Endemic avian influenza landscape in Asia: sustained zoonotic risks

Abstract

Avian influenza remains a persistent global health threat, with Asia at its epicentre due to dense poultry production, live bird markets, and cross-species interfaces with ducks and swine. Several pathogenic subtypes continue to cause recurrent zoonotic spillovers with varying human case fatality, reinforcing the region’s role as a pandemic hotspot. Surveillance highlights the main key ecological drivers: sustained viral circulation in live bird markets, subclinical infection in domestic ducks, wild birds serving as reservoirs, and multiple species with dual receptors that can act as mixing vessels enabling reassortment. Recent events in the United States, where H5N1 has emerged in dairy cattle with viral RNA detectable in retail milk and human cases arising from both poultry and dairy cattle exposures, further demonstrate the capacity of these viruses to invade new mammalian hosts and the food chain. Advances in poultry vaccination and next-generation antivirals show promise but are constrained by antigenic drift, incomplete protection, logistical barriers, and uneven uptake. Human preparedness remains weakened by diagnostic delays, limited access to therapeutics, and fragmented surveillance. Mitigation requires regionally tailored, One Health–driven strategies, market regulation, duck vaccination, swine surveillance, and rapid therapeutic deployment, together with equitable access to tools and transparent international collaboration to reduce zoonotic risk and strengthen global pandemic readiness. This review synthesizes recent evidence on avian influenza virus infections in Asia, outlining zoonotic risks, key drivers, and mitigation strategies, and concludes that the sustained circulation of these viruses in poultry and wild birds continues to present significant challenges for animal health, public health, and pandemic preparedness, highlighting the importance of strengthened One Health surveillance and control measures.

Introduction

Influenza A viruses remain one of the most persistent and unpredictable threats to global health due to their ability to infect multiple species, undergo antigenic shift, and generate novel subtypes from animal reservoirs [1]. Among them, avian influenza viruses (AIVs) are of particular concern, having caused repeated zoonotic spillovers in Asia and retaining the potential to evolve into pandemic-capable subtypes [2]. Since the first recognised H5N1 outbreak in Hong Kong in 1997, originating from the lineage of a previous isolate of A/goose/Guangdong/1/1996 (H5N1), avian influenza has become entrenched in Asian poultry systems, with recurrent human infections and high case fatality rates [3, 4]. The subsequent emergence of H7N9 and ongoing reports of H5N1, H9N2, and other H5Nx subtypes underscore the region’s role as a hotspot of sustained zoonotic transmission [5]. The risk of AIV spilling over increases in settings where animals and humans interact closely [1]. High-density animal farms, live animal trade, and varying levels of biosecurity contribute to the continued circulation [1]. At the same time, diagnostic and response capacities are often constrained. These factors highlight the importance of a One Health perspective that considers animal, human, and environmental health in the regional context, with particular emphasis on improving the sharing of surveillance findings and outbreak information across sectors and regions, providing the rationale for this narrative review [1, 6]. This review, therefore, covers the current epidemiology of avian influenza in Asia, highlights the ecological and systemic drivers of persistence, and discusses mitigation strategies needed to strengthen regional and global pandemic preparedness. For this review, we focused on literature published in the last five years (January 2020–July 2025) to capture recent trends and developments in avian influenza across Asia, in contrast with the recent North American outbreak.

Search strategy and selection criteria

For this narrative review, we searched PubMed/MEDLINE, Embase, and Web of Science for literature published between January 2020 and July 2025. Search terms combined MeSH and free-text keywords, including avian influenza, bird flu, H5N1, H7N9, H9N2, H5N6, poultry value chains, poultry vaccination, poultry market, live-bird market, together with “Asia” and the names of individual Asian countries. No language restrictions were applied, and relevant non-English publications were included. Grey literature and surveillance reports were reviewed from the World Health Organization (WHO), the Food and Agriculture Organization (FAO), and the World Organization for Animal Health (WOAH), along with regional public health bulletins. Reference lists of retrieved articles, books, and outbreak reports were also screened to identify additional studies. Relevant papers cited in these sources that were published before 2020 were included when they provided important historical or contextual information. Studies were included if they reported epidemiology, ecology, clinical features, or interventions related to avian influenza in Asia.

Virology of avian influenza

Of the four influenza virus types (A–D), only influenza A viruses have the potential to cause global pandemics, because they can infect multiple species, undergo antigenic shift, and emerge as novel strains from animal reservoirs, a combination not seen in influenza B, C, or D viruses [1]. Influenza A is further classified based on the surface glycoproteins, hemagglutinin (H1–H16), and neuraminidase (N1–N9) [1]. Among influenza A viruses, AIVs represent a major zoonotic concern, with spillovers from birds to humans and the capacity to evolve into strains with pandemic potential. The host range of influenza A viruses is primarily governed by receptor binding specificity, tissue tropism, and temperature preferences for viral replication [2]. In birds, AIVs mainly replicate in the gastrointestinal tract and bind to α2,3-linked sialic acid (avian-type) receptors [7]. Because α2,3 receptors are predominantly located in the lower respiratory tract of humans, AIVs must reach these deeper tissues to initiate infection, thereby limiting efficient infection and transmission [7]. Temperature is another barrier: human-adapted strains replicate optimally at ~ 33 °C, typical of the upper airway of humans, while AIVs prefer > 37 °C, aligning with the avian gut environment [2]. For example, pigs, minks, and particular poultry species can play a role in facilitating zoonotic emergence by supporting the adaptation of AIVs and enabling genetic reassortment with human influenza strains.

Avian influenza viruses are named according to a standardized system that captures their origin and genetic identity [8]. The conventional format is A/host species/geographic location/strain number/year (HA and NA subtype). For example, the prototype virus of the goose/Guangdong (gs/GD) lineage is written as A/goose/Guangdong/1/1996 (H5N1) [8]. To account for rapid evolution, especially within high pathogenicity H5 viruses, a clade-based classification system has been established based on the phylogeny of the hemagglutinin gene [8]. Each clade is defined by shared genetic characteristics and significant branch support, and clades can be subdivided into subclades when sufficient genetic divergence arises (e.g., clade 2.3.4.4). This approach enables tracking of virus diversification across time and geography. The gs/GD-like H5 lineage has exhibited remarkable genetic plasticity, reassorting with almost every neuraminidase subtype except N7 and N9 [8]. As a result, viruses such as H5N1, H5N2, H5N3, H5N5, H5N6, and H5N8 all fall under the gs/GD umbrella. Experts emphasize that while these viruses are often discussed as distinct subtypes, they are best understood as different genotypic outcomes of the same gs/GD lineage, highlighting the importance of lineage- and clade-based classification rather than subtype designation alone [8].

