Outbreak Science | Chapter 1: Emerging Pathogens

FIGURE 1.0 | Conceptual illustration of an outbreak unfolding across the globe.

CHAPTER 1

Emerging Pathogens

Selected Key Terms

As you dive in, we will introduce you to many new concepts typically used in Outbreak Science. However, we have selected a set of key terms in each chapter for you. By the end of this chapter, you should be able to recognize and apply the key terms and understand concepts introduced in the emerging pathogens chapter.

Airborne Transmission

Biological Weapon

Cross-species Spillover

Diagnostics

Droplet Transmission

Emerging Pathogens

Endemic

Exposure

Host

Infected

Infectious Diseases

Microbe

Pathogens

Reemerging Pathogens

Strains

Transmission

Vaccines

Zoonosis

Big Concepts

1.1: Infectious Diseases and Emerging Pathogens

The emergence of new disease-causing agents known as “pathogens” and the reemergence of previously contained pathogens threaten public health today. There is a broad range of infectious pathogens affecting human health, and we have dealt with the threats of infectious diseases since the beginning of our history. Societal changes have contributed to the emergence and reemergence of infectious diseases. Today, scientists study pathogens such as bacteria and viruses and how they arise in human populations to prevent the spread of disease.

1.2: Major Drivers of Infectious Disease in the Modern Era

Many emerging pathogens appear in the human population after human contact with wildlife through a process known as “zoonotic spillover.” Many of these emerging pathogens cause epidemics or pandemics. Several social factors contribute to these spillovers, including animal trafficking and poaching, industrial expansion spurred by population increase and deforestation, and climate change. Worldwide public health infrastructure and education are essential to contain zoonotic spillover events wherever they might occur.

1.3: Infection and Transmission of Emerging Pathogens

The ways pathogens spread significantly impact our efforts to contain them. Pathogens can spread in many ways but can only spread to particular hosts, known as their host range. Animals can pass infections to humans, and humans can spread pathogens to other humans through both direct and indirect pathways. Human-to-human spread is of great concern in our increasinglyconnected world. Knowing the types of interactions that allow a particular pathogen to spread is crucial to design effective containment strategies.

1.4: Future Threats and Countermeasures

Catastrophic infectious disease outbreaks have occurred repeatedly and will likely continue to occur. Fortunately, leading agencies have compiled a list of the diseases that should be prioritized for research and preparedness initiatives. In addition to devastating natural outbreaks, the unfortunate reality is that infectious agents can be created and used to cause intentional harm. Therefore, organizations at the local, regional, and international levels work together to establish regulations for public health safety and that researchers remain cautious of the ways pathogens, both known and yet to be discovered, spread and cause harm.

Vick’s Video Corner Watch “Vick’s Video Corner” as an entry point for this chapter.

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Emerging Pathogens 1

By the end of this chapter, you should understand the fundamentals of infectious diseases and how they spread. You will have a deeper appreciation for both the difficulties of studying emerging pathogens and how crucial it is to carry out this work, considering the impact of emerging pathogens on society. We will introduce you to a wide variety of concepts and many new vocabulary words. Do not worry if you don’t fully capture them in this chapter, as you will revisit them throughout this textbook. This chapter will lay the groundwork you’ll need to understand the chapters to come. Let’s dive in!

It’s January 3, 2020, and you’ve just received a package from a clinic in Wuhan, over 500 miles from your lab in Shanghai. It contains a swab from a patient battling a mysterious illness, which has swiftly become your lab’s number one priority. This illness appears to have arisen in Wuhan in late 2019 and passed from person to person throughout mainland China, wreaking havoc in many communities. You’re concerned that what you hold in your hand could cause a full-blown pandemic –a phenomenon where an agent that can cause a disease, known as a pathogen, has spread through many regions and often around the globe.

Based on its rapid spread, leading researchers are already encouraging elevated precautions when working with samples from patients with the new illness. They recognize its similarities to a different disease that caused a 2003 outbreak – or rapid rise in cases of the

particular disease — in China, which was named Severe Acute Respiratory Syndrome (SARS). The country has painful memories of the outbreak caused by the SARS coronavirus, which is a virus that can infect humans, which means they can cause disease, also known as an infection

“But however secure and wellregulated civilized life may become, bacteria, protozoa, viruses, infected fleas, lice, ticks, mosquitoes, and bedbugs will always lurk in the shadows ready to pounce when neglect, poverty, famine, or war lets down the defenses.”

—Hans Zinsser, American bacteriologist

Infectious diseases are illnesses caused by biological agents when they grow in humans or animals. The organisms that are infected – i.e. are invaded and entered by the pathogen – are known as the hosts. Studying these hosts is key to understanding infectious diseases, as interactions with other potential hosts are what drives the spread of disease. With increased transportation, trade, and worldwide connectivity, the chance of contracting and spreading one of these new diseases is on the rise. Since early reports indicate that the mystery virus you’re working with now may present very similar characteristics to SARS, the weight and urgency of your work are not lost on you. You get to work deciphering its genome, the complete set of genes found in an individual or species that guide their development and growth.

By January 5th, 2020 at 2 a.m., the genetic sequence is complete—you now have the entire genome of the pathogen responsible for this outbreak. You are alarmed to see that it bears a striking similarity to SARS, and you worry that its effects will be just as bad, if not worse. Like most careful scientists, you usually take time to closely scrutinize all of your work before publishing it. This time, however, you feel certain that it’s in the public’s best interest to make the sequence available immediately. Later that morning, you upload the sequence to a United States (US) biotechnology database and notify scientists in an international consortium you lead.

As you try to upload to the official, more broadlyaccessed databases, you encounter a severe delay in approval. You soon receive a call from your colleague, Dr. Eddie Holmes, who shares your concerns for what every moment of delay might mean on a global scale; the two of you agree that the sequence must be released as soon as possible. You plan for Dr. Holmes to send the sequence out into the world, as you suspect he will encounter fewer delays submitting it from

his lab in Australia. He posts the sequence on a popular viral research repository, and in a matter of hours, it has reached scientists around the globe. The world begins to investigate every unknown fact about this novel pathogen, or pathogen previously unknown to a population, now officially named SARS-CoV-2, and the original SARS pathogen is renamed to be SARS-CoV-1 (Figure 1.1). Researchers around the world start looking into the virus’s relatedness to other SARSlike viruses, and they begin devising strategies to fight it, including diagnostics — tests that either confirm or rule out the presence of a particular pathogen or disease — and vaccines — substances used to prepare the body to fight off future infections without actually contracting the disease.

1.1 | Microscopy image of SARS-CoV-2 viruses. Electron microscopy can magnify images up to 50 million times, providing incredibly detailed images of even the tiniest structures; here in yellow, we can see viral particles of the SARS-CoV-2 virus. Electron micrographs are typically black and white, but the image was digitally enhanced to show color and differentiate the viral particles from cell organelles. Image credit: NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.

FIGURE

The virus races around the world, and suddenly you and the rest of the global community are immersed in a pandemic. You continue to collaborate with other scientists to study the pathogen, and as you learn more and more about this new virus, you caution the world that previously-unidentified pathogens, such as SARS-CoV-2, pose a significant threat to health worldwide. You hope that researchers, policymakers, and the public alike will heed the warnings issued by you and thousands of other infectious disease researchers across the globe.

Your name is Zhang Yongzhen, the Chinese virologist who first identified the SARS-CoV-2 genome and paved the way for researchers around the world to begin the fight against COVID-19. You issue a message to the world: “If we don’t learn lessons from this disease, humankind will suffer another.”

1.1:

Infectious Diseases and Emerging Pathogens

In The Art of War, Sun Tzu, a famous Chinese military figure whose military strategies and philosophies from the 5th century Before the Common Era (BCE) are still respected worldwide, stated, “If you know the enemy and know yourself, you need not fear the result of a hundred battles.”

Although Sun Tzu was referring to human enemies in his famous quote, humanity has been fighting a war that has lasted far beyond a hundred battles against “invisible” enemies. These “enemies” are the pathogens (also referred to as “germs” or “bugs”) that cause infectious diseases.

