Emerging human infectious diseases and the links to global food production

Main

Infectious diseases are emerging at an unprecedented rate with significant impacts on global economies and public health¹. The social and environmental conditions that give rise to disease emergence are thus of particular interest, as are management approaches that might reduce the risk of emergence or re-emergence¹. At the same time, undernutrition — the insufficient intake of one or more nutrients — remains a major source of global ill health^2–5. Together, the unprecedented rate of infectious disease emergence and the need to sustainably feed the global population represent two of the most formidable ecological and public health challenges of the twenty-first century^5–9 (Fig. 1), and they interact in complex ways (Fig. 2).

Although modern agricultural technologies have reduced hunger, improved nutrition and spared some natural ecosystems from conversion to agriculture, current global agricultural production and distribution infrastructure still leaves billions of people’s diets deficient in one or more crucial nutrients, with major consequences for global morbidity and mortality¹⁰, and these deficiencies are expected to worsen with climate change^11–14. Credible estimates are available for specific nutrient shortfalls — for example, 1.6 billion people suffering iron- or vitamin B₁₂-deficiency anemia¹⁵, 0.8 billion people with insufficient dietary energy (that is, calorie) intake¹⁶, 33% of pre-school age children and 15% of pregnant women at risk of vitamin A deficiency¹⁷ — but the world still lacks a rigorous, recent assessment of the population suffering shortfalls of any one or more nutrients, although the number is surely in the billions. By 2100, the United Nations projects that the global population will grow by nearly 4 billion, to exceed 11 billion people¹⁸. Meeting the United Nations’ Sustainable Development Goal, to “eradicate hunger” (https://sustainabledevelopment.un.org/) for this expanding human population will necessitate a large increase in food supplies, with major changes to agricultural production and distribution systems, infrastructure and social protection programmes⁶ (Fig. 3). Despite large and, in many cases, growing inequalities, the global population is on average expected to become richer, and historically, with greater affluence has come greater consumption of food products in general and more animal-sourced foods in particular, both of which further increase food demand and thus the requirement for agricultural expansion and/or intensification¹⁹. Agriculture already occupies about half of the world’s land and uses more than two-thirds of the world’s fresh water²⁰, and recent studies have suggested that agricultural production might need to double or triple by 2100 to keep pace with projected population growth and food demand^6–8,21 (Fig. 3). Meeting this demand using present agricultural production systems could require replacing >10⁹ hectares of natural ecosystems with agricultural production, approximately 7% of the global land area, which is larger than the continental United States, although continuous efficiency improvements in agriculture will compel re-evaluation of these estimates. In turn, this agricultural expansion could result in an estimated ~2-fold increase in irrigation, ~2.7-fold increase in fertilizer^6,10,22 and 10-fold increase in pesticide use (Fig. 3).

The challenges of feeding >11 billion people and managing infectious diseases intersect in several ways (Figs. 1 and 2). First, the expansion and intensification of agriculture are disproportionately occurring in tropical, developing countries^6,22,23, where 75% of deaths are attributable to infectious diseases²⁴, where the risk of disease emergence might be greatest, and where disease surveillance and access to health care, particularly for those infections that accompany extreme poverty, are most limited^1,25. Second, agricultural expansion and intensification have historically come with massive habitat conversion, contamination with animal waste and increasing use of agricultural inputs, such as pesticides and antibiotic growth promoters. Beyond their direct adverse effects on human health^26,27, agricultural biochemical inputs are known to have direct effects on emerging human infectious diseases, and can also serve as indirect drivers by contributing to the emergence of wildlife diseases²⁸ that constitute important sources of emerging infections in humans^1,29. However, the strengthening of agricultural production systems can also improve nutrition, which has pronounced benefits for combating many infectious diseases at the individual and population levels^2,30.

Although concerns have been raised regarding the environmental impact of agricultural expansion and intensification^{6,8–10,22,31}, their effects on infectious disease risk have not been synthesized. Here, we review both the beneficial and adverse effects of agricultural expansion and intensification on the transmission of human infectious diseases. We synthesize the pathways through which agricultural practices influence human infectious diseases, and vice versa, and identify opportunities to minimize the adverse consequences of agricultural growth while maximizing the human health benefits of agricultural development (Fig. 1).