Historical context of avian influenza

The deadliest human pandemic in modern history, the 1918 influenza pandemic, serves as a stark reminder of the threat posed by avian influenza [9]. This devastating outbreak, which caused an estimated 50 million deaths worldwide, is believed to have originated from an avian-like virus that adapted to infect humans [9]. Although its precise evolutionary path from what was likely an unknown animal reservoir remains a puzzle, the 1918 pandemic underscores the critical importance of studying avian viruses and their potential to cross the species barrier [9].

The two main AIVs of concern in Asia are H5N1 and H7N9, though sporadic human infections with other subtypes have also been documented [5].

The first recognised human case of H5N1 occurred during a poultry outbreak in Hong Kong in 1997, caused by an Eurasian-lineage virus and resulting in 18 human infections, including six deaths [4]. Human cases surged between 2004 and 2007 with major outbreaks in Vietnam, Indonesia, and smaller clusters in Thailand, Turkey, Iraq, and China (Fig. 1). After 2008, Vietnam and Thailand saw declines, but Indonesia and Cambodia sustained transmission, with Cambodia experiencing a sharp spike in 2013 (Fig. 1) [10]. From 2015 to 2021, human cases dropped to sporadic single digits, marking a “quiet” period, yet since 2022, there has been a resurgence, particularly in Cambodia, alongside new human cases in Bangladesh and India [10]. Regarding poultry, H5N1 has become endemic across large parts of Asia. It must be noted that there is no evidence of sustained human-to-human transmission of H5N1 yet.

Fig. 1.

Avian Influenza confirmed human cases in Asia between 1997 and 2025 (as of 8.^th August 2025, reported by CDC, USA)

H7N9 was first identified in China in 2013 and caused over 1500 confirmed human infections between 2013 and 2019, initially in urban settings but later spreading into rural and peri-urban regions [4]. H7N9 was initially detected as a low-pathogenicity avian influenza virus in poultry as defined by the chicken challenge model, but later variants acquired molecular changes that rendered them with high pathogenicity, with major implications for both poultry outbreaks and human health. Although the incidence of H7N9 dropped sharply after 2017 due to aggressive poultry vaccination and market control measures, H5N1 continues to pose a significant threat [5].

Recent evidence and region-specific insights in Asia

In the past five years, studies across Asia have advanced understanding of avian influenza ecology and transmission (Table 1). Surveillance in poultry farms, live bird markets, and wild birds reveals ongoing contamination, outbreaks, and reassorted strains [11–18]. While poultry vaccination shows promise, uneven uptake and persistent gaps in biosecurity and reporting sustain zoonotic risk [19–21]. Recent evidence from selected Asian subregions is discussed in the following sections.

Table 1.

Summary of recent key studies on avian influenza virus in Asian regions

Author (Year, Ref)	Country	Type of study	Important findings
East Asia
Wang 2025 [16]	China	Environmental surveillance	Poultry slaughterhouses had the highest AIV positivity (41.83%)
Bo 2025 [22]	China	Environmental surveillance (live poultry markets)	High H9 subtype positivity was detected, especially in chopping boards, cages, and drinking water
Yin 2025 [21]	China (Xinjiang)	Environmental surveillance	Spatiotemporal analysis showed persistent AIV in markets
Xu 2025 [13]	China (Shanghai)	Wildlife virology	Novel reassortant H5N1 in black swans. • Likely reassortment of wild bird & poultry strains
Ding 2021 [14]	China (South)	Cross-species surveillance	10.3% pig farms are exposed to H9N2 (based on serological tests) 9.2% co-infected with the swine influenza virus
Li 2025 [10]	China	Experimental virology	H3 subtype AIV shows cross-species infection (canines, equines, cats, seals)
Wang 2025 [23]	China	Review/Policy	The new live-attenuated recombinant duck enteritis virus vaccine has been approved Protects against H5N1, H5N6, H5N8
Guan 2024 [19]	China	Case report (human infections)	Baloxavir reduced viral load in 5 severe H5N6 cases Improved cytokine profile 2/5 patients survived despite critical illness
Jiang 2025 [18]	China	Cross-sectional survey	Low awareness of avian flu symptoms (30.77%) and migratory birds’ role (40.27%) Knowledge influenced prevention; few used PPE (masks: 3.62%, gloves: 4.52%)
Taniguchi 2022 [20]	Japan	Experimental antivirals	Baloxavir is effective vs. H5N1, H5N6, and H5N8 Better than oseltamivir in mice Combo therapy improved delayed outcomes
Esaki 2025 [26]	Japan	Field outbreak investigation	> 1,500 endangered cranes died (H5N1) Airborne transmission suggested
Isoda 2025 [25]	Japan (Hokkaido)	Wildlife epidemiology	H5N1 circulated widely in crows (2022–24). • Multiple introductions; crows as urban reservoirs
Jeong 2023 [27]	South Korea	Virological case study	Novel reassortant H5N6 detected in mandarin duck
South Asia
Setu 2025 [35]	Bangladesh	Retrospective study	Lack of chick grading knowledge increased avian flu risk
Rahaman 2025 [33]	Bangladesh	Country Preparedness Evaluation	Weak surveillance (missed poultry farms, high-risk workers) No BSL-3 labs, unsafe practices Slow reporting due to reliance on media
Barman 2025 [15]	Bangladesh	Surveillance (2022–23)	Persistent circulation of H9N2 & H5N1 Environmental contamination key
Chanda 2025 [36]	India	Field epidemiology	Unique duck-paddy rotation farming spreads H5N1 outbreaks
Saleem 2025 [34]	Pakistan	Cross-sectional survey	Poor farm hygiene (infrequent cleaning, overcrowding) is linked to outbreaks Educated farmers had fewer outbreaks and better antibiotic use
South-East Asia
Dharmayanti 2025 [46]	Indonesia (East Java)	Genomic surveillance	11% of market environmental samples are positive H9N2 was detected on the knife, cutting board, and napkin
Other Asian regions
Kasianov 2025 [11]	Russia (Siberia)	Migratory bird surveillance	74 AIVs isolated (H3N6, H5N3, H7N7). • Mutations associated with mammalian adaptation
Wannigama 2025 [12]	Global South	Environmental guano surveillance	1.33% positive AIV in remote flyway sites
Karamendin 2025 [29]	Kazakhstan (Caspian)	Field outbreak investigation	Mass mortality in swans linked to H5N1
Sheikh 2025 [17]	Iraq	Molecular surveillance	H5N1 in seagulls; genetically similar to Kazakh strains

AIV Avian Influenza Virus, PPE Personal Protective Equipment, BSL-3 Biosafety Level 3

East Asia

In China, multiple avian influenza subtypes have been reported in humans over the past two decades, showing varying epidemiological patterns and severity. Beyond H5Nx human cases over the years, H7N9 caused the largest human outbreak historically (1,568 cases, 39.3% CFR), but has not been reported since 2019 [5]. H9N2 remains the most persistent, with generally mild human illness (135 cases, ~ 1.5% CFR, latest in June 2025) [5]. In recent years, other subtypes such as H3N8, H10N3, H10N5, and H7N4 have caused rare, mostly non-fatal human infections, highlighting this region’s role as a hotspot for diverse avian influenza spillovers [5]. Environmental surveillance in China has consistently shown high levels of AIV contamination in poultry slaughterhouses and live bird markets, with H9 subtypes frequently detected in chopping boards, cages, and drinking water [17, 22, 23]. Spatiotemporal studies demonstrate persistent AIV circulation in market environments [22]. At the policy level, poultry vaccination strategies have evolved, with new recombinant platforms showing high efficacy, including a live-attenuated recombinant duck enteritis virus vaccine now approved to protect against multiple H5 subtypes [24, 25]. Across the subregion, the dynamics of AIVs continue to reflect opportunities for reassortment and zoonotic spillover [11, 23].

