1 About Infectious Disease

Reading 2

Agents of Disease

The purpose of this reading is to introduce students to infectious agents including parasites, bacteria, and viruses. It is important for students to understand the differences among the different organisms, how they are transmitted and how they cause disease. Major epidemics and pandemics, which students will be exploring in the next activity, have been caused by viruses and bacteria. The modules in this series will focus primarily on viruses, specifically Ebola, measles, and COVID-19, but will also mention bacteria at times with resources that discuss the ecological, social, economic, cultural and biological factors that can lead to epidemics and pandemics - as well as the impact of these diseases on the infrastructure of societies.

The purpose of this reading is to introduce you to infectious agents including parasites, bacteria, and viruses, so that you can better understand the differences among the different organisms, how they are transmitted and how they cause disease.

I. Introduction

Long before microbes were identified as the causative agents of infectious disease, humans pondered the origins of disease and of the devastating epidemics that often decimated human populations. In trying to find a reason for this suffering, different cultures developed various explanations for disease: unknown poisons, bad air, evil spirits, and divine retribution. Disease was often viewed as divine punishment for sins or aberrant behavior, and afflicted individuals were tortured or even executed.

Even without any knowledge of microorganisms, careful observation of patterns of disease led groups of people to understand that certain diseases were communicable (spread by contact with other humans or animals and through air, food, and water) and that they could be prevented by good hygiene, effective sanitation systems, and careful food preparation practices. But what exactly was being communicated and causing disease?

In the centuries following Antonie van Leeuwenhoek’s discovery of the microworld that surrounds us, the nature of his “animalcule” and “cavorting beasties” have been explored and characterized, and the enormous diversity of ways in which they live in the world and in and on humans has been elucidated. In the following reading, you will learn about different kinds of microorganisms—parasites, bacteria, and viruses. The sheer number and diversity of each of these types of organisms is astonishing. They vary remarkably in size, shape, and, particularly the parasites, in their life cycles. Natural selection and evolution have resulted in very specific niches for each type of virus, bacterium, and parasite regarding where they live, how they grow, and how they reproduce.

II. Parasites

A. The Ubiquitous Organisms

Parasites are everywhere. There are far more kinds of parasitic than nonparasitic organisms in the world, and organisms that are not parasites are usually hosts, harboring parasites within and upon them. Their diversity in size, complexity, and life cycles is truly astonishing, ranging from single-celled amoebas responsible for diarrheal distress to the multicellular tapeworms that can grow to 20 feet in humans and 100 feet in whales. Table 1 illustrates examples of different types of parasites.

Table 1. Examples of parasites

Parasite Structure Mode of Transmission Disease Caused Damage Symptoms
Plasmodium Insect Causes Malaria Cell death (liver, blood); toxins released from cells Chills, high fever, profuse sweating, headache, nausea, vomiting, anemia, convulsions
Amoeba Food Causes Intestinal Distress Cell and tissue death Bloody diarrhea; intestinal lesions
Toxoplasma gondii Cat feces; undercooked beef Causes Toxoplasmosis Intracellular growth of parasite Often asymptomatic; flu- like symptoms; birth defects in pregnant women
Tapeworm Food Causes Anemia Absorbs nutrients from intestinal tract Often asymptomatic; weight loss, hunger, fatigue
Schistosome Water borne Causes Schistosomiasis Eggs shed by the adult worms lodge in the intestine or bladder; damage to liver, intestine, spleen, lung, bladder Rash, itchy skin, fever, chills, cough, muscle aches
Filarial worm Insect Causes river blindness Toxins from worm death Blindness, skin lesions
Tick Ectoparasite Causes inflammation; carries Lyme's disease Damage to epithelial cells Rash, red bumps
Flea Ectoparasite Causes inflammation; carries bubonic plague Damage to epithelial cells Rash, red bumps, very itchy
Mosquito Ectoparasite Causes inflammation; carries malaria Damage to epithelial cells Red spot or bump; itching

B. The Parasitic Way of Life

The parasitic way of life is highly successful and is one form of a living relationship called symbiosis, which involves a relationship between two organisms that live together in close association, often with mutually beneficial results. When a symbiont actually lives at the expense of the host—that is, uses nutrients required by the host—then it is called a parasite. Some parasites live their entire mature lives within or on the host and are totally dependent on their hosts for nutrients; these types of parasites are called endoparasites. Others, such as fleas or mosquitoes, only visit for a meal—they eat and run (or fly) and are termed ectoparasites. Parasites can be unicellular protozoa, such as the plasmodia that live inside red blood cells and are the causative agent of malaria, the major infectious disease in the world today.

