby wetland.
• Asia: LPAI H9N2 continues to be endemic in China and Vietnam. A novel reassortant H9N2 virus with internal genes derived from H5N1 was detected in live poultry markets in southern China, raising concerns about increased virulence.
• North America: LPAI H5N2 was detected in a turkey flock in Minnesota. The virus was genetically similar to strains circulating in wild ducks along the Mississippi flyway. No evidence of mutation to HPAI was found.
• Africa: LPAI H5N2 was reported in commercial chickens in Egypt. The outbreak was controlled through stamping out and movement restrictions.

Surveillance Challenges

Surveillance for LPAI faces several challenges in 2025. These include limited diagnostic capacity in low-resource settings, underreporting due to the mild clinical signs of LPAI, and the difficulty of monitoring wild bird populations over large geographic areas. Advances in environmental sampling, such as testing of water and fecal samples from wetlands, are being integrated into surveillance programs to improve early detection.

Conclusion

Low pathogenic avian influenza remains a persistent threat to global poultry health in 2025. The molecular distinction between LPAI and HPAI, based on the HA cleavage site, is fundamental to disease classification and regulatory response. LPAI viruses of the H5 and H7 subtypes are notifiable due to their potential to mutate into HPAI, and their detection triggers stringent control measures. The global distribution of LPAI is driven by wild bird migration, with hotspots in Asia, Europe, and North America. Clinical impact in chickens is typically mild but can be exacerbated by secondary infections. Continued surveillance, rapid molecular diagnostics, and robust biosecurity are essential for managing LPAI and preventing the emergence of HPAI.

References

[1] Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M., & Kawaoka, Y. (1992). Evolution and ecology of influenza A viruses. Microbiological Reviews, 56(1), 152-179.

[2] Swayne, D. E., & Suarez, D. L. (2000). Highly pathogenic avian influenza. Revue Scientifique et Technique (International Office of Epizootics), 19(2), 463-482.