Outbreaks in Japan and Korea highlight the consequences of high pathogenicity avian influenza in wild and endangered species [14, 26]. In Japan, more than 1500 endangered cranes died during a large-scale H5N1 event [27], while long-term surveillance in Hokkaido demonstrated widespread and repeated H5N1 introductions among crows [26]. In South Korea, surveillance of migratory waterfowl identified novel reassorted H5N6 viruses in mandarin ducks [28], pointing to the ongoing viral evolution at the wildlife–poultry interface.

Southeast Asia

Cambodia remains notable for both H5N1, which continues to cause severe outbreaks with high mortality, and H9N2, which produces sporadic mild human cases [5]. In September 2024, the WHO reported a fatal H5N1 infection in a 15 year-old girl in Cambodia [5]. A novel reassorted virus caused the infection. There were ten human cases in the country that year, most of them in children [29]. Most recently, between 20 and 26 June 2025, three new human H5N1 infections were reported from Cambodia, confirming that spillover events continue in 2025. Indonesia and Vietnam have historically reported numerous H5N1 infections with high human case fatality, while Vietnam has also documented occasional H9N2 cases [5]. Most recently, in 2025, Vietnam reported a human case of encephalitis due to H5N1 [10]. In the Lao PDR, H5N1 has been detected less frequently but with severe outcomes similar to those in neighbouring countries. Sporadic human infections, including paediatric cases, continue to be reported in parts of the subregion, highlighting the household-level risk associated with live poultry exposure.

In Southeast Asia, live bird markets remain critical amplification points. Genomic surveillance in East Java, Indonesia, confirmed contamination with H9N2 across multiple environmental samples, including knives, cutting boards, and napkins used during poultry processing [30]. The porous nature of cross-border poultry trade among Cambodia, Vietnam, Laos, and Thailand further complicates containment, allowing viruses to spread rapidly across national boundaries.

South Asia

South Asia demonstrates how farming practices and biosecurity shape viral ecology. Poultry outbreaks of AIV across India have been regularly reported since 2006 [31]. The first Indian human avian influenza case (H9N2) was reported from the Maharashtra region in 2019 [31]. Human H9N2 was reported again from India in 2024 [32]. Since the first report of human H5N1 in India in 2022, two H5N1 deaths have been reported in 2025 [31, 32]. In Bangladesh, surveillance between 2022 and 2023 confirmed persistent circulation of H9N2 and H5N1 in poultry, with environmental contamination central to ongoing transmission [16]. As of 31st May 2025, 11 human cases of H5N1 have been reported from Bangladesh, with the most recent case in May 2025 [10]. Preparedness evaluations have identified weak surveillance systems, limited laboratory capacity, and delays in outbreak reporting [33], while farmer-level surveys highlight poor hygiene, overcrowding, and low awareness of preventive measures [34, 35]. In India, particularly in Kerala, duck–paddy nomadic rearing systems have been shown to drive recurrent H5N1 poultry outbreaks, underscoring the role of agro-ecological practices in sustaining transmission [36]. Backyard poultry with minimal biosecurity remains a common risk factor, while new viral genotypes continue to emerge in the region, reflecting ongoing viral evolution [36].

These subregional insights highlight the heterogeneous but interconnected drivers of avian influenza across Asia. This geographic diversity highlights the urgent need for regionally tailored, yet globally coordinated, One Health strategies to strengthen preparedness and response.

Asian situation vs the U.S 2024 outbreak

Placing Asia’s experience in a global frame highlights how context shapes both epidemiology and perceived risk. The U.S. 2024 outbreak offers a useful counterpoint, showing how differences in exposure, viral genetics, surveillance, and healthcare access can produce markedly different clinical patterns [37, 38] (Table 2). In Asia, close contact with sick poultry in live-bird markets or backyard farms can result in respiratory exposure, driving severe pneumonia and human case fatality rates above 60%. By contrast, the U.S. dairy farm epizootic represents the first large-scale incursion of H5N1 into mammalian livestock, with implications for food safety and One Health preparedness [37, 38]. Viral RNA has been detected in retail milk and dairy products, and raw milk contained sufficient infectious virus to kill domestic cats that ingested it, underscoring the extent to which the food chain was invaded on a broad front [39]. These findings highlight a systemic agricultural and food system challenge. Human infections in the U.S. have so far been mostly mild and conjunctivitis-predominant, with only one fatality [37, 38]. Between March 2024 and June 2025, the U.S. reported around 70 human cases, with 41 linked to dairy cows, 24 to poultry, and several with unknown or other animal [39]. It should also be noted that the circulating U.S. clade 2.3.4.4b genotypes (notably B3.13 and D1.1) appear to have lower zoonotic potential than the gs/GD H5N1 strains that drove severe outbreaks in Asia [37–39]. These developments highlight the importance of extending surveillance in Asia beyond poultry to include cattle, pigs, and other potential mammalian hosts. Equally critical are improvements in genomic data sharing, event-based surveillance, livestock biosecurity, and transparent communication about potential food and feed safety risks. Reinforcing surveillance, pre-positioning vaccines and antivirals, and operationalizing a robust One Health response are essential steps to mitigate what could otherwise become a slowly evolving pandemic threat.

Table 2.