Nutrition and infectious disease

Agricultural development can yield direct improvements to nutrition, and through several mechanisms, nutrition can be a critical determinant of infectious disease susceptibility and progression^4,32 (Figs. 1 and 2). For example, immune responses are energetically costly³³ and thus undernutrition often reduces the development and effectiveness of immune responses that can limit or clear infections. The relationship between infectious disease and nutritional status can function in reverse as well, because many parasitic infections place direct demands on host nutrition, causing undernutrition when food is limited³⁴. In fact, some parasites, such as helminths, can even cause eating disorders, such as geophagy (desire to eat soil), bulimia and anorexia³⁵. Enduring infections often require rapid and effective repair of tissue damage caused by parasites, which is also costly. Hence, certain infections can cause undernutrition, which itself can compromise both resistance and tolerance to infections^34,36.

By improving nutrition, agricultural development should facilitate combating many infectious diseases. For example, death rates from acute respiratory infections, diarrhoea, malaria and measles, diseases that on average kill more than a child every 30 seconds (1 million per year)³⁷, are much higher in children who suffer undernutrition than in those that do not^3,4. In addition, poor maternal nutrition and associated impaired fetal growth are strongly associated with neonatal death from sepsis, pneumonia and diarrhoea⁴; undernourishment is a well-understood risk factor for tuberculosis³⁸; and micronutrient deficiencies, such as vitamin A deficiency, have been linked to diarrhoea severity and malaria morbidity in some populations⁴. Although the traditional Green Revolution approach to food production has succeeded in reducing undernourishment arising from insufficient calorie and protein intake, it has been very slow in reducing micronutrient deficiencies³⁹, which can be have significant effects on defence against disease. To make matters worse, where violence, unrest and terrorism impede access to food, such as in parts of Africa and central Asia, morbidity and mortality attributed to communicable diseases can be further exacerbated².

Although research suggests that improving nutrition will generally improve responses to infectious diseases, there may be important exceptions. For certain diseases, such as schistosomiasis and many respiratory infections, pathogenesis is a product of host immunity, often from hyperinflammation^40,41. Thus, undernutrition can actually decrease symptoms by reducing the strength and pathogenicity of immune responses⁴⁰. In addition, as nutrition improves, some parasites might proliferate faster than immunity can increase³⁴, resulting in more, rather than less, morbidity, with the classic example that dietary intake of iron can increase malaria-induced mortality⁴².

Rural economy, infrastructure and infectious disease

In this section, we review the links between rural economy, infrastructure and infectious disease.

Drugs use, agrochemicals and infectious disease

In this section, we review the effects of agricultural industrialization.

Agriculture, biodiversity, habitat and infectious disease

Conversion of natural habitat to agriculture can increase the abundance of ecotones (boundaries between ecological systems), change species composition and reduce native biodiversity^94,95. Ecotones play an important role in a number of important emerging infectious diseases^96,97, and reduced biodiversity that accompanies agricultural intensification can increase zoonotic disease emergence and can worsen already endemic diseases^98–100. A recent global meta-analysis suggests that, based on the available literature, such biodiversity losses generally increase infections of wildlife and zoonotic infections of humans¹⁰¹. However, studies of the relationship between biodiversity change and infectious disease risk tend to focus on a single parasite or disease, often of non-human animals, which limits the ability to determine more broadly the effects of agricultural intensification on the overall burden of infectious disease in human populations¹⁰². Recent studies have found that the local loss of dense forests, largely from agricultural expansion, affected diarrheal diseases, acute respiratory infections and general fever in Cambodian children¹⁰³ and infectious disease incidence in Nigerian children over a decade^104,105. Proximate causes probably included reduced regulation of microbial contaminants in surface and ground waters, increased smoke from biomass burning, shifts in the ranges of insect vectors and decreased access to forest ecosystem services.