So, how can we take Sun Tzu’s advice, and learn more about the pathogens that can endanger our health? The answer is through science:

the process of studying the natural world and its phenomena through systematic, testable approaches. There are many different types of sciences, each focused on specific aspects of the natural world, and many ways in which scientific discoveries impact our lives. Outbreak science focuses on the comprehensive understanding of infectious diseases, from the molecules inside pathogens to the societal factors that influence how diseases spread. As you will learn throughout this textbook, outbreak science is critical for protecting against the regular emergence of pathogens—as well as manmade biological threats—and it is also central to outbreak preparedness, or our readiness to respond to pathogenic threats. The remaining chapters in this textbook are designed to provide you with a background on outbreak science, and equip you with the skill sets needed to better understand key elements for prevention, preparation, and response.

You might already be familiar with infectious diseases, like the flu that circulates each winter, chicken pox, and the common cold. But do you know about the infectious agents that can cause the disease as they enter or infect your body? Infectious diseases, commonly caused by microorganisms typically invisible to the naked eye, are known as microbes, given their microscopic size. However, infectious diseases can also be caused by larger organisms or nonliving materials. When these infectious agents – both large and small – cause disease, they are classified as pathogens, derived from the Greek word pathos, meaning “suffering.” To win the war against infectious diseases, we must begin by understanding how the pathogens that drive them arise in the population. Pathogens include incredibly diverse categories of organisms, any living system that functions as one entity, including bacteria, viruses and many other agents. We will study these more closely in

Chapter 5: Biology of Infectious Agents, but we will start by exploring some striking differences between the two most common types: bacteria and viruses.

Bacteria are unicellular microorganisms––meaning that the whole organism is only one cell in size––that have a cell wall and reproduce by cell division. Most bacteria are beneficial, but some are pathogenic, which can cause disease. Viruses, on the other hand, are non-cellular microscopic particles that require a host cell to reproduce. They can’t survive for long on their own, so they infect the cells of living organisms and use the host cell’s machinery to make copies of their own viral material.

All organisms can host pathogens. In fact, even bacteria can themselves be infected by viruses. For the purposes of this textbook, we’ll focus mainly on agents that infect the human population. We’ll also see how most of our preventative measures–such as food-handling laws, vaccinations, and waste management–are designed to protect us from infectious diseases.

One thing that makes pathogens so formidable is their ability to move within the human population; one human host can spread the pathogen to another person, creating a second host. This passage of infectious material is known as transmission. A rise in the transmission of a pathogen can cause an outbreak.

A pathogen’s characteristics impact how the disease spreads between organisms and, therefore, our ability to contain the disease. Certain pathogens may have a more significant potential to trigger an epidemic — the rapid spread of infectious disease throughout a given region — than others. Some can even spread on a larger scale, causing a pandemic. On the other hand, diseases that are common and persistent in

a population are known as endemic. Importantly, diseases introduced to new geographical areas during an epidemic or pandemic have the concerning potential to become endemic within a given region.

We’ll go into detail about specific pathogens and learn about the components of their biology that provide them with the potential to cause epidemics in Chapter 5: Biology of Infectious Agents. For now, we will focus on understanding why pathogens emerge in the first place and their impact on humanity.

What Is An Emerging Pathogen?

An emerging pathogen is a pathogen that is either entirely new to a population (otherwise known as a novel pathogen) or one that quickly increases in prevalence and geographic range. The resulting diseases that manifest in infected hosts are therefore referred to as emerging infectious diseases (EID). SARS-CoV-2, the virus that causes the COVID-19 disease, is a recent example of an emerging pathogen. Reemerging pathogens, on the other hand, are those that experience an increase in prevalence either after a previous decline within a population or after a change in a pathogen’s geographic distribution. An example of a reemerging pathogen is the bacterium responsible for tuberculosis, Mycobacterium tuberculosis – shortened as M. tuberculosis – which attacks the lungs of its human hosts (Figure 1.2). Found frequently in the lungs of those whose immune systems have been weakened by human immunodeficiency virus (HIV), M. tuberculosis has seen a worldwide rise in recent decades due to drug resistance, a phenomenon by which a pathogen develops defenses against previously-effective drugs.

Now that we know what emerging pathogens are, let us ask ourselves the following: When did

FIGURE 1.2 | Mycobacterium tuberculosis is an example of a reemerging pathogen. M. tuberculosis attacks the lungs of humans, and due to drug resistance, it reemerged worldwide in recent decades.

pathogens emerge as infectious agents Now that we know what emerging pathogens are, let us ask ourselves the following: When did pathogens emerge as infectious agents of the human species? How has society and human behavior contributed to the emergence of infectious disease? And, lastly, where do these pathogens emerge from? To answer these questions, we must go back to the beginnings of human civilization.

History of Infectious Disease Emergence: A Societal Lens

As you may already know, humans are not unique in our ability to contract infectious diseases; all organisms have faced pathogenic threats throughout world history. Humans have, however, been responsible for some key events and transitions that contributed to the emergence, spread, and evolution of pathogens. These include the development of agriculture, the creation of permanent settlements, movements of people to new lands, engagement in conflict, and globalization, amongst others.

Many anthropologists believe a major shift in our interactions with emerging pathogens began over 12,000 years ago, during the first Agricultural Revolution. This social transition saw humanity shift from hunting and gathering

to producing their own food through farming and agriculture, kicking off what is known as the Neolithic period. In addition to cultivating crops, humans began domesticating livestock – farm animals such as sheep, pigs, and cows – and this prolonged contact with animals is believed to have exposed humans to novel pathogens. Archeologists have determined that smallpox, tuberculosis, and malaria, as well as many other infectious diseases, emerged from related pathogens originally found in animals. These pathogens then picked up mutations – or changes in parts of their genome – and began infecting humans. This “jump” of pathogens from animals to humans is termed zoonosis.

Another significant shift in the emergence of disease occurred with the rise of settlements that accompanied the shift to agricultural communities, such as the ancient river valley civilizations dating back to 4000 BCE. The Indus Valley civilization, who lived in present-day Pakistan, India, and Afghanistan, was among the first of its kind (that we know of), with large groups of individuals settling together rather than operating independently. Settlements were supported by infrastructure – or the basic equipment and structures needed for a society to function properly, such as sewage management, pest control, and general sanitation, among others. With increasingly urban lifestyles and the development of infrastructure, there was an increase in interactions with other humans leading to the rise of public health hazards.

As settlement inhabitants were forced into more crowded conditions, their potential for being exposed to pathogens increased. As a result, new “social” diseases like influenza – which you likely know as the cause of flu season every year – now had densely-populated communities to spread through, causing significant harm to these new settlements.

As humanity progressed deeper into community-based lifestyles, people started investigating the causes of emerging communicable diseases (a subgroup of infectious diseases), the diseases that could be passed from person to person. In Sumer, the earliest recorded civilization in Mesopotamia and one of the oldest known civilizations in the world, citizens had interactions with domesticated animals (Figure 1.3), and there are records of the link between diseases in livestock with similar diseases in human communities. The emergence of pathogens infecting the human population through zoonosis has been happening for thousands of years and remains a fundamental cause of many of the emerging pathogens we see today.

While some ancient cultures attributed these diseases to uncontrollable acts of God, different theories on the emergence and spread of disease gained popularity over time. One such example was Hippocrates’ four humors theory, popular in Ancient Greece, as well as North Africa and the Middle East, in which one was said to contract a disease if the four core fluids within the body – blood, phlegm, yellow bile, and black

bile – somehow became “imbalanced.” The miasma theory, which gained its name from the ancient Greek word meaning “pollution,” posited that disease was spread by toxic vapors within a community; while its Greek name is widely known, this theory likely originated in China. As new theories developed, they continued to spread as people crossed borders to travel further, interacting with new communities around the globe. Eventually, in the 1500s, germ theory, which stated that small microscopic organisms could be transmitted and cause disease, would become widely understood and adopted. We will learn more about germ theory and the different kinds of pathogens themselves in Chapter 5: Biology of Infectious Agents.

A major driver of emerging pathogens is migration – the movement of people to new lands – and colonization – the forceful process of establishing control over an existing community to take the land or its resources. As explorers and colonizers began venturing out into new environments, they may have been infected by various pathogens or even propagated them throughout their travels. Zheng He, a Chinese

FIGURE 1.3 | Sacred herd being fed by the king-priest and his acolyte. On this engraved cylinder from the Uruk period, circa 3200 BCE, we can see citizens of Mesopotamia interacting with domesticated animals. The emergence of pathogens infecting the human population through zoonosis has been happening for thousands of years.

