Infection, Infectious Disease, and Epidemiology

      Infection, Infectious Diseases,and Epidemiology Microbes in the Produce Aisle and Prevention (CDC). Basic epidemiological strategy is to look for factors common to those infected but not common in nonvictims that match the victims in age, geographical location, and similar factors. One factor the scientists noticed was that patients were more likely to have shopped at a particular grocery store before becoming hospitalized. This is puzzling, because while one might expect foodborne infections to be related to a grocery store, what would be a link for pneumonia? Imagine you are on the field team of the CDC sent to investigate this outbreak. ­ ­ ­ ­ In October, discussions in a small town in Louisiana, centered on dramatic world events, especially terrorism. However, an outbreak of pneumonia in 33 people from their community within a single week changed the talk in the coffee shops and community center. Epidemiologists with the state Department of Health began examining the patients for the most common causes of pneumonia in adults: the bacterial species Streptococcus pneumoniae, Mycoplasma pneumoniae, and Haemophilus influenzae and influenzaviruses and adenoviruses. The patients were negative for all of these pathogens, and they contacted the Centers for Disease Control 1. What first steps would you take to solve this mystery? 2. How would you isolate and identify the cause of the pneumonia? for sure; estimates range from 100 to more than 700 trillion microbes in and on a single person; and there are even more viruses, perhaps more than 100 trillion of a single type. We begin this section by considering types of symbiotic relationships. Types of Symbiosis LE A R N I N G O UTC O M E S 14.1 Distinguish among four types of symbiosis. 14.2 Describe the relationships among the terms parasite, host, and pathogen. Members of a symbiotic relationship are called symbionts. Biologists see symbiotic relationships as a continuum from cases that are beneficial to both symbionts to situations in which one symbiont lives at a damaging expense to the other. In the following sections, we examine four conditions along the continuum: mutualism, commensalism, amensalism, and parasitism. ­ In this chapter, we examine how microbes directly affect our bodies. Bear in mind that most microorganisms are neither harmful nor expressly beneficial to humans—they live their lives, and we live ours. Relatively few microbes either directly benefit us or harm us. We first examine the general types of relationships that microbes can have with the bodies of their hosts. Then we discuss sources of infectious diseases of humans, how microbes enter and attach to their hosts, the nature of infectious diseases, and how microbes leave hosts to become available to enter new hosts. Next, we explore the ways that infectious diseases are spread among hosts. Finally, we consider epidemiology, the study of the occurrence and spread of diseases within groups of humans and the methods by which we can limit the spread of pathogens within society. Go to the study area to solve the problem. Symbiotic Relationships Between Microbes and Their Hosts Symbiosis (sim-bī-o’sis) means “living together.” Each of us has symbiotic relationships with countless microorganisms, although often we are completely unaware of them. Your body’s 37 trillion or so cells provide homes for trillions of bacteria, protozoa, and fungi. How many? No one knows M14_BAUM7206_05_SE_C14.indd 411 Mutualism In mutualism (mū’tū-ăl-izm), both symbionts benefit from their interaction. For example, bacteria in your colon receive a warm, 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology hapter       C ­ moist, nutrient-rich environment in which to thrive, while you absorb vitamin precursors and other nutrients released from the bacteria. In this example, the relationship is beneficial to microbe and human alike but is not required by either. Many of the bacteria could live elsewhere, and you could get vitamins from your diet. Some mutualistic relationships provide such important benefits that one or both of the parties cannot live without the other. For instance, termites, which cannot digest the cellulose in wood by themselves, would die without a mutualistic relationship with colonies of wood-digesting protozoa and bacteria living in their intestines (FIGURE 14.1). The termites provide wood pulp and a home to the protozoa, while the protozoa break down the wood within the termite intestines using enzymes from the bacteria, which live on the protozoa. The microbes share with the termites the nutrients released. Beneficial Microbes: A Bioterrorist Worm describes another mutualistic relationship. LM 5 mm ▲ FIGURE 14.1 Mutualism. Wood-eating termites in the genus Reticulitermes cannot digest the cellulose in wood, but the protozoan Trichonympha, which lives in their intestines, can digest cellulose with the help of bacteria. The three organisms (termite, protozoan, bacterium) maintain a mutualistic relationship that is crucial for the life of the termite. What benefits accrue to each of the symbionts in this mutualistic relationship? ­ ­ In commensalism (kŏ-men’săl-izm), a second type of symbiosis, one symbiont benefits without significantly affecting the other. For example, microscopic animals—hair follicle mites—live on your skin without causing measurable harm to you. However, an absolute example of commensalism is difficult to prove because the host may experience unobserved benefits. Figure 14.1 The termite gets digested cellulose from the protozoa, which get a constant supply of wood pulp to digest, so the bacteria get a food source as well. Commensalism Amensalism Parasitism Amensalism (ā-men’săl-izm) is a symbiotic relationship in which one symbiont is harmed by a second symbiont, while the second is neither harmed nor helped by the first. For example, the fungus Penicillium (pen-i-sil’ē-ŭm) produces penicillin, which inhibits nearby bacteria, but the bacteria have no effect on the fungus. Of concern to health care professionals is a fourth type of symbiosis called parasitism1 (par’ă-si-tizm). A parasite derives benefit from its host while harming it, though some hosts sustain only slight damage. In the most severe cases, a parasite kills its host, in the process destroying its own home, which is not very beneficial Killed insect Steinernema BENEFICIAL MICROBES A Bioterrorist Worm Bioterrorism has been defined as The worm Steinernema (white) the deliberate release of viruses, kills by infecting insects with bacteria, or other germs to lethal Xenorhabdus bacteria. cause illness or death. A nematode worm, Steinernema, is by that definition a bioterrorist, releasing a mutualistic bacterial symbiont, Xenorhabdus. Nematodes are microscopic, unsegmented roundworms that live in soil worldwide. Steinernema preys on insects, including ants, termites, and the immature stages of various beetles, weevils, worms, fleas, ticks, and gnats. Steinernema crawls into an insect’s mouth or anus and then crosses the intestinal walls to enter the insect’s blood. The worm then releases its symbiotic Xenorhabdus. This bacterium inactivates the insect’s defensive systems; generates antibacterial compounds, which eliminate other bacteria; produces insecticidal LM 4 mm toxins to kill the insect; and secretes digestive enzymes. The bacterial enzymes turn the insect’s body into a slimy porridge of nutrients within 48 hours. Meanwhile, Steinernema nematodes mature, mate, and reproduce within the insect’s liquefying body. The nematodes’ offspring feed on the gooey fluid until they are old enough to emerge from the insect’s skeleton but not before taking up a supply of bacteria for their own future bioterrorist raids on new insect hosts. This is a true mutualistic symbiosis: the nematode depends on the bacterium to kill and digest the insect host, while the bacterium depends on the nematode to deliver it to new hosts. Both benefit. Farmers, too, can benefit. They can use Steinernema and its bacterium to control insect pests without damaging their crops, animals, or people. 1From M14_BAUM7206_05_SE_C14.indd 412 Greek parasitos, meaning “one who eats at the table of another.” 11/23/16 3:50 AM       Symbiotic Relationships Between Microbes and Their Hosts ­ for the parasite; therefore, parasites that allow their hosts to survive are more likely to spread. Similarly, hosts that tolerate a parasite are more likely to reproduce. The result over time will be coevolution toward commensalism or mutualism. Any parasite that causes disease is called a pathogen (path’ō-jen). A variety of protozoa, fungi, and bacteria are microscopic parasites of humans. Larger parasites of humans include parasitic worms and biting arthropods,2 including mites (skin-eating chiggers, not the commensal hair-follicle mites mentioned above), ticks, mosquitoes, fleas, and bloodsucking flies. You should realize that microbes that are parasitic may become mutualistic, or vice versa; that is, the relationships between and among organisms can change over time. TABLE 14.1 summarizes the types of symbiosis. Microbiome of Humans LE A R N I N G O U TC O M E SEM 14.3 Describe the microbiome, including resident and tran- sient members. 10 μm ▲ FIGURE 14.2 An example of normal microbiota. Bacteria ­ Even though many parts of your body are axenic 3 (ā-zen’ik) environments—that is, sites free of any microbes—other parts of your body shelter trillions of mutualistic and commensal symbionts. Each square centimeter of your skin, for example, contains millions of bacteria, and your large intestine contains perhaps more than 5000 different strains of bacteria alone, plus countless fungi, protozoa, and viruses. Microbes that colonize a body without normally causing disease constitute the body’s microbiome (FIGURE 14.2), also sometimes called the normal microbiota, or normal flora,4 or indigenous microbiota. The normal microbiome contains two main types of organisms: resident microbiota and transient microbiota. (pink) colonize the surfaces of human nasal cells (tan). Resident Microbiota Resident microbiota remain a part of the microbiome for most of a person’s life. These organisms are found on the skin and on the mucous membranes of the digestive tract, upper respiratory tract, distal5 portion of the urethra,6 and vagina. TABLE 14.2 on p. 414 illustrates these environments and lists some of the resident bacteria, fungi, and protozoa. Most resident microbiota are commensal; that is, they feed on excreted cellular wastes and dead cells without causing harm to the person. Transient Microbiota TABLE 14.1 Types of Symbiotic Relationships Organism 1 Organism 2 Mutualism Benefits Benefits Bacteria in human colon Example Commensalism Benefits Neither benefits nor is harmed Mites in human hair follicles Amensalism Is harmed Neither benefits nor is harmed Fungus secreting an antibiotic, inhibiting nearby bacteria Parasitism Benefits Is harmed Tuberculosis bacteria in human lung Greek arthros, meaning “jointed,” and pod, meaning “foot.” Greek a, meaning “no,” and xenos, meaning “foreigner.” 4This usage of the term flora, which literally means “plants,” derives from the fact that bacteria and fungi were considered plants in early taxonomic schemes. Microbiota is preferable because it properly applies to all microbes (whether eukaryotic or prokaryotic) and to viruses. 2From Transient microbiota remain in the body for only a few hours, days, or months before disappearing. They are found in the same locations as normal resident microbiota, but transient microbes cannot persist because of competition from other microorganisms, elimination by the body’s defenses, or chemical and physical changes in the body that dislodge them. Acquisition of the Microbiome You developed in your mother’s womb without a microbiome because you had surrounded yourself with an amniotic membrane and fluid, which generally kept microorganisms at bay, and because your mother’s uterus provided additional protection. Your normal microbiome began to develop when your protective amniotic membrane ruptured and microorganisms came in contact with you during birth. Microbes entered your mouth and nose as you passed through the birth canal, and your first breath was loaded with thousands of microbes, many of which quickly established themselves in your upper respiratory tract. Your first meals M14_BAUM7206_05_SE_C14.indd 413 5Distal refers to the end of some structure, as opposed to proximal, which refers to the beginning of a structure.   3From 6The tube that empties the bladder. 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology hapter       C TABLE 14.2 Some Resident Microbiota a Upper Respiratory Tract Nose Mouth Trachea Epiglottis Bronchi Genera Notes Fusobacterium, Haemophilus, Lactobacillus, Moraxella, Staphylococcus, Streptococcus, Veillonella, Candida (fungus) The nose is cooler than the rest of the respiratory system and has some unique microbiota. The microbiota of the trachea and bronchi are sparse compared to those of the nose and mouth. The alveoli of the lungs, which are too small to depict in this illustration, have no natural microbiota—they are axenic. Upper Digestive Tract Mouth Epiglottis Esophagus Liver Genera Notes Actinomyces, Bacteroides, Corynebacterium, Haemophilus, Lactobacillus, Neisseria, Staphylococcus, Treponema, Entamoeba (protozoan), Trichomonas (protozoan) Microbes colonize surfaces of teeth, gingiva, lining of cheeks, and pharynx; and they are found in saliva in large numbers. Dozens of species have never been identified. Lower Digestive Tract Pancreas Gallbladder Small intestine (section removed) Stomach Rectum Colon Genera Notes Bacteroides, Bifidobacterium, Clostridium, Enterococcus, Escherichia, Fusobacterium, Lactobacillus, Proteus, Shigella, Candida (fungus), Entamoeba (protozoan), Trichomonas (protozoan) The bacteria are mostly strict anaerobes, though some facultative anaerobes are also resident. Female Urinary and Reproductive Systems Cervix Ovary Uterus Rectum Bladder Vagina Urethra Genera Notes Bacteroides, Clostridium, Lactobacillus, Staphylococcus, Streptococcus, Candida (fungus), Trichomonas (protozoan) Microbiota change as acidity in the vagina changes during menstrual cycle. The flow of urine prevents extensive colonization of the urinary bladder or urethra. Male Urinary and Reproductive Systems Rectum Bladder Seminal vesicle Prostate gland Ductus (vas) deferens Dermis Hypodermis Orbicularis oculi muscle aGenera Notes Bacteroides, Fusobacterium, Lactobacillus, Mycobacterium, Peptostreptococcus, Staphylococcus, Streptococcus The flow of urine prevents extensive colonization of the urinary bladder or urethra. Eyes and Skin Testis Epidermis Genera Skin section Genera Notes Skin: Corynebacterium, Micrococcus, Propionibacterium, Staphylococcus, Candida (fungus), Malassezia (fungus) Conjunctiva: Staphylococcus Microbiota live on the outer, dead layers of the skin and in hair follicles and pores of glands. The deeper layers (dermis and hypodermis) are axenic.Tears wash most microbiota from the eyes, so there are few compared to the number on the skin. Conjunctiva are bacteria unless otherwise noted. provided the progenitors of resident microbiota for your colon, while hair follicle mites, bacteria, and other microbes transferred from the skin of both the medical staff and your parents and colonized your skin. Although you continue to add to and subtract from your transient microbiota, most of your resident microbiota was initially established during your first months of life. How Normal Microbiota Become Opportunistic Pathogens LE A R N I N G O U TC O M E 14.4 Describe three conditions that create opportunities for normal microbiota to cause disease. M14_BAUM7206_05_SE_C14.indd 414 Under ordinary circumstances, normal microbiota do not cause disease. However, these same microbes may become harmful if an opportunity to do so arises. In this case, normal microbiota (or other normally harmless transient microbes from the environment) become opportunistic pathogens, or opportunists. Conditions that create opportunities for pathogens include the following: • Introduction of a member of the normal microbiota into an unusual site in the body. As we have seen, normal microbiota are present only in certain body sites, and each site has only certain species of microbiota. If a member of the normal microbiota in one site is introduced into a site it normally does not inhabit, the organism may become an opportunistic pathogen. For example, Escherichia coli (eshě-rik’ē-ă kō’lī) is mutualistic in the colon, but should it 11/23/16 3:50 AM       Reservoirs of Infectious Diseases