31 Infection and Pathogenicity CHAPTER OVERVIEW This chapter focuses on infection and pathogenicity. The development of a disease state is a dynamic process that is dependent on the virulence of the pathogen and the resistance of the host. This dynamic process is illustrated in the discussions of viral and bacterial pathogenesis. Modes of transmission and development of diseased states are presented. The chapter includes a discussion of mechanisms used by viruses and bacteria to evade host defenses. CHAPTER OBJECTIVES After reading this chapter you should be able to: discuss the general characteristics of parasitic symbiosis discuss the concepts of pathogens, disease, infection, and infectious disease describes the modes by which pathogens are transmitted describe the stages that pathogens usually go through in order to cause disease distinguish exotoxins from endotoxins describe the modes of action of various toxins describe the mechanisms used by viruses and bacteria to evade host defenses CHAPTER OUTLINE I. II. Host-Parasite Relationships A. A parasitic organism is one that lives at expense of its host; any organism that causes disease is a parasite B. Infection—the state occurring when a parasite is growing and multiplying on or within a host 1. Infectious disease—a change from a state of health as a result of an infection by a parasitic organism 2. Pathogen—any parasitic organism that produces an infectious disease 3. Pathogenicity—the ability of a parasitic organism to cause a disease 4. Primary pathogen—organism that causes disease in a healthy host by direct interaction 5. Opportunistic pathogen—organism that is normally free-living or part of the host’s normal microbiota, but adopts a pathogenic role under certain circumstances (host weakness) C. Some infectious organisms can enter a latent state; this can be intermittent (e.g., cold sores) or quiescent (e.g., chickenpox/shingles) D. The final outcome of most host-parasite relationships is dependent on three main factors: 1. The number of pathogenic organisms present 2. The virulence of the organism 3. The host’s defenses or degree of resistance E. Virulence—the degree or intensity of pathogenicity of an organism The Infectious Disease Process A. Characteristic patterns of an infectious disease 1. Signs—objective changes in the patient (e.g., fever, rash) 2. Symptoms—subjective changes in the patient (e.g., pain, loss of appetite 3. Disease syndrome—set of signs and symptoms characteristic of a disease 4. Incubation period—the period after pathogen entry but before signs and symptoms appear 5. Prodromal stage—onset of signs and symptoms but not yet clear enough for diagnosis 6. Period of illness—disease is most severe and has characteristic signs and symptoms 7. Period of decline (convalescence)—signs and symptoms begin to disappear B. Source or reservoir 1. Source—location from which organisms are immediately transmitted to the host 332 2. Period of infectivity—the time during which the source is infectious or is disseminating the organism 3. Reservoir—site or natural environmental location where organism is normally found 4. Carrier—an infected individual who is a potential source of a pathogen; can be convalescent, healthy, or incubatory; can be acute, transient, or chronic carriers 5. Zoonoses—infectious diseases that occur in animals and can be transported to humans; the animals serve as a reservoir for the disease; transmission from animal to host can be direct or indirect; vectors are organisms that spread disease from one host to another C. Pathogen transmission 1. Airborne transmission—suspended in air; travels a meter or more a. Droplet nuclei—may come from sneezing, coughing, or vocalization b. Dust particles—may be important in airborne transmission because microorganisms adhere readily to dust 2. Contact transmission—touching between source and host; direct (person to person)involves physical interaction between infected person and host 3. Vehicle transmission—inanimate materials or objects are involved in transmission a. Common vehicle transmission—a single vehicle serves to spread the pathogen to multiple hosts, but does not support its reproduction b. Fomites—common vehicles such as surgical instruments, bedding, eating utensils c. Food and water also are common vehicles 4. Vector-borne transmission—living transmitters, such as arthropods or vertebrates a. External (mechanical) transmission—passive carriage of the pathogen on the body of the vector with no growth of the pathogen during transmission b. Internal transmission—carried within the vector 