Contrasting human H5N1 manifestations: Asia vs. USA (2024–2025)

Theme	Asia	USA
Exposure [37, 38, 66]	Exposure mainly in live-bird markets and backyard poultry	Exposure mainly through occupational contact with dairy cattle, raw milk, or fomites. Infections through poultry as well
Clinical manifestations [37, 38, 66]	Severe lower-respiratory disease and pneumonia are common	Conjunctivitis-predominant illness Few cases progressed to respiratory disease
Mortality [37, 38, 66]	Linked to high mortality (≈66% in confirmed cases)	Infections so far have been mostly mild, with conjunctival disease. One fatal case reported in 2025
Host factors & care pathways [37, 38, 66]	Severe cases are usually identified in hospitalised patients Delays in seeking care and limited antiviral availability worsened outcomes High-risk exposures among working-age poultry workers	Rapid occupational screening of exposed dairy workers Early testing and access to antivirals/supportive care The majority were detected at the mild stage, reducing the apparent severity
Ascertainment & surveillance bias [37, 38, 66]	Surveillance skewed toward hospitalised/severe cases Mild infections are likely under-recognised, inflating the case-fatality rate	Proactive monitoring of dairy workers captured mild/conjunctival infections Few hospitalisations were reported, lowering the observed severity
Zoonotic/ecological context [37, 38, 66]	Dense poultry systems and live-bird markets sustain viral amplification and reassortment Wild birds act as reservoirs enabling repeated spillover	Emergence in a novel maintenance host (dairy cattle) Large mammalian herds provide new evolutionary space

AIV Avian Influenza Virus, URTI Upper Respiratory Tract Infection, ≈ Approximately

Role of poultry farm practices and live bird vaccination in avian influenza

Human infections with AIVs arise from direct or indirect contact with infected birds or mammals, their secretions, or contaminated environments, particularly in high-risk settings such as poultry farms (Table 3) [17, 40, 41]. Poultry production is broadly divided into commercial and backyard systems, each with distinct biosecurity gaps [42]. The coexistence of these systems facilitates cross-contamination, while international poultry trade and particularly migratory wild birds contribute to long-distance spread [4]. Commercial farms, including layer and broiler operations, face structural vulnerabilities such as open conveyor systems for eggs and manure, prolonged production cycles in layer units (1.5–2 years), absence of chick grading, and inappropriate antibiotic use that can mask early disease signs [35, 42, 43]. Prolonged production cycles, in particular, extend the window of exposure to circulating viruses and lengthen bird–bird contact duration, thereby heightening the overall risk of infection. Backyard systems, common in rural areas, often lack formal biosecurity, allow free-roaming flocks within household premises, and promote close human–poultry contact, enabling viral transmission [24, 43–45]. Domestic ducks act as asymptomatic reservoirs in these settings, shedding virus for extended periods, contributing to low vaccination coverage, and sustaining the risk of zoonotic transmission [24, 46].

Table 3.

Risk factors and mitigation strategies for avian influenza in poultry

Poultry setting (References)	Key risk factors / biosecurity challenges	Potential solutions
Commercial farms [35, 41, 42]	Layer farms with open conveyor systems for eggs/manure Longer production cycle (1.5–2 years), increasing exposure Poor husbandry (no chick grading) Inappropriate antibiotic use	Improve structural biosecurity (closed systems) Shorten the production cycle or implement staged restocking Implement chick grading Regulate antibiotic use
Backyard farms [23, 42–44]	Lack of formal biosecurity Free-roaming flocks in homes Ducks as reservoirs with prolonged shedding Low vaccination compliance	Community education on hygiene Separation of poultry from living areas Targeted duck vaccination Regular flock health monitoring
Commercial–backyard interface [41]	Cross-contamination risk at farm interface	Implement controlled movement between systems Biosecure fencing and buffer zones
External drivers [4]	International poultry trade Migratory wild birds	Strengthen import screening Surveillance in wild bird populations Targeted vaccination in high-risk zones

AIV Avian Influenza Virus

Targeted interventions, such as upgrading to closed, biosecure housing in commercial farms; implementing community-based biosecurity training in backyard systems; separating poultry from living spaces; controlling movement between farm types; enhancing surveillance of wild birds; and promoting prudent antimicrobial use, can strengthen flock immunity, reduce viral transmission, and align with broader goals of sustainable poultry farming and antimicrobial resistance containment. Vaccination remains a central tool for reducing the impact of avian influenza in poultry, but several challenges constrain its effectiveness (Table 4). Viral evolution and antigenic drift can alter surface proteins, leading to a mismatch between circulating field strains and vaccine strains, thereby reducing protection [24, 25]. This is particularly evident in China, where domestic ducks act as long-lived reservoirs and may harbour strains such as H5N6 that differ substantially from those targeted by vaccines used in chickens. Even when matched, vaccines may not entirely prevent viral replication and shedding, allowing silent transmission within and between flocks, including movement into live bird markets [25]. Addressing these gaps requires practical policy levers: more frequent updating of vaccine strains, use of heterologous prime–boost strategies to broaden coverage, and improving cost-sharing and cold-chain delivery in rural Asia to expand access [25]. Equally critical are policies that formalize intersectoral and interdisciplinary collaborations within a One Health framework, ensuring that vaccination efforts are aligned across human health, animal health, and environmental health systems. Crucially, vaccination should be deployed where necessary or helpful but is insufficient on its own; it must operate in tandem with live bird market regulation, duck production management, strict biosecurity, active surveillance, and rapid culling, all within a coordinated One Health framework for sustainable avian influenza control [25].

Table 4.

Challenges and potential solutions for avian influenza vaccination in poultry

Challenge (references)	Key issues	Potential solutions
Viral evolution & antigenic drift [23]	Small genetic mutations alter viral surface proteins Reducing vaccine match and effectiveness Persistent circulation in ducks despite chicken vaccination	Regular antigenic monitoring; timely vaccine strain updates Development of universal vaccines targeting conserved epitopes
Strain mismatch	Field strains (e.g., H5N6 in ducks) differ significantly from vaccine strains in use	Region-specific vaccine design; adoption of broadly protective recombinant vaccines
Incomplete protection [24]	Vaccines prevent severe disease but may not stop replication/shedding, allowing silent transmission	Use of high-efficacy vaccines (e.g., live recombinant) Post-vaccination monitoring to detect subclinical infections
Logistical barriers [24]	Geographic remoteness Cold chain maintenance Large flock coverage challenges	Mobile vaccination units Thermostable vaccine formulations Coordinated regional campaigns
Economic constraints [24]	High costs for vaccines and labour	Subsidised vaccination programs Cost-sharing schemes Integration into government animal health services

AIV Avian Influenza Virus

Beyond individual farm-level practices, the broader poultry value chain plays a pivotal role in the persistence and spread of avian influenza. Value chains connect hatcheries, farms, traders, transporters, slaughter points, and retail markets, creating multiple nodes where viral transmission can occur. Studies demonstrate that poultry trading networks function as major conduits for avian influenza spread, with risks compounding as birds move between farms and markets [47]. The viral prevalence is amplified along marketing chains, with infections arising during transport and trade before birds even reach live bird markets [48]. The entanglement of actors, birds, and trading practices creates structural hotspots for disease emergence and complicates traceability [47, 49]. Together, these studies underscore that effective control requires interventions across the entire chain, targeting transport, trader networks, and slaughter nodes. Among the various nodes within these poultry value chains, live bird markets represent particularly critical points of amplification.