A major concern is the potential for positive feedbacks between poverty, biodiversity loss, soil degradation and infectious disease^106,107. Several mechanisms can underpin these reinforcing relationships. The first arises as a result of poor rural peoples’ reliance on limited biophysical assets for their livelihoods. As households clear forests, deplete soils or overharvest biota to meet near-term consumption needs, this resource degradation can compromise future economic productivity and increase disease risk. In addition, poverty, environmental degradation, biodiversity loss and disease can quickly become mutually reinforcing responses to natural shocks, such as droughts or floods, or to protracted conflict in a region. There are also more direct examples. For instance, global net losses of tropical forests remained unchanged during the 1990s and 2000s (at approximately 6 million ha yr⁻¹ or 0.38% annually¹⁰⁸; also see https://glad.umd.edu/projects/global-forest-watch and https://www.globalforestwatch.org) and forest clearing can lead to transmission of zoonotic disease by increasing contact with wild animals. Conversely, encroachment of people and domesticated animals into natural areas can introduce diseases to wildlife that can devastate wild populations and create reservoirs for the disease to be transmitted back to domesticated animals¹⁰⁹ (see next section for further discussion and citations). Especially as the agricultural frontier expands, considerable attention must be paid to monitoring and managing these biodiversity–poverty–disease feedbacks¹⁰⁶.

Human diseases from domestic and wild animals

A central tenet of epidemiology is that the incidence of many infectious diseases should increase proportionally with host density because of increased contact rates and thus transmission among hosts¹¹⁰. Hence, increasing human and livestock densities could cause increases in infectious diseases unless investments in disease prevention are sufficient to prevent these increases. Given that most of the increase in human and livestock densities are expected to occur in developing countries where disease surveillance, pest control, sanitation, and medical and veterinary care are limited, there is little reason to expect that control efforts will keep up with the expected increases in infectious diseases associated with increasing densities of these hosts.

As host densities and thus transmission increase, theory suggests that parasite virulence should also increase under some circumstances¹¹¹. When virulence of a pathogen is tied to its propagule generation within the body (such as occurs with many viral infections), the intermediate virulence hypothesis posits that an intermediate level of virulence maximizes parasite transmission because it balances producing many parasite offspring (increasing parasite fitness) with detriments to host survival due to pathology (decreasing parasite fitness). The balance in this trade-off determines parasite persistence. Hence, as host densities increase and transmission becomes more frequent, the cost of increased virulence declines, shifting the optimum towards higher virulence¹¹¹. Consequently, for pathogens that experience this virulence trade-off, increases in human, crop and livestock densities have the potential to augment both the incidence and severity of infectious diseases.

Feeding 11 billion people — and the associated increase of land converted to agricultural production and livestock grazing — is expected to cause a surge in human–livestock, human–wild animal and livestock–wild animal contact rates, increasing the likelihood of ‘spillover’ events, which are defined as pathogen transmission from a reservoir host population to a novel host population^112,113. As natural ecosystems are converted to crop land or range land, interactions among humans, and domesticated and wild animals, could increase⁶⁶. Furthermore, if developing countries follow a trajectory similar to developed countries, then their demand for meat will increase, further increasing human–livestock, human–wild animal and livestock–wild animal contact rates¹¹⁴. These interactions are crucial because 77% of livestock pathogens are capable of infecting multiple host species, including wildlife and humans¹¹⁵, and based on published estimates from the 2000s, over half of all recognized human pathogens are currently or originally zoonotic^29,116,117, as are 60–76% of recent emerging infectious disease events^1,29,117 (Fig. 4). Examples of recent zoonotic disease emergences with enormous impacts on either livestock, humans or both, many of which might have agricultural drivers, include avian influenza, salmonellosis (poultry and humans), Newcastle disease (poultry), swine flu, Nipah virus (pigs and humans), Middle East respiratory syndrome (camels and humans), bovine tuberculosis, brucellosis (mostly cattle and humans), rabies (dogs and humans), West Nile virus, severe acute respiratory syndrome (SARS) and Ebola (humans)^1,113.