1) Harborage—pathogen does not undergo morphological or physiological changes within the vector 2) Biologic—pathogen undergoes morphological or physiological changes within the vector D. Infectious dose 1. Size of initial inoculum affects rate at which infection proceeds and its severity 2. Infectious dose 50 (ID50)—number of microorganisms required to cause clinical disease in 50% of inoculated hosts E. Growth rate 1. Successful colonization requires favorable growth conditions 2. Intracellular parasites grow within host cells a. Facultative intracellular parasites can grow within cells or the environment b. Obligate intracellular parasites can only grow in host cells F. Host susceptibility—depends on defense mechanisms of the host and the pathogenicity of the pathogen G. Exiting the host—must be able to leave host or disease cycle will be interrupted and the bacterium will not be perpetuated 1. Active escape—movement of pathogen to portal of exit (e.g., many helminths 2. Passive escape—excretion in feces, urine, droplets, saliva, or desquamated cell III. Virulence A. Virulence is the magnitude of harm (pathogenicity) caused by a particular microorganism; intrinsic characteristics that contribute to pathogenicity are called virulence factors B. Pathogenicity islands 1. Large segments of DNA that carry virulence genes acquired during evolution by horizontal gene transfer; are not present in nonpathogenic members of same genus or species 2. Have unique sequence characteristics including several open reading frames with putative genes, a different G + C content than the host, and insertion-like elements at their ends F. Virulence factors 1. Adherence and colonization a. Bacterium must be able to adhere to and colonize (but not necessarily invade) host cells and tissue 333 b. G. H. Depends on ability of bacterium to successfully adhere to host and compete with normal microbiota for essential nutrients c. Adherence structures such as pili, fimbriae, and specialized adhesion molecules that facilitate attachment to host cell receptors are important virulence factors 2. Invasion a. Infectivity—ability of an organism to establish a focal point of infection b. Invasiveness—ability of an organisms to spread to other tissues c. Penetration of the host’s epithelial cells or tissues 1) Pathogen-associated mechanisms involve the production of lytic substances that: (i) Attack the ground substance and basement membranes of integuments and intestinal linings (ii) Degrade carbohydrate-protein complexes between cells or on cell surfaces (iii) Disrupt cell surfaces 2) Passive mechanisms of entry involve: (i) Breaks, lesions, or ulcers in the mucous membranes (ii) Wounds, abrasions, or burns on the skin surface (iii) Arthropod vectors that penetrate when feeding (iv) Tissue damage caused by other organisms d. Invasion of deeper tissues can be accomplished by production of specific products or enzymes that promote spreading (these are one type of virulence factor) or by entry into the circulatory system; presence of bacteria in the blood is bacteremia; septicemia is when toxins in the blood cause the disease process Resisting host defenses 1. Successful infection by a microorganism requires that it avoid host immunity 2. Some pathogens infect immune cells and diminish their function; others avoid phagocytosis with mucoidy capsules or specialized surface proteins 3. In some cases, pathogens use strategies to prevent detection by antimicrobial proteins 4. Some microorganisms survive inside host cells or can escape from hosts and spread 5. Many pathogens avoid the immune system by changing surface antigens, producing capsules that resemble the host, or producing enzymes that degrade host proteins that bind bacteria 6. Biofilm communities bring microorganisms together enhancing nutrient acquisition, safety from predators, and protection from the immune system and antibiotics Toxins 1. Toxigenicity—the capacity of an organism to produce a toxin 2. Intoxications—diseases that result from the entry of a specific toxin into the host; Toxins are specific substances, often a metabolic products of the organism, that damage the host in some specified manner 3. Exotoxins a. Soluble, heat-labile proteins produced by and released from a pathogen; generally associated with gram-positive bacteria; may damage the host at some remote site b. Toxins can be inactivated by neutralizing antibodies (antitoxins) or by chemical means that create immunogenic toxoids (used for vaccines) c. Can be grouped into four types based on structure and physiological activities 1) AB toxins can