Live bird markets act as persistent transmission hubs for avian influenza, driven by the dense co-mingling of diverse bird species and constant introduction of naïve hosts that facilitate viral amplification (Table 5) [17, 44]. It is essential to distinguish live-bird markets from broader wet markets, as the former uniquely concentrate risk through on-site slaughter and intermingling of poultry species. Environmental contamination is a major contributor, with high detection of AIVs on chopping boards, cages, drinking water, knives and napkins [16, 23, 50]. These settings repeatedly enable zoonotic spillover events, exemplified by the emergence of strains with human-type receptor affinity and a fatal H5N6 infection linked to a live poultry market in China [51]. Despite temporary closures during outbreaks, weak regulatory enforcement has allowed these markets to remain reservoirs and amplifiers of avian influenza [51–53]. Beyond outbreak-driven closures, experience shows that structural reforms within live-bird markets are critical for lasting impact [51–53]. In some countries, abrupt bans have unintentionally fueled informal poultry trade with weaker oversight, underscoring the limits of closure alone [54]. While permanent closure may be impractical due to consumer demand, evidence shows that closures can reduce human cases [4], highlighting the need for stricter regulation, improved sanitation, enhanced genomic surveillance, and context-specific vaccination strategies that address the variable efficacy of current vaccines across species and subtypes. Effective risk reduction in live bird markets requires a layered strategy tailored to local contexts. Temporary or staggered closures can interrupt transmission during outbreaks, while routine environmental sampling provides early signals of viral activity [55]. Consistent sanitation of high-contact surfaces, utensils, and water sources helps to reduce contamination pressure. Species segregation, off-site slaughter, and cold-chain distribution represent structural interventions that address the ecological drivers of avian influenza in live bird markets. Minimising interspecies viral exchange, removing high-risk practices from crowded urban centres, and replacing freshly slaughtered poultry with chilled products may reduce environmental contamination and zoonotic spillover risk while maintaining consumer access. Embedding genomic surveillance within these measures strengthens preparedness by allowing timely detection of novel strains and informing targeted vaccination policies.

Table 5.

Key risk factors, evidence, and potential interventions for avian influenza transmission in live bird markets

Theme (with References)	Findings	Proposed Solutions
Bird diversity and mingling [15, 16, 43]	Multiple bird species co-mingled in markets Live-bird markets act as transmission hubs Mixing of domestic ducks enables viral reassortment	Restrict multi-species trading Segregate high-risk species (e.g., ducks) Strengthen surveillance in mixed-species stalls
Environmental contamination [15, 46]	High H9 subtype positivity in chopping boards, cages, and water (China) H9N2 detected in knives, cutting boards, and napkins (East Java) Persistent H9N2 and H5N1 contamination in Bangladesh markets	Regular cleaning & disinfection Hygienic slaughtering practices Improved waste disposal systems
Human interaction [47]	Frequent close human contact with infected poultry and contaminated materials Novel strains with mutations for human-type receptor affinity identified in markets Dense mixing increases the risk of zoonotic spillover events	Enhance PPE use for workers Limit consumer exposure to slaughter areas Early outbreak detection and vaccination
Lack of regulation [47–49]	Markets act as persistent reservoirs due to weak enforcement Temporary closures reduce cases but lack long-term sustainability	Stronger market regulation Permanent hygiene standards Rapid outbreak containment protocols Consumer awareness campaigns

AIV Avian Influenza Virus, PPE Personal Protective Equipment

An effective decision framework for avian influenza control must be tailored to specific epidemiological contexts and production systems. Localized outbreaks in commercial farms are best managed through rapid stamping out measures with fair compensation to maintain farmer cooperation. In contrast, endemic circulation in duck-dense or backyard systems may require preventive or emergency vaccination strategies combined with movement restrictions. Historically, with the notable exception of China, most Southeast Asian countries have relied on targeted vaccination rather than mass campaigns [56]. Where transmission is closely linked to trade, zoning, and reforms in market practices become critical, while international spread underscores the importance of harmonized surveillance and transparent reporting. Integrating these measures, biosecurity, culling, vaccination, compensation, and market regulation, into a tiered response provides flexibility, reduces over-reliance on any single tool, and sustains both farmer compliance and public health protection.

Pigs as mixing vessels in Asia

Pigs occupy a central position in the ecology of influenza because they can act as mixing vessels, possessing receptors for both avian (SAα2,3Gal) and human (SAα2,6Gal) influenza viruses in their respiratory tract, which allows simultaneous infection and genetic reassortment [57, 58]. This receptor biology underpins documented avian-to-swine transmission events in Asia, including H5N1 infections reported in South China and Indonesia, where domestic pigs carried avian-derived viruses without overt disease [59, 60]. Experimental studies demonstrate that pigs are moderately susceptible to infection with diverse H5N1 genotypes, often resulting in subclinical or mild disease with limited transmission [61]. In the Asian context, where there is a rapid growth of poultry and pigs, and where pig–poultry mixed farming systems are common, limited susceptibility could facilitate silent virus circulation and genetic exchange (Table 6) [61]. The genetic landscape of swine influenza in the region is further complicated by frequent introductions of swine-adapted influenza A virus lineages through international trade, particularly from Europe and North America, creating a mosaic of co-circulating strains in Asian herds [60]. Importantly, pigs are not the only potential mixing vessels: turkeys, quail, and even humans also express dual receptor configurations, enabling reassortment events across species boundaries [62, 63]. These dynamics underscore a key surveillance implication: no single country can serve as a reliable proxy for swine influenza ecology in the region, reinforcing the need for minimum regional surveillance standards that capture the diversity of lineages across borders. Although vaccination campaigns in swine have been successful for other zoonoses such as Japanese Encephalitis, mass vaccination for influenza is unrealistic at scale, given the vast and dispersed pig populations, rapid viral evolution, and economic constraints [64]. Instead, control efforts should focus on targeted surveillance strategies: systematic sampling at pig–poultry–human interfaces, genomic monitoring to detect early reassortants, and integration of trade-route mapping to identify high-risk nodes [65]. Coupled with improved farm biosecurity and regional data sharing, such measures provide a more feasible pathway to mitigate the pandemic threat posed by swine reservoirs. Together with the ecological role of domestic ducks and the amplifying effect of live bird markets, the swine reservoir completes a triad of interconnected risks in Asia, highlighting that effective avian influenza control requires integrated policies that address cross-species dynamics rather than isolated interventions. Establishing sentinel surveillance sites in high-density pig production zones and cross-border trade hubs could be an early warning system to detect novel reassortants before they spread widely.

Table 6.