To quantify the relationship between agricultural factors and disease emergence in humans through time, we used the human disease emergence database of Jones et al.¹. We classified land-use change, food industry and agricultural industry as agricultural drivers of human disease emergence (see Supplementary Methods). These analyses revealed that agricultural drivers were associated with 25% of all diseases and nearly 50% of zoonotic diseases that emerged in humans since 1940 (Fig. 5). These values are even higher if we include the use of antimicrobial agents as an agricultural driver of human disease emergence, given that agricultural uses of antibiotics outpace medical uses in the developed world nearly nine to one^74,118.

Several factors have materialized that facilitate spillover events associated with disease emergence¹¹³. Spillover appears to be a function of the frequency, duration and intimacy of interactions between a reservoir and novel host population¹¹². For example, influenza is believed to have jumped from horses to humans soon after domesticating horses and then made additional jumps to humans from other domesticated animals, such as poultry and swine¹¹⁹. Similarly, when free-range turkeys were prevented from interacting with wild birds and when interactions between domesticated pigs and wild fruit bats were reduced, influenza and Nipah virus incidence dropped, respectively, suggesting wild-animal sources of these infections^120,121. In sub-Saharan Africa, the high frequency and duration of environmental interactions between different species of Schistosoma worms infecting humans and cattle has undoubtedly facilitated their hybridization, and these hybrid schistosomes are more virulent to humans than their non-hybrid counterparts¹²². These factors associated with spillover and disease emergence could be targeted to reduce transmission potential as human populations and agricultural productivity increase.

Exploitation of natural resources and infectious disease

Given that most human population growth is expected to occur in developing, tropical countries, hunting, fishing and gathering pressures will almost certainly rise in subsistence economies^13,123. The consequences of these pressures might initially increase contact rates between humans and wildlife. This could increase disease risk as bushmeat hunting is already thought to be responsible for several emerging human infectious diseases¹¹⁶. To make matters worse, bushmeat hunting is the second biggest threat to biodiversity behind habitat loss, and biodiversity losses can contribute to disease emergence¹⁰¹. However, if humans overexploit these natural resources, then human–wildlife interactions could eventually decline as species go extinct, which could reduce spillover events.

Changes in the composition of biodiversity associated with overhunting and overfishing can also have complex indirect effects on disease risk mediated by species interactions. For example, empirical evidence supports the notion that defaunation of large vertebrates in Africa should increase zoonotic disease risk by reducing the predators and competitors (large herbivores) of rodents, a common reservoir of human pathogens¹²⁴. Similarly, overfishing of snail-eating cichlids in Lake Malawi in Africa seems to have been a causal factor in snail population and human schistosomiasis increases there¹²⁵. Investigations of the effects of overexploitation on infectious diseases remain in their infancy, but the consequences for human populations could be profound.

Effects of human infectious diseases on food production

Up to this point, we have focused on the effects of feeding 11 billion people on infectious diseases, but the relationship is bidirectional. That is, human infectious diseases can also impact the agricultural and economic development necessary to feed the growing human population (Fig. 2). For example, the overuse of antibiotics, anthelmintics and pesticides to prevent diseases is driving resistance to these chemicals that will compromise future crop, livestock and aquaculture production. In sub-Saharan Africa, areas with higher historical tsetse-fly abundance, the vector of the parasite (Trypanosoma brucei) that causes African sleeping sickness in humans and cattle, experienced greater lags in the adoption of animal husbandry practices (for fertilizer and labour in agricultural enterprise) that hindered agricultural development and prosperity in Africa long before and after Europeans colonized¹²⁶. In rural subsistence communities, any source of ill health can significantly impact people’s productivity, yields and agricultural output^47–49. For example, human immunodeficiency virus/AIDS has reduced average life expectancy in sub-Saharan Africa by 5 years since 1997, and a Kenyan study found that crop production by rural subsistence-farming families dropped 57% after the death of a male head of household¹²⁷. Many neglected tropical diseases (NTDs) impose devastating productivity losses for affected people that can impede agricultural development from local to national to regional scales⁴⁹. Some low-income communities appear mired in this poverty–disease trap, and thus might require substantial investment in health systems to promote the necessary agricultural and economic growth to pull them out of the poverty–disease cycle^47–51.