of Humans Now that we have considered the relationships of the normal microbiota to their hosts, we turn our attention to the movement of microbes into new hosts by considering aspects of human diseases. TELL ME WHY Why is an absolute commensalism difficult to prove? Reservoirs of Infectious Diseases of Humans LE A R N I N G O U TC O M E 14.5 Describe three types of reservoirs of infection in humans. Most pathogens of humans cannot survive for long in the relatively harsh conditions they encounter outside the human body. If these pathogens are to enter new people, they must survive in some site from which they can infect new hosts. Sites where pathogens are normally maintained as a source of infection are called reservoirs of infection. In this section, we discuss three types of reservoirs: animal reservoirs, human carriers, and nonliving reservoirs. M14_BAUM7206_05_SE_C14.indd 415 Animal Reservoirs Many pathogens that normally infect either domesticated or sylvatic7 (wild) animals can also infect humans. The more similar an animal’s physiology is to human physiology, the more likely its pathogens can affect human health. Diseases that spread naturally from animal hosts to humans are called zoonoses (zō-ō-nō’sēz). Over 200 zoonoses have been identified throughout the world. Well-known examples include anthrax, bubonic plague, rabies, and Ebola hemorrhagic fever. Humans may acquire zoonoses from animals via a number of routes, including various types of direct contact with animals or their wastes, by eating animals, or via bloodsucking arthropods, which act as vectors. Human infections with zoonoses are difficult to eradicate because extensive animal reservoirs are often involved. The larger the animal reservoir (i.e., the greater the number and types of infected animals) and the greater the contact between humans and the animals, the more difficult and costly it is to control the spread of the disease to humans. This is especially true when the animal reservoir consists of both sylvatic and domesticated animals. In the case of rabies, for example, the disease typically spreads from a sylvatic reservoir (often bats, foxes, or skunks) to domestic pets, from which humans may be infected. The wild animals constitute a reservoir for the rabies virus, though transmission to humans can be limited by vaccinating domestic pets. TABLE 14.3 on p. 416 provides a brief view of some common zoonoses. Humans are usually dead-end hosts for zoonotic pathogens—that is, humans do not act as significant reservoirs for the reinfection of animal hosts—largely because the circumstances under which zoonoses are transmitted favor movement from animals to humans but not in the opposite direction. For example, animals do not often eat humans these days, and animals less frequently have contact with human wastes than humans have contact with animal wastes. Zoonotic diseases transmitted via the bites of bloodsucking arthropods are the most likely type to be transmitted back to animal hosts. ­ enter the urethra, it becomes an opportunist that produces a urinary tract infection and disease. • Immune suppression. Anything that suppresses the body’s immune system—including disease, malnutrition, emotional or physical stress, extremes of age (either very young or very old), the use of radiation or chemotherapy to combat cancer, or the use of immunosuppressive drugs in transplant patients—can enable opportunistic pathogens. AIDS patients often die from opportunistic infections that are typically controlled by a healthy immune system because HIV infection suppresses immune system function. • Changes in the normal microbiota. Normal microbiota use nutrients, take up space, and release toxic waste products, all of which make it less likely that arriving pathogens can compete well enough to become established and produce disease. This situation is known as microbial antagonism or microbial competition. However, changes in the relative abundance of normal microbiota, for whatever reason, may allow a member of the normal microbiota to become an opportunistic pathogen and thrive. For example, when a woman must undergo long-term antimicrobial treatment for a bacterial blood infection, the antimicrobial drug may also kill normal bacterial microbiota in the vagina. In the absence of competition from bacteria, Candida albicans (kan’did-ă al’bi-kanz), a yeast and member of the normal vaginal microbiota, grows prolifically, producing an opportunistic vaginal yeast infection. • Stressful conditions. Anything that strains a person’s normal metabolism or emotional state can disrupt the normal microbiota. Such conditions include hormonal changes, unresolved emotional stress, abrupt changes in diet, or exposure to overwhelming numbers of pathogens. Human Carriers Experience tells you that humans with active diseases are important reservoirs of infection for other humans. What may not be so obvious is that people with no obvious symptoms before or after a disease may also be infective in some cases. Further, some infected people can remain both asymptomatic and infective for years. This is true of tuberculosis, syphilis, and AIDS, for example. Whereas some of these carriers incubate the pathogen in their body and eventually develop the disease, others remain a continued source of infection without ever becoming sick. Presumably many such healthy carriers have defensive systems that protect them from illness. A true example of such a carrier is given in Clinical Case Study: A Deadly Carrier. 7From Latin sylva, meaning “woodland.” 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology hapter       C TABLE 14.3 Some Common Zoonoses Disease Causative Agent Animal Reservoir Mode of Transmission Tapeworm infestation Dipylidium caninum Dogs Ingestion of larvae transmitted in dog saliva Fasciola infestation Fasciola hepatica Sheep, cattle Ingestion of contaminated vegetation Malaria Plasmodium spp. Monkeys Bite of Anopheles mosquito Toxoplasmosis Toxoplasma gondii Cats and other animals Ingestion of contaminated meat, inhalation of pathogen, direct contact with infected tissues Trichophyton spp. Domestic animals Direct contact Helminthic Protozoan Fungal Ringworm Microsporum spp. Epidermophyton floccosum Bacterial Anthrax Bacillus anthracis Domestic livestock Direct contact with infected animals, inhalation Bubonic plague Yersinia pestis Rodents Flea bites Lyme disease Borrelia burgdorferi Deer Tick bites Salmonellosis Salmonella spp. Birds, rodents, reptiles Ingestion of fecally contaminated water or food Rabies Lyssavirus sp. Bats, skunks, foxes, dogs Bite of infected animal Hantavirus pulmonary syndrome Hantavirus sp. Deer mice Inhalation of viruses in dried feces and urine Yellow fever Flavivirus sp. Monkeys Bite of Aedes mosquito Viral A Deadly Carrier In 1937, a man employed to lay water pipes was found to be the source of a severe epidemic of typhoid fever. The man, who had recovered from typhoid, was still an asymptomatic carrier of Salmonella enterica serotype Typhi, the bacterium that causes the disease. He habitually urinated at his job site and in the process contaminated the town’s water supply with bacteria from his bladder. Over 300 cases of typhoid fever developed, and 43 people died before the man was identified as the carrier. 1. How do you think health officials were able to identify the source of this typhoid epidemic? ­ A c Clini al C SE STUDY Nonliving Reservoirs Inanimate things such as soil, water, and food can be nonliving reservoirs of infection. Soil can harbor species of Clostrid­ ium (klos-trid’ē-ŭm) bacteria, which cause botulism, tetanus, and other diseases. Fecally contaminated soil may serve as a M14_BAUM7206_05_SE_C14.indd 416 2. G  iven that antibiotics were not generally available in 1937, how could health officials end the epidemic, short of removing the man from the job site? reservoir for the pathogens of toxoplasmosis, hookworm infestation, or gastrointestinal bacteria and viruses. Water can be contaminated with feces and urine containing parasitic worm eggs, pathogenic protozoa, bacteria, and viruses. Meats and vegetables can also harbor pathogens. 11/23/16 3:50 AM       The Invasion and Establishment of Microbes in Hosts: Infection TELL ME WHY Why might animal reservoirs be involved in more diseases than are human reservoirs? Conjunctiva of eye Nose Mouth Ear The Invasion and Establishment of Microbes in Hosts: Infection Broken skin Insect bite In this section, we examine events that occur when hosts are exposed to microbes from a reservoir, the sites at which microbes can gain entry into hosts, and the ways entering microbes become established in new hosts. Placenta Vagina (in males: penis) Urethra Anus Exposure to Microbes: Contamination and Infection LE A R N I N G O U TC O M E 14.6 Describe the relationship between contamination and infection. ­ In the context of the interaction between microbes and their hosts, contamination refers to the mere presence of microbes in or on the body. Some microbial contaminants reach the body in food, drink, or the air, whereas others are introduced via wounds, biting arthropods, or sexual intercourse. Several outcomes of contamination by microbes are possible. Some microbial contaminants remain where they first contacted the body without causing harm and subsequently become part of the resident microbiota; other microbial contaminants remain on the body for only a short time as part of the transient microbiota. Pathogens overcome the body’s external defenses, multiply, and become established in the body; such a successful invasion of the body is called an infection. An infection may or may not result in disease; that is, it may not adversely affect the body. Next, we consider in greater detail the various sites through which pathogens gain entry into the body. Portals of Entry LE A R N I N G O U TC O M E 14.7 Identify and describe the portals through which patho- gens invade the body. ­ The sites through which most pathogens enter the body can be likened to the great gates, or portals, of a castle because those sites constitute the routes by which microbes gain entry. Pathogens can enter the body at several sites, called portals of entry (FIGURE 14.3), which are of three major types: the skin, the mucous membranes, and the placenta. A fourth entry point, the so-called parenteral route (pă-ren’ter-ăl), is not a portal but a way of circumventing the usual portals. Next we consider each type in turn. M14_BAUM7206_05_SE_C14.indd 417 ▲ FIGURE 14.3 Routes of entry for invading pathogens. The portals of entry include the skin, placenta, conjunctiva, and mucous membranes of the respiratory, gastrointestinal, urinary, and reproductive tracts. The parenteral route involves a puncture through the skin. Skin Because the outer layer of skin is composed of relatively thick layers of tightly packed, dead, dry cells (FIGURE 14.4), it forms a formidable barrier to most pathogens as long as it remains intact. Still, some pathogens can enter the body through natural openings in the skin, such as hair follicles and sweat glands. Abrasions, cuts, bites, scrapes, stab wounds, and surgeries open the skin to infection by contaminants. Additionally, the larvae of some parasitic worms are capable of burrowing through the skin to reach underlying tissues, and some fungi can digest the dead outer layers of skin, thereby gaining access to deeper, moister areas within the body. Mucous Membranes The major portals of entry for pathogens are the mucous mem­ branes, which line all the body cavities that are open to the outside world. These include the linings of the respiratory, gastrointestinal, urinary, and reproductive tracts as well as the conjunctiva (kon-jŭnk-tī’vă), the thin membrane covering the surface of the eyeball and the underside of each eyelid. Like the skin, mucous membranes are composed of tightly packed cells, but unlike the skin, mucous membranes are relatively thin, moist, and warm, and their cells are living. Therefore, pathogens find mucous membranes more hospitable and easier portals of entry. The respiratory tract is the most frequently used portal of entry. Pathogens enter the mouth and nose in the air, on dust particles, and in droplets of moisture. For example, the bacteria that cause whooping cough, diphtheria, pneumonia, strep 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology hapter       C Placenta Hair Sebaceous (oil) gland Cut (example of a parenteral route) Pore of sweat duct Blood capillaries Epidermis Nerve fiber Dermis Nerve ending Vein Artery Sweat gland A developing embryo forms an organ, called the placenta, through which the embryo obtains nutrients from the mother. The placenta is in such intimate contact with the wall of the mother’s uterus that nutrients and wastes diffuse between the blood vessels of the developing child and of the mother; however, because the two blood supplies do not actually contact each other, the placenta typically forms an effective barrier to most pathogens. Even so, in about 2% of pregnancies, pathogens cross the placenta and infect the embryo or fetus, sometimes causing spontaneous abortion, birth defects, or premature birth. Some pathogens that can cross the placenta are listed in TABLE 14.4. The Parenteral Route Fat cells Hair follicle ▲ FIGURE 14.4 A cross section of skin. The layers of cells constitute a barrier to most microbes as long as the skin remains intact. Some pathogens can enter the body through hair follicles, through the ducts of sweat glands, and parenterally. The parenteral route is not a portal of entry but instead a means by which the portals of entry are circumvented. To enter the body by the parenteral route, pathogens must be deposited directly into tissues beneath the skin or mucous membranes, such as occurs in punctures by a nail, thorn, or hypodermic needle. Some experts include in the parenteral route breaks in the skin by cuts, bites, stab wounds, deep abrasions, or surgery. The Role of Adhesion in Infection LE A R N I N G O UTC O M E S TABLE 14.4 14.8 List the types of adhesion factors and the roles they play in infection. 14.9 Explain how a biofilm may facilitate contamination and infection. After entering the body, symbionts must adhere to cells if they are to be successful in establishing colonies. The process by which microorganisms attach themselves to cells is called adhesion (ad-hē’zhŭn) or attachment. To accomplish adhesion, pathogens use adhesion factors, which are either specialized structures or attachment molecules. Examples of such specialized structures are adhesion disks in some protozoa and suckers and hooks in some helminths (see Chapter 23). In ­ throat, and meningitis; the viruses of measles, influenza, and colds; as well as some diseases caused by fungi or protozoa enter through the respiratory tract. Surprisingly, many viruses enter the respiratory tract via the eyes. They are introduced onto the conjunctiva by contaminated fingers and are washed into the nasal cavity with tears. Cold and influenza viruses often enter the body in this manner. Some parasitic protozoa, helminths, bacteria, and viruses infect the body through the gastrointestinal mucous membranes. These parasites are able to survive the acidic pH of the stomach and the digestive juices of the intestinal tract. Noncellular pathogens called prions can also enter the body through oral mucous membranes. Some Pathogens That Cross the Placenta Pathogen Condition in the Adult Effect on Embryo or Fetus Protozoan Toxoplasma gondii Toxoplasmosis Abortion, epilepsy, encephalitis, microcephaly, mental retardation, blindness, anemia, jaundice, rash, pneumonia, diarrhea, hypothermia, deafness Bacteria Treponema pallidum Syphilis Abortion, multiorgan birth defects, syphilis Listeria monocytogenes Listeriosis Granulomatosis infantiseptica (nodular inflammatory lesions and infant blood poisoning), death Cytomegalovirus Usually asymptomatic Deafness, microcephaly, mental retardation Erythrovirus Erythema infectiosum Abortion Lentivirus (HIV) AIDS Immunosuppression (AIDS) Rubivirus German measles Severe birth defects or death DNA Viruses RNA Viruses M14_BAUM7206_05_SE_C14.indd 418 11/23/16 3:50 AM       The Nature of Infectious Disease contrast, viruses and many bacteria have surface lipoprotein or glycoprotein molecules called ligands that enable them to bind to complementary receptors on host cells (FIGURE 14.5). Ligands are also called adhesins on bacteria and attachment pro­ teins on viruses. Adhesins are found on fimbriae, flagella, and glycocalyces of many pathogenic bacteria. Receptor molecules on host cells are typically glycoproteins, which are proteins bound to sugar molecules such as mannose