Role of pigs as mixing vessels in the ecology of avian influenza

Theme (with References)	Challenges	Proposed Solutions
Mixing vessel function [51, 52]	Pigs have receptors for both avian and human influenza viruses Co-infection allows reassortment and emergence of novel strains	Targeted surveillance for co-infections Rapid detection of reassortant viruses
Role in pandemics [51]	Reassortant viruses from pigs have contributed to past pandemics Ongoing zoonotic risk threatens global health security	Genomic monitoring of swine-origin viruses One Health-based early warning systems
Viral diversity and trade links [54]	Global swine trade drives circulation of diverse influenza strains No single region can act as a proxy for surveillance	International coordination of surveillance Data sharing across borders
Silent infections and spread [52, 53]	Many infections in pigs are asymptomatic, making detection difficult Movement and trade of pigs enable long-distance spread	Routine screening programs Biosecurity measures in farms and markets
Vaccination limitations [56]	Large pig populations make mass vaccination impractical Delays in emergency vaccination can allow viral adaptation	Strategic vaccination in high-risk zones Development of scalable, effective vaccines

Need for improved surveillance

Avian influenza surveillance in Asia continues to face significant challenges, with fragmented systems and poor integration between animal health, human health, and environmental health sectors limiting the capacity to detect early warning signals (Table 7) [26, 28, 36]. Current efforts remain heavily skewed toward poultry, while wild birds, mammals, and other important reservoirs receive far less attention [26]. Surveillance is frequently reactive and outbreak-driven, leading to substantial underestimation of the long-term ecological dynamics of AIVs. Socio-economic barriers, such as inadequate compensation schemes and farmers’ reluctance to report outbreaks, further compromise timely detection and response [26]. Although environmental sampling, including in live bird markets, farms, and wetlands, has proven valuable as an early-warning tool, it remains underutilised and inconsistently applied [66]. To build resilient surveillance systems, countries must strengthen One Health platforms, expand genomic surveillance across animal and human hosts, and institutionalise environmental monitoring as routine practice. Equally important are supportive policy measures, such as robust risk communication, transparent data sharing, and farmer-centred compensation frameworks, encourage reporting while reducing economic disincentives. Such comprehensive and sustainable surveillance strategies are critical to detect emerging avian influenza threats early, track viral evolution, and mitigate the risk of cross-species transmission and human spillover events.

Table 7.

Challenges and solutions for avian influenza surveillance in Asia

Theme (with references)	Challenges	Proposed solutions
Fragmented infrastructure & weak integration [25]	Underfunded surveillance systems Delayed data sharing Weak coordination between the animal, human, and environment sectors Limited molecular/genomic capacity	Strengthen One Health platforms Expand sequencing networks Mandate rapid cross-sectoral data sharing
Bias towards poultry, neglecting wild birds & mammals [25, 27, 36]	Over-reliance on poultry monitoring • Underestimation of wild bird/mammal roles Insufficient coverage along migratory flyways	Integrate wildlife and migratory bird sampling Establish flyway-based sentinel sites
Wildlife reservoirs & spillover events	Surveillance is often limited to outbreaks Urban reservoirs (e.g., crows) are under-recognised Lack of long-term ecological monitoring	Routine guano/environmental sampling Sentinel monitoring at migratory stopovers Targeted urban bird surveillance
Socio-economic barriers & underreporting [25]	Farmers are reluctant to report (fear of culling, poor compensation) Traditional farming (e.g., ducks in paddy fields) sustains viruses	Improve compensation schemes Develop risk communication strategies Promote safer farming practices
Expanding host range to mammals [25]	Rising detection in pets and marine mammals Veterinary surveillance gaps Risk of mammalian adaptation	Expand surveillance to companion/zoo/marine animals Link veterinary and human health data
Environmental surveillance as early-warning [57]	Underutilization of sewage and water sampling Lack of longitudinal monitoring	Institutionalise environmental sampling (water, faeces, sewage) Couple it with real-time genomic analysis

Alongside surveillance challenges, persistent gaps in data sharing undermine effective One Health responses. Existing systems are often fragmented across sectors, constrained by differing ethical, legal, and institutional requirements [67]. The absence of harmonized standards and interoperable platforms creates and maintains silos where human health data are privileged, while animal health data and environmental data remain underrepresented [67]. These asymmetries are reinforced by concerns over ownership, governance, and lack of demonstrable benefits to contributors, which can discourage the timely exchange of pathogen and surveillance information [67]. Also, although most One Health initiatives report multisectoral coordination, fewer embed systematic mechanisms for data, evidence, and knowledge sharing [68]. Monitoring, evaluation, and knowledge translation strategies are inconsistently applied, and in particular, the environmental sector is rarely integrated, leaving major blind spots in implementation [68]. Addressing these gaps requires transparent governance, interoperable data systems, and stronger cross-sectoral commitments to ensure surveillance outputs are equitably shared and translated into actionable insights [68].

Challenges in diagnosis, treatment, and prevention in humans

Early diagnosis of avian influenza in humans is challenging because symptoms are nonspecific, ranging from mild respiratory illness or conjunctivitis to severe pneumonia, often mimicking other infections (Table 8) [66]. This leads to delayed suspicion, especially without a clear exposure history. Although asymptomatic human infections are considered rare, seroprevalence studies suggest they may be underrecognized [69]. Confirmatory diagnosis requires polymerase chain reaction assay (PCR) on the respiratory specimens from exposed or suspected individuals [70], but in resource-limited areas, molecular testing and sequencing capacity remain inadequate, delaying outbreak recognition [64]. Strengthening surveillance, expanding diagnostic access, and training healthcare workers in early recognition, clinical management, and infection control are essential for reducing human risk.

Table 8.

Challenges in the early diagnosis of avian influenza in humans, highlighting clinical, diagnostic, and resource-related barriers along with proposed solutions

Theme (with references)	Challenges	Proposed solutions
Non-specific clinical features [57]	No distinct clinical manifestation Wide spectrum: asymptomatic, mild URTI, conjunctivitis, severe pneumonia Overlap with multiple differential diagnoses, making early suspicion difficult	Heightened clinical vigilance in endemic areas Use of exposure history as a key diagnostic clue
Underrecognized asymptomatic cases [58]	Asymptomatic/subclinical infections are considered rare but likely underestimated Limited seroprevalence studies in high-risk groups	Expanded sero-surveillance among exposed populations Regular screening of poultry workers and animal handlers
Laboratory diagnosis [59]	Requires PCR from respiratory specimens Case definition depends on recent high-risk exposure Reliance on specialised labs, not always available in peripheral settings	Strengthen point-of-care molecular diagnostics Expand laboratory networks for rapid confirmation
Resource limitations [56]	Delayed diagnostics in peripheral and resource-limited settings Limited access to molecular tools Low rates of genomic sequencing are hindering outbreak detection	Investment in decentralised diagnostic capacity Scale-up genomic sequencing infrastructure Training healthcare workers in outbreak recognition

Treatment of human avian influenza relies on early antiviral therapy with oseltamivir, peramivir, or zanamivir [71]. However, resistance, including to oseltamivir, and mammal-adaptive mutations have been reported in circulating strains [72]. Baloxavir, a cap-dependent endonuclease inhibitor, has shown potent activity against several avian subtypes (Table 9) [73]. Animal studies and limited human cases of severe H5N6 infection suggest baloxavir can rapidly reduce viral load, though delayed treatment lowers efficacy and may select resistance mutations [20, 21, 74]. Its role in humans may therefore be greatest in early disease or in patients unresponsive to neuraminidase inhibitors, but timely access and stockpiling remain challenges in Asia.