Advances and outlooks

The goal of identifying potential changes to infectious disease risk associated with feeding the growing human population is not only to draw attention to this important current and future problem but to also encourage preparation for these changes by stimulating agricultural- and disease-related research, management and policy that could maximize the human health benefits of agricultural development¹²⁸. One urgent challenge is the problem of antibiotic, anthelmintic and pesticide resistance. Analyses demonstrate that, in some cases, improvements in growth and feed consumption can be achieved by improved hygiene instead of antibiotics⁷⁶. Indeed, all antibiotics as growth promoters were banned in the European Union in 2006¹²⁹. To curb antimicrobial consumption in food animal production, Van Boeckel et al.⁷⁵ suggest: (1) enforcing global regulations to cap antimicrobial use, (2) adhering to nutritional guidelines leading to reduced meat consumption, and (3) imposing a global user fee on veterinary antimicrobial use. In addition, as recommended by the World Health Organization, International Organization for Epizootics, and Food and Agriculture Organization, national and international policies based on best management practices should be developed and implemented that document when and how antibiotics should be used, and agencies should be established to monitor their use, mandate reporting and enforce these policies⁷⁶. Finally, given that host genetic variability can reduce disease risk¹¹⁰, large-scale industrial livestock operations could add genetic variability into their artificially selected food animals in an effort to reduce epidemics and epizootics. These changes promise to secure the long-term viability of antibiotics and anthelmintics for curing diseases of humans and non-human animals.

Another challenge that seems surmountable is to enhance education and health literacy. Not surprisingly, education has been documented as a major contributing factor to reducing infectious diseases, especially NTDs, and reducing NTDs can have reinforcing positive effects on the ability of humans to fight more deadly diseases, such as AIDS, malaria and tuberculosis⁴⁹. Limiting NTDs could also have knock-on effects for education and health literacy because NTDs impede cognition, learning and school attendance⁴⁹. Indeed, an investment of just US$3.50 per child for NTD control can result in the equivalent of an extra school year of education⁴⁹. This is likely an underestimate because of unaccounted for indirect effects of deworming on learning. A recent study revealed large cognitive gains among children who were not dewormed but had older siblings who were¹³⁰. Thus, enhanced education and NTD control have the potential to synergistically fuel agricultural and economic development and facilitate escape from the poverty–disease trap.

National and international shifts in investments could also potentially pay large dividends for nutrition, infectious disease control and poverty reduction. There is considerable evidence that the developing world will struggle to feed its growing human population because of the poverty trap of infectious disease⁴⁹. However, evidence also suggests that this trap might be broken through investments in health infrastructure and preventive chemotherapy^47–49. Curing worm diseases has the potential added benefit of reducing nutritional needs of cured individuals by ceasing the feeding of their parasites. By reducing food demand, these drugs could also protect the environment by reducing the conversion rate of natural areas to agriculture. This, in turn, might help to curb climate change, which is one of the greatest threats to global food security¹¹ and might also increase disease risk^131,132. Understanding the economic relationships among infectious disease treatment and prevention, food production, poverty and climate change in the developing world are important areas of future research.

As human populations increase, there might be more pathogen spillover events that could result in new emerging human infectious diseases. Historically, humans have combated emerging diseases through early detection followed by coordinated quarantine, as demonstrated by the SARS outbreak in 2003 and the Ebola outbreak in 2014. We recommend continued and improved coordinated international disease surveillance, but this approach reacts to rather than prevents disease. We recommend a shift in both research and disease management efforts towards proactive management approaches. One proactive approach that has promise for preventing zoonotic disease emergence is biodiversity conservation^98,101, but more research is needed to evaluate its effectiveness across various types of zoonotic diseases and its costs and benefits relative to more proven reactive public health interventions. Ultimately, science needs a better understanding of pathogen spillover, the origins of disease emergence and post-spillover evolution so that human disease emergence can be better predicted and prevented^112,113,133.

