Infection and Disease

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Infection and Disease

WHY YOU NEED TO KNOW

HISTORY

Combating infection and disease has been throughout history, and continues to be now, as essential as the need for food and shelter. The causes of infection and disease have been and continue to be equally problematic. As pointed out in Chapter 1 (Scope of Microbiology), it wasn’t until the seventeenth century that the application of van Leeuwenhoek’s light microscope revealed “animalcules,” suggesting theories that microorganisms could be a cause of disease.

With improved technology and refinement of scientific logic, Robert Koch, Louis Pasteur, and others in the late 1800s developed what has come to be known as “Koch’s postulates.” These four postulates are the foundation of the germ theory of disease, and they have been used to identify numerous disease-causing organisms. In a laboratory setting with agar culture plates, Koch demonstrated the cause of anthrax to be Bacillus anthracis.

FUTURE

With today’s global connectivity, both through the movement of populations and the import/export of products along with increased mobility within national or local populations, the threat of the rapid spread of disease will remain a significant challenge for all levels of healthcare professionals. Whether combating the increasing threat of nosocomial infections, which is exacerbated by the emergence of antibiotic-resistant strains of organisms, or conducting research to determine host–pathogen relationships and the vector of transmission, all those in the healthcare and related fields will be instrumental in preventing the next outbreaks of infectious diseases. A local or institutional problem has the potential to expand into an epidemic if healthcare workers do not possess a working knowledge of infection and disease.

Host–Microbe Relationship

Microbes are found everywhere on earth and the interaction of humans with microorganisms is inevitable, complex, and not always completely understood. Under normal circumstances, humans and other animals are free of microbes in utero, but during birth the newborn is exposed to microbes, which will start to colonize the infant’s intestine. From this time on humans and microbes establish a symbiotic relationship that lasts a lifetime.

Symbiosis

Symbiosis is the term that describes a close relationship between two different types of organisms in a community. Depending on the outcome of this relationship, symbiosis can be classified as mutualism, commensalism, parasitism, or amensalism (Table 9.1):

TABLE 9.1

Symbiotic Relationships

Symbiosis Type Organism 1 Organism 2 Example
Mutualism Benefits Benefits Escherichia coli in human large intestine
Commensalism Benefits Neither harmed, nor helped Many microbes that make up the normal flora of the human skin and mucous membranes
Parasitism Benefits Harmed Tuberculosis bacterium in the human lung; certain protozoans, fungi, and helminths
Amensalism Not affected Impedes or restricts Penicillium (mold) secretes penicillin, which kills certain bacteria

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• Mutualism: Mutualism is a relationship between two organisms in which both members benefit from the interaction. For example, in the large intestine of humans, Escherichia coli releases vitamins during the breakdown of nutrients that are not digestible by the human gastrointestinal (GI) tract, but necessary for the survival of the bacteria. The vitamins released by E. coli can easily be absorbed by the intestinal epithelium of the human large intestine. As shown in the Life Application, probiotics are also examples of mutualism between specific bacterial species and the human gastrointestinal tract.

• Commensalism: Commensalism is a term used for a symbiotic relationship in which one of the organisms benefits and the other is neither harmed nor helped. Many microorganisms in the normal flora of the human skin and mucous membranes are commensals. Examples include certain saprophytic mycobacteria that inhabit the ear and external genitals, living on secretions and removed cells. These organisms do not appear to bring benefit or harm to the host.

• Parasitism: In parasitism one organism benefits, while the other is harmed, either slightly or to such an extreme that the host will be killed. A parasite that is capable of causing disease is called a pathogen. Species of bacteria, protozoans, algae, and fungi all can be microscopic human pathogens. Larger pathogens include the parasitic worms and biting arthropods.

• Amensalism: Amensalism is an interaction between two species in which one organism can hamper or prevent the growth and/or survival of another, without being positively or negatively affected by the other organism. A familiar example is Penicillium, a mold that secretes penicillin, a chemical capable of killing a wide range of bacteria (see Chapter 22, Antimicrobial Drugs).

Normal Flora (Microbiota)

A newborn’s first contact with microorganisms occurs while traveling through the birth canal, where lactobacilli residing in the mother’s vagina will become the predominant organisms in the newborn’s intestine. The next exposure of the newborn to microorganisms occurs with the beginning of breathing, and this is soon followed by feeding. From then on, other orally acquired bacteria such as E. coli will begin to colonize the large intestine and will remain there throughout life. In other words, starting at birth the human body enters a state of dynamic equilibrium with microorganisms. In addition, throughout a person’s life, other microorganisms will establish residency in mucous membranes that are open to the external environment, on the skin and its derivatives (Figure 9.1). Mucous membranes open to the external environment include those of the respiratory tract (Figure 9.2), gastrointestinal tract (Figure 9.3), and urogenital tract (Figure 9.4). The microbes that establish themselves on the skin and mucous membranes usually do not cause disease and constitute the normal flora (microbiota) of the human body. This normal flora consists of resident or transient microbes:

• A resident flora remains part of the normal flora throughout the life of a person. An example would be Staphylococcus epidermidis, a resident of the skin, or E. coli, which is part of the intestinal flora. A detailed listing of the various organisms that reside in/on the human body is provided in Table 9.2.

TABLE 9.2

Normal Flora in Selected Regions of the Human Body

Region Genera Observation
Skin Staphylococcus, Propionibacterium, Corynebacterium, Micrococcus, Acinetobacter, Candida (fungus), Malassezia (fungus) The varied environment of the skin results in locally dense or sparse populations, depending on moisture, temperature, and exposure to the environment. In general, the microbes live on the outer layer of the skin, in hair follicles, and in pores of glands
Eyes (conjunctiva) Staphylococcus, Propionibacterium, Micrococcus, Corynebacterium Although the microbiota is similar to that of the skin, tears reduce the normal flora and prevent others from colonizing
Upper respiratory tract Fusobacterium, Haemophilus, Lactobacillus, Moraxella, Staphylococcus, Streptococcus Microbes that are part of the normal flora are potential pathogens, but are generally kept at bay by an intact immune system, by nasal secretions, and by the ciliary escalator of the trachea
Mouth (upper digestive tract) Fusobacterium, Haemophilus, Lactobacillus, Staphylococcus, Streptococcus, Actinomyces, Treponema, Corynebacterium, Candida (fungus) Although saliva does contain antimicrobial substances, the moisture, warmth, and continuous supply of food support many microorganisms. Normally these microbes do not cause infections, but some of them are potential pathogens
Lower digestive tract Escherichia coli, Bacteroides, Fusobacterium, Lactobacillus, Enterococcus, Enterobacter, Bifidobacterium, Citrobacter, Proteus, Klebsiella, Candida (fungus) The large intestine contains the largest amount of resident microbes. Bacteria are mostly anaerobes but some facultative anaerobes also present
Female urogenital tract Lactobacillus, Bacteroides, Clostridium, Staphylococcus, Streptococcus, Candida (fungus), Trichomonas (protozoan) As the pH of the vagina changes so does the microbial flora. Flow of urine prevents extensive colonization of the urethra and urinary bladder
Male urogenital tract Lactobacillus, Bacteroides, Fusobacterium, Mycobacterium, Peptostreptococcus, Staphylococcus, Streptococcus Flow of urine prevents excessive colonization of microbes in the urethra or urinary bladder