Table 9.

Summary of mechanism, timing, and therapeutic role of baloxavir

Heading (with references)	Summary
Mechanism [20, 62]	Cap-dependent endonuclease inhibitor Blocks viral mRNA transcription Broad activity against seasonal and avian strains
Timing [20, 63]	Works best with early use Reduced effect if delayed ≥ 48–72 h Late start → higher resistance
Place in therapy [19, 20, 63]	Use if oseltamivir fails/resistance is suspected Active in vitro/animal H5 & H7 models Few human cases, some survival benefit
Practicalities for Asia [19, 20, 63]	Limited approval & stockpiles Role in specialised centres Add to pandemic preparedness pathways

mRNA Messenger Ribonucleic Acid; H5/H7 Hemagglutinin subtypes 5 and 7 of influenza A virus

Developing vaccines against avian influenza in humans is hindered by high viral variability and the limitations of egg-based production, with additional challenges arising from antigenic mismatch between circulating strains and available vaccine candidates (Table 10) [75–77]. Strategies to improve human vaccine effectiveness include adjuvants, prime–boost regimens, and mucosal priming [78–80]. At the same time, rapid-response platforms such as mRNA, adenoviral vectors, and cell-culture systems aim to bypass current production bottlenecks [79, 81]. A robust human pandemic response will depend on these scientific advances alongside prepandemic stockpiling, accelerated regulatory pathways, and international standardisation of immune correlates [79]. Equitable access must also be prioritised: global stockpiles, dose-sharing agreements, and support for Asian manufacturing hubs will be crucial to ensuring timely vaccine availability during future pandemics.

Table 10.

Challenges and opportunities for human vaccination against avian influenza

Theme (with References)	Challenges	Mitigation Strategies
Viral diversity & immunity [65, 66]	High Antigenic Diversity Poor Immunogenicity	Prime-Boost Regimens Mucosal Priming for a broad immune response Advanced Formulations for longer-lasting immunity
Manufacturing & scalability [65, 70]	Production Hurdles with traditional egg-based methods Need for a high amount of antigen per dose	Adjuvants to boost the immune response Use modern, rapid-development technologies like mRNA and adenoviral vectors Switch to cell-culture or plant-based manufacturing to avoid relying on eggs
Regulatory & standardisation [64, 68]	Lack of Standardised Assays for uniform testing methods	Regional Standardization Create faster regulatory pathways for vaccine approval
Pandemic Preparedness [68]	Timely Deployment to stop a fast-spreading outbreak	Strategic Stockpiling

Lack of awareness and need for improvement in preparedness

Controlling avian influenza effectively hinges on a robust strategy that addresses the critical human and systemic factors impacting all key stakeholders. The challenge is multi-layered, beginning with the general public, where low risk perception and socioeconomic reliance on practices like live bird markets hamper control efforts (Table 11) [4, 71]. It extends to farmers and poultry workers, who exhibit significant knowledge gaps regarding biosecurity and disease transmission, coupled with alarmingly low use of personal protective equipment (PPE) [19, 34, 35]. Hospital-level readiness adds another layer of concern: in many Asian countries, clinical suspicion remains heavily tied to narrow case definitions, while administrative hurdles such as referral requirements or centralised approvals delay testing [71]. Even where tertiary hospitals can perform PCR and subtyping, turnaround times are often prolonged, and peripheral facilities lack access, resulting in delays in confirmation, isolation, and treatment. These vulnerabilities are compounded by weaknesses at the administrative level, with critical gaps in pandemic preparedness, inadequate BSL-3 capacity, and poor data integration between human and animal health sectors, leading to delayed and reactive responses, some of which appear to be triggered by media reports rather than systematic monitoring [33]. Interoperable surveillance systems at the human–livestock–environment (including wildlife) interfaces are urgently needed under a One Health approach to ensure timely and coordinated detection of emerging events. In addition to routine surveillance, event-based signals must be systematically captured and acted upon through international, national, subnational, and local One Health platforms that integrate data and coordinate prevention and response. Thailand provides a strong regional example, where integrated avian influenza surveillance links human, animal, and environmental health sectors, combines community-based event reporting with robust laboratory networks, and enables joint outbreak investigations across ministries [82]. A successful mitigation strategy must therefore be comprehensive and tailored to each group. It requires meaningful community engagement to co-develop culturally sensitive public health campaigns, targeted education for farmers on biosecurity and PPE, and specialised training for healthcare workers on zoonotic disease protocols. At both hospital and administrative levels, strengthening triage protocols, expanding decentralised diagnostic access, reducing bureaucratic barriers, and investing in laboratory capacity and integrated data systems are essential steps toward building a resilient, proactive, and unified defence against avian influenza.

Table 11.

Challenges and mitigation strategies for avian influenza awareness and preparedness

Theme	Challenges	Mitigation Strategies
The Public [4, 60]	Low awareness of avian influenza risks Reliance on live bird markets Limited acceptance of control measures	Culturally sensitive health campaigns Clear public guidance Community engagement to sustain safe practices
Farmers & Poultry Workers [18, 34, 35]	Poor knowledge of transmission and biosecurity Low PPE use Weak farm hygiene	Targeted training on biosecurity and PPE Promotion of best practices (e.g., sanitation, chick grading)
Health Care Workers (Human & Animal) [60]	High risk of exposure Limited training in zoonotic protocols Gaps in diagnostic support	Specialised training in zoonotic preparedness Assured PPE supply Stronger linkage between surveillance and clinical response
Hospitals	Case suspicion tied to narrow definitions Referral/approval barriers for testing Limited PCR/subtyping access and long turnaround	Clear triage protocols Decentralised molecular diagnostics Streamlined testing pathways
Administration & Government [33]	Weak preparedness planning Poor human–animal health data integration Inadequate BSL-3 capacity	Investment in labs and biosafety infrastructure Integrated data systems Context-specific risk communication

PPE Personal Protective Equipment; PCR Polymerase Chain Reaction; BSL-3 Biosafety Level 3

Summary of risks and feasibility challenges

Asia’s persistent and evolving threat of avian influenza arises from a convergence of ecological, socio-economic, and infrastructural factors (Table 12). High-risk poultry production systems, poor farm-level biosecurity, and the continued operation of live bird markets drive viral amplification and zoonotic spillover. Inadequate surveillance beyond poultry and fragmented intersectoral coordination delay timely detection and response. For such systems to be sustainable, surveillance must also be cost-beneficial, balancing resource constraints with the need for early warning capacity. On the human side, nonspecific clinical features, limited access to diagnostics, and emerging antiviral resistance complicate recognition and management. Financial disincentives for reporting, low community awareness, and insufficient preparedness infrastructure further exacerbate these risks. These challenges are compounded by the exponential expansion of both poultry and pig production in the region, with intensive operations creating dense animal populations that facilitate viral amplification, while fragmented backyard and smallholder systems remain difficult to regulate. The growth of pig production adds another concern, as pigs can act as mixing vessels for influenza viruses, further increasing zoonotic potential.

