Impact of Climate Change on International Health Security: An Intersection of Complexity, Interdependence, and Urgency

Climate change (CC) can be defined as a long-term shift in global, continental, and/or local climate patterns. Although many equate CC to the rise in global temperatures, the issue is much more complicated and involves a large number of intercon-nected factors. Among some of the less discussed considerations of CC are its effects on a broad range of public health issues, including the emergence of novel infectious diseases, the encroachment of infectious disease vectors into previously unaffected geographic distributions, and crop failures resulting in threats of malnutrition and mass migration. This chapter will be devoted to key issues related to CC in the context of international health security (IHS).


Introduction
Planet Earth is a highly complex and truly unique celestial body, fine-tuned to sustain life within a very narrow range of tolerances [1,2]. Within this narrow band of environmental parameters, our civilization emerged over the past several thousand years. As we discovered ways in which to harness the energy stored within our planet, from burning wood, to coal, to petroleum products, we began to increasingly change the environment we live in [3,4]. The resultant slow but persistent climate change (CC) is beginning to manifest itself across multiple domains of human existence, from rising sea levels, to wind disasters and forest fires, to the emergence of new invasive species [5][6][7][8]. This chapter will discuss the impact of CC on various domains of human health and well-being, with specific focus on their relationship to international health security (IHS). Given the vastness of this important topic area, our goal will be to provide an overview of the most pressing issues and most relevant subdomains (Figure 1). However, it is simply not feasible to cover this entire subject within a single book chapter, thus limiting the current manuscript to a bullet-point synopsis.

Environmental pollution: air and water
The effects of air pollution on public health have become increasingly acute, heterogeneous, complex, and unpredictable [9][10][11][12]. In recent years, natural disasters such as wildfires and non-natural disasters such as human-made pollution have caused fundamental changes in air quality, leading to special measures and precautions deemed necessary to protect populations from air pollutants [13,14]. Various effects of air pollution, both in the indoor and outdoor setting, on health include but are not limited to: asthma, chronic obstructive pulmonary disease (COPD), cardiovascular diseases, and an array of pulmonary malignancies [15][16][17][18]. Although naturally evolving changes in climate and temperature have some effect on air quality, direct human contribution to air pollution may play and even greater role [19,20]. For example, humans are thought to be responsible for approximately 95% of all wildfires in California and in Mediterranean Europe [21,22]. Wildfires diminish air quality by scorching thousands of acres of

Climate change: increase in allergens
One effect of global warming is an increase in allergens. Allergens can be associated with various respiratory diseases such as Asthma or allergic reactions such as hay fever. An increase in hay fever can be attributable to global temperature increases due to synergistic effects of atmospheric warming on the pollination season of plants [44]. The observed rise in the number of airborne allergens is directly proportional to the increase in pollen content of the air [45]. From human health perspective, it can be expected that allergic reactions, as well as their severity, may worsen over time. This may be further exacerbated by the declining air quality, both indoors and outdoors [46,47].
The decrease in air quality is compounded by other factors such as smoking, diesel fuel utilization, and the generation of nitrogen dioxide [48][49][50]. Temperature fluctuations also lead to mold formation and propagation [51]. This can further decrease air quality and can cause intense allergic response in some people [52,53]. Some other common allergies include ragweed allergy causing hay fever and poison ivy causing contact dermatitis. Table 1 lists a set of common allergens. When an allergen enters the body, its presence leads to an immune response featuring the sensitization of mast cells [54,55]. When the allergen enters the body repeatedly, it attaches to the specific antibodies on mast cells resulting in mast cell degranulation, which leads to the release of histamine and other inflammatory mediators [56,57]. Associated symptoms may include commonly encountered reactions such as watery eyes, itching, sneezing, and nasal/ sinus congestion. Pertinent to CC and global warming, it has been noted that patterns and distribution of common allergens typically present in different parts of the globe are changing [58]. The awareness and the ability to identify these patterns, coupled with modern mobile technology advances and point-of-care testing, will allow health-care providers to adequately prepare for the evolution and changing incidence of allergic reactions, especially in the context of preventive health measures and effective clinical management approaches [59-61].