• A transient flora can be found in the same locations as the resident flora, but remains in the body for only a few hours, days, or months before it vanishes. These organisms cannot survive for reasons such as competition with other microorganisms for nutrients, elimination by the host’s immune system, or chemical and physical changes in the body of the host. An example would be Bacillus laterosporus, sometimes found in the intestines; when present the organism helps to keep fungal populations such as Candida in check.

LIFE APPLICATION

Probiotics: Yogurt as Medicine?

One often-used definition of probiotics, developed by the World Health Organization (WHO), is that they are live microorganisms, mostly bacteria, which when taken in proper amounts result in a health benefit for the host. These bacteria are called “friendly” or “good” bacteria and are the same or similar to the normal flora found in healthy individuals. For centuries, home remedies and medicinal folklore have suggested that some fermented milk products conferred a certain health benefit to the user. Modern probiotic products have taken forms other than just milk products, such as by the addition of probiotics to juices and soy beverages. Capsules, tablets, and powders are also available and can be added to food products or directly ingested. The list of potential health benefits of probiotics is growing, some of which have specific potential in the control of infectious diseases. These include competition of “friendly” bacteria with pathogens, replenishment of normal intestinal flora after depletion caused by antibiotics, and stimulation of certain immune system components. Thus far research has uncovered some rather minor side effects such as mild digestive discomfort, but there is also a potential infection problem when introducing bacteria into a host with an already depressed immune system. In these cases the normally “friendly” bacteria may become opportunistic pathogens and require treatment with antibiotics. Concerns have also been raised about overstimulation of the immune system, effects of metabolic activities as a result of increased bacterial numbers, or gene transfers between pathogens and probiotic microorganisms.

Opportunistic Pathogens

In general, this balance between the normal flora and the human host can be maintained, but when the balance is interrupted for whatever reason, the microorganisms can cause infection and disease. They become opportunistic pathogens. An opportunistic pathogen does not cause disease in its normal habitat in a healthy person, but can cause infection under conditions of immune suppression, changes in the normal flora, or when a member of the normal flora gains access into an area of the body it normally does not inhabit.

• Compromised immune system immune suppression (see Chapter 20, The Immune System): Any factors that suppress or weaken the immune system can enable opportunistic pathogens to cause infections and disease. These factors include acute and chronic diseases, especially those involving the immune system directly (e.g., AIDS); malnutrition, stress (emotional and physical), age (very young or very old), the use of radiation and chemotherapy in the treatment of cancer, or the use of immunosuppressive drugs in transplant patients.

• Changes in the normal flora: The normal flora plays a somewhat protective role regarding pathogens, because it takes up space, uses available nutrients, and releases toxic waste products, all of which present a problem for arriving pathogens, which must compete well enough to become established to infect and cause disease in the desired host. This condition is acknowledged as microbial competition or antagonism. When the normal flora changes for any reason it may allow one of the members to become an opportunistic pathogen and thrive. Examples include vaginal yeast infections by Candida albicans in women after prolonged antibiotic therapy, or oral thrush also caused by Candida spp. in cancer patients after chemotherapy. Other conditions that change the normal flora include hormonal changes, stress, changes in the diet, or exposure to an excessive number of pathogenic organisms.

• Entrance of a member of the normal flora into areas of the body where it is not present under normal conditions: This can occur after injury, in burn victims, or even when an intestinal organism such as E. coli enters the urethra, where it then becomes opportunistic.

Stages of Infection

In terms of infection in the human body, contamination refers to the presence of microbes in or on the body, or on objects. Contaminants can reach the body in food, drink, by air, or they can be introduced by wounds, insect bites, and sexual intercourse. The outcome of a contamination varies. Some microbes remain at the site at which they first came in contact with the body, such as on the skin and mucous membranes; they do not cause harm and become part of the resident (normal) flora, or a transient flora. To initiate an infection the microorganism must gain entry into the host and its tissues. The term infection refers to the presence and growth of a microorganism in the body, with the exception of organisms in/on the normal flora. Notably, an infection may or may not cause disease.

Portal of Entry

The site where a pathogen enters the body is referred to as the portal of entry, which can be the skin, mucous membranes, the placenta, or the so-called parenteral route (other then the digestive tract route). The source of the infectious agent can be exogenous, from outside the body, or endogenous, in which case the organism is already in the body, such as in the normal flora.

Portals of entry are generally the same areas that support normal flora: the skin and the mucous membranes of the gastrointestinal, respiratory, and urogenital tracts (Figure 9.5). The majority of pathogens have their preferred portal of entry, which provides the necessary habitat for further growth and eventual spreading. Most often, if a pathogen enters the wrong portal, infection will not occur. For example, influenza virus uses the respiratory mucosa as its portal of entry, where it may successfully infect its host, but when limited to contact with the skin only, influenza virus will not cause an infection. Some infectious agents can enter via more than one portal of entry, such as the skin and mucous membranes, where the infection then can lead to various diseases. For example, Streptococcus and Staphylococcus have adapted to several portals of entry such as the skin and the urogenital and respiratory tracts.

Mucous Membranes

Mucous membranes line all the body cavities and the canals that come in contact with the outside, such as the canals of the gastrointestinal, respiratory, and urogenital tracts, as well as the conjunctiva, the thin membrane covering the eye and the underside of the eyelids. The skin and the outer layer of the mucous membranes are composed of tightly packed epithelial cells. However, in contrast to the epidermis, the mucosal lining is thin, moist, and warm, and composed of living cells.

• The gastrointestinal (GI) tract serves as the portal of entry for pathogens present in food, liquid, and other ingested substances. Microorganisms that can survive in the GI tract are adapted to survive the action of digestive enzymes and environments that undergo drastic changes in the pH. Enteric bacterial pathogens include Salmonella, Shigella, Vibrio, and certain strains of E. coli. Viruses using the GI tract as a portal of entry include poliovirus, hepatitis A virus, echovirus, and rotavirus. The most common enteric protozoans are Entamoeba histolytica and Giardia lamblia. Helminths, although not considered microbes, are infectious agents entering through the GI tract and include trematodes, cestodes, and nematodes (see Chapter 8, Eukaryotic Microorganisms).