Table 12.

Summary of key challenges, mitigation strategies and implementation leads for avian influenza in Asia

Domain	Key Challenges	Priority Mitigation Strategies	Implementation Leads
Live Bird Markets & Poultry Practices	High virus positivity in markets and slaughterhouses Poor husbandry and biosecurity Long production cycles, antibiotic misuse Ducks as silent reservoirs	Stricter regulation/temporary closure during outbreaks Farmer training and responsible antimicrobial use Improved biosecurity in farms (commercial & backyard) Segregation of ducks and high-risk species	Government (Agriculture, Veterinary Services) Poultry Industry & Farmer Associations Regional/Local Authorities
Vaccination	Antigenic drift undermines poultry vaccine efficacy Incomplete protection → silent transmission Cold chain and cost barriers in rural areas Slow progress in human vaccine development	Next-generation poultry vaccines (universal, mucosal, live-attenuated) Strain updates and heterologous prime-boost strategies Subsidised vaccination programs Development of rapid-response human vaccines (mRNA, vector-based)	Government (Agriculture & Health Ministries) International Agencies (WHO, FAO, WOAH) Vaccine Manufacturers & Research Institutes
Surveillance	Fragmented, poultry-centric systems Limited molecular/genomic capacity Underreporting due to farmer disincentives Neglect of wild birds, mammals, and the environment	Expand to wild birds, mammals, and environmental sampling Strengthen One Health coordination Introduce farmer compensation schemes Scale-up genomic sequencing and real-time data sharing	Government (Health, Agriculture, Environment); One Health Coordination Platforms Academic & Regional Reference Labs International Agencies
Human Diagnosis & Clinical Management	Nonspecific clinical presentation Limited diagnostic access Antiviral resistance emerging Delayed care in resource-limited settings	Training for early recognition and isolation Wider access to antivirals (including baloxavir, zanamivir) Decentralised diagnostics and POC molecular tools Strengthen outbreak-ready clinical pathways	Government (Health Ministries, Public Health Agencies) Hospitals & Clinical Networks International Health Partners
Community Awareness & Risk Communication	Low awareness of risk factors Poor PPE use and hygiene Socioeconomic disincentives for reporting	Co-developed, culturally sensitive health messaging Practical farmer/worker training on PPE and hygiene Community-based surveillance and engagement	Government (Local Health & Agricultural Extension) NGOs Community Health Workers Media & Communication Platforms
Wildlife & Environmental Transmission	Virus persistence in wild birds and wetlands Cross-species transmission (including mammals) Sparse wildlife health surveillance	Targeted wildlife surveillance in hotspots/flyways Urban bird monitoring (e.g., crows) Environmental sampling as an early warning system	Government (Forestry, Wildlife, Environment Ministries) Conservation NGOs Academic & Research Institutes

WHO World Health Organization, FAO Food and Agriculture Organization of the United Nations, WOAH World Organization for Animal Health (formerly OIE), POC Point-of-Care, PPE Personal Protective Equipment, NGOs Non-Governmental Organisations

Mitigation strategies must be multidimensional, encompassing improved husbandry, stricter market regulation, expanded One Health surveillance, next-generation vaccines, strengthened clinical readiness, and active community engagement. A fuller consideration of economic and operational feasibility is also essential, particularly with respect to vaccination strategies, value chain interventions, and the sustainability of surveillance. The feasibility of these measures is uneven across the region, with resource constraints in many low-resource settings limiting surveillance and response capacity, while countries with greater resources have made large-scale investments that enable broader deployment of interventions. Recognising these contextual differences is crucial for identifying approaches that are both realistic and sustainable. Systematic evaluations of cost-effectiveness across diverse settings could help identify the most viable approaches for integration into national and regional public health systems, while stronger intersectoral frameworks would enhance the translation of scientific insights into feasible policies and practices. A context-sensitive One Health approach, integrating human health, animal health, and environmental health, remains central, though challenging to operationalise across local, national, and regional levels. Regionally tailored frameworks should prioritise joint preparedness drills, transparent cross-sector and cross-border reporting, coordinated stockpiling of antivirals and protective equipment, and harmonised market regulations. Effective strategies must be aligned with ecological, social, and political realities to enhance regional and global pandemic preparedness.

Conclusion

Complete eradication of avian influenza is unlikely given its ecological entrenchment in wild birds and its expanding host range. As the epicentre of repeated avian-to-human spillovers, Asia highlights three urgent priorities. First, control must focus on early detection and rapid response at high-risk interfaces, including live bird markets, domestic ducks, and swine as mixing vessels. Second, investment in targeted antivirals and rapid-response therapeutics is needed to buffer delays in vaccine effectiveness. Third, animal and human vaccine policies should be pragmatic, with context-appropriate deployment and recognition that vaccines alone are insufficient.

Importantly, recent experiences in North America, particularly the incursion of H5N1 into dairy cattle and the detection of viral RNA in retail milk, demonstrate that avian influenza is no longer confined to Asian production systems and live bird markets. While human cases in Asia have often been severe and linked to direct poultry exposure, infections in North America have thus far been milder and associated with both poultry and dairy cattle, suggesting possible differences in viral clade characteristics and exposure routes. Including these contrasts underscores that while Asia remains the epicentre, the risk is global, and responses must be adapted to regional epidemiological realities.

Advancing these priorities demands a strengthened One Health framework, robust surveillance across livestock and wildlife sectors, cross-border data sharing, and, critically, sustained funding from national and international agencies. Only by linking regional realities in Asia with emerging lessons from North America can global resilience against future influenza pandemics be achieved.

Author contributions

NG, PJ, and MPG contributed to conceptualization and methodology. Literature search and data curation were performed by NG, MPG, JFD, JRPP, FXL, ST, AB, GPS, and PJ. NG prepared the original draft and figures. All authors (NG, MPG, JFD, JRPP, FXL, ST, AB, GPS, PJ) contributed to the review and editing of the manuscript.

Funding

This study did not receive specific funding from government, commercial, or non-profit agencies.

Data availability

This article is a narrative review based on previously published literature and publicly available reports from international agencies. No new datasets were generated or analysed for this study.

Declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

This is a narrative review and therefore ethics approval is not applicable.

Consent to participate

Not applicable, as this work did not involve human participants.

Consent for publication

All authors have reviewed and approved the final manuscript and consent to its publication in Infection.