Most parasites, however, are multicellular. Parasitic worms include tapeworms, which live in the digestive tract and cause anemia, and schistosomes, which inhabit the veins of the bladder or intestines and are the causative agents of the disease schistosomiasis. Nematodes, another form of worm, are responsible for heartworm in dogs and blindness in humans. Arthropods, such as fleas and ticks, are temporary parasites that visit the host for frequent or occasional feedings and can also act as vectors (carriers) of parasites that cause disease. Parasitic fungi, including mushrooms, molds, and mildews, feed on plants or animals. By this definition of parasite, certain bacteria and viruses can be considered to live as such, but conventionally the term parasite refers only to eukaryotic organisms—that is, organisms that have a nucleus and other subcellular organelles.

Parasites can be transmitted in a variety of ways: in contaminated food or drinking water, by swimming in lakes and rivers, or in the feces or saliva of an insect or other animal. Table 1 indicates modes of transmission for several parasites.

A parasite is often associated with damage to the host (see Table 1). A parasite may harm its host in any number of ways: by mechanical injury, such as boring a hole in it; by eating or digesting and absorbing its tissues; by poisoning the host with toxic metabolic products; or simply by robbing the host of necessary nutrients. Most parasites inflict a combination of these conditions on their hosts. Of course, the parasite is only trying to survive, taking from its environment—its host—what it needs to sustain its life processes so that it can reproduce. Parasites do not have evil intent, any more than bacteria or viruses do.

C. Prevention and Treatment

The treatment of parasitic diseases reflects the great diversity of parasites. Many unicellular parasites can be treated with drugs, such as quinine for malaria and arsenic derivatives for sleeping sickness (which is caused by the unicellular parasite Trypanosoma brucei). Tapeworms and nematodes can also be treated with drugs that interfere with their metabolism. Although much progress has been made in developing vaccines against three major parasitic diseases of humans —malaria, leishmaniasis, and schistosomiasis—to date, no truly effective vaccines are available that protect against parasitic diseases. Interestingly, vaccines protective against several protozoan and nematode parasites are available for animals. One reason for this may be that the conditions for testing vaccine efficacy in animals are less stringent than for humans, leading to a more rapid identification of effective vaccines.

Although no effective vaccines for any human parasitic disease exist yet, good hygiene, clean drinking water, sanitary facilities, and effective programs of insect control can prevent many parasitic diseases. A simple change of habits, such as staying out of lakes and rivers or sleeping under mosquito netting, could prevent many serious, debilitating diseases.

III. Bacteria

A. The Oldest Organisms — Bacteria

For the first two billion years of Earth’s existence, bacteria were its major if not only tenants. Structurally the simplest of life forms, bacteria are single-celled prokaryotic organisms. Although capable of carrying out all of the cellular life functions, bacteria lack the internal structures, such as a nucleus and mitochondria, found in eukaryotic cells. Their genetic information is found on a single chromosome within the cell. Bacteria are also characterized by a cell wall made up of polysaccharides that surrounds the cell membrane.

Bacteria constitute a large and diversified group of organisms. Capable of growing in a remarkably wide range of habitats and conditions, bacteria can be found just about anywhere—in the saltiest sea, in the hottest hot spring, and in the most acidic or alkaline conditions. They make the soil fertile: in every gram of fertile soil there exist about 100,000,000 living bacteria; this amounts to about 90–250 kg (200–550 lb) of bacteria for every acre of soil. Bacteria decompose dead organic matter, help plants obtain vital nitrogen from the air, help humans synthesize vitamins and fend off undesirable microbes, and provide us with some of life’s pleasures, such as yogurt and cheese. Most mammals are walking apartment complexes for a wide variety of bacteria, some of which are essential to the well-being of the animal, but most of which are just along for the ride. Bacteria make up about 10% of the dry weight of a human; that is, a 150-lb. person comprises about 4 lbs. of bacteria.