• The respiratory tract is the most frequently used portal of entry. Pathogens are able to enter the mouth and nose by air, via dust particles, moisture, and respiratory droplets from an infected person. Mucous membranes that line the upper respiratory tract are continuous with the membranes of the sinuses and of the auditory tubes, and pathogens can be transferred from one site to the other. Examples of bacteria using this portal of entry include the causative agents of sore throat, meningitis, diphtheria, and whooping cough. Examples of viral agents include those causing the common cold, influenza, measles, meningitis, mumps, rubella, and chickenpox (see Chapter 11, Infections of the Respiratory System).

• The urogenital tract is a portal of entry for pathogens that are generally contracted by sexual contact (see Chapter 17, Sexually Transmitted Infections/Diseases). However, girls and women who are not sexually active are also susceptible to lower urinary tract infections because of the close proximity of the anus to the female urethra. Therefore urinary tract infections caused by E. coli, as opportunistic organisms, are more common in women than men. Vaginal yeast infections are common in women who are under stress; taking birth control pills, antibiotics, and/or steroids; who are pregnant; or because of other factors. Vaginal yeast infections are usually due to an overgrowth of Candida albicans.

• The conjunctiva is generally a good barrier against infectious agents, but some bacteria such as Haemophilus aegyptius (pinkeye), Chlamydia trachomatis, and Neisseria gonorrhoeae can easily attach to this membrane.

Placenta

The placenta, an organ formed by maternal and fetal tissues, is usually an effective barrier against microorganisms that may be present in the maternal circulation. However, some microbes can cross the placenta and infect the embryo or fetus, sometimes causing spontaneous abortions, birth defects, or premature births.

HEALTHCARE APPLICATION
Pathogens That Cross the Placenta

Microbe Pathogen Condition Effect on Unborn
RNA viruses Lentivirus (HIV) AIDS Immunosuppression (AIDS)
Rubivirus German measles Severe birth defects or death
DNA viruses Cytomegalovirus Usually asymptomatic Deafness, microcephaly, mental retardation
Parvovirus B-19 Erythema infectiosum Abortion
Bacteria Treponema pallidum Syphilis Abortion, multiorgan birth defects, syphilis
Listeria monocytogenes Listeriosis Granulomatosis infantiseptica, death
Protozoans Toxoplasma gondii Toxoplasmosis Abortion, epilepsy, encephalitis, microcephaly, mental retardation, blindness, anemia, jaundice, rash, pneumonia, diarrhea, hypothermia, deafness

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Virulence and Pathogenicity

After pathogens have gained entry into the body they must undergo adhesion and several other steps to be able to multiply, thereby causing an infection and possible disease.

Virulence refers to the degree of pathogenicity or disease-evoking power of a specific microbe. Virulence therefore is the degree of pathogenicity of a microbe and is based on virulence factors. A pathogen is a microorganism that is capable of causing disease. The ability of a microorganism to cause disease is directly related to the number of infecting organisms, the portal of entry, the host defense mechanisms (see Chapter 20, The Immune System), and the intrinsic characteristics of the bacteria and their virulence factors. These include the following:

• Adhesion: Adhesion is the first and probably the most crucial step in infection, because without adhesion to the host cells or tissue, the microbes will be removed by ciliary motion (see Chapter 3, Cell Structure and Function), sneezing, coughing, swallowing, urine flow, flow of tears, or intestinal peristalsis. Bacteria must first bind to the host cell, via pili, fimbriae, or specific membrane receptor sites. Viral adhesion occurs by capsid or envelope proteins. The mechanism of the adhesion process can be nonspecific or specific:

• Nonspecific adhesion involves nonspecific attractive forces or interactions the microorganism uses to move toward the eukaryotic host. These interactions and forces can include the following:

• Specific adhesion involves a permanent lock-and-key interaction between complementary molecules on each cell surface and under normal physiological conditions this attachment becomes irreversible. Examples of such specific attachments/adhesions are illustrated in Table 9.3.

TABLE 9.3

Examples of Specific Adhesions of Bacteria to the Host

Species Adhesion Factor Host Receptor Site Disease
Chlamydia Unknown Sialic acid Conjunctival or urethral epithelium Conjunctivitis or urethritis
Bordetella pertussis Fimbriae Galactose on sulfated glycolipids Respiratory epithelium Whooping cough
Escherichia coli, enteropathogenic Type 1 fimbriae Species-specific carbohydrate(s) Intestinal epithelium Diarrhea
E. coli, uropathogenic Type 1 fimbriae Complex carbohydrate Urethral epithelium Urethritis
E. coli, uropathogenic P pili Globobiose linked to ceramide lipid Upper urinary tract Pyelonephritis
Mycoplasma Membrane proteins Sialic acid Respiratory epithelium Pneumonia
Neisseria gonorrhoeae N-Methylphenyl-alanine pili Glucosamine–galactose carbohydrate Urethral/cervical epithelium Gonorrhea
Staphylococcus aureus Cell-bound protein Amino terminus of fibronectin Mucosal epithelium Various
Streptococcus mutans Glycosyltransferase Salivary glycoprotein Pellicle of tooth Dental caries
Streptococcus pneumoniae Cell-bound protein N-Acetylhexosamine–galactose disaccharide Mucosal epithelium Pneumonia
Streptococcus pyogenes Protein F Amino terminus of fibronectin Pharyngeal epithelium Sore throat
Streptococcus salivarius Lipoteichoic acid Unknown Buccal epithelium of tongue None
Treponema pallidum Peptide in outer membrane Surface protein Mucosal epithelium Syphilis
Vibrio cholerae N-Methylphenylalanine pili Fucose and mannose carbohydrate Intestinal epithelium Cholera

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• Colonization: Another essential step in the development of an infection is the establishment of the pathogen at the portal of entry once adhesion of the pathogen has occurred. Human pathogens usually colonize tissues that are in contact with the external environment, such as the urogenital tract, the digestive tract, the respiratory tract, and the conjunctiva of the eye. Some virulent bacteria may produce special proteins that allow them to colonize these parts to cause disease.

• Invasion: The invasive qualities of a pathogen may be aided by the production of extracellular substances, allowing it to disrupt host cell membranes, breaking down the primary and secondary defensive barriers of the host. These substances are referred to as invasins (Table 9.4) and their activity then facilitates the growth and spread of the pathogen.

