Background

The 21st century has already experienced significant global health crises, including the coronavirus disease 2019 (COVID-19) pandemic [4]. COVID-19, caused by the novel Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2), is the seventh known member of the coronavirus family to infect humans, following diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Distress Syndrome (SARS) [4]. This pandemic resulted in over one hundred million infections and more than two million deaths globally [4].

Infectious disease outbreaks and emergence events are influenced by various factors, including anthropogenic (human-caused) land use changes [13]. These changes encompass agricultural expansion, deforestation, road construction, dam building, irrigation, wetland modification, mining, and the concentration or expansion of urban environments [13]. These activities can lead to a cascade of issues such as forest fragmentation, disease introduction, pollution, poverty, and human migration, all of which can exacerbate the emergence of infectious diseases [13].

Climate change is another critical factor, reported to exacerbate the spread of plant diseases and is a recurring theme in discussions about global health security [3, 15, 16]. The Lancet Countdown reports from 2020, 2023, and 2024 highlight the converging crises of health and climate change, emphasizing the increasing threats from delayed action and the imperative for a health-centered response [2, 15, 16]. Lessons from past outbreaks, such as the Ebola virus disease epidemic in West Africa, have brought renewed attention to global health security and the need for governments to strengthen core public health capacities as required by International Health Regulations [10].

Key findings

  • **Emerging Pathogens and Zoonotic Threats:** Plant disease outbreaks are increasing and pose a threat to global food security, particularly for vulnerable populations [3]. These outbreaks are exacerbated by climate change, global food trade networks, pathogen spillover (transmission from one host species to another), and the evolution of new pathogen lineages [3].
  • **Influenza Viruses and Animal Reservoirs:** Influenza pandemics, defined as global outbreaks caused by viruses with new antigenic subtypes, have historically caused high death tolls [14]. Avian influenza A viruses are significant contributors to the emergence of human influenza pandemics [14]. The last two pandemics were caused by hybrid viruses, or reassortants, that contained a combination of avian and human viral genes [14]. In 1997, an H5N1 influenza virus was directly transmitted from birds to humans in Hong Kong, leading to 18 infections and 6 deaths [14]. Another avian virus, H9N2, has also been directly transmitted from birds to humans [14].
  • **Pigs as "Mixing Vessels":** Pigs are susceptible to infection from both avian and human influenza viruses, leading to the "mixing vessel" theory [12]. This susceptibility allows for the genetic reassortment of influenza viral segments in pigs, which can generate novel reassortant influenza viruses [12]. While there is no direct evidence that pigs were the origin of the 1918, 1957, or 1968 pandemic influenza viruses, genetic reassortment among avian, human, and/or swine influenza virus gene segments has occurred in pigs, resulting in novel reassortant swine viruses [12].
  • **Highly Antigenically Diverse Viruses:** Certain human pathogens, including HIV, influenza, and hepatitis C viruses, evade the immune system by rapidly mutating the surface protein sites targeted by antibody responses [11]. This characteristic makes vaccine development challenging for these "highly antigenically diverse viruses" [11]. However, these viruses also possess highly conserved exposed sites, often essential for their function, which can be targeted by broadly neutralizing antibodies [11].
  • **Environmental Factors:** Anthropogenic land use changes, such as deforestation and urban expansion, drive infectious disease emergence and modify the transmission of existing infections [13]. Additionally, outdoor air pollutants, including particulate matter, sulfur dioxide, and nitrogen oxides, are major factors in respiratory diseases [8]. Evidence supports a clear association between air concentrations of some pollutants and the transmission and severity of respiratory viral infections [8].

Methods

The information presented is drawn from a variety of scientific literature. This includes comprehensive reviews [1, 8, 9, 12], systematic reviews [5], and analytical modeling studies [6]. Many of the sources are preprints, which are scientific manuscripts posted online before formal peer review [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]. Other sources include reflections by global health practitioners [10] and studies assessing the impacts of specific pandemics [4, 7].

Interpretation

The provided evidence collectively suggests that future pandemics could emerge from a variety of sources, including novel or reassorted influenza viruses from animal reservoirs like pigs, and increasingly prevalent plant diseases exacerbated by environmental changes [3, 12, 14]. Human activities, particularly land use changes, are identified as significant drivers of infectious disease emergence and transmission [13]. Climate change further compounds these threats by influencing disease spread and contributing to overall health crises [2, 3, 15, 16]. The challenge of developing vaccines for highly antigenically diverse viruses highlights the ongoing need for advanced immunological research [11]. The experience of past pandemics, such as COVID-19 and Ebola, underscores the critical importance of robust global health security measures and rapid development of effective interventions like mRNA vaccines [1, 4, 10].

Limitations

A significant limitation is that many of the supplied sources are preprints [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]. Preprints have not undergone formal peer review, meaning their findings should be interpreted with caution. Some sources are reviews, which synthesize existing literature but do not present new primary data [1, 5, 8, 9, 12]. While the link between air pollution and respiratory viral infections is supported by evidence, it is described as an association [8]. The "mixing vessel" theory for influenza viruses in pigs is presented, but direct evidence for its role in specific historical pandemics (1918, 1957, 1968) is not clearly established [12]. The generalizability of some findings may also be limited, as some studies focus on specific regions or contexts, such as the West African Ebola epidemic [10] or US college campuses [6].

What's next

To prevent future outbreaks of plant diseases, a new set of tools is needed, including disease surveillance, improved detection technologies like pathogen sensors, and predictive modeling and data analytics [3]. For human health, advancements in vaccine technology, such as mRNA vaccines, offer a powerful alternative to traditional vaccines due to their high potency, safety, efficacy, rapid clinical development, and potential for rapid, low-cost manufacturing [1]. Modified Vaccinia virus Ankara (MVA) is another example of a safe viral vector with potential for developing new candidate vaccines against infectious diseases [9].

Addressing global health security concerns requires strengthening core public health capacities, as highlighted by lessons from the Ebola outbreak [10]. Furthermore, understanding and mitigating the impacts of anthropogenic land use changes on infectious disease emergence is crucial for policy recommendations [13]. The ongoing reports from The Lancet Countdown on health and climate change emphasize the need for a health-centred response to climate-related threats [15, 16]. Finally, there is a recognized need for psychological preparedness and resilient response mechanisms to cope with infectious diseases and pandemics [17].