be separated into two distinct portions: one that binds the host cell and one that causes toxicity (e.g., diphtheria toxin—binds host cell surface receptor by the B portion and is taken into the cell by the formation of clathrin-coated vesicles; toxin is then cleaved, releasing A fragment, which enters cytosol; the A fragment inhibits protein synthesis) 2) Specific host site exotoxins: neurotoxins damage nervous tissue (e.g., botulinum toxin and tetanus toxin), enterotoxins damage the small intestine (e.g., cholera toxin), and cytotoxins do general tissue damage (e.g., shiga toxin); some host-sitespecific exotoxins are also AB toxins (e.g., cholera toxin) 3) Membrane-disrupting exotoxins—two subtypes, those that bind cholesterol in the host cell membrane and then form a pore ( e.g., leukocidins and hemolysins) and those that are phospholipases (e.g., gas gangrene-associated toxin) 334 4) I. J. Superantigens—pathogen proteins (e.g., staphylococcal enterotoxin) that provoke massive cytokine releases, causing endothelial cell damage, circulatory shock, and multiorgan failure 4. Endotoxins—LPS of many gram-negative bacteria a. Released only when the microorganism lyses or divides b. Usually capable of producing fever, septic shock, blood coagulation, weakness, diarrhea, inflammation, intestinal hemorrhage, and/or fibrinolysis; many of these effects are indirect and are mediated by host molecules and cells (e.g., macrophages, endogenous pyrogens, host cytokines) Mycotoxins—Secondary metabolites in fungi commonly found in food crops and water-damaged buildings; include aflatoxin from Aspergillus (liver damage and cancer), satratoxins from Stachybotrys (inhibit DNA, RNA, and protein synthesis), and ergot alkaloids from Claviceps (hallucinogen) Measuring virulence—determined as lethal dose 50 (LD50), the number of pathogens that kills 50% of hosts in a specified period of time; a variety of virulence also can be measured TERMS AND DEFINITIONS Place the letter of each term in the space next to the definition or description that best matches it. a. adhesins ____ 1. An organism that supports the growth of a parasitic b. antitoxin organism c. bacteremia ____ 2. A host that is used by a parasitic organism as a vehicle for d. endogenous pyrogen reaching a final host e. endotoxin unit ____ 3. A host infected by a parasitic organism that can also f. endotoxins infect humans g. exotoxins ____ 4. The colonization of a host by a parasitic organism h. fomites i. hemolysins j. host k. infection l. infectious disease m. infectivity n. intoxications o. invasiveness p. leukocidins q. LPS-binding proteins r. opportunistic pathogen s. pathogen w pathogenic potential x. primary (frank) pathogen y. reservoir z. reservoir host aa. septicemia bb. toxemia cc. toxigenicity dd. toxin ee. toxoids ff. transfer host gg. vector hh. virulence ii. virulence factors 335 ____ 5. ____ 6. ____ 7. ____ 8. ____ 9. ____ 10. ____ 11. ____ 12. ____ 13. ____ 14. ____ 15. ____ 16. ____ 17. ____ 18. ____ 19. ____ 20. ____ 21. ____ 22. ____ 23. ____ 24. ____ 25. ____ 26. ____ 27. ____ 28. ____ 29. ____ 30. ____ 31. ____ 32. A change from a state of health due to the presence of an t pathogenic potential organism or its products in the host u. primary (frank) pathogen An organism that causes infectious disease v. reservoir An organism that causes disease in a healthy host by a w. reservoir host direct interaction x. septicemia An organism that causes disease only when the host’s y. toxemia resistance is impaired z. toxigenicity The degree or intensity of pathogenicity aa. toxin The ability of a pathogen to spread to adjacent or other bb. toxoids tissues cc. transfer host The ability of a pathogen to establish a focal point of dd. vector infection ee. virulence The degree that a pathogen causes damage ff. virulence factors A pathogen’s ability to produce toxins Organisms (e.g., insects) that transfer pathogens from one host to another A place where a pathogen lives before and after causing an infection Inanimate objects that harbor and transmit pathogens Molecules on the surface of a pathogen that mediate attachment to host cells or tissues Products or structural components of a pathogen that contribute to its virulence or pathogenicity The presence of viable bacteria in the bloodstream Disease caused by the presence of pathogens or bacterial toxins in the blood Diseases that result from the entry of preformed toxins into the body of the host A substance, often a metabolic product of the organism, that alters the metabolism of host cells with deleterious effects on the host The