TABLE 9.4

Survey of Bacterial Invasins

Invasin Organism(s) Producing Invasin Mechanism
Hyaluronidase Streptococci, staphylococci, clostridia Assaults the matrix of connective tissue by depolymerizing hyaluronic acid
Collagenase Clostridium histolyticum, Clostridium perfringens Breaks down collagen
Neuraminidase Vibrio cholerae, Shigella dysenteriae Degrades neuraminic acid of the intestinal mucosa
Kinases Streptococci and staphylococci Converts plasminogen to plasmin, which digests fibrin
Leukocidin Staphylococcus aureus Disrupts neutrophil membranes and causes discharge of lysosomal granules
Streptolysin Streptococcus pyogenes Repels phagocytes and disrupts phagocyte membrane, causing discharge of lysosomal granules
Hemolysins Streptococci, staphylococci, clostridia Phospholipases or lecithinases that destroy erythrocytes and other cells by lysis
Phospholipases Clostridium perfringens Destroys phospholipids of the plasma membrane
Lecithinases Clostridium perfringens Destroys lecithin in cell membranes
Anthrax EF Bacillus anthracis An adenylate cyclase that causes increased levels of intracellular cAMP
Pertussis AC Bordetella pertussis An adenylate cyclase that causes increased levels of intracellular cAMP and subsequent increase in respiratory secretions

cAMP, Cyclic adenosine monophosphate.

• Evasion of host defenses: The ability to avoid the host response can be due to the presence of a capsule, the production of proteins that bind to the host cell antibodies, or mutation of the organism to alter its antigenicity. Various strategies are used by microbes to avoid being eliminated by the host phagocytes, but usually they involve blocking one or more steps of phagocytosis (see Chapter 20, The Immune System). Some of these strategies include but are not limited to the following:

• Avoidance of contact with phagocytes by invading or remaining in regions that are inaccessible to phagocytes or are not patrolled by them. Some pathogens induce minimal or no inflammation to avoid provoking an intense immune response. Other organisms inhibit phagocyte chemotaxis; for example, Clostridium produces a toxin that inhibits neutrophil chemotaxis. In addition, some bacteria hide their antigenic surface so that phagocytes do not recognize the organism as non-self.

• Inhibition of phagocytic engulfment is used by some bacteria that have substances on their surfaces that inhibit phagocytic activity or engulfment.

• Survival inside phagocytes, either neutrophils or macrophages, is another way by which some microbes can resist killing. These organisms are considered intracellular parasites.

• Yet another, aggressive strategy used by some organisms is to produce products that kill or damage phagocytes either before ingestion or after ingestion.

• Toxins: Another virulence factor is determined by the ability of the organism to produce enzymes, exotoxins, and endotoxins that will damage the host cells or interfere with a vital host cell function. Toxins constitute a major virulence factor.

Toxins

An organism that produces toxins is called toxigenic. This is an underlying mechanism by which many microorganisms, especially bacteria, produce disease.

Chemically, bacterial toxins are either lipopolysaccharides associated with the cell wall of gram-negative bacteria, or proteins released from the bacterial cell. Toxins associated with the cell wall are called endotoxins, and proteins released from a bacterium are referred to as exotoxins (Figure 9.6). Bacterial toxins are among the most powerful toxins known to humankind.

Exotoxins

Exotoxins are typically soluble proteins secreted by bacterial cells during their exponential growth phase. They can act at sites other than the location of the infection and bacterial growth. Often the toxins produced are species specific and associated with a particular disease (Table 9.5). For example, Clostridium tetani is the only organism to produce the tetanus toxin, and Corynebacterium diphtheriae makes diphtheria toxin. As with other proteins, these enzymes can be denatured by heat, acid, and proteolytic enzymes (enzymes that break down proteins).

TABLE 9.5

Examples of Bacterial Exotoxins

Organism Toxin Activity Pathology
Bacillus anthracis Anthrax toxin (EF) Edema factor (EF) causes increased levels of intracellular cAMP in phagocytes and the formation of ion-permeable pores in membranes Hemolysis
Bordetella pertussis Adenylate cyclase (AC) toxin Causes increased levels of cAMP in phagocytes and the formation of ion-permeable pores in membranes Hemolysis; whooping cough
Escherichia coli Heat-labile (LT) toxin Increases the level of cAMP in cells of the GI tract, causing secretion of water and electrolytes Severe abdominal cramps; bloody diarrhea; high fever
  Heat-stable (ST) toxin Stimulates guanylate cyclase, promotes secretion of water and electrolytes from intestinal epithelium Severe abdominal cramps; bloody diarrhea; high fever
Pseudomonas aeruginosa Exotoxin A Inhibits protein synthesis Various
Vibrio cholerae Cholera enterotoxin Increases the level of cAMP in cells of the GI tract, causing secretion of water and electrolytes Cholera
Clostridium botulinum Botulinum toxin Disrupts secretion of acetylcholine at neuromuscular synapse, preventing muscular contraction Botulism
Clostridium tetani Tetanus toxin Prevents the breakdown of acetylcholine by enzymes at the neuro-muscular synapse, causing constant muscle contraction Tetanus

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cAMP, Cyclic adenosine monophosphate; GI, gastrointestinal.

Like enzymes, many bacterial exotoxins are substrate specific and generally the site of damage caused by the toxin indicates the location of the substrate for that particular toxin. This has led to naming these toxins according to their target, such as enterotoxin, neurotoxin, leukocidin, or hemolysin to name a few.

Endotoxins

Endotoxins are lipopolysaccharides and structural components of gram-negative bacterial cell walls (e.g., Shiga toxin). Endotoxins are released from the cell walls during lysis initiated by an effective host defense or by the action of antibiotics. After release, these toxins can also act on sites remote from the original site of infection and growth. In contrast to exotoxins, endotoxins are less potent and less specific in their actions. Because these toxins are lipopolysaccharides and not proteins, they are heat stable and even boiling for 30 minutes does not destabilize them. However, certain oxidizing agents such as superoxide, peroxide, and hypochlorite have been reported to be effective in neutralizing them. A general comparison between bacterial exotoxins and endotoxins is presented in Table 9.6.

TABLE 9.6

Comparison of Bacterial Exotoxins and Endotoxins

Feature Exotoxin Endotoxin
Chemical nature Protein Lipopolysaccharides
Location Extracellular Part of cell wall
Specificity High degree Low degree
Potency Relatively high Relatively low
Denatured by heat Yes No
Antigenic Yes Yes
Toxoid* Yes No

*A toxoid is an endotoxin modified so that it is no longer toxic, but still causes the host to generate antitoxin.

