We included cross-sectional studies, case-control studies, cohort studies, randomized controlled trials (RCTs), and modelling studies that investigated the risk factors associated with SIV spillover at the human–swine interface. Articles were eligible if they were published up to February 2024. We excluded conference abstracts, editorials, opinion pieces, and articles not published in English.

We conducted a comprehensive literature search using PubMed and EMBASE to identify relevant articles. Key search terms included Influenza, Swine, Human, Zoonosis, Animal, Interfaces, Risk Factors, and Spillover. The retrieved articles were imported into Rayyan for duplicate removal and screening. We used two reviewers for title/abstract screening and full-text screening. Both reviewers received training in the use of Rayyan, and individual login credentials were created to ensure independent access and blinded screening. The detailed PubMed search strategy is provided in Supplementary Appendix S1.

We followed a two-stage screening process. Two authors, JP and JL, independently assessed all titles and abstracts, following the removal of duplicates, to identify studies eligible for full-text screening. We included the studies that investigated the risk of spillover at human-swine interfaces. The same authors were involved in full-text screening, and all full-texts were re-assessed against the key inclusion criteria. Disagreements that surfaced during the full-text, title, and abstract screening were resolved by the third author.

We used a data extraction form to obtain pre-specified details from the included articles using Microsoft Excel. Three authors were involved in data extraction (JP, JL, AS). Consensus was sought between the three extracting authors in cases of conflict. We extracted details such as author, year of publication, country, study design, study sample, interface or study setting, virus details, risk factors, key findings, and risk factor category, and summarized the findings as frequencies.

We included 1,667 articles from two databases and 10 from grey literature. We removed duplicates (n = 637) and included 1,040 articles for screening. During title and abstract screening, we excluded 938 articles and included 102 articles for full-text screening. Further, 47 articles were [No risk factor (n = 20); wrong study design (n = 6); other influenza virus (n = 6); wrong publication type (n = 7); wrong outcome (n = 2); in-vitro study (n = 1); duplicates (n = 5)] excluded based on the inclusion and exclusion criteria during the full-text screening. We included 55 articles for data extraction. The selection process is represented in the PRISMA flow diagram (Figure 1).

Most studies were from the USA (n = 27), followed by China (n = 6), Mexico (n = 4), and Brazil (n = 3) (Figure 2). Most of the studies were published after 2015 (n = 30). Most of the studies reported occupational risk factors (n = 14), followed by lack of biosecurity (n = 10) and environmental (n = 6). A large majority of the studies were cross-sectional studies (n = 28), followed by cohort studies (n = 3). More than one-fifth of studies were done on agricultural fairs (n = 13), followed by large-scale commercial farming (n = 12), and backyard farming (n = 8) (Supplementary Table 1). We classified the risk factors into two broad categories: (1) risk factors that influence the transmission of SIV among swine and from swine to human, and (2) risk factors associated with the type of human-swine interfaces. The first category includes factors such as pig attributes and rearing practices, the extensiveness of interfaces, occupational exposure, environmental conditions, host factors, and lack of biosecurity measures. The second category focuses on the specific settings where such interactions occur, which include backyard farming, mixed farming systems, large-scale or commercial pig farms, live animal markets and slaughterhouses or abattoirs, swine exhibitions and agricultural fairs, and veterinary hospitals, clinics, or research facilities.

Several studies reported that age, sex, and rearing practices of pigs significantly influence susceptibility to SIV infection [13, 14, 45, 64]. Younger pigs were consistently reported to have higher odds of SIV positivity compared to older pigs [14, 45, 64]. For instance, piglets aged 1–10 days demonstrated significantly greater odds of infection [14], and SIV was most frequently isolated from weaned piglets aged 4–8 weeks [45]. In addition to age, sex was identified as a contributing factor; female pigs had higher seroprevalence than males (PR = 2.84) [13]. Other factors such as a high number of breeding sows (OR = 3.98) [23], free-ranging swine in contact with domestic ducks and wild birds [61], animals from outside sources, and the presence of crossbred pigs were similarly linked to elevated SIV risk and seroprevalence.

Several studies highlight that close and repeated human-swine contact in settings such as agricultural fairs, exhibitions, and backyard farming facilitates viral spillover. For instance, one study reported that even a small proportion of IAV-positive swine arriving at fairs could contribute to transmission dynamics [53], while another observed frequent human-swine contact in backyard systems as a potential risk factor [59]. The unique setting of agricultural fairs enables sustained close interactions with swine, thereby amplifying the potential for interspecies transmission [38, 39, 47, 51, 63, 65]. Duration of exposure also plays a crucial role. One study identified significant associations between hours spent with pigs (R² = 0.90, P = 0.0018) and with pigs from different farms (R² = 0.91, P = 0.0001) and the presence of IAV [60]. The risk of suspected zoonotic infection increased with intensity of swine contact, ranging from no exposure to visiting swine exhibits to direct physical contact [32]. Additionally, the scale of swine operations and the degree of trade connectivity were associated with heightened transmission risk [16, 31]. The attitude towards and awareness about recommended practices also play a key role [55]. However, not all studies reported definitive associations. For example, one study found concurrent IAV circulation among pigs, poultry, and humans on farms, but did not identify significant risk factors for human-to-swine transmission [50].