Muslim royal guard-turned-explorer who traveled throughout Southeast Asia and East Africa, is suspected to have ultimately succumbed to an infectious disease in 1433. His body was said to have been tossed overboard into the sea by his crew to reduce the risk of infection. Those journeying to the “New World”— colonizers like Christopher Columbus and others — are believed to be directly responsible for the emergence of major infectious diseases and epidemics that spread through their travels and wreaked havoc on the indigenous peoples –communities, peoples, and nations native to a region, sometimes known as native communities – that they colonized. You may be familiar with the history of diseases like measles and smallpox sweeping through indigenous communities in the Americas, resulting in hundreds of thousands of deaths. The indigenous communities were susceptible populations (sometimes also known as naive populations), which are groups of people that have never encountered, and therefore have no defenses against, a particular disease.

It is important to remember that there have been many explicitly intentional incidents where indigenous populations were infected with pathogens. For example, in 1763, under the direction of high-ranking officer Jeffrey Amherst, British soldiers gave two blankets taken from smallpox patients to the Lenape people in the area that we now call Delaware. An eyewitness is said to have commented, “I hope it will have the desired effect.” While there is some academic debate about whether any infections resulted from this plan, the intent is clear. This represents an example of a “deliberately emerging” pathogen, better known as a biological weapon, a toxin or an infectious agent used as a weapon to cause death or disease. This biological warfare represents a form of colonial violence, as well as the pursuit of a political agenda with lethal means.

Other political conflicts and wars continuously placed different, historically-separated groups in close contact, in some cases with the purposeful spread of disease. For example, as China’s Qing dynasty sought to conquer Mongolia in the early 1700s CE, they introduced smallpox to many previously isolated Central Asian populations, causing a vast proportion of all the deaths. Amursana, the last ruler of a prominent Mongol tribe, was killed by smallpox in 1757—a critical death that signaled the end of Mongolia’s fight against China, as well as Mongolian power as a whole throughout Eurasia. During World War I, one of the largest global conflicts in human history, the leading cause of death among soldiers was not the violence of conflict; rather, it was an infectious disease called influenza. Influenza greatly proliferated during this time of increased global interactions between individuals who wouldn’t have otherwise met, with soldiers living in often-unsanitary, close quarters with one another and then traveling back to their countries and cities of origin. Experts now believe that 50 million people died of influenza during this period, nearly 3% of the world’s population at that time.

Emerging Pathogens of the Modern Era

The 20th century was a century of major advances in science alongside increased globalization and global conflict; with it came a number of devastating infectious disease outbreaks and the discovery of numerous pathogens. One of the most catastrophic was the 1918 influenza pandemic. Within the pandemic’s first six months, an estimated 25 million people had lost their lives around the world; the high death rates in healthy individuals 20-40 years old were particularly alarming. The 20th century also brought a host of newlydiscovered viruses, including Zika in 1947, Lassa in 1969, and Ebola in 1976.

FIGURE 1.4 | NIAID 2017 world map tracking emerging pathogens. This map highlights emerging infectious disease threats around the globe. Classification is given by newly emerged (red), re-emerging (blue), and deliberately emerging (black).

Then, in 1984 alone, the US documented nearly 7,700 cases and 3,665 Acquired Immunodeficiency Syndrome (AIDS) deaths –just three years after HIV, the virus that causes AIDS, rose to public awareness. After Dr. Anthony Fauci was appointed as director of the National Institute of Allergy and Infectious Diseases (NIAID) in 1984, he testified before Congress and displayed the world map shown in Figure 1.4, highlighting HIV/AIDS as an EID threat. Every year since, NIAID has added one, two, sometimes even three, new EID to this now-famous map.

By the early 1990s, public health concerns around the rise of HIV/AIDS, the reemergence of tuberculosis, and the increased opportunity for disease spread were crystallized in a landmark report by the US Institute of Medicine titled “Emerging Infections: Microbial Threats to Health in the US.” There they made popular the concepts of emerging pathogens and EID that they cause. While EID are the diseases that emerge in a population, for the purposes of this textbook, we will focus on the emerging pathogens themselves — the “bugs” ultimately causing the diseases.

Stop to Think

1. What’s the difference between microbes and pathogens?

2. Historically, what have been the main drivers for emerging pathogens in society?

3. How do reemerging pathogens differ from emerging ones?

4. How do political conflicts and wars aid in spreading infectious disease?

Cholera Lassa fever

hemorrhagic fever Plague

H10N8 influenza E.coli O157:H7 E.coli O104:H4

MDR/XDR tuberculosis

1.2: Major Drivers of Emerging Infectious Diseases in the Modern Era

It’s clear that both emerging and reemerging pathogens continue to pose a threat to human health and wellness worldwide. So let’s ask ourselves, from where exactly do these pathogens originate? We’ll elaborate here on the main driver of pathogen emergence and spread, zoonosis.

Zoonosis

Groups of organisms sharing the same biological characteristics and capable of reproducing with each other are known as species. Pathogens can spread from species to species in what we know as a zoonotic spillover event. While every pathogen is different, many of the pathogens that cause epidemics or pandemics are the result of spillovers. Zoonotic spillover events occur when a pathogen in one species (such as bats) mutates enough to be able to infect a different species (such as humans) for the first time and “jumps” from the original host to the new one. Pathogens that can jump from one species to another are said to have zoonotic potential; we call it a “spillover” because the pathogen has spilled into a new species. Spillover events can occur wherever domesticated animals or wildlife come into contact with humans.

When humans and other animals come into contact, pathogens can be transferred from one host to the other. In fact, it’s estimated that 60 - 70% of human infectious diseases originate in animals. These pathogens are not always able to infect the new host due to various differences in the biology of the potential host organisms. However, pathogens that are equipped to infect a new susceptible host population can wreak havoc as the hosts would lack the defenses to stop them. The animal species that originally

houses the pathogen is called a natural reservoir host, and interestingly, frequently harbors the pathogen without becoming ill themselves. For example, fruit bats are believed to be the natural reservoir hosts for a variety of pathogens that affect the human population, including Ebola virus, Nipah virus, and some coronaviruses, but do not typically demonstrate signs of illness when infected by these pathogens.

Sometimes pathogens require intermediate hosts to bridge the gap between their reservoir hosts and humans, transmitting from the reservoir to an intermediate host, and finally, to humans. For example, the natural reservoir for Hendra virus are bats, also known as flying foxes. However, all seven known human cases of Hendra virus infection have been instead linked to contact with sick horses and not to sick flying foxes. These horses therefore appear to be intermediate hosts; the horses can become infected after being in contact with bodily fluids of infected flying foxes, producing a high amount of virus in their bodies, and ultimately passing the infection to humans.

Past flu pandemics have been caused by an intermediate host, paired with other important phenomena, reassortment – the swapping of genome components to make a brand new but genetically related pathogen. When two or more hosts transmit different genetically related pathogens into the same host, the pathogens have a chance to interact and form an entirely new, recombinant pathogen –that is, a pathogen with genetic material coming from more than one parent pathogen. The parent pathogens’ genomes mix and combine, reassorting themselves into a new pathogen.

The 2009 flu pandemic was caused by a recombinant pathogen, H1N1, also known as Swine Flu (swine meaning pig), that originated

FIGURE 1.5 | Reassortment in a swine host. Birds (avian), pigs (swine), and humans each have different viruses that infect them. Sometimes, however, viruses are able to transmit to other species. By having multiple viruses co-infecting the same host, there is a chance that their genetic material can mix and form a new, never-before-seen pathogen. The resulting novel viruses can be especially dangerous to humans. The H1N1 Swine Flu virus causing the 2009 swine flu pandemic emerged after the reassortment of three viruses in a swine host.

from multiple flu strains. Strains are subsets of a class of pathogens or viruses that are genetically unique. Both a human flu strain and avian flu (avian meaning bird) strain are believed to have simultaneously infected the same pig. The human and avian flu strains were then able to reassort with two different swine flu strains (classical swine H1N1 virus and Eurasian swine virus) to make a brand new strain of influenza (Figure 1.5). This reassorted, novel virus contained components of all four strains (human, avian, classical swine, and Eurasian swine), including the ability to transmit to humans, making it a new, dangerous flu virus.