or galactose. If ligands or their receptors can be changed or blocked, infection can often be prevented. The specific interaction of adhesins and receptors with chemicals on host cells often determines the specificity of pathogens for particular hosts. For example, Neisseria gonor­ rhoeae (nī-se’rē-ă go-nor-rē’ī) has adhesins on its fimbriae that adhere to cells of humans; therefore, this pathogen cannot affect other hosts. Some bacteria, including Bordetella (bōr-dě-tel’ă; the cause of whooping cough), have more than one type of adhesin. Other pathogens, such as Plasmodium (plaz-mō’dē-ŭm; the cause of malaria), change their adhesins over time, helping the pathogen evade the body’s immune system and allowing the pathogen to attack more than one kind of cell. Bacterial cells and viruses that have lost the ability to make ligands—whether as the result of some genetic change (mutation) or exposure to certain physical or chemical agents (as occurs in the production of some vaccines)—become harmless, or avirulent (ā-vir’ū-lent). Some bacterial pathogens do not attach to host cells directly but instead interact with each other to form a sticky web of bacteria and polysaccharides called a biofilm, which adheres to a surface within a host. A prominent example of a biofilm is dental plaque (FIGURE 14.6), which contains the bacteria that cause dental caries (tooth decay). E. coli TELL ME WHY Why does every infection start with contamination but not every contamination results in an infection? The Nature of Infectious Disease LE A R N I N G O UTC O M E 14.10 Compare and contrast the terms infection, disease, morbid­ ity, pathogenicity, and virulence. Most infections succumb to the body’s defenses (discussed in detail in Chapters 15 and 16), but some infectious agents not only evade the defenses and multiply but also affect body function. By definition, every parasite injures its host. When the injury is significant enough to interfere with the normal functioning of the host’s body, the result is termed disease. Thus, disease, also known as morbidity, is any change from a state of health. Infection and disease are not the same. Infection is the invasion of a pathogen; disease results only if the pathogen multiplies sufficiently to adversely affect the body. Some illustrations will help to clarify this point. While caring for a patient, a nurse may become contaminated with the bacterium Staphylococcus aureus (staf’i-lō-kok’us o’rē-ŭs). If the pathogen is able to gain access to his body, perhaps through a break in his skin, he will become infected. Only if the multiplication of Staphylococcus results in adverse conditions, for example, in the production of a boil, will the nurse have a disease. Another example: A drug addict who shares needles may become contaminated and subsequently infected with HIV without experiencing visible change in body function for years. Such a person is infected but not yet diseased. Ligand (adhesion factor) Microbe Mucous membrane of intestine Cytoplasmic membrane Receptor (glycoprotein) Host cell surface Host cell (a) (b) TEM 2 µm ▲ FIGURE 14.5 The adhesion of pathogens to host cells. (a) An artist’s rendition of the attachment of a microbial attachment molecule (ligand) to a complementary surface receptor on a host cell. (b) A photomicrograph of cells of a pathogenic strain of E. coli attached to the mucous membrane of the intestine. Although the thick glycocalyces (black) of the bacteria are visible, a bacterium’s attachment molecules are too small to be seen at this magnification. M14_BAUM7206_05_SE_C14.indd 419 SEM 0.5 µm ▲ FIGURE 14.6 Dental plaque. This biofilm consists of bacteria that adhere to one another and to teeth by means of sticky capsules; an extracellular, slimy matrix; and fimbriae. 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology Diseases may become manifest in different ways. Symptoms are subjective characteristics of a disease that can be felt by the patient alone, whereas signs are objective manifestations of disease that can be observed or measured by others. Symptoms include pain, headache, dizziness, and fatigue; signs include swelling, rash, redness, and fever. Sometimes pairs of symptoms and signs reflect the same underlying cause: nausea is a symptom, and vomiting a sign; chills are a symptom, whereas shivering is a sign. Note, however, that even though signs and symptoms may have the same underlying cause, they need not occur together. Thus, for example, a viral infection of the brain may result in both a headache (a symptom) and the presence of viruses in the cerebrospinal fluid (a sign), but viruses in the cerebrospinal fluid are not invariably accompanied by headache. Symptoms and signs are used in conjunction with laboratory tests to make diagnoses. Some typical symptoms and signs are listed in TABLE 14.5. A syndrome is a group of symptoms and signs that collectively characterizes a particular disease or abnormal condition. For example, acquired immunodeficiency syndrome (AIDS) is characterized by malaise, loss of certain white blood cells, diarrhea, weight loss, pneumonia, toxoplasmosis, and tuberculosis. Some infections go unnoticed because they have no symptoms. Such cases are asymptomatic, or subclinical, infections. Note that even though asymptomatic infections by definition lack symptoms, in some cases certain signs may still be detected if the proper tests are performed. For example, leukocytosis (an excess of white blood cells) may be detected in a blood sample from an individual who feels completely healthy. TABLE 14.6 lists some prefixes and suffixes used to describe various aspects of diseases and syndromes. Causation of Disease: Etiology LE A R N I N G O U TC O M E S 14.12 Define etiology. 14.13 List Koch’s postulates, explain their function, and describe their limitations. TABLE 14.5 Using Koch’s Postulates In our modern world, we take for granted the idea that specific microbes cause specific diseases, but this has not always been the case. In the past, disease was thought to result from a variety of causes, including bad air, imbalances in body fluids, or astrological forces. In the 19th century, Louis Pasteur, Robert Koch, and other microbiologists proposed the germ theory of disease, which states that disease is caused by infections of pathogenic microorganisms (at the time called germs). But which pathogen causes a specific disease? How can we distinguish the pathogen that causes a disease from all the other biological agents (fungi, bacteria, protozoa, and viruses) that are part of the normal microbiota and are in effect “innocent bystanders”? Koch developed a series of essential conditions, or postu­ lates, that scientists must demonstrate or satisfy to prove that a particular microbe is pathogenic and causes a particular disease. Using his postulates, Koch proved that Bacillus anthracis (ba-sil’ŭs an-thrā’sis) causes anthrax and that Mycobacterium tuberculosis (mī-kō-bak-tēr’ē-ŭm too-ber-kyū-lō’sis) causes tuberculosis. To prove that a given infectious agent causes a given disease, a scientist must satisfy all of Koch’s postulates (FIGURE 14.7): ­ 14.11 Contrast symptoms, signs, and syndromes. 1 1 The suspected agent (bacterium, virus, etc.) must be present in every case of the disease. 1 2 That agent must be isolated and grown in pure culture. 1 3 The cultured agent must cause the disease when it is inoculated into a healthy, susceptible experimental host. 1 4 The same agent should be found in the diseased experimental host. Typical Manifestations of Disease Symptoms (Sensed by the Patient) Signs (Detected or Measured by an Observer) Pain, nausea, headache, chills, sore throat, fatigue or lethargy (sluggishness, tiredness), malaise (discomfort), itching, abdominal cramps Swelling, rash or redness, vomiting, diarrhea, fever, pus formation, anemia, leukocytosis/ leukopenia (increase/decrease in the number of circulating white blood cells), bubo (swollen lymph node), tachycardia/ bradycardia (increase/decrease in heart rate) It is critical that all the postulates be satisfied in order. The mere presence of an agent does not prove that it causes a 8Neoplasms (cancers). M14_BAUM7206_05_SE_C14.indd 420  LE A R N I N G O U TC O M E Even though our focus in this chapter is infectious disease, it’s obvious that not all diseases result from infections. Some diseases are hereditary, which means they are genetically transmitted from parents to offspring. Other diseases, called congenital diseases, are diseases that are present at birth, regardless of the cause (whether hereditary, environmental, or infectious). Still other diseases are classified as degenerative, nutritional, endocrine, mental, immunologi­ cal, or neoplastic.8 The various categories of diseases are described in TABLE 14.7. Note that some diseases can fall into more than one category. For example, liver cancer, which is usually associated with infection by hepatitis B and D viruses, can be classified as both neoplastic and infectious. The study of the cause of a disease is called etiology (ē-tēol’ō-jē). Because our focus here and in subsequent chapters is on infectious diseases, we next examine how microbiologists investigate the causation of infectious diseases, beginning with an examination of the work of Robert Koch.  Manifestations of Disease: Symptoms, Signs, and Syndromes  hapter       C are tumors, which may either remain in one place (benign tumors) or spread 11/23/16 3:50 AM       The Nature of Infectious Disease TABLE 14.6 Terminology of Disease Prefix/Suffix Meaning Example carcino- Cancer Carcinogenic: giving rise to cancer col-, colo- Colon Colitis: inflammation of the colon dermato- Skin Dermatitis: inflammation of the skin -emia Pertaining to the blood Viremia: viruses in the blood endo- Inside Endocarditis: inflammation of lining of heart -gen, gen- Give rise to Pathogen: giving rise to disease hepat- Liver Hepatitis: inflammation of the liver idio- Unknown Idiopathic: pertaining to a disease of unknown cause -itis Inflammation of a structure Meningitis: inflammation of the meninges (covering of the brain) -oma Tumor or swelling Papilloma: wart -osis Condition of Toxoplasmosis: being infected with Toxoplasma -patho, patho- Abnormal Pathology: study of disease septi- Literally, rotting; refers to presence of pathogens Septicemia: pathogens in the blood terato- Defects Teratogenic: causing birth defects tox- Poison Toxin: harmful compound TABLE 14.7 Categories of Diseasesa Description Examples Hereditary Caused by errors in the genetic code received from parents Sickle-cell anemia, diabetes mellitus, Down syndrome Congenital Anatomical and physiological (structural and functional) defects present at birth; caused by drugs (legal and illegal), X-ray exposure, or infections Fetal alcohol syndrome, deafness from rubella infection Degenerative Result from aging Renal failure, age-related farsightedness Nutritional Result from lack of some essential nutrients in diet Kwashiorkor, rickets Endocrine (hormonal) Due to excesses or deficiencies of hormones Addison’s disease Mental Emotional or psychosomatic Skin rash, gastrointestinal distress Immunological Hyperactive or hypoactive immunity Allergies, autoimmune diseases, agammaglobulinemia Neoplastic (tumor) Abnormal cell growth Benign tumors, cancers Infectious Caused by an infectious agent Colds, influenza, herpes infections Iatrogenicb Caused by medical treatment or procedures; are a subgroup of healthcare-associated diseases Surgical error, yeast vaginitis resulting from antimicrobial therapy Idiopathicc Unknown cause Alzheimer’s disease, multiple sclerosis Healthcare-Associated (nosocomiald) Disease acquired in health care setting Pseudomonas infection in burn patient aSome diseases may fall in more than one category. Greek iatros, meaning “physician.” cFrom Greek idiotes, meaning “ignorant person,” and pathos, meaning “disease.” dFrom Greek nosokomeion, meaning “hospital.” bFrom disease. Although Koch’s postulates have been used to prove the cause of many infectious diseases in humans, animals, and plants, inadequate attention to the postulates has resulted in incorrect conclusions concerning some disease causation. For instance, in the early 1900s Haemophilus influenzae (hē-mof’i-lŭs in-flū-en’zī) was found in the respiratory systems of flu victims and identified as the causative agent of influenza based on its M14_BAUM7206_05_SE_C14.indd 421 presence. Later, flu victims who lacked H. influenzae in their lungs were discovered. This discovery violated the first postulate, so H. influenzae cannot be the cause of flu. Today, we know that an RNA virus causes flu and that H. influenzae was part of the normal microbiota of those early flu patients. (Later studies, correctly using Koch’s postulates, showed that H. influenzae can cause an often-fatal meningitis in children.) 11/23/16 3:50 AM hapter       C 14    Infection, Infectious Diseases, and Epidemiology 1 The suspected agent must be present in every case of the disease. Diseased subjects Agent not typically found in healthy subjects Healthy subject Petri plate Bacterial colonies 2 The suspected agent must be isolated and grown in pure culture. Streaked plates Injection 3 The cultured suspect should cause the disease when it is inoculated into a healthy, susceptible experimental host (animal or plant). 4 The same agent must be reisolated from the diseased experimental host. ▲ FIGURE 14.7 Koch’s postulates. Exceptions to Koch’s Postulates Clearly, Koch’s postulates are a cornerstone of the etiology of infectious diseases, but using them is not always feasible, for the following reasons: • Some pathogens have not been cultured in the laboratory. For example, pathogenic strains of Mycobacterium leprae (lep’rī), which causes leprosy, have never been grown on laboratory media. • Some diseases are caused by a combination of pathogens or by a combination of a pathogen and physical, environmental, or genetic cofactors. In such cases, the pathogen alone is M14_BAUM7206_05_SE_C14.indd 422 unable to cause disease, but when accompanied by another pathogen or the appropriate cofactor, disease results. • Ethical considerations prevent applying Koch’s postulates to diseases and pathogens that occur in humans only. In such cases, the third postulate, which involves inoculation of a healthy susceptible host, cannot be satisfied within ethical boundaries. For this reason, scientists have never applied Koch’s postulates to prove that HIV causes AIDS; however, observations of fetuses that were naturally exposed to HIV across their placentas from their infected mothers, as well as accidentally infected health care and laboratory workers, have in effect satisfied the third postulate. 