Though most people are scarcely aware of the bacteria around (and within) them, life would be very difficult—if not impossible—without bacteria. Despite all the important processes and products bacteria provide, people generally only recognize the existence of bacteria when they become ill. For this reason, bacteria are generally viewed as “bad.” Like all living things, however, bacteria are only carrying out the processes of life, which include taking nutrients from their environment so that they can grow and reproduce. For the majority of bacteria, this environment is the soil or water, but for others, it is another organism that may become sick as a result. These troublesome, pathogenic bacteria, however, represent only a small proportion of the total bacterial world.

Despite their abundance and diversity of species, bacteria are remarkably lacking in variety when it comes to shape and distinguishing structural features (see Table 2). They can be spherical, as are the bacteria Streptococcus pyogenes (the causative agent of sore throats); rod-shaped, as are Salmonella typhi (the cause of typhoid fever), Vibrio cholerae (the causative agent of cholera), and Pseudomonas aeruginosa (bacteria commonly found in soil); or helical or spiral-shaped, as are Treponema pallidum (the cause of syphilis) and Spirochaeta picatilis (large and harmless spirochetes commonly found in water).

Table 2. Examples of bacteria

Bacteria Structure Mode of Transmission Disease Caused Damage Symptoms
Streptococcus Direct contact with respiratory and other body fluids Sore throat, necrotizing fasciitis, toxic shock syndrome Cell, tissue, and muscle destruction Sore throat, rash, cellulitis
Salmonella Food Salmonellosis Endotoxins Diarrhea, fever, and abdominal cramps
Vibrio Cholera Water Cholera Enterotoxins Watery diarrhea, abdominal and leg cramps, fever
Treponema Sexual contact Syphilis Destruction of epithelial and endothelial cells Small, painless ulcers, rosy rash, paralysis, blindness, dementia
Yersinia pestis Insect Bubonic Plague Bacterial growth in the lymph nodes Fever, headache, chills, weakness, and swollen, tender lymph glands
Mycobacteria Direct contact with respiratory fluids Tuberculosis Intracellular growth of bacteria causing lung tissue destruction Fever, fatigue, chronic cough with blood and phlegm

B. The Bacterial Way of Life

Because bacteria have limited mobility, many of them rely on carriers or vectors to deliver them to their host. Blood sucking and biting insects, such as mosquitoes, ticks, and fleas, transmit a wide variety of pathogenic bacteria. Fecal material from birds, rodents, cats, and other animals can transfer bacteria generally when it is ingested. Ingestion of contaminated food and water and direct contact with infected body fluids are a source of many serious bacterial infections (see Table 2).

When bacteria do cause disease they can do it in a variety of ways. Living in blood, on skin, on mucous membranes, and sometimes within cells, these tiny invaders may secrete toxic substances that damage vital tissues, feast on nutrients intended for the cell, or form colonies that disrupt normal functions in the host’s body. Directly or indirectly, their actions can cause extensive damage to the host.

C. Prevention and Treatment

Unlike the lack of vaccines for parasitic infection, effective and safe vaccines have been developed against many pathogenic bacteria, including those causing diphtheria, tetanus, pertussis, Haemophilus influenzae type B, cholera, typhoid fever, and pneumonia. Similarly to parasitic infections, certain bacterial infections can be prevented through good hygiene, the availability of clean drinking water and sanitary facilities, and proper food preparation and storage The significant differences in the biology of bacteria and eukaryotes has allowed the use of antibiotics that specifically target bacterial cells but are mostly harmless to eukaryotic cells. This typically involves targeting bacterial-specific processes such as the synthesis of bacterial cell walls, bacterial DNA replication, and bacterial protein synthesis. Antibiotics are chemical compounds that either kill or inhibit the growth of bacteria. Certain antibiotics act by interfering with the synthesis of the cell wall. Because animal cells do not have cell walls, antibiotics affect only the infecting bacteria. When first discovered in the 1920s, antibiotics were viewed as miracle drugs capable of saving humankind from the devastating diseases that had plagued them throughout history. However, almost as soon as a new antibiotic was discovered, certain bacteria with the ability to resist its killing effect were found. These were able to survive and multiply while the more susceptible bacteria were killed. Bacterial resistance to antibiotics is, today, one of the biggest challenges facing medical practitioners.
IV. Viruses

A. The Viral Invader

Viruses have an enormous impact on human beings and, like bacteria, have been part of our lives since at least the beginning of recorded time. A bas relief from 1500 B.C. Egypt depicts a priest with a shriveled leg, suggestive of a prior infection with polio virus. A thirteenth-century manuscript shows a dog, mouth foaming, attacking a terrified man destined to die from the rabies virus transmitted from a bite. Smallpox is believed to have helped a small band of Spaniards under Cortés subdue the vast and powerful Aztec nation.