Improved and diversified plant and animal genetic material could also help to simultaneously reduce hunger and disease. Many efforts are already well underway; for example, introducing C₄ traits into rice to enhance higher photosynthetic capacity in a warming world, and breeding drought- and flood-tolerant cereals, pulses and vegetables better suited to increased frequency of extreme weather events that can help sustainably enhance productivity. Crops and livestock genetically adapted to resist more pests can reduce pesticide and antibiotic use. In addition, given that micronutrient deficiencies are now the most widespread source of undernutrition globally, commodity research must diversify beyond merely boosting productivity of staple cereals. Far greater attention is needed on approaches that add mineral and vitamin content to foods³⁹.

Other, perhaps more challenging, interventions also merit attention. Closing ‘yield gaps’ on underperforming lands, increasing cropping efficiency, eating less meat and excess per capita food consumption — which also have adverse health impacts on non-infectious diseases, such as high blood pressure, diabetes and heart disease — and reducing food waste and loss have the potential of doubling global food supplies^{6,114,134,135}, while simultaneously allowing financial savings to be redirected towards health infrastructure to control disease. In addition, family planning, promoting female education and job market prospects, and enhancing early childhood survival have proved very effective at reducing human population growth¹³⁶. Finally, producing food in more urban and suburban environments through vertical farming (the practice of growing produce in vertically stacked layers) also has potential to enhance food production locally, and might have reduced agrochemical and transportation costs and non-target effects relative to more traditional farming¹³⁵.

Investments into predictive models could also pay dividends. Agricultural environments are complicated, multi-species systems that exhibit interactions at many levels. The complexity further increases from the tensions that arise in balancing expanding agricultural systems, social benefits and infectious disease risk. All of this complexity can overwhelm many analytical tools and experiments, which makes advances in mathematical modelling especially crucial to addressing these issues. Box 1 describes several examples of advances in mathematical modelling that illustrate their promise for analysing the links between agricultural practices and the dynamics of infectious diseases, projecting risks to future decades, influencing risks through either intentional (policies and interventions) or unintentional (continued habitat conversion and antibiotic use) actions, and incorporating economic and social costs of various public health or agricultural interventions. These models should help direct field experiments, which are desperately needed to parameterize and validate these models and to quantify key sources of uncertainty.

Ultimately, we believe ‘win–win’ scenarios for controlling infectious diseases, increasing agricultural productivity and improving nutrition are attainable. Although this sort of integrative thinking has been historically rare because agriculture and public health have been perceived as disparate disciplines, it is beginning to slowly penetrate these distinct fields of study. For example, several agrochemicals seem to increase the risk of human schistosomiasis and agriculturally derived zoonotic pathogens, and thus researchers are actively attempting to identify agrochemicals that might ‘kill two birds with one stone’, reducing crop pests and thus increasing food production while not increasing or even decreasing human pathogens^137–139. Similarly, researchers are beginning to consider the introduction of prawns as biological control agents of schistosomiasis, which could simultaneously decrease disease and increase nutrition — because restored prawns can be fished, harvested and consumed without compromising their disease-controlling benefits^61,140. We believe that more resourceful and creative thinking and interdisciplinary interactions (among medicine, public health, agriculture professionals, economists, anthropologists, sociologists, modellers, empiricists and wildlife biologists, in the developed and developing world) have great promise for sustainably and simultaneously improving human nutrition while controlling infectious diseases.

In conclusion, we hope that by synthesizing the complex intersection of food production and human health, we have highlighted the value of increasing agricultural- and disease-related research, management and policy, maximizing the benefits of agricultural development while minimizing its adverse effects on human health and the environment, and preparing for the imminent changes driven by the 11 billion people expected to inhabit Earth by 2100.

Supplementary information

Author contributions

J.R.R. developed the idea and wrote most of the paper. Figure 1 was developed by S.H.S. and G.A.D., Figs. 2 and 4 were developed by J.R.R., Fig. 3 was developed by K.H.N. and B.D., Fig. 5 was developed by D.J.C., M.E.C. and R.S.O., and Box 1 was developed by D.J.C., M.E.C. and J.V.R. All authors substantially contributed ideas, revisions and edits.

Competing interests

The authors declare no competing interests.

Supplementary information

Supplementary information is available for this paper at 10.1038/s41893-019-0293-3.