11/23/16 3:50 AM       The Nature of Infectious Disease Some additional circumstances may make satisfying Koch’s postulates difficult: More virulent • It is not possible to establish a single cause for such infectious diseases as pneumonia, meningitis, and hepatitis because the names of these diseases refer to conditions that can be caused by more than one pathogen. For these diseases, laboratory technicians must identify the etiologic agent involved in any given case. • Some pathogens may have been ignored. For example, gastric ulcers were long thought to be caused by excessive production of stomach acid in response to stress, but the majority of such ulcers are now known to be caused by a long-overlooked bacterium, Helicobacter pylori (hel’ĭ-kōbak’ter pī’lō-rē). Yersinia pestis (plague) Bordetella pertussis (whooping cough) Pseudomonas aeruginosa (infections of burns) Clostridium difficile (antibiotic-induced colitis) Candida albicans (vaginitis, thrush) ­ If Koch’s postulates cannot be applied to a disease condition for whatever reason, how can we positively know the causative agent of a disease? Epidemiological studies, discussed later in this chapter, can give statistical support to causation theories but not absolute proof. For example, some researchers have proposed that the bacterium Chlamydophila pneumoniae (kla-mēdof’ī-lă noo-mō’nē-ī) causes many cases of arteriosclerosis, in part on the basis of the bacterium’s presence in patients with the disease. Debate among scientists about such cases fosters a continued drive for knowledge and discovery. For example, we are still searching for the causes of chronic fatigue syndrome, multiple sclerosis, and Alzheimer’s disease. Francisella tularensis (rabbit fever) LE A R N I N G O U TC O M E 14.14 Explain how microbial extracellular enzymes, toxins, adhesion factors, and antiphagocytic factors affect virulence. Microbiologists characterize the disease-related capabilities of microbes by using two related terms. The ability of a microbe to cause disease is termed pathogenicity (path’ō- jě-nis’i-tē), and the degree of pathogenicity is termed virulence. In other words, virulence is the relative ability of a pathogen to infect a host and cause disease. Neither term addresses the severity of a disease; the pathogen causing rabbit fever is highly virulent, but the disease is relatively mild. Organisms can be placed along a virulence continuum (FIGURE 14.8); highly virulent organisms almost always cause disease, whereas less virulent organisms (including opportunistic pathogens) cause disease only in weakened hosts or when present in overwhelming numbers. Pathogens have a variety of traits that interact with a host and enable the pathogen to enter a host, adhere to host cells, gain access to nutrients, and escape detection or removal by the immune system. These traits are collectively called virulence factors. Virulent pathogens have one or more virulence factors that nonvirulent microbes lack. We discussed two virulence factors—adhesion factors and biofilm formation—previously; now we examine three other virulence factors: extracellular enzymes, toxins, and antiphagocytic factors. Other virulence M14_BAUM7206_05_SE_C14.indd 423 Less virulent ▲ FIGURE 14.8 Relative virulence of some microbial pathogens. Virulence involves ease of infection and the ability of a pathogen to cause disease; the term does not indicate the seriousness of a disease. factors can be examined online at the MasteringMicrobiology Study Area. ▶ ANIMATION: Virulence Factors: Inactivating Host Defenses Extracellular Enzymes Many pathogens secrete enzymes that enable them to dissolve structural chemicals in the body and thereby maintain an infection, invade further, and avoid body defenses. FIGURE 14.9a illustrates the action of some extracellular enzymes of bacteria: • Hyaluronidase and collagenase degrade specific molecules to enable bacteria to invade deeper tissues. Hyaluronidase digests hyaluronic acid—the “glue” that holds animal cells together—and collagenase, which breaks down collagen, the body’s chief structural protein. • Coagulase causes blood proteins to clot, providing a “hiding place” for bacteria within a clot. • Kinases, such as staphylokinase and streptokinase, digest blood clots, allowing subsequent invasion of damaged tissues. ­ Virulence Factors of Infectious Agents Lactobacilli, diphtheroids Many bacteria with these enzymes are virulent; mutant strains of the same species that have defective genes for these extracellular enzymes are usually avirulent. Pathogenic eukaryotes also secrete enzymes that contribute to virulence. For example, fungi that cause “ringworm” produce keratinase, which enzymatically digests keratin—the main component of skin, hair, and nails. Entamoeba histolyt­ ica (ent-ă-mē’bă his-tō-li’ti-kă) secretes mucinase to digest the mucus lining the intestinal tract, allowing the amoeba entry 11/23/16 3:50 AM Infection, Infectious Diseases, and Epidemiology          CHAPTER 14 Hyaluronidase and collagenase Coagulase and kinase Bacterium Hyaluronidase Bacterium Coagulase Clot Clotting protein Epithelial cells Collagenase Collagen layer Invasive bacteria reach epithelial surface. Kinase Bacteria produce hyaluronidase and collagenase. Bacteria invade deeper tissues. Bacteria produce coagulase. Clot forms. Bacteria later produce kinase, dissolving clot and releasing bacteria. (a) Extracellular enzymes Exotoxin Endotoxin Bacterium Exotoxin Phagocyte Phagocytized Gram– bacteria Exocytosis Endotoxin Dead Gram– bacterium Blood vessel Bacteria secrete exotoxins; in this case, a cytotoxin. Cytotoxin kills host’s cells. Dead Gram-negative bacteria release endotoxin (lipid A), which induces effects such as fever, inflammation, diarrhea, shock, and blood coagulation. (b) Toxins Phagocytosis blocked by capsule Capsule around bacterium Phagocyte Incomplete phagocytosis Capsule around bacterium Bacteria reproduce Phagocytic vesicle Lysosome V T - utor ▲ FIGURE 14.9 Some virulence factors. (a) Extracellular enzymes. Hyaluronidase and collagenase digest structural materials in the body. Coagulase in effect “camouflages” bacteria inside a blood clot, whereas kinases digest clots to release bacteria. (b) Toxins. Exotoxins (including cytotoxin, shown here) are released from living pathogens and harm neighboring cells. Endotoxins are released from dead Gram-negative bacteria and can trigger widespread disruption of normal body functions. (c) Antiphagocytic factors. Capsules, one antiphagocytic factor, can prevent phagocytosis or stop digestion by a phagocyte. How can bacteria prevent a phagocytic cell from digesting them once they have been engulfed by pseudopods? ideo (c) Antiphagocytic factors Figure 14.9 Some bacteria secrete a chemical that prevents the fusion of lysosomes with the phagosome containing the bacteria. M14_BAUM7206_05_SE_C14.indd 424 11/23/16 3:50 AM       The Nature of Infectious Disease to the underlying cells, where it causes amebic dysentery. Exotoxins Many microorganisms secrete exotoxins that are central to their pathogenicity in that they destroy host cells or interfere with host metabolism. Exotoxins are of three principal types: • Cytotoxins, which kill host cells in general or affect their function (FIGURE 14.9b) • Neurotoxins, which specifically interfere with nerve cell function • Enterotoxins, which affect cells lining the gastrointestinal tract ­ ­ ­ ­ Examples of pathogenic bacteria that secrete exotoxins are the clostridia that cause gangrene, botulism, and tetanus; pathogenic strains of S. aureus that cause food poisoning and other ailments; and diarrhea-causing E. coli, Salmonella enterica (sal’mŏ-nel’ă en-ter’i-kă), and Shigella (shē-gel’lă) species. Some fungi and marine dinoflagellates (protozoa) also secrete exotoxins. Specific exotoxins are discussed in the chapters that examine specific diseases. ▶ ANIMATION: Virulence Factors: Exotoxins The body protects itself from exotoxins with protective molecules called antibodies that bind to specific toxins and neutralize them. Antibodies against toxins are called antitoxins. Health care workers stimulate the production Endotoxins Gram-negative bacteria have an outer (wall) membrane composed of lipopolysaccharides, phospholipids, and proteins (see Chapter 3, Figure 3.15). Lipopolysaccharide (LPS) is called endotoxin because early microbiologist thought this poisonous molecule came from within Gram-negative bacteria. The toxic part of LPS is the lipid, which is called lipid A. Lipid A is not a single molecular structure but an array of similar lipid molecules that vary between different Gram-negative bacteria and among bacterial strains. Endotoxins can be released when Gram-negative bacteria divide, die naturally, or are digested by phagocytic cells such as macrophages (see Figure 14.9b). Lipid A stimulates the body to release chemicals that can cause fever, inflammation, diarrhea, hemorrhaging, shock, and blood coagulation. Most Gramnegative pathogens can be potentially life threatening because the release of endotoxin from dead cells can produce serious systemic effects in the host. ▶ ANIMATION: Virulence Factors: ­ Toxins are chemicals that either harm tissues or trigger host immune responses that cause damage. The distinction between extracellular enzymes and toxins is not always clear because many enzymes are toxic and many toxins have enzymatic action. In a condition called toxemia (tok-sē’mē-ă), toxins enter the bloodstream and are carried to other parts of the body, including sites that may be far removed from the site of infection. There are two types of toxin: exotoxins and endotoxins. ­ Toxins TABLE 14.8 of antitoxins by administering immunizations composed of toxoids, which are toxins that have been treated with heat, formaldehyde, chlorine, or other chemicals to make them nontoxic but still capable of stimulating the production of antibodies. (Chapters 16 and 17 further discuss antibodies, toxoids, and immunizations.) ­ ▶ ANIMATION: Virulence Factors: Penetrating Host Tissues Endotoxins TABLE 14.8 summarizes differences between exotoxins and endotoxins. Antiphagocytic Factors Typically, the longer a pathogen remains in a host, the greater the damage, and the more severe the disease. To limit the extent and duration of infections, the body’s phagocytic cells, such as the white blood cells called macrophages, engulf and remove invading pathogens. Here, we consider some virulence factors related to the evasion of phagocytosis, beginning with bacterial capsules. ▶ ANIMATION: Phagocytosis: Microbes That Evade It A Comparison of Bacterial Exotoxins and Endotoxins Exotoxins Endotoxins Source Mainly Gram-positive and Gram-negative bacteria Gram-negative bacteria Relation to Bacteria Metabolic product secreted from living cell Lipopolysaccharide (LPS) portion of the outer (cell wall) membrane released upon cell death Chemical Nature Protein or short peptide Lipid portion (lipid A) of LPS Toxicity High Low but may be fatal in high doses Heat Stability Typically unstable at temperatures above 60°C Stable for up to 1 hour at autoclave temperature (121°C) Effect on Host Variable, depending on source; may be cytotoxin, neurotoxin, enterotoxin Fever, lethargy, malaise, shock, blood coagulation Fever Producing? No Yes Antigenicitya Strong: stimulates antitoxin (antibody) production Weak Toxoid Formation for Immunization? By treatment with heat or formaldehyde Not feasible Representative Diseases Botulism, tetanus, gas gangrene, diphtheria, cholera, plague, staphylococcal food poisoning Typhoid fever, tularemia, endotoxic shock, urinary tract infections, meningococcal meningitis aRefers to the ability of a chemical to trigger a specific immune response, particularly the formation of antibodies. M14_BAUM7206_05_SE_C14.indd 425 11/23/16 3:50 AM hapter       Number of microorganisms or intensity of signs or symptoms C Incubation period (no signs or symptoms) 14    Infection, Infectious Diseases, and Epidemiology Prodromal period (vague, general symptoms) Illness (most severe signs and symptoms) Decline (declining signs and symptoms) Convalescence (no signs or symptoms) ◀ FIGURE 14.10 The stages of infectious diseases. Not every stage occurs in every disease. Time ­ Capsules The capsules of many pathogenic bacteria (see Figure 3.5a) are effective virulence factors because they are composed of chemicals normally found in the body; as a result, they do not stimulate an immune response. For example, hyaluronic acid capsules in effect deceive phagocytic cells into treating the encapsulated bacteria as if they were a normal part of the body. Additionally, capsules are often “slippery,” making it difficult for phagocytes to surround and phagocytize them—their pseudopods cannot grip the capsule, much as wet hands have difficulty holding a wet bar of soap (FIGURE 14.9c). Antiphagocytic Chemicals Some bacteria, including the cause of gonorrhea, produce chemicals that prevent the fusion of lysosomes with phagocytic vesicles, allowing the bacteria to survive inside phagocytes (see Figure 14.9c). Streptococcus pyogenes (strep-tō-kok’ŭs pī-oj’en-ēz) produces a protein on its cell wall and fimbriae, called M protein, that inhibits phagocytosis and thus increases virulence. Other bacteria produce leukocidins, which are chemicals capable of destroying phagocytic white blood cells outright. ▶ ANIMATION: Virulence Factors: Hiding from Host Defenses The Stages of Infectious Diseases LE A R N I N G O U TC O M E 14.15 List and describe the five typical stages of infectious diseases. Following exposure and infection, a sequence of events called the disease process can occur. Many infectious diseases proceed through five stages following infection: an incubation period, a prodromal period, illness, decline, and convalescence (FIGURE 14.10). Incubation Period The incubation period is the time between infection and occurrence of the first symptoms or signs of disease. The length of the incubation period depends on the virulence of the infective M14_BAUM7206_05_SE_C14.indd 426 agent, the infective dose (initial number of pathogens), the state and health of the patient’s immune system, the nature of the pathogen and its reproduction time, and the site of infection. Some diseases have typical incubation periods, whereas for others the incubation period varies considerably. TABLE 14.9 lists typical incubation periods for selected diseases. Prodromal Period The prodromal period9 (prō-drō’măl) is a short time of generalized, mild symptoms (such as malaise and muscle aches) that precedes illness. Not all infectious diseases have a prodromal stage. Illness Illness is the most severe stage of an infectious disease. Signs and symptoms are most evident during this time. Typically, the patient’s immune system has not yet fully responded to the pathogens, and their presence is harming the body. This stage is usually when a physician first sees the patient. TABLE 14.9 Incubation Periods of Selected Infectious Diseases Disease Incubation Period Staphylococcus foodborne infection <1 day Influenza About 1 day Cholera 2 to 3 days Genital herpes About 5 days Tetanus 5 to 15 days Syphilis 10 to 21 days Hepatitis B 70 to 100 days AIDS 1 to >8 years Leprosy 10 to >30 years 9From Greek prodromos, meaning “forerunner.” 11/23/16 3:50 AM       Modes of Infectious Disease Transmission Decline Eyes (tears) Ear (earwax) Nose (secretions) ­ During the period of decline, the body gradually returns to normal as the patient’s immune response and/or medical treatment vanquish the pathogens. Fever and other signs and symptoms subside. Normally the immune response and its products (such as antibodies in the blood) peak during this stage. If the disease doesn’t decline, then the disease is fatal—the patient dies. Broken skin (blood) Mouth (saliva, sputum) Skin (flakes) In females: Mammary glands (milk, secretions) Convalescence During convalescence (kon-vă-les’ens), the patient recovers from the illness; tissues are repaired and returned to normal. The length of a convalescent period depends on the amount of damage, the nature of the pathogen, the site of infection, and the overall health of the patient. Thus, whereas recovery from staphylococcal food poisoning may take less than a day, recovery from Lyme disease may take years. A patient is likely to be infectious during every stage of disease. Even though most of us realize we are infective during the symptomatic periods, many people are unaware that infections can often be spread during incubation and convalescence as well. For example, a patient who no longer has any obvious herpes sores is always capable of transmitting herpesviruses, and a convalescent carrier of Salmonella may excrete the bacterium for a year or more (see Clinical Case Study: A Deadly Carrier on p. 416). Good aseptic technique can limit the spread of many pathogens from recovering patients. TELL ME WHY Why is mutated Streptococcus pneumoniae, which cannot make a capsule, unable to cause pneumonia? The Movement of Pathogens out of Hosts: Portals of Exit Just as infections occur through portals of entry, so pathogens must leave infected patients through portals of exit in order to infect others (FIGURE 14.11). Many portals of exit are essentially identical to portals of entry. However, pathogens often exit hosts in materials that the body secretes or excretes. Thus, pathogens may leave hosts in secretions (earwax, tears, nasal secretions, saliva, sputum, and respiratory droplets), in blood (via arthropod bites, hypodermic needles, or wounds), in vaginal secretions or semen, in milk produced by the mammary glands, and in excreted bodily wastes (feces and urine). As we will see, health care personnel must consider the portals of entry and exit in their efforts to understand and control the spread of diseases within populations. TELL ME WHY Why is the tube emptying the bladder (the urethra) more likely to be a portal of exit than a portal of entry? M14_BAUM7206_05_SE_C14.indd 427 Vagina (secretions, blood) Anus (feces) Seminal vesicles (semen and lubricating secretions) Urethra (urine) ▲ FIGURE 14.11 Portals of exit. Many portals of exit are also portals of entry. Pathogens often leave the body via bodily secretions and excretions produced at those sites. Modes of Infectious Disease Transmission LE A R N I N G O UTC O M E S 14.16 Contrast contact, vehicle, and vector transmission of pathogens. 14.17 Contrast droplet transmission and airborne transmission. 