Etiology of Infectious Diseases

As mentioned earlier, not all infections cause disease and it is essential to differentiate between an infection and a disease. An infection is the colonization of a host by an infectious agent. When an infectious agent causes pathological changes and interferes with the normal functioning of the body it is termed infectious disease. The study of the cause of disease is called etiology.

Patterns of Infection

Infections have varied patterns and are named accordingly as local infections, focal infections, systemic infections, mixed infections, acute and chronic infections, and primary and secondary infections.

• Local infections are the simplest ones; the organism enters the body and remains confined to a specific tissue. This is the case with boils, fungal skin infections, and warts.

• Focal infections occur when the pathogen spreads from a local infection to other tissues.

• Systemic infections occur when an infection spreads to several sites and tissue fluids, usually by way of the circulatory system.

• Mixed infections occur when several infectious agents concurrently establish themselves at the same site. Some mixed infections are synergistic infections in which microbes cooperate in breaking down the tissue.

• Acute infections are infections that appear rapidly, with pronounced (severe) symptoms, but then rapidly vanish.

• Chronic infections have usually less severe symptoms than acute infections, but they persist for long periods of time.

• A primary infection is an initial infection, which is followed by complications due to another microbe.

• A secondary infection follows a primary infection. In general, secondary infections are caused by a different microbe, which gains access to the body through a lesion of either the skin or the mucous membrane damaged by the first pathogen, or they can be microbes of the normal flora that become opportunistic because of a compromised immune system.

• A subclinical infection is one that does not cause any apparent symptoms, and can be carried over long periods of time without causing symptoms of illness in the individual.

Koch’s Postulates

The germ theory of disease was proposed by Louis Pasteur and Robert Koch (see Chapter 1, Scope of Microbiology). Although Louis Pasteur was convinced that microbes caused disease in humans he was not able to link a specific microbe with a particular disease. After many years of experimentation, Koch was able to establish that specific microorganisms cause specific diseases. Koch developed a series of conditions—postulates—that must be met to identify a particular microbe as pathogenic and the cause of a particular disease. Using his postulates he proved that Bacillus anthracis is the causative agent for anthrax and that Mycobacterium tuberculosis causes tuberculosis. This concept is now known as Koch’s postulates (Figure 9.7), and can be summarized as follows:

Exceptions to Koch’s Postulates

Although Koch’s postulates provide the basics of the etiology of infectious disease, they are not always appropriate to use, for the following reasons:

• Some pathogens cannot be cultured in the laboratory.

• Many infectious diseases can be caused by several different pathogens.

• A particular pathogen can cause different diseases, depending on the portal of entry.

• Some diseases are caused by a combination of pathogens, such as liver infections caused by both the hepatitis B virus and the hepatitis D virusoid. The latter cannot cause infection without the hepatitis B virus. Other exceptions are polymicrobial diseases caused by biofilms.

• Some pathogens are exclusively human pathogens and ethical considerations prevent human inoculation to prove Koch’s postulates. These exceptions include diseases caused by viruses or animal parasites. Also, Rickettsia and Chlamydia are obligate intracellular parasites without an animal model.

Although Koch’s postulates do not always seem to apply, scientists have found other means to reach the desired outcome of the postulates by following other routes. Furthermore, Koch’s postulates are at work in the food industry, where microbes need to be carefully monitored, and the desired microbe must be isolated in the desired end product. Despite the challenges Koch’s postulates remain useful for confirming microbial roles in infection, disease, and other processes. The concepts used to prove cause have been employed as modules of proof in other scientific disciplines. For example, Eccles used a similar pattern to show that acetylcholine (ACh) was a chemical transmitter in the central nervous system, which established mammalian neurotransmission as being chemical, when it had previously been promoted as electrical.

Epidemiology and Public Health

Epidemiology is the study of the distribution and causes of disease in populations, and serves as the foundation of interventions needed in the interest of public health and preventive medicine. Epidemiologists study how many people or animals are affected, where they are distributed, and the outcome of the disease, such as recovery, death, and disability. In addition, they study the factors that influence the distribution and outcome of the disease. Epidemiologists use three basic approaches to study the dynamics of diseases in populations: descriptive, analytical, and experimental.

• Descriptive epidemiology is the collecting and tabulating of data concerning the disease. These data generally include information about the affected individuals and the location and period of time of disease occurrence. Information about patients may include age, gender, occupation, health history, sexual behavior, eating habits, travel history, and socioeconomic status. Seasonal variations in the climate may also be a consideration. The time course and chain of transmission are important in descriptive epidemiology and investigators make every effort to identify the index case, the first case, of the disease. This might be difficult because the victim of the disease may have recovered, moved, or died.

• Analytical epidemiology attempts to demonstrate a probable cause-and-effect relationship, using analysis of the data collected by descriptive epidemiology. Analytical studies may be retrospective if the data are analyzed after an epidemic has subsided, or prospective if the data collection is done during an ongoing epidemic. Analytical epidemiology is often applied when it is unethical to apply Koch’s postulates, because the disease is a human disease only and does not have an animal model.

• Experimental epidemiology starts with a hypothesis about a particular disease, followed by the design of experiments and studies to test the hypothesis. The application of Koch’s postulates is a perfect example of experimental epidemiology.

Epidemiology is a subject of major importance to state and federal public health departments. The Centers for Disease Control and Prevention (CDC) is the central source of epidemiological information in the United States. The CDC publishes the Morbidity and Mortality Weekly Report (MMWR), which can be viewed at the CDC website (www.cdc.gov). This publication contains data on morbidity (the incidence of specific notifiable diseases), and mortality (the number of deaths associated with a particular disease). The morbidity rate reflects the number of people affected by a particular disease during a given time in relation to the total population. The mortality rate shows the number of deaths resulting from a disease in a population during a given period of time in relation to the total population. The Morbidity and Mortality Weekly Report is of interest to microbiologists, physicians, and other healthcare and public health professionals. Nationally notifiable infectious diseases are diseases that must be reported by physicians to the U.S. Public Health Service and are shown in Box 9.1. A well-developed network of individuals and agencies keeps track of infectious diseases at the local, district, state, national, and international levels. The CDC shares its information and statistics with the World Health Organization (WHO) for the purpose of worldwide tabulation and control.