Vector borne diseases and climate change
Another important aspect of the ongoing CC, and a source of indirect evidence for global warming, is the gradual evolution in disease vector distribution [8,62]

Food and water borne diseases
Global CC exerts impact on rainfall, humidity, length of growing season, and other environmental factors that are vital to the development of certain crops [118,119]. Shifting environmental factors, along with the emergence of biofuels, are pushing food producers to implement various techniques that increase the yield of the crops [120]. One such method involves treating crops with antibiotics. However, unintended consequences of longer growing seasons and higher crop yields have resulted in greater frequency and intensity of food-and water-borne illness (Table 4) [121,122]. Another way of coping with CC in terms of international food security is the introduction of insect-based, microbial/fungal-based, and laboratory-based food substitutes [123][124][125][126][127][128][129].
Of note, salmonella and campylobacter infections tend to be more common when the climate is warmer [130]. Relevant to human consumption, these bacteria have been shown to have higher growth rates at warmer temperatures during food preparation and storage [131], which in turn corroborates one possible relationship between CC and emerging human disease patterns.
The effect of CC on water borne diseases is equally important, yet it appears to be disproportionately neglected [132]. It is well known that precipitation can influence the transport and dissemination of infections, especially as it relates to existing water and sanitation systems [133]. More direct impact of the above can be seen during the increasingly more frequent coastal flooding as it relates to sea-level rise. Due to various factors, including human activity, water contamination exposes local populations to a variety of potential fecal-oral pathogens [134]. Indirect factors affecting the overall risk of water-borne infection propagation include changes in temperature and humidity, leading to alterations in pathogen lifecycle and survival, up to and including the creation of environments where new patterns of geographic disease spread emerge [135]. The effects of CC on water borne diseases, both indirect and direct, can be profound and unpredictable, mandating that dedicated scientific research efforts in this critically important area are increased.

Food security
Because agriculture relies heavily on the presence of favorable environmental parameters, any uncertainty related to agricultural conditions places food security into a state of flux and thus creates a potential threat to food sustainability and security for humans [136,137]. Threats to food security are vast, diverse, and have increased sharply during the past three decades. Issues affecting food security involve agricultural, industrial, and climate-related components (e.g., from natural disasters to heavy pollution) [138,139]. Protein-based food products from animal derived sources may contain significant antibiotic residue because antibiotics are increasingly utilized to maintain product viability and longevity during transport and distribution [140,141]. Downstream effects of using antimicrobials in animal feed include various patterns of antibiotic resistance seen in both animals and humans who ingest animal-based food products [121,142,143]. Consequently, we are increasingly seeing emerging antibiotic resistance patterns that render many of our available therapeutics ineffective, leading to excess mortality [144][145][146]. Moreover, antibiotics have also leaked into water and food chains, creating complex and challenging matrices for the detection of their source of origin, which is vital to effective disease control [147,148]. The importance of this complex phenomenon, in addition to introducing excess risk into the food chain and endangering the overall food security, is the potential for synergistic interactions between CC, emerging novel pathogens, and often unpredictable patterns of antimicrobial resistance [149 -151]. As such, the confluence of the above factors is projected to result in significant food shortages, on per capita basis, by the year 2050. The attributable mortality may exceed 500,000 deaths around the globe [152]. Increased focus on ensuring food availability will be a crucial component of IHS in the future, and will be inextricably tied with the ongoing CC [7, 14]. Among promising sustainable growth strategies in this important area is the introduction and increasing implementation of the vertical farm concept [153]. Last, but not least, the gradual acidification of the oceans is beginning to affect the overall aquaculture and food chain sustainability, especially across the densely populated coastal areas that heavily rely on fish and other forms of seafood for ongoing food security [154][155][156]. Associated phenomena include harmful algal blooms which further damage aquatic ecosystems [157].