14.18 Contrast mechanical and biological vectors. By definition, an infectious disease agent must be transmitted from either a reservoir or a portal of exit to another host’s portal of entry. Transmission can occur by numerous modes that are somewhat arbitrarily categorized into three groups: contact transmission, vehicle transmission, and vector transmission. ▶ ANIMATION: Epidemiology: Transmission of Disease Contact Transmission Contact transmission is the spread of pathogens from one host to another by direct contact, indirect contact, or respiratory droplets. Direct contact transmission, including person­to­person spread, typically involves body contact between hosts. Touching, kissing, and sexual intercourse are involved in the transmission of such diseases as warts, herpes, and gonorrhea. Touching, biting, or scratching can transmit zoonoses such as rabies, ringworm, and tularemia from an animal reservoir to a human. The transfer of pathogens from an infected mother to a developing baby across the placenta is another form of direct contact transmission. Direct transmission within a single individual can also occur if the person transfers pathogens from a portal of exit 11/23/16 3:50 AM E Vehicle Transmission ­ Vehicle transmission is the spread of pathogens via air, drinking water, and food, as well as bodily fluids being handled outside the body. Airborne transmission involves the spread of pathogens farther than 1 meter to the respiratory mucous membranes of a new host via an aerosol (ār’ō-sol)—a cloud of small droplets and solid particles suspended in the air. Aerosols may contain pathogens, either on dust or inside droplets. (Recall that ▲ FIGURE 14.12 Droplet transmission. In this case, droplets are propelled, primarily from the mouth, during a sneeze. By convention, such transmission is considered contact transmission only if droplets transmit pathogens to a new host within 1 meter of their source. By what portal of entry does airborne transmission most likely occur? Figure 14.12 The most likely portal of entry of airborne pathogens is the respiratory mucous membrane. M14_BAUM7206_05_SE_C14.indd 428 ▲ FIGURE 14.13 Poorly stored foods can harbor pathogens and transmit diseases. transmission via droplet nuclei that travel less than 1 meter is considered to be a form of direct contact transmission.) Aerosols can come from sneezing and coughing, or they can be generated by such means as air-conditioning systems, sweeping, mopping, changing clothes or bed linens, or even from flaming inoculating loops in microbiology labs. Dust particles can carry Staphylococcus, Streptococcus, and Hantavirus (han’tavī-rŭs), whereas measles virus and tuberculosis bacilli can be transmitted in airborne droplets. Fungal spores of Histoplasma (his-tō-plaz mă) and Coccidioides (kok-sid-ē-oy dēz) are typically inhaled. Waterborne transmission is important in the spread of many gastrointestinal diseases, including giardiasis, amebic dysentery, and cholera. Note that water can act as a reservoir as well as a vehicle of infection. Fecal-oral infection is a major source of disease in the world. Some waterborne pathogens, such as Schistosoma (shis-tō-sō mă) worms (see Chapter 23) and enteroviruses (see Chapter 20), are shed in the feces, contaminate a water source, and enter through the gastrointestinal mucous membrane or skin. They subsequently can cause disease elsewhere in the body. Foodborne transmission involves pathogens in and on foods that are inadequately processed, undercooked, or poorly refrigerated (FIGURE 14.13). Foods may be contaminated with normal microbiota (e.g., E. coli and S. aureus), with zoonotic pathogens such as Mycobacterium bovis (bō vis) and Toxoplasma (tok-sō-plaz mă), and with parasitic worms that alternate between human and animal hosts. Contamination of food with feces and pathogens such as hepatitis A virus is another kind of fecal-oral transmission. Because milk is particularly rich in nutrients that microorganisms use (protein, lipids, vitamins, and sugars), it can be associated with the transmission of many diseases from infected animals and milk handlers if it is not properly pasteurized. Because blood, urine, saliva, and other bodily fluids can contain pathogens, everyone—but especially health care workers—must take precautions when handling these fluids ­ directly to a portal of entry—as occurs, for example, when people with poor personal hygiene unthinkingly place fingers contaminated with fecal pathogens into their mouths. Indirect contact transmission occurs when pathogens are spread from one host to another by fomites (fōm’i-tēz; singular: fomes, fōm’mēz, or fomite, fō’mīt), which are inanimate objects that are inadvertently used to transfer pathogens to new hosts. Fomites include needles, toothbrushes, paper tissues, toys, money, diapers, drinking glasses, bedsheets, medical equipment, and other objects that can harbor or transmit pathogens. Contaminated needles are a major source of infection of the hepatitis B and AIDS viruses. Droplet transmission is a third type of contact transmission. Pathogens can be transmitted within droplet nuclei (droplets of mucus) that travel less than a meter from the body during exhaling, coughing, and sneezing (FIGURE 14.12). Pathogens such as cold and flu viruses may be spread in this manner. If pathogens travel more than 1 meter in respiratory droplets, the mode is considered to be airborne transmission (discussed shortly) rather than contact transmission. ­       Chapter 14    Infection, Infectious Diseases, and pidemiology 3/9/18 8:25 PM       Classification of Infectious Diseases ­ Vectors are arthropods that transmit diseases. Vectors can be either biological or mechanical. Biological vectors not only transmit pathogens but also serve as hosts for the multiplication of a pathogen during some stage of the pathogen’s life cycle. The biological vectors of diseases affecting humans are typically biting arthropods, including mosquitoes, ticks, lice, fleas, bloodsucking flies, bloodsucking bugs, and mites (see Figure 12.29). After pathogens replicate within a biological vector, often in its gut or salivary gland, the pathogens enter a new host through a bite. The bite site becomes contaminated with the vector’s feces, or the vector’s bite directly introduces pathogens into the new host. Mechanical vectors are not required as hosts by the pathogens they transmit; such vectors only passively carry pathogens to new hosts on their feet or other body parts. Mechanical vectors, such as houseflies and cockroaches, may introduce pathogens such as Salmonella and Shigella into drinking water and food or onto the skin. TABLE 14.10 on p. 430 lists some arthropod vectors and the diseases they transmit. TABLE 14.11 on p. 430 summarizes the modes of disease transmission. Classification of Infectious Diseases LE A R N I N G O UTC O M E S 14.19 Describe the basis for each of the various classification schemes of infectious diseases. 14.20 Distinguish among acute, subacute, chronic, and latent diseases. 14.21 Distinguish among communicable, contagious, and noncommunicable infectious diseases. Infectious diseases can be classified in a number of ways. No one way is “the correct way”; each has its own advantages. One scheme groups diseases based upon taxonomic groups. A difficulty with this method of classification is that many different pathogens may cause a disease; for example, some Grampositive bacteria, Gram-negative bacteria, protozoa, fungi, DNA viruses, and RNA viruses can cause pneumonia. Another classification system deals with diseases according to body systems. (Chapters 18–24 examine diseases based on this approach.) Every disease (not just infectious diseases) can also be classified according to its longevity and severity. If a disease develops rapidly but lasts a relatively short time, it is called c Clini al C SE STUDY Why can’t we correctly say that all arthropod vectors are reservoirs? ­ Vector Transmission TELL ME WHY ­ in order to prevent bodily fluid transmission. Special care must be taken to prevent such fluids—all of which should be considered potentially contaminated with pathogens—from contacting the conjunctiva or any breaks in the skin or mucous membranes. Examples of diseases that can be transmitted via bodily fluids are AIDS, hepatitis, and herpes, which as we have seen can also be transmitted via direct contact. A TB in the Nursery In the early fall, a neonatal nurse in a large metropolitan hospital became ill with a cough and fever. His physician believed he had seasonal allergies and so treated him with cough suppressant, antihistamines, and aerosol steroids. He returned to work in the hospital’s nursery. Three weeks later, his condition had worsened; his symptoms were complicated by shortness of breath and bloody sputum. Upon further questioning, his physician noted that he was working in the United States on a work visa and was a native of South Africa. He had a positive M14_BAUM7206_05_SE_C14.indd 429 skin test for tuberculosis (TB) but had always believed this was his body’s natural reaction to the TB vaccine he had received as a child. His chest X-ray films in the past had always been clear of infection. This time, however, his sputum smear tested positive for acid-fast bacilli. He was diagnosed with active tuberculosis and began a standard drug regimen for TB. He was restricted from work and placed in respiratory isolation for six weeks, but during the three weeks that he had continued to work in the nursery, he had exposed over 900 obstetric patients, including 620 newborns, to TB, an airborne infectious disease. 1. How can private physicians quickly assess their clients for the possibility of an infectious disease? 2. What policies should be in place at hospitals to protect patients from exposure to infectious staff members? 3. How could doctors’ offices improve public knowledge and protect the public from tuberculosis and other infectious diseases? Reference: Adapted from MMWR 54:1280–1283, 2005. 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology hapter       C TABLE 14.10 Selected Arthropod Vectors Disease Causative Agent (bacteria unless otherwise indicated) Biological Vectors Mosquitoes Anopheles Aedes Malaria TABLE 14.11 Modes of Disease Transmission Mode of Transmission Examples of Diseases Spread Contact Transmission Direct Contact (e.g., handshaking, kissing, sexual intercourse, bites) Cutaneous anthrax, genital warts, gonorrhea, herpes, rabies, staphylococcal infections, syphilis Indirect Contact (e.g., drinking glasses, toothbrushes, toys, punctures) Common cold, enterovirus infections, influenza, measles, Q fever, pneumonia, tetanus Whooping cough, streptococcal pharyngitis (strep throat) Yellow fever Plasmodium spp. (protozoan) Elephantiasis Flavivirus sp. (virus) Dengue Wuchereria bancrofti (helminth) Droplet Transmission (e.g., droplets from sneezing, within 1 meter) Flavivirus spp. (virus) Vehicle Transmission Alphavirus spp. (virus) Airborne (e.g., dust particles or droplets carried more than 1 meter) Chicken pox, coccidioidomycosis, histoplasmosis, influenza, measles, pulmonary anthrax, tuberculosis Waterborne (e.g., streams, swimming pools) Campylobacter infections, cholera, Giardia diarrhea Foodborne (e.g., poultry, seafood, meat) Food poisoning (botulism, staphylococcal); hepatitis A, listeriosis, tapeworms, toxoplasmosis, typhoid fever Viral encephalitis Ticks Ixodes Lyme disease Borrelia burgdorferi Dermacentor Rocky Mountain spotted fever Rickettsia rickettsii Bubonic plague Yersinia pestis Endemic typhus Rickettsia typhi Epidemic typhus Rickettsia prowazekii Mechanical (e.g., on bodies of flies, roaches) E. coli diarrhea, salmonellosis, trachoma Glossina African sleeping sickness Trypanosoma brucei Biological (e.g., lice, mites, mosquitoes, ticks) Chagas’ disease, Lyme disease, malaria, plague, Rocky Mountain spotted fever, typhus fever, yellow fever Simulium River blindness Onchocerca volvulus (helminth) Chagas’ disease Trypanosoma cruzi (protozoan) Scrub typhus Orientia tsutsugamushi Foodborne infections Shigella spp., Salmonella spp., Escherichia coli Foodborne infections Shigella spp., Salmonella spp., Escherichia coli Fleas Xenopsylla Lice Pediculus Bloodsucking Flies Vector Transmission Bloodsucking Bugs Triatoma Mites (chiggers) Leptotrombidium Mechanical Vectors Houseflies Musca Cockroaches Blatella, Periplaneta ­ ­ ­ an acute disease. An example is the common cold. In contrast, chronic diseases develop slowly (usually with less severe symptoms) and are continual or recurrent. Infectious mononucleosis, hepatitis C, tuberculosis, and leprosy are chronic diseases. Subacute diseases have durations and severities that lie somewhere between acute and chronic. Subacute bacterial endocarditis, a disease of heart valves, is one example. Latent diseases are those in which a pathogen remains inactive for a long period of time before becoming active. Herpes is an example of a latent disease. When an infectious disease comes from another infected host, either directly or indirectly, it is a communicable disease. Influenza, herpes, and tuberculosis are examples of communicable diseases. If a communicable disease is easily transmitted between hosts, as is the case for chicken pox or measles, it is also called a contagious disease. Noncommunicable diseases arise outside hosts or from normal microbiota. In other words, they are not spread from one host to another, and diseased patients are not a source of contamination for others. Tooth decay, acne, and tetanus are examples of noncommunicable diseases. TABLE 14.12 defines these and other terms used to classify infectious diseases. Yet another way in which all infectious diseases may be classified is by the effects they have on populations rather than on individuals. Is a certain disease consistently found in a given group of people or geographic area? Under what circumstances is it more prevalent than normal in a given geographic area? How prevalent is “normal”? How is the disease transmitted throughout a population? We next examine issues related to diseases at the population level. M14_BAUM7206_05_SE_C14.indd 430 TELL ME WHY Why is an acute disease with a high rate of mortality unlikely to be associated with a pandemic? 11/23/16 3:50 AM       Epidemiology of Infectious Diseases Term Definition Acute disease Disease in which symptoms develop rapidly and that runs its course quickly Chronic disease Disease with usually mild symptoms that develop slowly and last a long time Subacute disease Disease whose time course and symptoms range between acute and chronic Asymptomatic disease Disease without symptoms Latent disease Disease that appears a long time after infection Communicable disease Disease transmitted from one host to another Contagious disease Communicable disease that is easily spread Noncommunicable disease Disease not passed from person to person Local infection Infection confined to a small region of the body Systemic infection Widespread infection in many systems of the body; often travels in the blood or lymph Focal infection Infection site that serves as a source of pathogens for infections at other sites in the body Primary infection Initial infection within a given patient Secondary infection Infections that follow a primary infection; often by opportunistic pathogens Epidemiology of Infectious Diseases Epidemiologists keep track of the occurrence of diseases by using two measures: incidence and prevalence. Incidence is the number of new cases of a disease in a given area or population during a given period of time; prevalence is the total number of cases, both new and already existing, in a given area or population during a given period of time. In other words, prevalence is a cumulative number. Thus, for example, the estimated number of new cases—the incidence—of HIV infection/AIDS in adults in the United States in 2013 was 47,352. However, the prevalence of HIV infection/AIDS in the same year was 1,194,039 because more than 1,100,000 patients who got the disease prior to 2013 still survived. (FIGURE 14.14) illustrates this relationship between incidence and prevalence. Epidemiologists report their data in many ways, including maps, graphs, charts, and tables (FIGURE 14.15). Why do they report their data in so many different ways? Using a variety of formats enables epidemiologists to observe patterns that may give clues about the causes of or ways to prevent diseases. For example, West Nile virus encephalitis occurs across the United States, but when data are reported by age group, it becomes obvious that elderly Americans are most at risk. The occurrence of a disease can also be considered in terms of a combination of frequency and geographic distribution (FIGURE 14.16). A disease that normally occurs continually (at moderately regular intervals) at a relatively stable incidence within a given population or geographical area is said to be endemic11 to that population or region. A disease is considered sporadic when only a few scattered cases occur within an area or population. Whenever a disease occurs at a greater frequency than is usual for an area or population, the ­ TABLE 14.12 Terms Used to Classify Infectious Diseases LE A R N I N G O U TC O M E 14.22 Define epidemiology. Frequency of Disease LE A R N I N G O U TC O M E S  14.23 Contrast incidence and prevalence. 