It’s important to recognize that spillover events often go undetected at first. After all, if a child, too young to speak, was playing unsupervised near a bat’s nest and got infected, how would we know that the child had been exposed, much less how they became infected? We would remain in the dark until the child became ill and started

to show the symptoms of their disease. By then, they most likely would have already spread the infectious disease to their family, who could have gone on to spread it on to others, who spread it on to others, and so on. This is what is believed to happen four months before an Ebola outbreak was declared in West Africa in March 2014. While we’ve used an example featuring a child here, anybody could have an unknowingly be infected, and they might not be able to recognize the dangers until it is too late.

Contemporary Social Factors Driving Emerging Infectious Disease

While all interactions between humans and animal life have the potential to result in zoonotic spillover, three important drivers of EID have been identified as a result of modern social activities: (1) animal trafficking and poaching; (2) industrial expansion including population increase and deforestation; and (3) climate change.

Eurasia Swine Flu Virus

North American “Triple reassortment” H1N2 Flu Virus

1: Animal Trafficking and Poaching

We’ll start with animal trafficking, which is the illegal trade of living wildlife, and poaching, the illegal hunting of wildlife, or removal from areas that the poacher should not have access to. These and other exploitation of animal species increase the likelihood of zoonotic spillover events. In many parts of the world, exotic animals are sold in the pet trade or live animal markets called wet markets. These markets, though often relied upon for sustenance, bring together animals that would not have otherwise encountered one another in nature. Moreover, trafficked animals are usually subjected to stressful, cramped, and unsanitary living or slaughtering conditions. For instance, in many wet markets, animal cages are stacked atop one another, and the animals in cages at the bottom get contaminated with body fluids from the caged animals above. These factors create unprecedented environments for pathogens

to jump to new hosts; both the 2003 SARS outbreak and the COVID-19 pandemic are believed to have originated in wet markets. The pandemic has reached 229 countries and territories at the time of writing (15 March 2023) and continues to spread worldwide. Over 6.8 million people have died as a result.

Scan this QR code or click on this link to visit Our World in Data, a COVID-19 Tracker, to explore the most recent numbers.

2: Industrial Expansion

The second key driver of EID is the expansion of industrial efforts to support our current pace of life. The human population is currently at almost 8 billion people (Figure 1.6), with projections of up to 10 billion by 2050. As the population grows, we continue

FIGURE 1.6 | World population over the last 12,000 years. This chart shows the massive increase in the world population in the previous thousand years, alongside a concurrent rise in global life expectancy. The industrial and living conditions needed to support the human population are major drivers of zoonosis in modern society, as we expand our habitat and disrupt wildlife habitats, increasing human-animal interactions.

1.7 | Satellite images showing deforestation in the Amazon Rainforest (Rondônia in western Brazil) over the course of 34 years. Progression of the deforestation of nearly 52 million acres of Amazon rainforest between 1975 (left) and 2009 (right) where we see the loss of green areas. This catastrophe has been linked to an increase in the emergence of infectious diseases, such as malaria, in Brazil.

to expand our habitat, building new towns and communities, and our demand for natural resources and products continues to increase, encouraging us to encroach upon and disrupt existing wildlife habitats. The resulting interactions with animal life drive an uptick in outbreaks.

In some countries, various industries are known to cut down trees and deliberately set fire to rainforests through a process called deforestation , which is frequently undertaken to increase the land available for livestock farming, mining, and other infrastructure development. Because of deforestation, the Amazon rainforest is being destroyed at a rate of approximately 20,000 square miles per year (Figure 1.7), which is roughly the size of the state of West Virginia or a bit bigger than the island of Taiwan. The loss of rainforest and resulting havoc on surrounding ecosystems has been linked to

an increased burden of infectious diseases such as malaria in communities across Brazil, as displaced animals carry these diseases into the environments inhabited by humans, newly or otherwise, and force further interspecies interactions that can potentially propagate pathogen outbreaks.

Human interactions with the environment have radically changed over the past few generations. Through increased industrialization – the transformation of economies from primarily agricultural to manufacturing-based – we’ve not only reshaped the way we live and produce things but also changed the way in which humans and wildlife interact. The quantity of natural resources harvested 100 years ago is dwarfed by the consumption of natural resources today. Specifically, as technology rapidly advances, the demand for rare materials, like the precious metals inside of our phones and

FIGURE

computers, grows. To access these materials, we push humanity into previously-untouched habitats. The deeper we dive into diverse ecosystems, the more we risk encountering new pathogens that pose a threat to global health.

One example of industrialization-driven wildlife encroachment is the story of columbite-tantalite, or coltan — a rare mineral you can likely find in your cell phone. Industrial workers use coltan to make what are known as “tantalum capacitors,” which power many electronic devices because tantalum has a high melting point and resists corrosion. Coltan is mined in the rainforests of the Democratic Republic of the Congo (DRC) through a process called artisanal mining. Usually performed by villagers in

poor communities, artisanal mining requires clearing the land to dig for precious metals such as coltan (Figure 1.8). This clearing process brings miners into frequent contact with wildlife, as the mining can attract bats to the newly-hollow location, posing a risk to workers who might unknowingly flush them out of the ceilings of the caves. Furthermore, while they’re working in the region, artisanal miners often hunt and consume surrounding wildlife, preparing what is known as bushmeat for their meals.

Despite its cultural significance, consuming bushmeat can pose a threat to surrounding communities, as various popular types of bushmeat have been found to contain microbes that could potentially spill over into the human population once consumed.

FIGURE 1.8 | Artisanal mining in the DRC often necessitates close contact with animals and their environments. This type of work is one-way a spillover event from animals to humans can occur.

Since they are an underlying factor of resource procurement and consumption, many socioeconomic factors – like income, education status, and access to other similar resources –lead to the emergence of pathogens as well. Lower-income nations often bear the brunt of the labor demanded by global industrialization. As a result, their inhabitants face an increased risk of being infected by emerging pathogens and can lack the resources necessary to contain them. When entire economies and livelihoods depend on the export of natural resources, the workers might have little say over the conditions under which they are willing to work.

That said, it is important to recognize that there is similar spillover potential in any community that eats any kind of game or meat acquired by hunting or as roadkill. Some hunt or consume this meat out of necessity, others may hunt as part of cultural practice, and some even for sport. As such, worldwide public health infrastructure and education is important to contain zoonotic spillover wherever it might occur.

3: Climate Change

The third driver of EID we’ll discuss is climate change , which is the long-term change in typical patterns of weather and weather-events (i.e. hurricanes, snowstorms, and floods). Climate change is another factor affecting the rate of spillover and the spread of infectious disease, as it has been shown to influence both the geographic and seasonal distribution of many disease-causing vectors. A vector is a small living organism, such as a mosquito or tick, that carries an infectious agent between an infected animal and a new animal or human. Vectors, as you might imagine, are responsible for causing vector-

borne diseases , such as tick-borne Lyme disease and Crimean-Congo hemorrhagic fever (CCHF). We have seen a rise in vectorborne diseases as a consequence of our increasing carbon footprint. For instance, rising global temperatures have extended the duration of many insect seasons, allowing vectors accustomed to warmer climates to expand their habitats away from the equator towards higher latitudes. When diseasecausing vectors spread to new environments, they carry pathogens into susceptible populations. With no protection, the disease can spread through the population with little to no hindrance.

We can illustrate this spread, and change in spatial distribution, of vectors by examining the habitats of Aedes aegypti and Aedes albopictus , two of the most destructive mosquito species in the world. These two species are broadening their habitat ranges in the US and Europe, respectively, at an alarming rate. Both mosquitoes are vectors of the viral pathogens which cause Yellow Fever, Dengue fever, Chikungunya, and Zika; if they continue to expand their habitats at the current rate, researchers estimate that they will present a major disease threat to roughly half of the global human population by 2050.

The expansion of A. albopictus and A. aegypti poses a particular threat due to its ability to bring infectious disease to extremely susceptible populations. Since these new communities had never been in contact with these types of mosquitoes, they would have no prior protection against the diseases these species carried. As such, approaches to the diseases like the ones carried by A. albopictus and A. aegypti must not only alleviate the suffering of those currently infected, but also work towards containment before they spill over to new populations.