Occupational exposure significantly contributes to the spillover of influenza viruses at the human-swine interface due to frequent, close, and often unprotected contact with pigs. Several studies reported that individuals working on swine farms had markedly higher odds of infection [19, 21, 35, 37, 42], particularly among farm residents [20], swine workers [18, 20, 22, 36, 52, 57, 67], contact among wild species and swine [44], and those employed in the pig industry [21, 66]. Farm workers were more likely to test positive at the end of the working day (OR = 1.98; 95% CI: 1.14–3.41) [24], and swine workers showed significantly higher seroprevalence of swine H3N2 (17.3% vs. 7.0%; adjusted OR = 3.4; 95% CI: 1.1–10.7) [28]. The veterinarian also has a high risk of transmission [19, 20]. One study reported that the cumulative incidence of acute respiratory illness was high among pig workers [34]. Specific occupational tasks such as walking the aisles (27%), handling pigs (21%), and handling contaminated equipment (21%) also increased the risk of SIV transmission [46].

Environmental conditions such as temperature, humidity, seasonality, and airflow play a critical role in influencing the transmission dynamics of influenza viruses. One study reported a significant association between temperature and humidity with the presence of antibodies against H1N1 and H3N2 strains in pigs, suggesting that these factors impact viral circulation. This study reports that for every degree Celsius increase in average temperature, pigs had 2.26 times higher odds of having positive titres for the virus (p < 0.05, CI 1.22, 4.18) [29]. One study reported a significant association between temperature and humidity with the presence of antibodies against H1N1 and H3N2 strains in pigs, suggesting that these factors impact viral circulation. This study reports that for every degree Celsius increase in average temperature, pigs had 2.26 times higher odds of having positive titres for the virus (p < 0.05, CI 1.22, 4.18) [25]. Specific environmental conditions were linked to higher IAV positivity rates. Detection was increased at outdoor temperatures of 5.0 °C–13.9 °C (OR = 3.06; 95% CI: 1.04–8.98) and 14.0 °C–23.9 °C (OR = 3.44; 95% CI: 1.08–10.95). Additionally, IAV detection rates were elevated in summer (OR = 3.32; 95% CI: 1.16–9.50) and fall (OR = 4.12; 95% CI: 1.47–11.54) [14]. Other factors, such as the presence of wild birds and poultry, were also associated with a high risk of SIV [29]. Similarly, a study found that seasonal trends were also evident, with a smaller peak from May to July (24%). In contrast to this, it was also found that the highest infection risk was observed between January and March (accounting for 54% of estimated peaks). Although some level of infection risk was present throughout the year, infection trends were positively correlated with humidity and closely mirrored influenza patterns in domestic swine and human populations [26].

Host factors in infectious diseases refer to the biological, physiological, and immunological characteristics of pigs or humans that influence susceptibility to infection, viral shedding, and transmission dynamics. Few studies have highlighted such factors in the context of swine influenza. For example, the age and vaccination status of veterinarians were significantly associated with seropositivity for swine-origin influenza viruses [27, 28]. Similarly, limiting the duration of swine exhibitions (e.g., ≤72 h) was shown to drastically reduce IAV prevalence in exhibition swine [41]. Additionally, the presence of influenza-like illness (ILI) among individuals with swine contact was linked to higher seroprevalence [28]. Human population density has also been identified as a contributing factor to the increased risk of infection [58]. Furthermore, ecological factors such as the presence of wild birds and domestic swine populations near human settlements were associated with elevated seropositivity rates [56] underscoring the complex interplay between host characteristics and environmental exposure in shaping disease risk.

Multiple studies have demonstrated that the absence of adequate biosecurity measures is a key driver of interspecies transmission. For instance, farms lacking biosecurity protocols, poor husbandry, and a lack of biosafety practices for workers exhibited a higher risk of infection, underscoring the urgent need for stronger preventive practices [17, 29, 33, 43, 48, 49, 54, 62]. One intervention study reported a 21% reduction in viral positivity when sow vaccination was combined with enhanced biosecurity, indicating that integrated approaches can effectively reduce IAV transmission and support the production of IAV-free piglets at weaning [30]. Furthermore, unrestricted access to farms has also been identified as a significant risk factor for disease spread [15]. In addition, the lack of structured mitigation strategies at agricultural fairs has been highlighted as a vulnerability, prompting calls for reinforced biosecurity to safeguard both animal and public health [40].

This study has a few limitations. We included only articles published in English and retrieved data only from two databases. This paper discusses the risk factors associated with the SIV at the interface between human-swine. The design of the included studies varies, which limits the comparison between the studies. Furthermore, we were unable to rank the identified risk factors due to variations among studies in how they prioritized the risks.

We identified several key factors contributing to the risk of SIV spillover from swine to humans. Frequent and close contact between humans and swine, inadequate biosecurity practices, and poor surveillance systems emerged as major risk factors. Additional contributing elements included specific pig-rearing practices, environmental conditions such as temperature and humidity, and occupational exposure among farm workers and veterinarians. Evidence suggests that implementing strict biosecurity measures, vaccinating both pigs and workers, and using PPE can significantly reduce transmission risk. These findings emphasize the need for comprehensive, multi-layered strategies to mitigate the spread of SIV and reduce the likelihood of future zoonotic outbreaks.