14.24 Differentiate among the terms endemic, sporadic, epidemic, and pandemic. 10From Greek epidemios, meaning “among the people,” and logos, meaning “study of.” M14_BAUM7206_05_SE_C14.indd 431 Incidence (thousands) Incidence 100 80 500 60 40 Prevalence (thousands) 1000 Prevalence 20 1985 1990 1995 2000 Year 2005 2010 2015 ▲ FIGURE 14.14 Curves representing the incidence and the estimated prevalence of AIDS among U.S. adults. Note that the scales for the two curves are different. Why can the incidence of a disease never exceed the prevalence of that disease? Figure 14.14 Because prevalence includes all cases, both old and new, prevalence must always be larger than incidence. Our discussion so far has centered on the negative impact of microorganisms on individuals. Now we turn our attention to the effects of pathogens on populations. Epidemiology10 (ep-idē-mē-ol’ō-jē) is the study of where and when diseases occur and how they are transmitted within populations. During the 20th century, epidemiologists expanded the scope of their work beyond infectious diseases to also consider injuries and deaths related to automobile and fireworks accidents, cigarette smoking, lead poisoning, and other causes; however, we will limit our discussion primarily to the epidemiology of infectious diseases. ▶ ANIMATION: Epidemiology: Overview 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology hapter       C disease is said to be epidemic within that area or population. ▶ ANIMATION: Epidemiology: Occurrence of Disease ­ Cases per 100,000 population 0.50–0.74 0.75–0.99 Ú1.00 0 0.01–0.24 0.25–0.49 (a) 16 Percentage of cases 14 12 10 8 6 4 2 0 January March May July September November (b) 25 Number of deaths The commonly held belief that a disease must infect thousands or millions to be considered an epidemic is mistaken. The time period and the number of cases necessary for an outbreak of disease to be classified as an epidemic are not specified; the important fact is that there are more cases than expected, based on historical statistics. For example, fewer than 70 cases of an emerging disease—hemolytic uremic syndrome caused by a strain of E. coli—occurred in Germany in 2011, but because there are typically fewer than five cases annually, the 2011 outbreak was considered an epidemic. The same year, thousands of cases of flu occurred in Germany, but there was no flu epidemic because the number of cases observed did not exceed the number expected. FIGURE 14.17 illustrates how epidemics are defined according to the number of expected cases and not according to the absolute number of cases. If an epidemic occurs simultaneously on more than one continent, it is referred to as a pandemic (see FIGURE 14.16d). H1N1 flu, so-called swine flu, became pandemic worldwide in 2009. Obviously, for disease prevalence to be classified as either endemic, sporadic, epidemic, or pandemic, good records must be kept for each region and population. From such records, incidence and prevalence can be calculated, and then changes in these data can be noted. Health departments at the local and state levels require doctors and hospitals to report certain infectious diseases. Some are also nationally notifiable; that is, their occurrence must be reported to the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, which is the headquarters and clearinghouse for national epidemiological research. Nationally notifiable diseases are listed in TABLE 14.13 on p. 434. Each week, the CDC reports the number of cases of most of the nationally notifiable diseases in the Morbidity and Mortality Weekly Report (MMWR) (FIGURE 14.18). 20 15 Epidemiological Studies 10 LE A R N I N G O UTC O M E 14.25 Explain three approaches epidemiologists use to study 5 0 diseases in populations. 0–9 10–19 20–29 30–39 40–49 50–59 60–69 70–79 Age group (yrs) (c) ▲ FIGURE 14.15 Epidemiologists report data in a variety of ways. Here, incidence of cases of an emerging disease—West Nile virus disease—in which the virus invades the nervous system. Data for the decade 1999–2008 are presented. (a) Average annual incidence for the United States is on a map by state. (b) Percentage of cases by week of onset. (c) Percentage of deaths by age. How do the data help support the idea that mosquitoes carry West Nile virus? Epidemiologists conduct research to study the dynamics of diseases in populations by taking three different approaches, called descriptive, analytical, and experimental epidemiology. Descriptive Epidemiology Descriptive epidemiology involves the careful tabulation of data concerning a disease. Relevant information includes the location and time of cases of the disease as well as information about the patients, such as ages, gender, occupations, health histories, and socioeconomic groups. Because the time course and chains of transmission of a disease are an important part of descriptive epidemiology, epidemiologists strive to identify Figure 14.15 Most cases of the disease occur in late summer, when mosquitoes are likely biting and people are more likely to be outdoors. 11From M14_BAUM7206_05_SE_C14.indd 432 Greek endemos, meaning “native.” 11/23/16 3:50 AM       Epidemiology of Infectious Diseases ◀ FIGURE 14.16 Illustrations of the different terms for the occurrence of disease. (a) An endemic disease, which is normally present in a region. (b) A sporadic disease, which occurs irregularly and infrequently. (c) An epidemic disease, which is present in greater frequency than is usual. (d) A pandemic disease, which is an epidemic disease occurring on more than one continent at a given time. Regardless of where you live, name a disease that is endemic, one that is sporadic, and one that is epidemic in your state. Figure 14.16 Some possible answers: Flu is endemic in every state; tuberculosis is sporadic in most states; AIDS is epidemic in every state. (a) Endemic disease (b) Sporadic (c) Epidemic (d) Pandemic = Normal range = New case of disease ◀ FIGURE 14.17 Epidemics may have fewer cases than nonepidemics. These two graphs demon- 2000 strate the independence between the absolute number of cases and a disease’s designation as an epidemic. Even though the number of cases of disease A always exceeds the number of cases of disease B, only disease B is considered epidemic—at those times when the number of cases observed exceeds the number of cases expected. How can scientists know the normal prevalence of a given disease? Number of cases per 100,000 individuals 1600 1400 1200 1000 Epidemic 2 Figure 14.17 Scientists record every case of the disease so that they will have a “baseline” prevalence, which then becomes the expected prevalence for each disease. 1800 Epidemic 1 800 600 400 1999 2000 Time 2001 Expected number of cases Actual number of cases Disease A Actual number of cases Disease B the index case (the first case) of the disease in a given area or population. Sometimes it is difficult or impossible to identify an index case because the patient has recovered, moved, or died. The earliest descriptive epidemiological study was by John Snow (1813–1858), who studied a cholera outbreak in London in M14_BAUM7206_05_SE_C14.indd 433 1854. By carefully mapping the locations of the cholera cases in a particular part of the city, Snow found that the cases were clustered around the Broad Street water pump (FIGURE 14.19). This distribution of cases, plus the voluminous watery diarrhea of cholera patients, suggested that the disease was spread via contamination of drinking water by sewage. 11/23/16 3:50 AM E       Chapter 14    Infection, Infectious Diseases, and pidemiology emolytic uremic syndrome, postdiarrheal Coccidioidomycosis Cryptosporidiosis Cyclosporiasis Dengue virus infections hrlichiosis/anaplasmosis Giardiasis Gonorrhea aDiseases P P P H R H IV infection (including stage III, which is IDS) Influenza-associated infant deaths Invasive pneumococcal disease Legionellosis Leptospirosis Listeriosis Lyme disease Malaria Measles R T etanus oxic shock syndrome, nonstreptococcal richinellosis uberculosis ularemia abies, animal and human ubella ubella, congenital syndrome Salmonellosis Severe acute respiratory syndrome (S S) Shiga-toxin-producing Escherichia coli Shigellosis yphoid fever Vancomycin-intermediate Staphylococcus aureus Vancomycin-resistant Staphylococcus aureus Vibriosis Viral hemorrhagic fever Yellow fever Smallpox Spotted fever rickettsiosis for which hospitals, physicians, and other health care workers are required to report cases to state health departments and then forward the data to the CDC. Analytical Epidemiology Analytical epidemiology investigates a disease in detail, including analysis of data acquired in descriptive epidemiological studies, to determine the probable cause, mode of transmission, and possible means of prevention of the disease. Analytical epidemiology may be used in situations where it is not ethical to apply Koch’s postulates. Thus, even though Koch’s third postulate has never been fulfilled in the case of AIDS (because it is unethical to intentionally inoculate a human with HIV), analytical epidemiological studies indicate that HIV causes AIDS and that it is transmitted primarily sexually. Often analytical studies are retrospective; that is, they attempt to identify causation and mode of transmission after an outbreak has occurred. Epidemiologists compare a group of people who had the disease with a group who did not. The groups are carefully matched by factors such as gender, environment, and diet and then compared to determine which pathogens and factors may play a role in morbidity. Experimental Epidemiology Experimental epidemiology involves testing a hypothesis concerning the cause of a disease. The application of Koch’s postulates to determine etiology is an example of experimental epidemiology. Experimental epidemiology also involves studies to test a hypothesis resulting from an analytical study, such as the efficacy of a preventive measure or certain treatment. For example, analytical epidemiological studies suggested that the bacterium Chlamydophila pneumoniae may contribute to arteriosclerosis, resulting in heart attacks. If so, antimicrobial drugs that kill Chlamydophila should prevent some heart attacks by M14_BAUM7206_05_SE_C14.indd 434 killing the bacteria. However, when researchers administered these drugs to 7700 patients with a history of heart disease, infection with C. pneumoniae was reduced, but the number of heart attacks was not. Thus, an experimental epidemiological study disproved a hypothesis suggested by an analytical epidemiological analysis. Hospital Epidemiology: HealthcareAssociated (Nosocomial) Infections LE A R N I N G O UTC O M E S 14.26 Explain how healthcare-associated infections differ from other infections. 14.27 Describe the factors that influence the development of healthcare-associated infections. 14.28 Describe three types of healthcare-associated infections and how they may be prevented. Of special concern to epidemiologists and health care workers are healthcare-associated infections (HAIs), which were formerly called nosocomial (nos-ō-kō’mē-ăl) infections. HAIs are infections acquired by patients or health care workers while they are in health care facilities, including hospitals, dental offices, nursing homes, and doctors’ waiting rooms. The CDC estimates that about 10% of American patients acquire an HAI each year. Healthcare-associated diseases (formerly called nos­ ocomial diseases) increase the duration and cost of medical care and result in some 100,000 deaths annually in the United States. ­ E Diphtheria epatitis C sittacosis Q fever R Cholera Hepatitis B AR Chlamydia trachomatis infection epatitis A lague oliomyelitis A Chancroid H Campylobacteriosis H Brucellosis ertussis T Botulism infections T Hantavirus pulmonary syndrome Syphilis Novel influenza type P Babesiosis Streptococcal toxic-shock syndrome Mumps T H ansen disease (leprosy) Meningococcal disease T Haemophilus influenzae, invasive disease A rboviral diseases (e.g. West Nile encephalitis, chikungunya, etc.) T nthrax A A TABLE 14.13 Nationally Notifiable Infectious Diseasesa ▶ ANIMATION: Nosocomial Infections: Overview 3/9/18 8:30 PM MMWR Weekly/Vol.65/No.43 November 4, 2016 TABLE II. (Continued) Provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected low frequency diseases, United States and U.S. territories, weeks ending October 29, 2016, and October 31, 2015 (43rd week)* Giardiasis Reporting area United States New England Connecticut Maine Massachusetts New Hampshire Rhode Island Vermont Haemophilus influenzae, invasive† All ages, all serotypes Gonorrhea Current Previous 52 weeks Cum Med Max week 2016 Cum 2015 Current Previous 52 weeks Cum Med Max week 2016 Cum 2015 Current Previous 52 weeks Cum week Med Max 2016 Cum 2015 145 15 — 3 9 — 3 N 256 20 3 2 11 2 1 0 873 32 9 8 21 6 8 0 10,935 850 134 97 467 83 69 N 11,381 977 190 99 567 94 27 N 4,483 17 — — — 11 6 — 8,160 166 46 9 90 8 9 2 9,235 223 9 20 130 53 25 7 341,157 7,026 1,855 335 3,887 486 366 97 320,405 5,793 1,616 292 3,117 182 463 123 44 12 — — 2 — 10 — 81 5 1 0 2 0 0 0 189 12 3 3 8 3 2 2 3,468 223 37 24 121 15 15 11 3,272 204 32 31 95 18 17 11 Mid. Atlantic New Jersey New York (Upstate) New York City Pennsylvania 49 — 25 16 8 51 5 17 16 11 80 13 42 24 30 2,158 186 799 697 476 2,334 362 683 731 558 579 56 211 128 184 954 148 182 347 282 1,191 347 344 497 350 41,569 6,620 7,883 15,020 12,046 37,320 6,017 7,014 13,846 10,443 6 — 3 2 1 13 2 4 2 5 34 9 20 7 11 549 102 176 94 177 503 110 150 78 165 E.N. Central Illinois Indiana Michigan Ohio Wisconsin 9 N — — 8 1 26 0 3 8 6 9 102 0 9 24 13 74 1,454 N 130 412 237 675 1,269 N 150 369 321 429 343 16 78 152 — 97 1,131 254 176 226 363 122 1,430 421 304 278 434 154 46,517 10,147 7,658 9,605 13,942 5,165 46,728 14,116 6,451 8,517 13,462 4,182 5 — — 1 4 — 14 4 2 3 3 1 32 9 8 10 8 6 582 149 75 136 149 73 570 158 86 105 132 89 W.N. Central Iowa Kansas Minnesota Missouri Nebraska North Dakota South Dakota S. Atlantic Delaware District of Columbia Florida Georgia Maryland North Carolina South Carolina Virginia West Virginia E.S. Central Alabama Kentucky Mississippi Tennessee 1 — — — — 1 — — 30 — N 12 7 7 N 3 1 — 5 5 N N N 13 4 2 0 0 2 1 2 46 0 0 21 11 4 0 2 5 1 4 4 0 0 0 40 13 6 16 9 9 4 7 77 3 6 53 34 11 0 9 26 6 13 13 0 0 0 508 191 77 — 6 98 40 96 2,034 13 N 964 467 194 N 99 240 57 208 208 N N N 1,241 185 93 514 199 119 31 100 2,049 25 N 864 605 203 N 93 202 57 158 158 N N N 254 13 26 5 191 17 — 2 825 36 61 266 136 102 — 204 — 20 242 — 104 77 61 481 47 57 92 213 41 16 19 1,646 32 63 515 280 157 325 177 154 18 510 141 105 118 175 574 66 86 123 277 63 29 39 2,409 59 137 727 362 252 822 267 776 29 723 236 405 177 249 17,294 1,830 2,104 3,348 7,274 1,328 555 855 70,880 1,017 2,312 19,493 13,208 5,150 15,515 6,642 6,919 624 20,922 6,050 3,259 4,602 7,011 — — — — — — — — 7 — — 3 — 3 — — 1 — 8 1 2 1 4 3 0 1 0 0 0 0 0 20 0 0 4 4 2 3 2 3 0 7 1 1 1 3 16 0 5 7 4 3 3 2 89 2 3 65 8 6 8 6 16 3 19 5 4 5 11 125 — 47 1 4 27 28 18 876 15 15 265 142 101 131 82 99 26 294 70 52 45 127 256 2 32 79 96 27 19 1 811 17 7 212 159 68 136 86 85 41 250 70 35 35 110 W.S. Central Arkansas Louisiana Oklahoma Texas 2 2 — N N 6 3 2 0 0 20 12 11 0 0 225 134 91 N N 269 88 181 N N 1,095 73 220 20 782 1,226 105 197 106 828 1,917 189 1,077 159 1,422 20,919 2,019 2,631 3,854 9,338 1,676 716 685 69,610 1,359 2,801 21,480 11,468 6,492 9,736 7,374 8,182 718 20,869 4,663 4,169 4,612 7,425 52,469 4,387 8,778 4,310 34,994 49,009 3,693 7,759 5,343 32,214 4 — — — 4 9 1 1 1 5 21 5 5 15 12 384 39 42 60 243 189 38 53 89 9 Mountain Arizona Colorado Idaho Montana Nevada New Mexico Utah Wyoming Pacific Alaska California Hawaii Oregon Washington 8 1 — 4 2 — — 1 — 26 2 13 — 2 9 14 2 0 3 2 0 1 3 0 69 1 49 1 6 7 31 7 14 13 8 4 3 9 2 647 5 73 4 14 601 568 109 — 149 92 17 48 127 26 2,930 63 2,116 33 270 448 956 128 303 140 79 41 66 165 34 2,128 81 1,726 31 290 — 236 109 76 15 11 — 4 21 — 892 — 657 — 112 123 474 182 106 11 18 60 60 40 3 1,442 25 1,183 25 79 124 629 258 253 36 30 93 83 58 16 1,626 44 1,356 46 111 211 20,377 7,638 4,707 482 734 2,428 2,494 1,725 169 61,801 1,043 51,281 1,081 3,443 4,953 17,504 6,549 3,554 357 665 2,984 2,029 1,224 142 54,955 872 