As perpetrators of disease, viruses have been viewed as one of the “bad guys” of the microbial world. Variously termed “pirates of the cell,” “viral hitchhikers,” “cellular hijackers,” and “pieces of bad news wrapped up in protein,” these tiny microbes have been perceived as having evil intent. In reality, viruses are just simple microbes, genetic material (that is, nucleic acid) surrounded by protein.

viral genome
Figure 1: Structure of the T4 Bacteriophage virus.
Adapted from the Wikimedia Commons file Image: Bacteriophage Structure located in Wikipedia's Bacteriophage article.

A virus is not a cell. It cannot maintain the characteristics of life on its own. Lacking the biochemical and structural components (cellular machinery) that enable an organism to carry out the life processes—they have, no nuclei, no mitochondria, and thus no capacity to take up and utilize nutrients—they cannot reproduce, metabolize, or conduct any of the basic processes of life on their own.

A virus cannot replicate outside a cell but must seek out an environment that provides not only the nutrients it needs to carry out life processes but also the cellular machinery required for these processes—that is, the environment of a cell. Viruses can infect cells in every kind of organism, including bacteria, plants, fungi, and animals. Viruses show specificity for the organisms and cell types they infect. That is, a specific type of virus will infect only certain organisms and only certain kinds of cells within that organism.

Much smaller than any cell, a typical virus comprises a protein “coat” surrounding its viral genetic material, which can be single-stranded DNA, double-stranded DNA, single-stranded RNA, or double-stranded RNA.

viral genome
Figure 2: The viral genome within.
Adapted from the Wikimedia Commons file Image: Simplified Virus Structure located in Wikipedia's Introduction to Viruses article.

This genetic material contains specific instructions for making the proteins and nucleic acid the virus needs to reproduce identical copies of itself. The proteins encoded by the viral genes must be able to take over the cellular machinery of the cell; this “commandeered machinery” is then used to aid the reproduction of the virus and, in many cases, is no longer available for the growth and reproduction of the infected cell.

Viruses show great diversity in structure, mode of transmission (see Table 3), and manner in which they “hijack” a cell. Unlike bacteria and parasites, whose genomes are double-stranded DNA (dsDNA), viruses can differ in the nature of their genetic material. Some viruses store information in dsDNA. Other viruses have single-stranded DNA (ssDNA), double-stranded RNA (dsRNA), or single-stranded RNA (ssRNA) as their genetic material (see Table 3).

B. The viral way of life

When genetic information is encoded in double-stranded DNA, the enzyme RNA polymerase copies the information from DNA into messenger RNA, which then directs the synthesis of proteins that are responsible for traits of an organism. This flow of information, DNA —> RNA —> protein, is often referred to as the “central dogma.” Because viruses use the host cell’s translational machinery to make viral proteins, they too must use mRNAs to guide the production of proteins. Viruses containing dsDNA will use the host RNA polymerase to produce mRNA (Figure 1 category I).

viruses and us with respect to nucleic acid processing
Figure 3: Viruses categorized by the type of nucleic acid that is composed within their genomes and the mechanisms used to generate messenger RNA.

What happens when information is stored in ssDNA or in ssRNA or dsRNA? When the viral genome is ssDNA, a viral enzyme (or polymerase) must first synthesize a complementary strand of DNA to produce dsDNA from which mRNA is generated (Figure 3 category II). When the viral genome is dsRNA, mRNA is produced by a viral RNA polymerase that the virus carries into the cell (Figure 3 category III).