Flooding and flood-related events
Over the past several decades, floods have become a growing problem throughout the world [158,159]. This has been especially problematic among low-lying areas of the planet, including large river deltas [160][161][162][163][164], and thought to be associated with rising sea levels [165][166][167]. It has been estimated that roughly 40-50% of environmental disasters are due to floods, and there is also a significant correlation between flooding and wind disasters [165][166][167][168]. From IHS perspective, floods may lead to drinking water contamination and associated increases in water borne and diarrheal diseases [169,170]. It is therefore vital that we understand how to address and prevent deleterious public health consequences associated with flooding, inclusive of additional focus on a plethora of downstream effects of flooding on human populations [171][172][173][174].
In addition to immediate loss of life and property, there is a noticeable increase in diarrheal diseases, and studies suggest that there may also be an increased risk of all-cause mortality during the year following a flooding event [175,176]. This troubling trend can be further exacerbated when flooding occurs in the presence of human overcrowding [176]. Of importance in this particular context, when planning and preparing for natural disasters it is important to understand the ecosystem of communicable diseases within the region and understand the vectors that may come into play. Effective management of flooding and subsequent post-event recovery requires proper sanitation, clean water supply at shelters/temporary housing for displaced individuals, as well as adequate control of disease vectors (e.g., rodents, mosquitoes) [177,178]. Consequently, preventing contamination of standing water with mosquitoes should be priority during a flooding event [179,180]. Governments planning for natural calamities, including floods and wind disasters, should ensure that appropriate supplies of clean water and food are readily available to large number of individuals. At the same time, it is also important to educate individuals on the importance of proper food and water preparation, through boiling, during any natural disaster that may potentially affect water supply [181][182][183][184].

Wildfires
Rising global temperature affects public health in urban and rural communities across the world [185]. In recent years urban heat waves have become more severe, which has corresponded with an increase in heat-attributable deaths during times of extreme summer temperatures [186]. In rural communities, phenomena such as dust storms and crop failures, along with invasive insect infestations and invasions, have increasingly appeared [187][188][189][190][191][192][193]. To make things worse, CC also creates an environment more prone to wildfires, which are affecting rural communities with increased frequency, and are progressively more common near more densely populated areas [7,14,194]. Human consequences of all of the above factors, especially when acting synergistically, will be both profound and difficult to calculate [7, 14]. As average global temperatures continue to rise it is imperative to quantify the burden that the health systems will face due to more severe heatwaves and wildfires [195].
Heatwaves are often defined as 2 or more consecutive days with temperatures above the 95th percentile for the summer [196,197]. Relative risk of mortality increases during heatwaves in urban centers, particularly among elderly patients and patients with pre-existing cardiorespiratory conditions [198,199]. This was demonstrated during an August 2003 heatwave in Europe, when heatwaveattributable mortality reached 14,800, the risk of out-of-hospital cardiac arrests increased by 14%, and hospitalizations significantly increased among asthma patients [200,201]. Patients with pre-existing cardiorespiratory conditions were most at-risk for heat-related mortality [200,201]. It is important to consider cardiovascular and respiratory conditions because they are among the most common pre-existing conditions within a progressively aging general population [202][203][204][205]. The specific physiologic processes causing increased mortality in patients with existing cardiovascular conditions during heatwaves are still poorly understood. However, it can be postulated that longer and more severe heatwaves place more strain on the cardiovascular system to maintain physiologic body temperatures via thermoregulation. Additionally, high temperatures are associated with elevated heart rate, increased blood viscosity from dehydration, and higher blood cholesterol levels. These factors together with sub-optimal electrolyte balance and reduced cerebral perfusion place higher demands on the cardiovascular system, which could exacerbate symptoms in vulnerable patients [206,207].
Respiratory conditions on the other hand could be worsened because of lengthening frost-free periods and increasing levels of dusts and other pollutants in the urban atmosphere [208,209]. This can be further exacerbated by the simultaneous presence of wildfires (e.g., California or Colorado, Summer 2020) [7,14,210,211]. Evidence suggests that as carbon dioxide levels increase, ragweed (which is ubiquitous in urban communities) flowers earlier and produces 30-90% more pollen [212,213]. By association, allergic sensitivity may lead to exacerbations of respiratory illness like asthma, but the phenomenon may have other synergistic components that are also directly or indirectly tied to CC [214].
Traditionally, rural communities have offered a relative escape from the smog and heat trapping environment of the city [215]. However, rising global temperatures are diminishing the air quality of rural communities by creating a dry landscape that is prone to wildfires and dust storms [216][217][218]. More specifically, particulate matter smaller than 2.5 um (PM2.5), carbon monoxide, nitrogen oxide, ozone precursors, and other harmful substances are released from wildfires, with various other components present within the cloud of a typical dust storm [154,219,220]. Of note, PM2.5 exposure during wildfires has been associated with increases in emergency department and hospital visits related to respiratory illnesses [221], with asthma exacerbations and wheezing in patients 65 and older having the greatest morbidity impact [222]. Evidence of cardiovascular and noncardiopulmonary morbidity from particulate matter exposure is less consistent, with clear need for further research to better characterize any potential underlying associations [7].