BOX 9.1   Nationally Notifiable Infectious Diseases

Botulism

Brucellosis

Chancroid

Chlamydia trachomatis, genital infections

Cholera

Coccidioidomycosis

Cryptosporidiosis

Cyclosporiasis

Diphtheria

Ehrlichiosis

Giardiasis

Gonorrhea

Haemophilus influenzae, invasive disease

Hansen’s disease (leprosy)

Hantavirus pulmonary syndrome

Hemolytic uremic syndrome, postdiarrheal

Hepatitis, viral, acute

Hepatitis, viral, chronic

HIV infection

Influenza-associated pediatric mortality

Legionellosis

Listeriosis

Lyme disease

Malaria

Measles

Meningococcal disease

Mumps

Novel influenza A virus infections

Pertussis

Plague

Poliomyelitis, paralytic

Poliovirus infection, nonparalytic

Psittacosis

Q fever

Rabies

Rocky Mountain spotted fever

Rubella

Rubella, congenital syndrome

Salmonellosis

Severe acute respiratory syndrome–associated coronavirus (SARS-CoV) disease

Shiga toxin–producing Escherichia coli (STEC)

Shigellosis

Smallpox

Streptococcal disease, invasive, Group A

Streptococcal toxic shock syndrome

Streptococcus pneumoniae, drug resistant, invasive disease

Streptococcus pneumoniae, invasive disease, nondrug resistant, in children less than 5 years of age

Syphilis

Syphilis, congenital

Tetanus

Toxic shock syndrome (other than streptococcal)

Trichinellosis (trichinosis)

Tuberculosis

Tularemia

Typhoid fever

Vancomycin-intermediate Staphylococcus aureus (VISA)

Vancomycin-resistant Staphylococcus aureus (VRSA)

Varicella (morbidity)

Varicella (deaths only)

Vibriosis

Yellow fever

Data from http://www.cdc.gov/ncphi/disss/nndss/PHS/infdis.htm (accessed April 29, 2009).

Diseases in the Population

Diseases in a population can be reported as the prevalence of the disease, which is the total number of existing cases in the entire population, or the disease can be measured by incidence, which is the number of new cases over a certain period of time compared with the general healthy population. The equations used to determine these rates are as follows:

< ?xml:namespace prefix = "mml" />Prevalence=(total number of cases in populationtotal number of persons in population)×100=%

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Incidence=(number of new casestotal number of susceptible persons)(usually reported per 100,000 persons)

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Changes in prevalence and incidence of diseases are generally monitored every season, annually, and on a long-term basis to predict trends. These monitoring statistics make it possible to define the frequency of a disease in a population. The frequency of a disease and the geographic location of the occurrence allow for classification of the disease into endemic, sporadic, epidemic, and pandemic disease categories.

Reservoirs

For an infectious disease to continue to exist, its causative agent(s) must have a permanent place to reside. Sites where pathogens are maintained as a source of infection are called reservoirs of infection. These can be in the form of animal, human, or nonliving reservoirs.

Animal Reservoirs

Many of the pathogens that normally infect animals, either domesticated or wild, also can affect humans. Diseases that occur primarily in animals and can be transmitted to humans are referred to as zoonoses (Table 9.7). Humans can be infected by zoonoses by several routes: direct contact with the infected animal; contact with animal waste, or with waste-contaminated food or water; contact with dust from contaminated hides, fur, or feathers; consumption of infected animal products; or through the medium of insect vectors. Humans often are the definitive (final) host for zoonotic pathogens and usually are not a significant reservoir for reinfection of animal hosts. However, zoonotic diseases transmitted by blood-sucking arthropods are likely to be transmitted back to the species of the animal host.

TABLE 9.7

Examples of Zoonoses

Disease Infectious Agent Animal Reservoir Mode of Transmission
Viral
Rabies Lyssavirus spp. Bats, skunks, raccoons, foxes, dogs Direct contact via bite or scratch of infected animal
Hantavirus pulmonary syndrome Hantavirus spp. Rodents, primarily deer mice Inhalation of viruses from dried feces and urine or direct contact with rodent saliva, feces, or urine
Yellow fever Flavivirus spp. Monkeys Bite of Aedes mosquito
Influenza (some) Influenza virus Swine, birds Direct contact
Bacterial
Anthrax Bacillus anthracis Domestic livestock Direct contact with infected animals, inhalation
Brucellosis Brucella spp. Domestic livestock Direct contact with contaminated meat, milk, or animal
Lyme disease Borrelia burgdorferi Deer Tick bites
Rocky Mountain spotted fever Rickettsia rickettsii Rodents Tick bites
Typhus

Rodents Louse bites Bubonic plague Yersinia pestis Rodents Flea bites Leptospirosis Leptospira spp. Wild animals, domestic dogs and cats Direct contact with urine, soil, water Psittacosis (parrot fever) Chlamydia psittaci Birds, especially parrots Direct contact, bird droppings Salmonellosis Salmonella spp. Poultry, rats, reptiles Ingestion of contaminated food and water Fungal Ringworm

Domestic animals Direct contact Protozoan Malaria Plasmodium spp. Monkeys Bite of Anopheles mosquito Toxoplasmosis Toxoplasma gondii Cats and other animals Ingestion of contaminated meat, inhalation of pathogen, direct contact Helminthic Tapeworm infestation Dipylidium caninum Dogs Ingestion of larvae transmitted in dog saliva Fasciola infestation Fasciola hepatica Sheep, cattle Ingestion of contaminated meat Trichinellosis Trichinella spiralis Pigs, bears Ingestion of undercooked contaminated meat

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Modes of Transmission

Infectious diseases are transmitted either by a reservoir or via a portal of exit to a portal of entry of another host, or by autoinoculation (self-inoculation). Infectious agents can be transmitted to a host in many ways, including contact, vehicle, or vector transmission.

Contact Transmission

In contact transmission the pathogen is spread from one host to another either by direct contact, indirect contact, or respiratory droplets.

• Direct contact transmission involves direct physical contact of the infectious agent between hosts, such as by person-to-person contact; no intermediate object is involved. Common forms of direct contact transmission are touching, kissing, and sexual intercourse. Examples of pathogens transmitted this way include agents causing respiratory tract infections, staphylococcal infections, measles, scarlet fever, and sexually transmitted diseases. Zoonoses can also be transmitted from an animal reservoir to a human by direct contact through touching, biting, or scratching. Furthermore, direct transmission is possible within a single individual with poor personal hygiene when putting fingers in the mouth that are contaminated with fecal material.

• Indirect contact transmission occurs when the pathogen is transmitted from the reservoir to the susceptible host by a fomite—a nonliving object. Fomites can be tissues, handkerchiefs, towels, bedding, toys, clothes, diapers, money, eating utensils, drinking cups/glasses, medical equipment and devices, contaminated needles, and any other items that can harbor or transmit pathogens. Contaminated needles are a common fomite for the transmission of HIV and hepatitis B and C.