FIGURE 1.9 | Potential transmission pathways between animals and humans. Human-animal contact is a driver of zoonotic spillover events and can occur through live animal markets, wildlife hunting, and livestock farming. of outbreak surveillance is closely monitoring activities that increase human and animal contact to mitigate the risk of future zoonotic spillover events.

While all of the drivers of pathogen emergence might not initially seem related, they share a key commonality: the pathogenic threat posed once humans and new wildlife come into contact (Figure 1.9). For this reason, a core component

Stop to Think

1. What are two industrial drivers of zoonotic spillover events?

2. How does climate change contribute to the frequency of pathogen species jumps?

1.3: Infection and Transmission of Emerging Pathogens

Now that you know the general ways that pathogens emerge, let’s talk about infection and transmission to better understand how EID spread.

Three Steps of Zoonotic Spillover

You will read more about the biological mechanisms of pathogen infection in Chapter 5: Biology of Infectious Agents. For now, let’s walk through the general pattern of events that introduces an emerging pathogen into a population: (1) exposure, (2) infection, and (3) transmission.

The first step is exposure – the act of coming into contact with an infectious agent. In the context of zoonotic spillover, exposure allows for a cross-species spillover – the transmission of an infectious agent between hosts belonging to different species. The second step is infection: after a new species is exposed to an existing host, the new host species is infected by the pathogen if and only if the pathogen and new species are compatible, i.e., the pathogen is able to successfully replicate and make more copies of itself within the new host. Many pathogens have a specific host range, meaning they can only infect certain species or varieties of organisms.

Host range is often guided by host biology. For example, for several viral pathogens, the proteins that viruses use to attach to the host cell require the presence of specific receptors or entry points on the surface of host cells. Think of the viral proteins as a key, and the surface receptors on the host like a lock; in the case of crossspecies spillover, if the virus does not have the correct “key” for the host cell receptor’s

“lock,” the virus will not be able to enter or infect, replicate, and cause disease (Figure 1.10). Pathogens may, over time, pick up mutations that change this key, allowing them to fit new locks, which may in turn facilitate cross-species spillover to occur. If the pathogen gets better at infecting a species through mutation, it is said to adapt. Adaptation is a process of change, during which pathogens may accumulate mutations (discussed further in Chapter 4: Fundamentals of Genetics) that could result in more effective binding to the receptor on a new host cell.

But replicating in one new host doesn’t mean that the pathogen will spread throughout a new species. After exposure and infection, the third step of the process is called sustained transmission . This transmission is from one host of the new species to another, which often occurs. Without sustained transmission, the pathogen will not spread across the new population, and a species jump is not achieved.

F IGURE 1.10 | Infection is dependent on the host’s cellular structures. Using special proteins, viruses can “unlock” the host cell’s surface receptors and gain entry into the cell (here labeled as entry receptor). If the virus’s proteins are not the correct size or shape, it will be unable to infect a particular host species, preventing successful cross-species spillover.

Entry receptor

Host’s cellular structures

Viral entry Virus

We can illustrate the three steps of zoonotic spillover by examining the animal origin of AIDS, the disease caused by HIV. It is believed that HIV’s precursor — or the ancestor of the pathogen — is the simian immunodeficiency virus (SIV), a virus found in a range of nonhuman primates (e.g., apes, gorillas, monkeys). Though the origin of HIV has been a subject of heated debate within the scientific community for many years, it is hypothesized to have jumped to humans in the 1920s through a route described as the hunter theory (Figure 1.11), named after its observation of hunters’ interaction with wildlife:

1. Exposure: the pathogen SIV was introduced to humans from non-human primates, likely through open human wounds exposed to infected primate blood, or by humans’ eating infected primates after hunting.

2. Infection: in most cases, SIV would not have been able to persist in human reservoirs, but it is believed that the virus overcame this barrier by mutating and adapting to infect human hosts, evolving into what is now known as HIV. There are two primary types of HIV, HIV-1 and HIV-2, which are known to have been caused by distinct zoonotic spillover events; scientists have shown that HIV-1 is closely related to SIV found in chimpanzees, while HIV-2 is closely related to SIV found in sooty mangabey monkeys. Notably, the multiple HIV-1 strains we see today are also the result of multiple different SIV spillover events.

3. Sustained Transmission: once in human populations, the HIV pathogens began to spread amongst humans. This typically occurs via a variety of ways, including, but not limited to: sexual intercourse; exchanging bodily fluids through blood transfusion or contaminated – exposed to waste or infections (i.e., used needles) – pathogen-covered appliances; or

F IGURE 1.11 | The three steps of HIV spillover to humans: the hunter theory. 1. Exposure to infected primate blood. 2. Infection of the human host with the virus (Here you see an electron microscopy image of a tissue culture infected with the HIV virus). 3. Transmission between humans, which can occur through sexual contact, mother to baby or through contaminated needles.

vertical transmission where mothers with HIV spread the infection to their babies during childbirth. While both HIV-1 and HIV-2 cause AIDS, the two have very different transmission patterns, and only HIV-1 is responsible for the global AIDS pandemic.

Propagation of the Infection

Once an infection has been introduced to a new host population, it spreads, or transmits, through a community in a number of different ways. There are two main categories of transmission: direct and indirect (Figure 1.12).

Direct transmission of a pathogen occurs when an individual who is infected with a pathogen and an individual who is susceptible and has the potential to become infected with the pathogen come into direct or very close contact with each other. This can happen with physical contact like hugging or kissing or even just standing close to each other while having a conversation through respiratory droplets.

Indirect transmission, on the other hand, involves no human-to-human contact. Instead, the pathogen is spread through contaminated materials or objects, also known as fomites, and sometimes even by vectors, insects that carry the disease.

You might be wondering why infectious disease researchers bothered to define and name all the varying transmission types; the answer lies in our ability to respond effectively to outbreaks. Ebola, for example, is spread by droplet transmission, which involves spread of the virus in liquid droplets such as saliva and mucus. These droplets are spread through close contact. As such, containment and protective measures for diseases spread by droplet transmission should focus on limiting close proximity to

infected people, and encouraging everyone to wear masks. Combating the spread of measles virus, however, is far more challenging because the virus has the ability to remain suspended in the air for another person to breathe in, causing what is known as airborne transmission. As such, our containment and protective measures require we avoid sharing airspace with sick people. Airborne and droplet transmission differ in that airborne pathogens can remain in the air after the infectious person is long gone, and be breathed in by others. Droplet transmission, on the other hand, requires that the susceptible person come into direct, physical contact with the secretions from the infected person.

This looks very different from our response to a pathogen such as HIV that is spread by direct (usually sexual) contact, where we focus on reducing high-risk activities, through promoting safe sex and using barrier methods, disposing of used needles, along with other harm reduction

F IGURE 1.12 | Modes of disease transmission. 1. The passage of infectious material within a population can occur through direct or indirect transmission. Direct transmission occurs when an infected individual and an individual who is susceptible come into very close contact, i.e., “direct” contact with each other through 1) person-to-person contact or 2) the spread of respiratory droplets. With indirect transmission, the pathogen is spread 3) through the air (airborne), 4) through contaminated materials or objects (fomites), or 5) by insects or arthropods that carry the disease (vectors).

1.PERSON-TO -PERSON 2. DROPLET

3. AIRBORNE 4. FOMITES 5. INSECT BITE

methods to prevent exchanging bodily fluids. In this way, the mode of transmission gives us crucial insight into how the spread of the disease might be stopped. We will dive deeper into varying aspects of transmission in Chapter 2: Epidemiology.

Interconnected World

Human-to-human transmission patterns and resource interconnectedness are increasingly important in understanding emergence and reemergence of infectious diseases. In our heavily industrialized and globalized world, we have a greater capacity to engage with an ever-increasing number of people around the globe; the majority of the world lives in cities and urban areas, and each day, nearly 2 million people travel internationally via air (Figure 1.13). Even our food staples are frequent flyers – we in the US import half of our fruit and more than

Stop to Think

80 percent of our seafood, a far cry from the local agricultural practices that marked early civilization. All of these global practices put us at higher risk of infectious diseases.

We’re constantly encountering people from other parts of the world in ways that were previously impossible. Whereas a pathogen hundreds of years ago may have required several months to launch a full-scale pandemic thousands of miles from where the first human was infected, the huge networks of people with which we interact today drastically reduces the time it takes to infect many, many people. By arming ourselves with the knowledge of how these pathogens emerge and travel through our populations, we can better understand these threats and how to respond to them more effectively than the generations before us.