44,701 1,024 2,513 5,845 2 1 1 — — — — — — — — — — — — 6 2 1 0 0 0 1 1 0 4 0 1 0 2 0 17 11 6 3 2 3 4 3 2 12 2 4 6 4 5 270 94 60 22 12 7 44 26 5 165 16 46 29 68 6 332 113 74 21 9 25 53 34 3 157 20 53 7 77 — 0 — 0 0 0 0 — 0 3 0 — — — 19 — — — 1 22 — 0 — 0 12 0 0 — 0 28 4 — — — 514 15 — — — 525 48 — — — — N 0 — 0 0 0 0 — 0 2 0 — — — 5 N — — — — N Territories American Samoa C.N.M.I. Guam Puerto Rico U.S. Virgin Islands — — — — — — — — 5 — C.N.M.I.: Commonwealth of Northern Mariana Islands. U: Unavailable. —: No reported cases. N: Not reportable. NN: Not Nationally Notifiable. NP: Nationally notifiable but not published. Cum: Cumulative year-to-date counts. Med: Median. Max: Maximum. *Case counts for reporting year 2015 and 2016 are provisional and subject to change. For further information on interpretation of these data, see http://wwwn.cdc.gov/nndss/ document/ProvisionalNationaNotifiableDiseasesSurveillanceData20100927.pdf. Data for TB are displayed in Table IV, which appears quarterly. †Data for H. influenzae (age <5 for serotype b, non typable serotype, other serotype, and unknown serotype) are available in Table I. ▲ FIGURE 14.18 A page from the MMWR. The CDC’s Morbidity and Mortality Weekly Report (MMWR) provides epidemiological data state by state for the current week, for the current year to date, and for the corresponding week in the previous year to date. The MMWR also publishes reports on epidemiological case studies. This page shows the incidence of three diseases in one week in 2016. Contrast the number of cases of giardiasis in California with the number of cases in Alaska. Which state has an epidemic? Figure 14.18 An epidemic is defined as more cases of a disease than expected. We cannot classify incidence of giardiasis in either state as an epidemic unless we have more historical data. M14_BAUM7206_05_SE_C14.indd 435 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology hapter       C Oxford Factors Influencing HealthcareAssociated Infections Street HAIs arise from the interaction of several factors in the health care environment, which include the following (FIGURE 14.20): ad Bro • Exposure to numerous pathogens present in the health care setting, including many that are resistant to antimicrobial agents • The weakened immune systems of patients who are ill, making them more susceptible to opportunistic pathogens • Transmission of pathogens among patients and health care workers—from staff and visitors, to patients, and even from one patient to another via activities of staff members (including invasive procedures and other iatrogenic factors) eet Str nt ge Re eet Str Control of Healthcare-Associated Infections Marylebon e Street Deaths from cholera Pump illy cad Pic ▲ FIGURE 14.19 A map showing cholera deaths in a section Nosocomial Infections: Prevention Numerous studies have shown that the single most effective way to reduce HAIs is effective handwashing by all medical and support staff. In one study, deaths from HAIs were reduced by over 50% when hospital personnel followed strict guidelines about washing their hands frequently. ­ of London, 1854. From the map he compiled, Dr. John Snow showed that cholera cases centered around the Broad Street pump. Snow’s work was a landmark in epidemiological research. Aggressive control measures can noticeably reduce the incidence of HAIs. These include disinfection; medical asepsis, including good housekeeping, handwashing, bathing, sanitary handling of food, proper hygiene, and precautionary measures to avoid the spread of pathogens among patients; surgical asepsis and sterile procedures, including thorough cleansing of the surgical field, use of sterile instruments, and use of sterile gloves, gowns, caps, and masks; isolation of particularly contagious or susceptible patients; and establishment of an HAI control committee charged with surveillance of nosocomial diseases and review of control measures. ▶ ANIMATION: Types of Healthcare-Associated Infections Presence of microorganisms in hospital environment Immunocompromised patients HAI Transmission of pathogens between staff and patients and among patients ­ ­ ­ When most people think of HAIs, what likely comes to mind are exogenous HAIs (eks-oj’ě-nŭs), which are caused by pathogens acquired from the health care environment. After all, hospitals are filled with sick people shedding pathogens from every type of portal of exit. However, we have seen that members of the normal microbiota can become opportunistic pathogens as a result of hospitalization or medical treatments such as chemotherapy. Such opportunists cause endogenous HAIs (en-doj’ě-nŭs); that is, they arise from normal microbiota within the patient that become pathogenic because of factors within the health care setting. Iatrogenic infections (ī-at-rō-jen’ik; literally meaning “doctor-induced” infections) are a subset of HAIs that ironically are the direct result of modern medical procedures such as the use of catheters, invasive diagnostic procedures, and surgery. Superinfections may result from the use of antimicrobial drugs that, by inhibiting some resident microbiota, allow others to thrive in the absence of competition. For instance, longterm antimicrobial therapy to inhibit a bacterial infection may allow Clostridium difficile (di’fe-sēl), a transient microbe of the colon, to grow excessively and cause a painful condition called pseudomembranous colitis. Such superinfections are not limited to health care settings. HAIs most often occur in the urinary, respiratory, cardiovascular, and integumentary (skin) systems, though surgical wounds can become infected and result in HAIs in any part of the body. M14_BAUM7206_05_SE_C14.indd 436 ▲ FIGURE 14.20 The interplay of factors that result in healthcare-associated infections (HAIs). Although HAIs can result from any one of the factors shown, most are the product of the interaction of all three factors. 11/23/16 3:50 AM       Epidemiology of Infectious Diseases Epidemiology and Public Health LE A R N I N G O U TC O M E 14.29 List three ways public health agencies work to limit the spread of diseases. As you have likely realized by now, epidemiologists gather information concerning the spread of disease within populations so that they can take steps to reduce the number of cases and improve the health of individuals within a community. In the following sections, we will examine how the various public health agencies share epidemiological data, facilitate the interruption of disease transmission, and educate the public about public health issues. Public health agencies also implement immunization programs (Chapter 17 discusses immunization). The Sharing of Data Among Public Health Organizations ­ ­ Numerous agencies at the local, state, national, and global levels work together with the entire spectrum of health care personnel to promote public health. By submitting reports on incidence and prevalence of disease to public officials, physicians can subsequently learn of current disease trends. Additionally, public health agencies often provide physicians with laboratory and diagnostic assistance. City and county health departments report data on disease incidence to state agencies. Because state laws govern disease reporting, state agencies play a vital role in epidemiological studies. States accumulate data similar to those in the MMWR and assist local health departments and medical practitioners with diagnostic testing for diseases such as rabies and Lyme disease. Data collected by the states are forwarded to the CDC, which is but one branch of the U.S. Public Health Service, the national public health agency. In addition to epidemiological studies, the CDC and other branches of the Public Health Service conduct research in disease etiology and prevention, make recommendations concerning immunization schedules, and work with public health organizations of other countries. The World Health Organization (WHO) coordinates efforts to improve public health throughout the world, particularly in poorer countries, and the WHO has undertaken ambitious projects to eradicate such diseases as polio, measles, and mumps. Some other current campaigns involve AIDS education, malaria control, and childhood immunization programs in poor countries. The Role of Public Health Agencies in Interrupting Disease Transmission As we have seen, pathogens can be transmitted in air, food, and water as well as by vectors and via fomites. Public health agencies work to limit disease transmission by a number of methods: • Enforce standards of cleanliness in water and food supplies. • Work to reduce the number of disease vectors and reservoirs. • Establish and enforce immunization schedules (see Figure 17.3). M14_BAUM7206_05_SE_C14.indd 437 • Locate and prophylactically treat individuals exposed to contagious pathogens. • Establish isolation and quarantine measures to control the spread of pathogens. A water supply that is potable (fit to drink) is vital to good health. Organisms that cause dysentery, cholera, and typhoid fever are just some of the pathogens that can be spread in water contaminated by sewage. Filtration and chlorination processes are used to reduce the number of pathogens in water supplies. Local, state, and national agencies work to ensure that water supplies remain clean and healthful by monitoring both sewage treatment facilities and the water supply. Food can harbor infective stages of parasitic worms, protozoa, bacteria, and viruses. National and state health officials ensure the safety of the food supply by enforcing standards in the use of canning, pasteurization, irradiation, and chemical preservatives and by insisting that food preparers and handlers wash their hands and use sanitized utensils. The U.S. Department of Agriculture also provides for the inspection of meats for the presence of pathogens, such as E. coli and tapeworms. Milk is an especially rich food, and the same nutrients that nourish us also facilitate the growth of many microorganisms. In the past, contaminated milk has been responsible for epidemics of tuberculosis, brucellosis, typhoid fever, scarlet fever, and diphtheria. Today, public health agencies require the pasteurization of milk, and as a result disease transmission via milk has been practically eliminated in the United States. Individuals should assume responsibility for their own health by washing their hands before and during food preparation, using disinfectants on kitchen surfaces, and using proper refrigeration and freezing procedures. It is also important to thoroughly cook all meats. Public health officials also work to control vectors, especially mosquitoes and rodents, by eliminating breeding grounds, such as stagnant pools of water and garbage dumps. Insecticides have been used with some success to control insects. Public Health Education Diseases that are transmitted sexually or through the air are particularly difficult for public health officials to control. In these cases, individuals must take responsibility for their own health, and health departments can only educate the public to make healthy choices. Colds and flu remain the most common diseases in the United States because of the ubiquity of the viral pathogens and their mode of transmission in aerosols and via fomites. Health departments encourage afflicted people to remain at home, use disposable tissues to reduce the spread of viruses, and avoid crowds of coughing, sneezing people. As we have discussed, handwashing is also important in preventing the introduction of cold and flu viruses onto the conjunctiva. We as a society are faced with several epidemics of sexually transmitted diseases. Syphilis, gonorrhea, genital warts, and sexually transmitted AIDS are completely preventable if the chain of transmission is interrupted by abstinence or mutually faithful monogamy. Their incidence can be reduced but not eliminated 11/23/16 3:50 AM C S ase EMERGING D tudy 14    Infection, Infectious Diseases, and Epidemiology isease hapter       C Hantavirus Pulmonary Syndrome M14_BAUM7206_05_SE_C14.indd 438 Why are all iatrogenic infections healthcare associated, but not all healthcare-associated infections are iatrogenic? ­ ­ ­ The good news is that there are drugs that can be used to effectively treat chloroquine-resistant Plasmodium. Dr. Dalton prescribes a seven-day course of atovaquone-proguanil. At her follow-up visit, Ellen has no remaining physical symptoms and no trace of Plasmodium in her blood. 1. What is the difference between signs and symptoms of an infection? Review Ellen’s case, and distinguish her signs from her symptoms. ­ ­ The doctor does another physical exam and orders blood work. Ellen has a fever (101°F), increased respiration rate, body aches, and weakness. The results of the blood work indicate that Ellen is anemic (low iron levels in the blood), and microscopic analysis of her blood reveals the presence of Plasmodium, the causative agent of malaria. Ellen is shocked—she used chloroquine as antimalarial prophylaxis (a drug taken to prevent a disease) during her time in India—how could she have malaria? Since he didn’t prescribe the chloroquine, Dr. Dalton wants to know where she got it; she explains that a friend had some left over from a previous trip, and so she used it rather than pay for a new prescription. Dr. Dalton explains that chloroquine-resistant Plasmodium is common in India, and therefore chloroquine isn’t the most effective prophylactic. TELL ME WHY ­ Just Jet Lag? 1. Why didn’t doctors treat Atsa with antibiotics, such as penicillin or tetracycline? 2. Cases of Hantavirus pulmonary syndrome are often seen following years with higher-than-average rainfall. Why? 3. What was the likely way that epidemiologists showed that the virus was the cause of the pulmonary condition? ­ by the use of condoms. Based on the premise that “an ounce of prevention is worth a pound of cure,” public health agencies expend considerable effort in public campaigns to educate people to make good choices—those that can result in healthier individuals and improved health for the public at large. symptoms; all had died. Atsa’s prognosis was the same: She was comatose. Her blood platelet level had dropped precipitously. Excessive proteins were in her blood. Her kidneys’ function was deteriorating. A week after her classmates had cheered their team’s victory, they gathered to mourn their friend. Within two weeks, epidemiologists had isolated a suspect virus, sequenced its genes, and identified the cause of her death as Hantavirus pulmonary syndrome (HPS). Scientists have established that HPS is acquired when victims inhale the virus in aerosolized deer-mouse urine or feces stirred up by sweeping. (For more about Hantavirus pulmonary syndrome, see pp. 695–697.) ­ Atsa was excited. Her Navajo basketball team had won the divisional championship, and she was high point (the high scorer) for the championship game. The thrill of the moment made her forget the argument with her parents earlier in the The deer mouse, Peromyscus maniculatus. week about sweeping out the storage shed. They were champions; life was good. The next morning, Atsa woke with deep muscle pain that she attributed to the exertions of the game. By noon she had a headache, nausea, and the chill associated with a fever. “The flu,” her mother concluded, and sent Atsa to bed with acetaminophen and plenty of fluids. Over the next few days, Atsa’s lungs began to congest; she struggled to breathe, and her heart raced. Atsa was drowning in her own bodily fluid. Desperately worried, Atsa’s parents drove her 60 miles to the Navajo medical center, where bewildered doctors provided respiratory and cardiac care while searching for answers. They discovered three patients in the surrounding counties with the same signs and 2. Malaria is a zoonotic disease; Ellen was infected by a bite from the Anopheles mosquito. Identify each of the following for Ellen’s case: portal of entry, mode of transmission, and reservoir. 11/23/16 3:50 AM       Chapter Summary CHAPTER SUMMARY 3. Opportunistic pathogens cause disease when the immune system is suppressed, when normal microbial antagonism (microbial competition) is affected by certain changes in the body, or when a member of the normal microbiome is introduced into an area of the body unusual for that microbe. Reservoirs of Infectious Diseases of Humans (pp. 415–417) 1. Living and nonliving continuous sources of infectious disease are called reservoirs of infection. Animal reservoirs harbor agents of zoonoses, which are diseases of animals that may be spread to humans via direct contact with the animal or its waste products or via an arthropod. Humans may be asymptomatic carriers. 