• Droplet transmission occurs when infectious agents are transmitted through respiratory droplets that travel a distance less than 1 meter. These droplets are released into the environment by normal exhaling, laughing, coughing, or sneezing. Sneezing is the most effective form of droplet transmission. Examples include the transmission of the common cold, influenza, pneumonia, and pertussis.

Vehicle Transmission

Any transmission of pathogens that require some sort of medium is considered a vehicle transmission. Modes of transmission in this category include airborne, waterborne, and foodborne transmissions, as well as transmission through bodily fluids and intravenous fluids. Foodborne, waterborne, and airborne diseases are also shown in the Healthcare Applications tables of Chapter 1 (Scope of Microbiology).

• Airborne transmission refers to the spread of pathogens by droplet nuclei (droplets of mucus), other aerosols, and dust that travel more than 1 meter from the reservoir to the host. Aerosols may originate from coughing or sneezing and from air conditioning and other cooling systems. Pathogens can attach themselves to dust particles and be transmitted by air via sweeping, mopping, changing of bed linens, changing of clothes, or simple dusting.

• Waterborne transmission generally occurs through untreated or poorly treated sewage. Many gastrointestinal diseases including giardiasis, amebic dysentery, and cholera are transmitted by water. Waterborne shigellosis and leptospirosis can also be transmitted via this route. Fecal–oral infections are the major source of diseases in the world as pathogens such as Schistosoma worms and enteroviruses are shed in feces, get into the water supply, subsequently enter the gastrointestinal mucosa or skin, and then cause disease elsewhere in the body.

• Foodborne transmission generally involves pathogens in or on foods that are incompletely cooked, poorly processed under unsanitary conditions, not refrigerated, or poorly refrigerated. This type of contamination can be by normal microbial flora, with zoonotic pathogens, and with parasitic worms that alternate between human and animal hosts. Viruses such as the hepatitis A virus can also be transmitted this way.

• Bodily fluid transmission needs to be considered, especially in healthcare workers, who must take precautions when handling these fluids, which can potentially be contaminated with pathogens. Blood, urine, saliva, and other bodily fluids can be reservoirs for different pathogens. Examples of diseases that can be transmitted via this route include AIDS, hepatitis, and herpes.

Vector Transmission

Vectors are animals, usually arthropods, that carry pathogens from one host to another. Vectors can transmit the pathogens either biologically or mechanically (Box 9.2).

Healthcare-associated (Nosocomial) Infections

Nosocomial infections are infections acquired in the course of treatment in a hospital or hospital-like setting, but secondary to the patient’s original conditions. Infections obtained by patients or healthcare providers while they are treated or working in a healthcare setting such as a hospital, clinic, nursing home, dental office, and other healthcare facility are referred to as healthcare-associated infections (HAIs). HAIs are among the top 10 leading causes of death in the United States. In the latest update (2009) by the CDC, it is estimated that in American hospitals alone HAIs account for an estimated 1.7 million infections and 99,000 associated deaths each year (Box 9.3).

The CDC developed the National Nosocomial Infections Surveillance (NNIS) system in the early 1970s to monitor the incidence of HAIs and their associated risk factors and pathogens. The purpose of the system is to help infection control professionals and hospitals stay up to date on the rapidly expanding science and practice of infection prevention and control, and to be able to better manage endemic and epidemic episodes of HAI. This voluntary system included approximately 300 hospitals in 2005, at which time it started to undergo a major redesign into a web-based knowledge management and adverse events reporting system. This system is now called the National Healthcare Safety Network (NHSN), and is a secure Internet-based surveillance system that integrates patient and healthcare personnel safety surveillance systems managed by the Division of Healthcare Quality Promotion (DHQP) at the CDC. Initially enrollment into the system was given to a limited number of facilities in 2005, followed by a national open enrollment for hospitals and outpatient hemodialysis centers in 2007.

Types of Nosocomial Infections

Healthcare facilities, by their very nature, are filled with sick people capable of shedding a variety of pathogens from different portals of exit. Furthermore, people with infections and/or diseases have a stressed, weakened, and often a compromised/suppressed immune system, making them even more susceptible to any infectious or opportunistic agents. Healthcare-associated infections can be categorized as exogenous, endogenous, and iatrogenic infections.

• Exogenous HAIs are caused by pathogens in the healthcare environment, shed from sick people.

• Endogenous infections are caused by microbes in the normal flora of a patient, which become pathogenic because of a variety of factors associated with the healthcare setting. These factors include the state of the patient’s immune system, immovability (bedridden), diet, and many others. Another factor is the use of antimicrobial drugs that may inhibit some of the normal flora, allowing the overgrowth of others, causing superinfections in the absence of the usual competition. Superinfections, however, are not limited to healthcare settings.

• Iatrogenic infections are a set of infections that may result from the use of medical procedures such as the use of catheters, invasive diagnostic procedures, and surgery.

Nosocomial infections can be caused by a variety of organisms (Table 9.8), some of which cause specific infections and disease; others have the capacity to cause a variety of infections, depending on their portal of entry. Bacteria that gain entrance to the bloodstream have the chance to settle at a site different from the site of entry if not treated promptly. Septicemia is less common, but can occur when surgery is performed on an infected area or an area where bacteria normally grow (i.e., intestine).

TABLE 9.8

Infectious Diseases That May Be Acquired in Healthcare Facilities

Pathogen Disease
Acinetobacter Variety, ranging from pneumonia to serious blood or wound infections
Blood-borne pathogens  
 Hepatitis B Hepatitis
 Hepatitis C Hepatitis
 HIV/AIDS HIV/AIDS
Burkholderia cepacia Respiratory infections, pneumonia, especially in patients with cystic fibrosis
Clostridium difficile Diarrhea, colitis
Clostridium sordellii Pneumonia, endocarditis, arthritis, peritonitis, myonecrosis, toxic shock syndrome (gynecologic infections)
Creutzfeldt-Jakob prion Creutzfeldt-Jakob disease
Ebola Viral hemorrhagic fever
Enteric bacteria Gastrointestinal infections
Hepatitis A Hepatitis
Influenza viruses Influenza
Methicillin-resistant Staphylococcus aureus (MRSA) Potentially life-threatening infections such as pneumonia, surgical site infection, bloodstream infections
Mumps virus Mumps
Norovirus Gastroenteritis
Parvovirus Erythema infectiosum (fifth disease)
Poliovirus Poliomyelitis (rare)
Rubella virus Rubella
Coronavirus SARS
Pseudomonas aeruginosa Infections in burn patients
Streptococcus pneumoniae (drug resistant) Meningitis, bacteremia, pneumonia, otitis media
Mycobacterium tuberculosis Tuberculosis
Varicella Chicken pox
Vancomycin-intermediate Staphylococcus aureus (VISA) Potentially life-threatening infections such as pneumonia, surgical site infection, bloodstream infections
Vancomycin-resistant enterococci (VRE) Various infections

SARS, Severe acute respiratory syndrome.