1. What are the three steps of zoonotic spillover? What does each entail?

2. Why do most zoonotic exposures not lead to spillover events?

3. What is the difference between direct and indirect transmission?

FIGURE 1.13 | Interconnected world and human contact. With the advent of air travel and international trade between the world’s major airports, as this network shows, humans are now in unprecedented contact with one another. As a result, an infectious disease outbreak anywhere is a threat everywhere.

1.4: Future Threats and Countermeasures

Researchers today have a better understanding of how emerging pathogens may arise and pass from person to person, and we have developed tools to help us track the spread of infectious diseases through populations. However, it is still challenging to predict where and when a pathogen might emerge, pinpoint the origin after a pathogen has spread, and ultimately contain a viral threat. Furthermore, the environments in which pathogens reside are constantly changing. These, among many other reasons, make predicting how pathogens will appear over time extremely difficult. No single field of research or discipline can effectively predict pathogen emergence on its own. If we want to be more proactive in our approach to outbreaks and better prepared for future pandemics. In that case, it’s important that we build multidisciplinary teams — involving experts from public health and veterinary medicine to climate science and biology. In short, we need to form a global surveillance system to contain outbreaks after detecting the first few cases well before they become pandemics.

Prioritizing Emerging Pathogens

collection and analysis of data that can show us what pathogens exist within a population and help us determine what kind of measures we need to take to protect the global population.

While we would ideally be able to study and contain all of the world’s infectious agents, resources are finite, so it’s impossible to track or plan against every potential emerging pathogen. So how do we determine which ones should keep us on high alert?

The World Health Organization (WHO) has compiled a list of the emerging pathogens and their EID that should be prioritized for research and development or containment strategies , which are measures that we take to protect the global population against infectious diseases. Different pathogens’ characteristics are weighed to help calculate the risk that they pose to public health, with those that are estimated to present the greatest risk prioritized at the top of the list. This list helps to determine which emerging pathogens have the highest risk of causing an epidemic or pandemic, also known as having pandemic/ epidemic potential

As part of present-day outbreak response, public health teams flag many potential pathogenic threats through a practice that is known as disease surveillance , which is the Scan this QR code or click on this link to enter an Epidemic Tracker where you can watch the current epidemics happening around the world.

Pathogen’s Pandemic Potential Factors

There is a range of factors that researchers must assess to determine a pathogen’s pandemic potential. One of the first is how contagious it is – or a pathogen’s capacity to be transmitted between people. We scientifically assess this through pathogen’s transmissibility or the probability that infectious material is passed from host to host. Transmissibility can sometimes be hard to determine, as most individuals infected with a pathogen never present to clinical care or are

not properly diagnosed when they do. The ranking of a given pathogen also depends on its pathogenicity, the ability of an agent to cause disease after infection. Pathogenicity is a quality inherent to the infectious agent based on its structure and cellular machinery.

Relatedly we consider virulence, which measures the ability of an infectious agent to cause damage to a host, with the most severe cases ending in death; fatality rate is a key metric of virulence, as it describes the number of people who die from a disease as a proportion of the number of people who are infected. It is exceedingly challenging to calculate an accurate fatality rate, as it is nearly impossible to identify and document every single case of a disease. Instead, we often calculate the case fatality rate (CFR), or the number of people who die from a disease as a proportion of the number of cases reported.

Case Fatality Rate

= (# of Deaths from Disease) (# of Known Cases of the Disease)

Case Fatality Rate = # of Deaths from Disease / # of Known Cases of the Disease

Another important component to consider when determining the threat posed by a particular pathogen is the availability of sufficient countermeasures or tools to counteract the threat like vaccines and therapies. This makes sense, as the diseases we don’t have any protection against will likely cause the most harm to the global population.

As you have likely already realized, there have been a few notable EID in recent history. A subset of these outbreaks is reflected in Table 1.1.

As you may have noticed, this list is full of viral diseases. A key reason for virus’ prioritization is our lack of treatment options

available. Unlike a number of widely available anti-bacterial broad-spectrum drugs, which make it possible to target a wide range of bacteria with just one drug, there are very few drugs available that can treat against a wide variety of viruses. Furthermore, viruses can spread and mutate very quickly, increasing the risk that they might evade therapies designed to fight them, become more contagious or more deadly. That said, bacterial infections like cholera and tuberculosis are both ancient as well as current threats.

Weaponizing Infectious Disease

A special threat for which experts are always on the lookout is the weaponization of emerging pathogens, or the human use of pathogens for harm. You might remember an example of this earlier in the chapter, where Jeffrey Amherst and his troops intentionally gave smallpox infected blankets to indigenous communities. These sort of biological weapons involve the use of toxins or infectious agents as a weapon to cause death or disease. From Mongol forces launching plague-infected bodies at their enemies in the 14th century, to the British troops passing blankets contaminated with smallpox to Native Americans in the 18th century, people have employed pathogens as weapons for hundreds of years.

More recently, present-day governments and terrorist groups have already used or have plans to develop and use biological weapons. For example, on April 2nd, 1979, there was an accidental release of a bacteria called anthrax from a secret bioweapons facility in Sverdlovsk, a city in the former Union of Soviet Socialist Republics (USSR).

Table 1.1 | Emerging infectious diseases in recent history

1930

Isolated from sheep in Rift Valley, Kenya

Rift Valley Fever (RVF) Rift Valley Fever Virus

Through contact with infected animals, the pathogen can be found in their blood, body fluids, or tissues

Through bites from infected mosquitoes and, rarely, from other biting insects

1944

Discovered in the Crimean peninsula during an outbreak among the Soviet military, it is unclear what animal originated from Crimean Congo Hemorrhagic Fever (CCHF) CCHF orthonairovirus (CCHFV)

1947

Isolated from macaque monkeys in Uganda Zika Zika Virus

1967

Diagnosed in simultaneous cases in Germany and Yugoslavia Marburg Virus Disease Marburg virus

Through contact with infected animals such as ticks or livestock, the pathogen can be found in their blood

Human-to-human through infectious blood or body fluids

<1%; however CFR can rise to ~50% when the disease manifests in its hemorrhagic form

Endemic to subSaharan Africa

1969

Diagnosed in missionary nurse in Lassa, Nigeria Lassa Fever Lassa Virus

Through bites from infected Aedes species mosquitoes

From pregnant women to their fetus

Human-to-human through sex from a person who has Zika to his, her, or their partners

Unknown how it’s transmitted from host to human. However, it’s suggested that the most likely routes are through contact with bat feces or aerosols

Human-to-human through infectious blood, body fluids or objects contaminated with the virus

From infected rodents to humans

Through ingestion or inhalation when in contact with the Mastomys natalensis rodent, its urine or excretions

Human-to-human through infectious blood or body fluids

10-40% Endemic to the Middle East, Asia, Africa, Eastern Europe, and Balkans

~8% during 2015 Brazil outbreak Virus found in subtropical and tropical areas

~50% Appears in occasional outbreaks across Africa

CFR is ~30% in lab-confirmed patients and over 50% in fetuses

However, surveys of prevalence suggest fatality rate is ~1% more broadly in the population

Endemic to regions of West Africa

Table 1.1 | Emerging infectious diseases in recent history (continued)

1976

Discovered during an outbreak of hemorrhagic fever in a village in the region now known as the Democratic Republic of Congo, it likely originated in African fruit bats although it is unclear

2003

Believed to originate through bats and spread through other infected animals in Asia, and first identified in China

2012

Believed to originate from dromedary camels and spread through other infected animals in Saudi Arabia

2019

Believed to originate through bats in China

Ebola Virus Disease (EVD) Ebola virus

Severe Acute Respiratory Syndrome

SARS-CoV-1 virus

Through direct contact with an infected animal, such as a fruit bat or nonhuman primate such as apes and monkeys.

Human-to-human through infectious blood, body fluids, or objects contaminated with the virus

~65%. Survival is highly dependent on region of illness and care

Endemic to tropical regions of Africa

Middle East Respiratory Syndrome MERS virus

Human-to-human through respiratory secretions, contaminated body fluids, objects or surfaces.