Wind disasters
The number and severity of wind disasters appears to be increasing over the past two decades [168,223,224]. This connection between CC and increasing number and intensity of major hurricanes and other similar weather events is not fully understood [225], but more recent evidence does support a more causative effect [226,227]. The current 2020 hurricane season in the United States is among the worst on historical record [228]. Its logistical impact is further compounded by the co-presence of the Novel Coronavirus pandemic [228]. Similar to flood disasters (which may also occur simultaneously), wind disasters and their aftermath may also have significant impact on life within the affected regions [229]. The impact of wind disasters on humans goes far beyond direct physical damage and bodily injuries [230]. Forced human migrations and post-traumatic stress add a massive component of complexity to the overall post-disaster recovery process [231][232][233]. Moreover, there seems to be an association between post-traumatic stress following wind disasters and the emergence of cardiovascular and other comorbid disease manifestations (or exacerbations) [231,234]. Such longer-term manifestation appear to be more pronounced among members of underrepresented minorities, further highlighting issues of social and health-care inequity [231,235,236].

Climate change: effects on mental health and societal crises
Public health is influenced by a diverse collection of factors, many discussed in earlier sections of this chapter. One of the most under-appreciated factors is the effect of CC on mental health, both directly and indirectly, at both personal and societal levels [237,238]. One of many subtle manifestations of societal distress is the proposed link between global warming, crop failures, and armed conflict [239,240]. As a result, we begin to see greater incidence of mass migrations and refugee crises [241,242]. An associated surge in mental disorders and stress related diseases is inextricably tied to such occurrences [243,244]. Given the intersectionality of stress related disorders and their effect on the mental health of populations, it is not surprising that many are being pushed to their coping limits when faced with food insecurity, environmental pollution, increasing frequency of natural disasters, crops failures, and economic and political instability [245]. Moreover, long-term effects of such new global status quo are equally difficult to predict [246].
Large scale human migrations due to natural disasters, conflict, famine, or political and economic instability, have been associated with mental health and stress related illnesses across the globe [247][248][249]. All population segments are affected, from rich to poor, from urban to rural, from young to old, without exception [250][251][252]. Exposures to potentially traumatic events, regardless of the exact nature of the event, are known to cause an increased risk for mental disorders including post-traumatic stress disorder (PTSD) [253][254][255]. Associated downstream consequences may include increased incidence of depression and increased suicide rates [256].
Significant proportion of the world's population does not have sufficient access to mental health support, including both high income regions (HIRs) and lowand-middle-income regions (LMIRs) [257][258][259][260]. Individuals from regions affected by CC (and secondary phenomena related to CC) may find themselves experiencing a myriad of stressors affecting mental health and resulting in various stress related diseases (including substance abuse) [245]. At the personal level, a number of different approaches can be used to effectively manage behavioral health symptoms, including cognitive behavioral therapies, medical-based treatments, as well as short-and long-term coping management therapies, with generally positive outcomes [261,262]. At the societal level, public health education regarding mental health and wellness is of great importance [263][264][265]. Of course, governments and societies must continue to curb and address situations that contribute to ongoing stress and mental health related disorders. This focus in particular is critical to stabilizing populations affected most by CC and related crises [266].

Conclusion
Global climate change creates a multifactorial, highly complex matrix of direct and indirect effects that have the potential to threaten international health security. The many domains that synergistically affect human health in the context of CC include environmental pollution, the emergence of invasive species and novel pathogens, food security, wildfires, and a broad range of destructive weather events. Of course, the complete list is much more extensive, and beyond the scope of the current chapter. In summary, the global community must come together to more effectively and more systematically address issues associated with the ongoing CC and its many direct and indirect effects. To pretend that CC "does not exist" will be, simply said, too costly.       [143] Iwu, C.D., L. Korsten, and A.I. Okoh, The incidence of antibiotic resistance within and beyond the agricultural ecosystem: A concern for public health. MicrobiologyOpen, 2020: p. e1035. [