Transmission

Because of the large number and variety of pathogens in the healthcare environment and the compromised state of the patients, the routes and chain of transmission constitute an ongoing concern for healthcare providers and their patients. The principal routes of concern are as follows:

Therefore certain hospital areas are reserved for specialized care, including burn, hemodialysis, recovery, intensive care, and oncology units. Unfortunately, these environments also provide a risk for an epidemic spread of nosocomial infections from patient to patient.

Diagnostic and certain therapeutic procedures provide a possible route of transmission through fomites. For example, the urinary catheter, commonly used to drain the urinary bladder, is a fomite in many nosocomial infections. Intravenous catheters, used for the delivery of fluids, nutrients, or medication, need to penetrate the skin and can be a potential fomite for infection. Other potential fomites are the various components of respiratory equipment, needles, and surgical dressings. All these potential ways of transmission are the reason for the use of many control measures aimed at the prevention of nosocomial infections in the healthcare environment.

Antimicrobial Resistance in Healthcare Settings

Drug-resistant pathogens are becoming an increasing threat to the population (see Chapter 18, Emerging Infectious Diseases), particularly in healthcare settings. Of all patients with nosocomial infections in the United States, 99,000 annually die as a result of their infection. More than 70% of the bacteria causing these infections are resistant to at least one of the drugs commonly used to treat them. Persons infected with drug-resistant organisms generally have longer hospital stays and require second- or third-choice drugs that may be less effective and more toxic.

Control and Prevention

Each healthcare facility has a safety program, policies, and procedures (see Chapter 5, Safety Issues) that will include procedures and precautions designed to reduce the incidence of HAIs. These procedures are aimed at preventing the transmission of pathogens to patients and healthcare personnel. In general, these measures include disinfection, medical asepsis (good housekeeping, hand washing, bathing, sanitary food handling, proper hygiene, measures to prevent the spread of pathogens between patients), surgical asepsis, and isolation of contagious and particularly susceptible patients.

Any source of agents that can cause nosocomial infections must be kept clean and disinfected, including items such as humidifiers, which provide both a suitable environment for bacteria to grow and a method of airborne transmission. Furthermore, according to the CDC hand washing is the single most important means of preventing the spread of infection. It has been shown in several studies that effective hand washing by all medical and support staff significantly reduced (by 50%) deaths from nosocomial infections when the hospital personnel followed strict guidelines about washing their hands frequently. Unfortunately, it has been reported by the CDC that on average healthcare workers wash their hands only 40% of the time before interacting with patients.

All accredited hospitals have an infection control committee and most hospitals have at least one infection control nurse, epidemiologist, or specialized microbiologist. The role of these individuals is to identify problem sources such as improper adherence to hospital guidelines for disease prevention and control, and the occurrence of antibiotic-resistant strains of bacteria.

The CDC has published guidelines and recommendations for the prevention of healthcare-associated infections, including guidelines for the protection of patients, guidelines for the protection of healthcare workers, and other guidelines and recommendations for other topics dealing with infection control. All these guidelines are available at the CDC website.

Summary

• Under normal circumstances the newborn is initially exposed to microbes during birth, followed by many more exposures. This is the start of the development of a relationship between humans and microbes. The relationship between two different types of organisms is referred to as symbiosis, and, depending on the outcome of the relationship, symbiosis is classified as mutualism, commensalism, parasitism, or amensalism.

• Microorganisms that establish residency on the skin and in the mucous membranes that open to the external environment, and do not cause disease, represent the normal flora.

• Whenever the balance between the normal flora and the human host is interrupted, the microorganisms of the normal flora can cause infection and disease—they become opportunistic pathogens.

• Contamination is the presence of microbes in or on the body; it can result in infection and disease, and the microorganisms can enter the host via several possible portals of entry.

• After gaining entry into the host, the pathogen must undergo adhesion and several other steps to be able to cause an infection, but not all infections cause disease.

• Infections have varied patterns, and when an infectious agent causes pathological changes and interferes with the normal functioning of the body it is termed infectious disease; the study of the cause of the disease is called etiology.

• Robert Koch established a series of conditions—postulates—that must be met to identify a particular microbe as pathogenic and the cause of a particular disease. Although these postulates provide the basics of the etiology of an infectious disease, they are not always applicable.

• Epidemiology is the study of the distribution and causes of diseases in a population, and is the foundation for necessary interventions in the interest of public health. It is a subject of major importance for state and federal public health departments. Diseases in a population are reported as the prevalence of the disease, measured by incidence, which is the number of new cases over a certain period of time compared with the healthy population.

• For an infectious disease to continue to exist, its causative agent must have a permanent place to reside, a reservoir of infection. Infectious agents can be transmitted to a host by contact, vehicle, or vector transmission.

• Healthcare-associated (nosocomial) infections (HAIs) are infections acquired as a result of treatment or working in healthcare facilities. Healthcare facilities serve sick people, capable of shedding pathogens. Transmission of pathogens and the development of resistant strains in this setting are becoming an increasing problem to public health.

Review Questions

1. Which type of symbiosis benefits both members?

2. The mold that produces penicillin is an example of:

3. The presence of microbes in or on the body is a(n):

4. All of the following areas of the human body contain normal flora except the:

5. Bacterial endotoxins are:

6. When a pathogen spreads from the original site to other tissues or organs it is called a(n) ___________ infection.

7. A disease that is generally present in a given population is:

8. Which of the following is not considered to be a vehicle transmission?

9. Which of the following is likely to be the most frequently used portal of entry?

10. Infections that may result from the use of catheters are classified as:

11. The symbiotic relationship in which one of the organisms benefits and the other is not harmed or helped is referred to as __________.

12. A flora found in the same location as the resident flora, but which remains only for a given amount of time, is called a(n) __________ flora.

13. A microorganism capable of causing disease is called a(n) __________.

14. A vector that transmits pathogens and also serves as host for a part of the pathogen’s life cycle is a(n) __________ vector.

15. A worldwide epidemic is considered a(n) __________ disease.

16. Describe how microbes of a normal flora in the human body can become opportunistic pathogens.

17. Describe the three basic approaches used by epidemiologists to study the dynamics of a disease in a population.

18. Discuss Koch’s postulates and its limitations.

19. Describe the necessary steps a microbe must take before it can cause infection and disease.

20. Discuss healthcare-associated (nosocomial) infections (HAIs).

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