Coronavirus disease

SARS-CoV-2 (COVID-19)

Human-to-human through respiratory secretions

11% during 2002 outbreak No cases reported since 2004

Human-to-human through respiratory secretions, contaminated body fluids, objects or surfaces.

~33% Present in a number of regions, including the Middle East, Africa and South Asia

~1.6% in US, with strong variation between vaccinated and unvaccinated individuals Endemic status is yet to be determined, but will likely be global.

This release killed 66 people, making it the deadliest human outbreak of inhalation anthrax to date (Figure 1.14).

Amidst the Cold War era, as well as during war times within the preceding decades, major powers including the US, United Kingdom (UK), and Soviet Union developed biowarfare programs. Recognizing the danger of these adoptions, the Biological Weapons Convention, which took effect in 1975 and is currently signed by 183 nations, was designed to end the development of biological weapons. However, according to the Nuclear Threat Initiative in 2015, about 16 countries have had or are currently suspected of having ongoing biological weapons programs.

As biotechnology improves, so does the ability to create a designed organism for malicious purposes. We’ve already witnessed countless examples across history detailing how naturally evolving diseases have upended the world,

whether wielded as weapons or transmitted unintentionally through various populations. However, disease-causing pathogens that are modified (engineered) to be more infectious or lethal could be even more devastating to the human population.

One relevant field of research is known as gainof-function, which is the study of pathogens that are intentionally genetically modified to become more contagious, capable of infecting additional hosts, or capable of inducing more severe disease. In Chapter 7: Diagnostic Tests, you will be introduced to gene-editing techniques that allow for the modification of pathogens. Proponents of this research say that it can be safely and securely performed and can shed light on how pathogens in the wild gain these functions, potentially aiding us in outbreak containment and response. However, the dangers are quite clear: if pathogens with heightened abilities to infect humans somehow escape into communities (in what is known as

FIGURE 1.14 | Olga Vyatkina is seen adorning the grave of her son. Her son was killed in the 1979 accidental anthrax release in Sverdlovsk, USSR. Image credit: With permission from Lynn Johnson.

a lab leak), intentionally or unintentionally, the results could be tragic. A lab leak is generally understood as an unintentional event, but you will find that the term is also trivially used for the intentional action.

Frontline Defense

As concerning as outbreaks are, we are not defenseless against pathogens, regardless of their origin; many organizations are on the lookout for these diseases as they may emerge. International organizations are vital in the frontline defense against infectious disease outbreaks. The WHO takes on many essential roles in global public health, including coordinating international health policy, improving sanitation practices, and coordinating high-level leadership for initiatives on the ground. Among other initiatives, the WHO supports pandemic readiness by helping low- and middle-income countries (LMICs) improve their disease-fighting capacity by distributing necessary medical supplies to vulnerable populations, and collating data from many countries around the world. All of these initiatives help provide the global community with a cohesive framework to work together to combat pathogens and prevent infectious disease outbreaks.

In addition to global organizations, it’s equally important that all the individual nations of the world are equipped with organizations that focus on diseases within their specific populations, ensuring swift response initiatives. One example of this type of organization is the Centers for Disease Control and Prevention (CDC), a branch of the US Government’s Department of Health and Human Services. Although the CDC does extensive international work and has offices around the globe, it is domestically oriented,

meaning its focus is on the protection of Americans at home and abroad. The CDC aims to be the premier health promotion, prevention, and preparedness agency of the US, and its priorities include pandemic preparedness, eliminating disease, and ending epidemics within the country, in addition to studying various chronic health conditions, including cancer and diabetes.

As you might already be starting to appreciate, infectious disease surveillance takes place around the globe, with many groups participating on local and national levels. Organizations like the Africa Centres for Disease Control and Prevention (Africa CDC) work to coordinate national and regional response teams across the continent, alerting members to events and threats as they arise, as well as coordinating research and support. The Africa CDC also helps to bridge the gap between the national ministries of health on the continent that manage their individual nation’s current needs and circumstances. The collaboration between local clinics and research institutions, national departments of health, and international organizations is instrumental to the successful implementation of public health programs around the world.

Disease X

Approximately one brand-new infectious disease emerges each year. While not all of them exhibit human-to-human transmission, even the possibility that some of them do is enough to cause concern. For this reason, there is an additional disease that belongs on the WHO’s shortlist of diseases prioritized for further research that will indefinitely demand our attention: Disease X. Disease X is a substitute name acknowledging a serious international

outbreak caused by a pathogen currently unknown, undiscovered, or not-yet-existent. Beginning near the end of 2019, COVID-19 was the world’s “Disease X”. The next unknown and unnamed Disease X may already be lurking somewhere on planet earth, waiting to be discovered, or worse, spread. It is vital that we remain vigilant to prevent the next infectious disease outbreak. Health institutions can increase their response capacity by focusing

their research efforts on entire classes of infectious diseases, rather than just individual strains, and by investing in the infrastructure needed to respond to an outbreak.

The remaining chapters in this textbook are designed to provide you with a background on outbreak science, and equip you with the skill sets needed to better understand key elements for prevention, preparation, and response.

Stop to Think

1. Why are viruses such high risk pathogens?

2. How might you justify more political, scientific, and financial investments to prevent the next infectious disease outbreak?

3. Imagine that you are working for the Director-General of the WHO and your job is to create a new strategy to prevent the reemergence of a deadly viral disease. Based on what you have learned in this chapter, what would you do?

Stop to Think Answers

1.1: Infectious Diseases and Emerging Pathogens

1. Microbes are tiny organisms too small to see by eye, and pathogens are disease-causing agents including microbes as well as larger organisms, and non-living things.

2. Some major drivers for emerging pathogens in society, historically speaking, include:

a. the development of agriculture

b. creation of permanent settlements

c. migration across borders and colonizations

d. engagement in conflict (war)

e. globalization

3. Reemerging pathogens have already been found in a given region, whereas emerging pathogens are new to the geographic region.

4. Political conflicts and wars spread infectious disease by bringing new groups into contact with each other, and encouraging sub-optimal living conditions, including crowded quarters with limited infection-prevention measures.

1.2: Major Drivers of Emerging Infectious Diseases in the Modern Era

1. Industrial causes of spillover events include deforestation, industrialization, mining, and encroachment into wildlife habitat.

2. Climate change can contribute to the frequency of which pathogen species “jump” to new species by altering the geographic ranges of pathogens and their potential hosts, as well as increasing human interaction with wildlife.

1.3: Infection and Transmission of Emerging Pathogens

1. Exposure, infection and transmission.

• Exposure: exposure allows for crossspecies spillover, the transmission of an infectious agent between hosts belonging to different species.

• Infection: the new host species is infected by the pathogen if and only if the pathogen and new species are compatible, i.e., the pathogen is able to replicate successfully and make more copies of itself within the new host.

• Transmission: transmission occurs when the pathogen spreads from one host of the new species to another.

2. Zoonotic exposure frequently occurs between a current host and an organism outside of the pathogen’s host range, meaning that the pathogen cannot attach to the receptors or enter the cells of the new host organism. This inability to infect the new host prevents the occurrence of a spillover event.

3. Direct transmission occurs when there is a physical interaction between susceptible and infected individuals, while indirect transmission does not require human-tohuman contact.

1.4: Future Threats and Countermeasures

1. Viruses are particularly high-risk pathogens because of our lack of treatment options, as well as their rapid rate of replication, mutation, and spread.

2. Answers will vary but may reflect the need to keep people healthy, our responsibility to make a more equitable world, concerns about world peace, and even economic arguments.

3. Answers will vary but may include research into pathogen biology, financial investment in preventative measures, and culturallycompetent mitigation strategies.

Glossary

Adaptation: When something becomes more suitable for a specific purpose. In the context of infectious agents, adaptation occurs when pathogens undergo changes, usually through genetic mutation, that allow them to better infect, transmit, or otherwise thrive and spread.

Airborne Transmission: Able to be transmitted and remain infectious while suspended in the air.

Animal Trafficking: The illegal trading of wildlife. Exploiting animal species through trafficking and poaching increases the likelihood of zoonotic spillover events.

Bacteria: Unicellular prokaryotic microorganisms of which many species are pathogens.

Biological Weapon: The use of toxins or infectious agents that are biological in origin, such as bacteria and viruses, as a weapon to cause death or disease.