Viruses with ssRNA can be one of three types:

  1. positive-strand ssRNA (+ssRNA) viruses in which the viral genome serves directly as mRNA for protein synthesis (Figure 1 category IV). Additionally, the + ssRNA genome serves as a template for producing a negative-strand ssRNA (-ssRNA) via the viral RNA polymerase. The resulting - ssRNA then serves as a template for the production of more + ssRNA again via the viral RNA polymerase. These new + ssRNA can serve as mRNA and also will be encapsulated as the genome of the progeny virus.
  2. negative-strand ssRNA (-ssRNA) viruses in which the RNA genome is copied into mRNA for protein synthesis by the viral RNA polymerase (Figure 1 category V). Additionally, the - ssRNA serves as a template for synthesis of a +ssRNA via the viral RNA polymerase. The resulting +ssRNA then itself serves as a template for production of more - ssRNA, again via the viral RNA polymerase. These - ssRNA genomes can again be copied to mRNA by the viral RNA polymerase or encapsulated as the genome for the progeny virus.
  3. negative-strand ssRNA-reverse transcriptase (-ssRNA-RT) viruses in which a double stranded DNA is synthesized from the viral RNA strand by the enzyme reverse transcriptase. This double stranded DNA molecule is then inserted into the host DNA where it is transcribed into mRNA (Figure 1 category VI)

See Table 3 for examples of viruses with the different types of nucleic acids.

The ways different viruses invade and take over a cell varies to some degree but all demonstrate a common pattern. A virus enters the cell and, using different mechanisms depending on the kind of virus it is, takes over the cellular protein synthesis machinery to generate the proteins it needs for itself to reproduce. Like an unwanted guest who eats everything in the refrigerator, uses every clean towel in the house, and on leaving reduces your house to a pile of rubble, the virus utilizes the building blocks and energy stored that the cell has generated for its own growth and reproduction.

The cell is depleted of the materials and energy it needs to repair the damage. The machinery the cell needs to make more of itself is no longer under its control. As a result, the cell often dies from this invasion. A virus may exit a cell by simply lysing (blowing up) the cell or by budding from the cell, picking up some host membrane as it exists. As you will see in the measles and Ebola viruses, a virus that buds from a cell rather than exploding the cell can spread throughout the body efficiently by traveling in infected cells.

Table 3. Examples of viruses

Virus Structure Mode of Transmission Disease Caused Damage Symptoms
SARS-CoV-2 person-to-person apread; contact with contaminated surfaces or objects COVID-19 damages the wall and lining cells of the alveolus as well as the capillaries; provokes a destructive immune response cough, fever, tiredness, difficulty breathing
Polio Water, oral Poliomyelitis Destroys motor neuron cells Fever, sore throat, headache, vomiting, fatigue, muscle pain and weakness, paralysis
Influenza Aerosol, Inhalation of infectious droplets; Direct contact with respiratory fluids Flu Death of epithelial cells in nose, throat, and lungs Fever, cough, sore throat, runny or stuffy nose, muscle aches, headaches, fatigue
Ebola Direct contact with body fluids Hemorrhagic fever Infects cells of immune system and endothelial cells of vascular system causing blood leakage Nausea, high fever, muscle pain, malaise, diarrhea, red eyes,, severe weight loss, occasionally bleeding from eyes, ears nose, rectum
Measles Aerosol, inhalation of infectous droplets Rubeola (measles) Infects cells of immune system and epithelial cells High fever, cough, runny nose, red and watery eyes, rash
HIV Sexual contact; blood AIDS Destroys immune cells (CD4 cells) Lack of energy, weight loss, fevers and sweats, frequent yeast infections, skin rashes or flaky skin, short-term memory loss, mouth, genital, or anal sores
Rotavirus Direct contact with contaminated surfaces; fecal-oral Gastroenteritis Epithelial cells of the gastrointestinal tract Severe diarrhea, vomiting, fever, dehydration
Canine Parvovirus Direct contact with contaminated surfaces; fecal-oral Gastroenteritis Epithelial cells of the gastrointestinal tract Severe bloody diarrhea, lethargy, anorexia, fever, vomiting, severe weight loss
Vaccinia Direct contact with contaminated objects and people; airborne with infected droplets of saliva Smallpox Epithelial cells lining respiratory tract and other organs including skin High fever, fatigue, headache, backache, rash with flat red sores
Adenovirus Direct contact with contaminated objects and people; airborne with infected droplets; fecal-oral Common cold, sore throat, bronchitis, pneumonia, diarrhea, pink eye (conjunct-tivitis), gastro-enteritis Inflammation and destruction of epithelial cells Fever, cough, runny nose, bladder inflammation or infection (cystitis), inflammation of stomach and intestines