2. Nonliving reservoirs of infection are inanimate objects, including soil, water, and food. The Invasion and Establishment of Microbes in Hosts: Infection (pp. 417–419) 1. Microbial contamination refers to the mere presence of microbes in or on the body or object. Microbial contaminants include harmless resident and transient members of the microbiome as well as pathogens, which after a successful invasion cause an infection. 6. Pathogenicity is a microorganism’s ability to cause disease; virulence is a measure of pathogenicity. Virulence factors, such as adhesion factors, extracellular enzymes, toxins, and antiphagocytic factors, affect the relative ability of a pathogen to infect and cause disease. ▶ ­ANIMATIONS: Virulence Factors: Hiding from Host Defenses, Inactivating Host Defenses, Penetrating V T Host Tissues; Phagocytosis: Microbes That Evade It 7. Toxemia is the presence in the blood of poisons called toxins. Exotoxins are secreted by pathogens into their environment. Endotoxins, are lipopolysaccharides (LPS) released from the cell wall of dead and dying Gram-negative bacteria and can have fatal effects. The toxic portion of LPS is the lipid, called lipid A. ▶ ANIMATIONS: Virulence Factors: Exotoxins, Endotoxins 8. Antitoxins are antibodies the host forms against exotoxins. 9. The disease process—the stages of infectious diseases—typically consists of the incubation period, prodromal period, illness, decline, and convalescence. The Movement of Pathogens out of Hosts: Portals of Exit (p. 427) 1. Portals of exit, such as the nose, mouth, and urethra, allow pathogens to leave the body and are of interest in studying the spread of disease. Modes of Infectious Disease Transmission (pp. 427–429) ▶ ANIMATION: Epidemiology: Transmission of Disease 1. Direct contact transmission of infectious diseases involves person-to-person spread by body contact. Transmission of pathogens via inanimate objects (called fomites) is called indirect contact transmission. 3. Pathogens attach to cells—a process called adhesion—via a variety of structures or attachment proteins called adhesion factors. Some bacteria and viruses lose the ability to make adhesion factors called adhesins and thereby become avirulent. 4. Some bacteria interact to produce a sticky web of cells and polysaccharides called a biofilm that adheres to a surface. The Nature of Infectious Disease (pp. 419–427) 1. Disease, also known as morbidity, is a condition sufficiently adverse to interfere with normal functioning of the body. 2. Symptoms are subjectively felt by a patient, whereas an outside observer can observe signs. A syndrome is a group of symptoms and signs that collectively characterizes a particular abnormal condition. M14_BAUM7206_05_SE_C14.indd 439 ­ ­ 2. Portals of entry of pathogens into the body include skin, mucous membranes, and the placenta. These portals may be bypassed via the parenteral route, by which microbes are directly deposited into deeper tissues. 5. Nineteenth-century microbiologists proposed the germ theory of disease, and Robert Koch developed a series of essential conditions called Koch’s postulates to prove the cause of infectious diseases. Certain circumstances can make the use of these postulates difficult or even impossible. ideo 2. Organisms making up the microbiome live in and on the body. Some of these microbes are resident microbiota, whereas others are transient microbiota. 4. Etiology is the study of the cause of a disease. utor ­ 1. Microbes live with their hosts in symbiotic relationships, including mutualism, in which both members benefit; parasitism, in which a parasite benefits while the host is harmed; amensalism, in which one member is harmed while the second is neither harmed nor helped; and, more rarely, commensalism, in which one member benefits while the other is relatively unaffected. Any parasite that causes disease is called a pathogen. 3. Asymptomatic, or subclinical, infections may go unnoticed because of the absence of symptoms, even though clinical tests might reveal signs of disease. ­ Symbiotic Relationships Between Microbes and Their Hosts (pp. 411–415) 2. Droplet transmission (a third type of contact transmission) occurs when pathogens travel less than 1 meter in droplets of mucus to a new host as a result of speaking, coughing, or sneezing. 3. Vehicle transmission involves airborne transmission, waterborne transmission, and foodborne transmission. Aerosols are clouds of water droplets that travel more than 1 meter in airborne transmission. Fecal-oral infection can result from drinking sewage-contaminated water or from ingesting fecal contaminants. Bodily fluid transmission is the spread of pathogens via blood, urine, saliva, or other fluids. 4. Vectors transmit pathogens between hosts. Biological vectors are animals, usually biting arthropods, that serve as both host 11/23/16 3:50 AM 14    Infection, Infectious Diseases, and Epidemiology and vector of pathogens. Mechanical vectors are not hosts to the pathogens they carry. 3. Descriptive epidemiology is the careful recording of data concerning a disease; it often includes detection of the index case—the first case of the disease in a given area or population. Analytical epidemiology seeks to determine the probable cause of a disease. Experimental epidemiology involves testing a hypothesis resulting from analytical studies. Classification of Infectious Diseases (pp. 429–431) 1. There are various ways in which infectious disease may be grouped and studied. When grouped by time course and severity, disease may be described as acute disease, subacute disease, chronic disease, or latent disease. 4. Healthcare-associated infections (HAIs) (nosocomial infections) and healthcare-associated diseases (nosocomial diseases) are acquired by patients or workers in health care facilities. They may be exogenous HAIs (acquired from the health care environment), endogenous HAIs (derived from the normal microbiome that become opportunistic while in the hospital setting), or iatrogenic infections (induced by treatment or medical procedures). 1. Epidemiology is the study of where and when diseases occur and of how they are transmitted within populations. ▶ ­ANIMATION: Epidemiology: Overview ­ ▶ ANIMATION: Epidemiology: Occurrence of Disease 5. Health care workers can help protect their patients and themselves from exposure to pathogens by handwashing and other aseptic and disinfecting techniques. 2. Epidemiologists track the incidence (number of new cases) and prevalence (total number of cases) of a disease and classify disease outbreaks as endemic (usually present), sporadic (occasional), epidemic (more cases than usual), or pandemic (epidemic on more than one continent). ▶ ANIMATION: Nosocomial Infections: Overview  ­ Epidemiology of Infectious Diseases (pp. 431—438) ­ ­ ­ ­ 2. When an infectious disease comes either directly or indirectly from another host, it is considered a communicable disease. If a communicable disease is easily transmitted from a reservoir or patient, it is called a contagious disease. Noncommunicable diseases arise either from outside of hosts or from members of the microbiome. ▶ ANIMATION: Nosocomial Infections: Prevention ­ hapter       C 6. Public health organizations, such as the World Health Organization (WHO), use epidemiological data to promulgate rules and standards for clean, potable water and safe food; to prevent disease by controlling vectors and animal reservoirs; and to educate people to make healthy choices concerning the prevention of disease. QUESTIONS FOR REVIEW Answers to the Questions for Review (except Short Answer questions) begin on p. A-I. Multiple Choice 3. Which of the following is false concerning microbial contaminants? a. Contaminants may become opportunistic pathogens. b. Most microbial contaminants will eventually cause harm. c. Contaminants may be a part of the transient microbiota. d. Contaminants may be introduced by a mosquito bite. 4. The most frequent portal of entry for pathogens is _____________. a. the respiratory tract c. the conjunctiva b. the skin d. a cut or wound 5. The process by which microorganisms attach themselves to cells is __________________. a. infection c. disease b. contamination d. adhesion 6. Which of the following is the correct sequence of events in infectious diseases? a. incubation, prodromal period, illness, decline, convalescence b. incubation, decline, prodromal period, illness, convalescence c. prodromal period, incubation, illness, decline, convalescence d. convalescence, prodromal period, incubation, illness, decline M14_BAUM7206_05_SE_C14.indd 440 8. The nature of bacterial capsules __________________. a. causes widespread blood clotting b. allows phagocytes to readily engulf these bacteria c. affects the virulence of these bacteria d. has no effect on the virulence of bacteria 9. When pathogenic bacterial cells lose the ability to make adhesins, they typically __________________. a. become avirulent c. absorb endotoxin b. produce endotoxin d. increase in virulence 10. A disease in which a pathogen remains inactive for a long period of time before becoming active is termed a(n) __________________. a. subacute disease c. chronic disease b. acute disease d. latent disease 11. Which of the following statements is the best definition of a pandemic disease? a. It normally occurs in a given geographic area. b. It is a disease that occurs more frequently than usual for a geographical area or group of people. c. It occurs infrequently at no predictable time scattered over a large area or population. d. It is an epidemic that occurs on more than one continent at the same time. ­ 2. An axenic environment is one that __________________. a. exists in the human mouth c. exists in the human colon b. contains only one species d. both a and c 7. Which of the following are most likely to cause disease? a. opportunistic pathogens in a weakened host b. pathogens lacking the enzyme kinase c. pathogens lacking the enzyme collagenase d. highly virulent organisms ­ 1. In which type of symbiosis do both members benefit from their interaction? a. mutualism c. commensalism b. parasitism d. pathogenesis 11/23/16 3:50 AM       Questions for Review 12. Which of the following types of epidemiologists is most like a detective? a. descriptive epidemiologist b. analytical epidemiologist c. experimental epidemiologist d. reservoir epidemiologist 13. Consider the following case. An animal was infected with a virus. A mosquito bit the animal, was contaminated with the virus, and proceeded to bite and infect a person. Which was the vector? a. animal c. mosquito b. virus d. person 14. A patient contracted athlete’s foot after long-term use of a medication. His physician explained that the malady was directly related to the medication. Such infections are termed __________________. a. healthcare-associated infections b. exogenous infections c. iatrogenic infections d. endogenous infections 5. List in the correct sequence the five stages of infectious diseases. 6. Describe three modes of disease transmission. 7. Describe the parenteral route of infection. 8. In general, contrast transient microbiota with resident microbiota. 9. Contrast the terms infection and morbidity. 10. Contrast iatrogenic and healthcare-associated diseases. VISUALIZE IT! 1. Each map below shows the locations (dots) of cases of a disease that normally occurs in the Western Hemisphere. Label each map with a correct epidemiological description of the disease’s occurrence. 15. Which of the following phrases describes a contagious disease? a. a disease arising from fomites b. a disease that is easily passed from host to host in aerosols c. a disease that arises from opportunistic members of the normal microbiome d. both a and b Fill in the Blanks 1. A microbe that causes disease is called a __________________. 2. Infections that may go unnoticed because of the absence of symptoms are called __________________ infections. 3. The study of the cause of a disease is __________________. 4. The study of where and when diseases occur and how they are transmitted within populations is __________________. 5. Diseases that are naturally spread from their usual animal hosts to humans are called __________________. 6. Nonliving reservoirs of disease, such as a toothbrush, drinking glass, and needle, are called __________________. 7. __________________ infections are those acquired by patients or staff while in health care facilities. a. ____________ b. ____________ c. ____________ 2. Examine the graph of the red epidemic and the blue epidemic. Neither red disease nor blue disease is treatable. A person with either disease is ill for only one day and recovers fully. Both epidemics began at the same time. Which epidemic affected more people during the first three days? What could explain the short time course for the red epidemic? Why was the blue epidemic longer lasting? 9. An animal that carries a pathogen and also serves as host for the pathogen is a __________________ vector. 10. Endotoxin, also known as __________________, is part of the outer (wall) membrane of Gram-negative bacteria. Short Answer 1. List four types of symbiotic relationships, and give an example of each. 2. List three conditions that create opportunities for pathogens to become harmful in a human. Number of individuals infected 8. The total number of cases of a disease in a given area is its __________________. 3. List three portals through which pathogens enter the body. 0 4. List Koch’s four postulates, and describe situations in which not all may be applicable. Onset of epidemics M14_BAUM7206_05_SE_C14.indd 441 1 2 3 4 5 6 7 Time (days) 8 9 10 11 12 11/23/16 3:50 AM E A T R C I IC L INKING TH       Chapter 14    Infection, Infectious Diseases, and pidemiology Based only on the information given, can you classify this outbreak as an epidemic? Why or why not? If you were an epidemiologist, how would you go about determining which pools in the water park were contaminated? What factors might account for the fact that no older children or adults developed disease? What steps could the park operators take to reduce the chance of future outbreaks of gastroenteritis? 1. Explain why Ellen H., a menopausal woman, may have developed gingivitis from her normal microbiome. 2. Will P. died of E. coli infection after an intestinal puncture. Explain why this microbe, which normally lives in the colon, could kill this patient. 3. A 27-year-old woman went to her doctor’s office with a widespread rash, fever, malaise, and severe muscle pain. The symptoms had begun with a mild headache three days previously. She reported being bitten by a tick one week prior to that. The doctor correctly diagnosed Rocky Mountain spotted fever (RMSF) and prescribed tetracycline. The rash and other signs and symptoms disappeared in a couple of days, but she continued on her antibiotic therapy for two weeks. Draw a graph showing the course of disease and the relative numbers of pathogens over time. Label the stages of the disease. 5. A lichen is an intimate relationship between a fungus and a photosynthetic microbe in which the fungus delivers water and minerals to its partner while the photosynthetic partner delivers sugar to the fungus. What type of symbiosis is involved? 6. Corals are colonial marine animals that feed by filtering small microbes from seawater in tropical oceans worldwide. Biologists have discovered that the cells of most corals are hosts to microscopic algae called zooxanthellae. Design an experiment to ascertain whether corals and zooxanthellae coexist in a mutual, commensal, or parasitic relationship. M 7. If a mutation occurred in Escherichia coli that deleted the gene for an adhesin, what effect might it have on the ability of E. coli to cause urinary tract infections? ING APP CONC EPT 4. Over 30 children younger than three years of age developed gastroenteritis after visiting a local water park. These cases represented 44% of the park visitors in this age group on the day in question. No older individuals were affected. The causative agent was determined to be a member of the bacterial genus Shigella. The disease resulted from oral transmission to the children. Using the following terms, fill in the following concept map that describes disease transmission. Vehicle transmission Waterborne Indirect contact Mosquito Vector transmission Contact transmission Droplet transmission Foodborne Arthropods Biological Body Disease transmission may occur through 1 5 may be may be Direct contact with may be Airborne 2 3 via Fomites 6 4 such as Sneezing 7 M14_BAUM7206_05_SE_C14.indd 442 8 involving Mechanical 10 9 such as 11 Tick 3/6/18 5:00 PM