Case Fatality Rate (CFR): The number of people who die from a disease as a proportion of the number of cases reported.

Communicable Diseases: Diseases that can be passed from person to person.

Contagious: A pathogen’s capacity to be transmitted between people through direct contact or close proximity.

Containment Strategies: Measures we take to protect the global population against infectious disease include vaccine development, mask production, and policy guidance.

Contaminated: The process of making something dirty, polluted, or poisonous by adding or coming in contact with a chemical, waste, or infection (e.g., used needles, pathogenresident medical devices, etc.).

Countermeasures: The possible measures that a community could take to respond to an infectious disease outbreak and control its spread; and/or tools to counteract the threat. This might include vaccines and therapeutic drugs, the production and distribution of personal protective equipment like masks, and public policies aimed at slowing disease spread.

Case Fatality Rate

= (# of Deaths from Disease)

Case Fatality

(# of Known Cases of the Disease)

Rate = (Number of deaths from a Disease/ (Number of Known Cases of the Disease)

Climate Change: The long-term alteration of temperature and typical weather patterns worldwide.

Colonization: The forceful process of establishing control over an existing community in order to take the land, the people, or its resources.

Cross-species Spillover: The transmission of an infectious agent between hosts belonging to different species.

Deforestation: Cutting down or deliberately setting fire to trees and reforests in order to plant more crops and expand plantations or for urban expansion.

Diagnostics: Tests that either confirm or rule out the presence of a particular disease.

Direct Transmission: Passage of a pathogen through direct, or very close contact between two people.

Disease Surveillance: The measurement and analysis of data that can show us what pathogens exist within a population and help us determine what kind of measures we need to take to protect the global population.

Disease X: A substitute name acknowledging a serious international outbreak caused by a pathogen currently unknown, undiscovered, or not-yet-existent.

Droplet Transmission: the spread of pathogens in tiny drops of liquid as might be as saliva or mucus.

Drug Resistance: A phenomenon by which a pathogen becomes impervious to previouslyeffective drugs.

Emerging Infectious Diseases (EID): Infectious diseases new to a population or previously existed but that quickly increases in prevalence and geographic range.

Emerging Pathogens: Pathogens that are either entirely new to a population (also known as a novel pathogens), or quickly increase in prevalence and geographic range.

Endemic: Diseases that are common and persistent in a population; it is important to appreciate that diseases introduced during an epidemic or pandemic can become endemic to a given region.

Epidemic: The rapid spread of an infectious disease within a given region.

Exposure: The act of coming into contact with an infectious agent.

Fatality Rate: Describes the number of people who die from a disease as a proportion of the number of people who are infected; a key metric of virulence.

Fomites: Objects or materials that, when contaminated with or exposed to infectious agents, can transfer disease to a new host.

Gain-of-Function: The study of pathogens that are modified to gain abilities such as increased contagiousness, the ability to infect additional hosts, or increased severity of illness.

Genome: The entire genetic information of an organism, a virus or a given species. Also can be thought of as the “instruction manual” in every organism on earth that allows it to exist and take on its physical form.

Host: The organism infected by a pathogen; can be most types of organisms, including bacteria.

Host Range: The certain species or varieties of organisms a pathogen has the ability to infect.

Indigenous Peoples: People native to any region around the world. During the colonization of the land that we now know as the US, indigenous people were killed in large numbers as a result encountering new pathogens colonizers had previously been exposed to and carried, devastating these communities.

Indirect Transmission: Passage of a disease between two people in a way that does not involve direct, physical contact, for example through insects or contaminated objects.

Industrialization: The transformation of economies from primarily agricultural to manufacturing-based.

Infect: to enter an organism’s cells and cause disease.

Infected: To have invaded or entered by a pathogen, usually through penetration. In the

context of infectious disease, it refers to when a pathogen has entered another organism, and made a new host.

Infection: A disease caused by an infectious agent.

Infectious Agents: Microbes, as well as some other non-microbes, that can spread between organisms causing disease.

Infectious Diseases: Illnesses caused by small infectious agents, including living and non-living agents.

Infrastructure: The structures needed in a region or country to keep cities functional and organized. For example transportation systems, sewage management, pest control, or general sanitation.

Intermediate Host: Bridges the gap between reservoir hosts and humans, transmitting pathogens in this order: reservoir -> intermediate host -> humans.

Lab Leak: When pathogens with heightened abilities to infect humans are leaked, intentionally or unintentionally, into human populations.

Microbes: Microorganisms, typically referring to infectious agents of microscopic size.

Migration: The movement of animals and other organisms, including humans, to new lands.

Mutation: Changes to the genetic makeup of an organism.

Natural Reservoir Host: The animal that originally houses the pathogen; they often harbor the pathogen safely without becoming ill themselves.

Novel Pathogen: A pathogen that has not been encountered by a population before.

Organism: Any living system that functions as a one entity. Bacteria, viruses, plants, and humans are some examples.

Outbreak: Sudden increase in the occurrence of an infectious disease within a particular community.

Outbreak Preparedness: Our readiness to respond to infectious agent threats that can cause an outbreak.

Outbreak Science: The science that focuses on the comprehensive understanding of infectious diseases, from the molecules inside pathogens to the societal factors that influence how diseases spread.

Pandemic: An epidemic that encompasses a wide geographical breadth, on an international or even global scale.

Pandemic/Epidemic Potential: Emerging pathogens that have the highest risk of causing an epidemic or pandemic.

Pathogen: Agents living or otherwise, that have the potential to cause disease (e.g., bacteria, viruses, fungi).

Pathogenicity: The ability of an agent to cause disease after infection, measured as the proportion of persons infected by an agent who then experience clinical disease.

Poaching: Illegal hunting of wildlife; exploiting animal species through trafficking and poaching increases the likelihood of zoonotic spillover events.

Reassortment: When virus strains rearrange themselves and swap genetic components with each other, creating a new strain.

Receptors: Entry points on the surface if host cells; surface receptors on the host are like a lock, and if a virus doesn’t have the correct “key,” it won’t be able to infect a host and cause disease.

Recombinant Pathogens: Pathogens that have genetic components of more than one “parent” pathogen.

Reemerging Pathogens : Infectious agents that experience an increase in prevalence after a previous decline within a population, or a change in a pathogen’s geographic distribution.

Science: The process of studying the natural world and its phenomena through systematic, testable approaches.

Species : A specific group of organisms sharing the same biological characteristics capable of exchanging genes and/or interbreeding.

Strains : The subsets of a class of microbes or viruses that are genetically unique.

Susceptible : To have the potential to become infected; populations that have never encountered a specific disease and therefore have no defenses against it, also known as naïve populations.

Sustained Transmission : Easy transmission from one host of a particular species to another..

Transmission : Passage of the infectious material.

Transmissibility : The probability that passage of infectious material will occur, given an instance of contact between an infected host and a noninfected host.

Vaccines : Substances used to prepare the body to fight off future infections without actually contracting the disease.

Vector : A small living organism, such as an arthropod like a mosquito or tick, that carries an infectious agent between an infected animal and a new animal or human. Vectors are responsible for causing vector-borne diseases.

Vector-Borne Disease : An illness transmitted to humans and other animals by a vector such as a mosquito.

Vertical Transmission : Transmission from parent to offspring through the development process; without the proper precautions, HIVpositive mothers have the potential to spread the disease to their child during childbirth.

Virulence: The ability of an infectious agent to cause severe disease, measured as the proportion of persons with the disease who become severely ill or die.

Viruses: Tiny infectious agents composed of a protein capsid, genome (RNA or DNA), and proteins for infection and replication. They infect cells and hijack the cell’s machinery in order to propagate.

Wet Markets: Markets in many parts of the world where exotic animals are sold in the pet trade or live animal markets; although these markets are often relied upon for sustenance, they bring together animals that would not have otherwise encountered one another. These animals are often in stressful and unsanitary conditions, creating unprecedented environments for pathogens to jump to new hosts.

Zoonosis: The “jump” of pathogens from animals to humans; a fundamental cause of many of the emerging pathogens we see today.

Zoonotic Spillover Event: When a pathogen jumps from one type of animal, such as a bat or a pig, to a human. Pathogens that can do this are said to have zoonotic potential, and we call it a “spillover” because the pathogen has found a new species of hosts to infect.