C. Prevention and Treatment

Viruses are not susceptible to antibiotics and, unlike the discovery of antibiotics for treating bacteria, no “miracle” drugs have been discovered for the treatment of viruses. In fact, to date, no truly effective viricidal (virus killing) drugs exist. While drugs exist that can block the replication of certain viruses (for example glanciclover drugs inhibit the growth of a number of different herpesviruses and a multi-drug cocktail prolongs the life of HIV-infected individuals), they do not clear the body of thevirus. In most instances, treatment of viral infections involves prevention (vaccines) or in helping the body to help itself, through the restorative powers of sleep, drinking plenty of fluids, and consuming vast quantities of chicken soup.
V. Identifying the cause of infectious diseases

In the late 1970s and 1980s, as the AIDS (Acquired Immune Deficiency Syndrome) pandemic was sickening and killing millions of people around the world, scientists worked relentlessly to identify the causative agent of the disease in the hopes of developing effective drugs and vaccines against it. In 1983, HIV (Human Immunodeficiency Virus) was identified as the cause.

How do scientists determine what causes an infectious disease and how do they prove it? The first conclusive demonstration that bacteria could cause disease was described in the work of Louis Pasteur and Robert Koch. Working independently, each scientist demonstrated that anthrax, a serious disease in domestic animals, which is also transmissible to humans, was caused by bacteria found in the bloodstream. The work of Pasteur, Koch, and other scientists in the field ushered in an era of discovery in which bacteria, viruses, and parasites were shown to be the causes of infectious diseases around the world.

In 1876, Koch proposed a set of criteria by which a microorganism could be determined to be an infectious agent (or pathogen). These criteria included:

  1. The microorganism must be present when the disease is present but absent in healthy organisms.
  2. It must be possible to isolate the microorganism.
  3. The isolated microorganism must cause disease when placed into a healthy organism.
  4. It must be possible to re-isolate the microorganism from the second diseased host.

These criteria, called Koch’s Postulates, are still used today to determine whether a disease is caused by an infectious agent. All organisms live in some kind of environment that provides them with nutrients and shelter in which to grow and replicate. In some cases, an infectious agent can survive in a number of different environments such as soil, water, a plant, or an animal, and it is only a matter of chance where the agent finally appears. In other cases, as you have seen in your reading, an infectious agent, for one reason or another, can live only within another organism—the host. Often the reason for this is that these pathogens require the nutrients that the host organism provides. The host becomes the environment from which the infectious agent derives everything it needs to survive. These organisms can only survive in one specific environment, which may be a plant or an animal or a bacterium. In some cases, the specificity may even extend to the type of tissue or cell in which the pathogen must live.

Wherever it lives, an infectious agent must grow and replicate. To do this, it must locate a suitable environment, take up nutrients, and release byproducts of its own metabolism. In carrying out these processes of life, the organism may deplete the nutrients in the environment, release toxic substances, and cause physical damage to its surroundings. The depletion of nutrients, damage from toxic substances, and mechanical damage can all contribute to causing the symptoms characteristic of the host’s disease associated with that infectious agent.

Scientists working to prove that HIV was the cause of AIDS were able to fulfill the first two criteria of Koch’s Postulates. For obvious ethical reasons, they could not fulfill the last two. However, the availability of animal models that demonstrated the same disease caused by a similar virus allowed researchers to demonstrate that HIV was responsible for this devastating disease by fulfilling all four of Koch’s Postulates.

VI. Analysis
  1. How would you define an infectious disease? A noninfectious disease?
  2. What is meant when an organism is termed an “infectious agent”?
  3. Create a table that compares an example of each type of infectious agent—bacterium, virus, and parasite. Using the following criteria, compare how the three types of infectious agents are similar and how they differ:
    1. biological characteristics of this agent
    2. how the agent is spread
    3. the symptoms this agent might cause
    4. methods of treatment and prevention
    5. Why is it important to specify that a parasite must be of a different species from the host? Can you think of an example of a parasitic-like relationship where the “host” and “parasite” are of the same species?
    6. Design an experiment using primates and simian immunodeficiency virus that would prove that this virus is the causative agent of AIDS in primates.