conditions caused by toxins that have entered the blood of the host Soluble proteins that are released by a pathogen into the host; they may damage the host at some site remote from the site of infection Antibodies capable of neutralizing toxins Chemically altered forms of toxins that are immunogenic but are no longer toxic Toxins that kill leukocytes Toxins that kill erythrocytes Substances that are part of the cell wall of gram-negative bacteria and cause toxic reactions A substance released by macrophages during infection that triggers fever Proteins in the plasma membranes of macrophages and monocytes that bind endotoxin A unit of measure used to indicate the level of endotoxin contamination in drugs, media, or other products. FILL IN THE BLANK 1. 2 3. 4. By convention, an organism that causes harm or that lives at the expense of another organism is called a __________ organism; when just the term __________ is used, it refers to harmful protozoa and helminths. The relationship between a harmful organism and its host is called . If the harmful organism lives on the surface of its host, it is called an ____________; while if it lives within its host, it is called an ____________. Some pathogens release substances that kill leukocytes. These are called ____________. Many pathogens possess mechanical, chemical, or molecular abilities to damage the host and cause disease. Based on the way damage occurs, two distinct categories of disease can be recognized. If the disease is due to the pathogen’s growth, metabolism, reproduction, or tissue alterations, it is called an __________ disease. However, if the disease results from the entry of a preformed toxin into the host, it 336 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. is called an ____________. The term ____________ is used if specific symptoms are caused by toxins in the blood of the host. Soluble proteins produced and released by an organism that can act at sites remote from the site of infection are called ____________. They are divided into four types based on their structure and physiological activities. One type is the toxin, which has two parts, one that binds the target cell and another that has toxic activity. A second type may also have this structure, but is distinguished by its specificity for certain host sites. Those toxins that target the nervous system are called ____________; those that cause cell death are called ____________; and those that damage the intestinal tract are referred to as ____________. A third type does not have two different portions. These toxins target cell membranes and are called __________ __________. The fourth type is the superantigen that stimulates T cells to release cytokines. Many bacteria have large segments of DNA, called , that carry genes responsible for virulence. An example of virulence genes carried this way is a set of genes that code for proteins of . Viruses are usually spread throughout the body by the bloodstream and lymphatic system. The presence of viruses in blood is called . As viruses are spread, they specifically infect certain cells, tissues, and organs. These specificities are called . The term __________ refers to the ability of an organism to cause disease. The term __________ refers to the intensity of this ability and it is measured experimentally by the __________ (the dose of pathogens that kills 50% of an experimental group of hosts) or by the __________ (the dose of pathogens that infects 50% of an experimental group of hosts. A number of bacterial pathogens produce , which lyse red blood cells. This can be observed by culturing the bacteria on blood agar plates. A complete zone of clearing around a bacterial colony is called __________ __________, and a partial clearing is called __________ __________. A is an illness caused by a pathogen that can be transmitted from an infected host or (site where the pathogen is normally found). The immediate location from which the pathogen is transmitted to a host (either directly or through an intermediate) is called the ____________. A is an infected individual who can transmit a pathogen to other hosts. If the infected individual has an overt clinical case of the disease, the individual is referred to as an ____________ carrier. If the person has recovered from the infectious disease but can still transmit the pathogen, the person is referred to as a ____________ carrier. If the individual can transmit the organism but is not ill, the individual is a ____________ carrier. If the individual is not yet ill but will become ill, the individual is referred to as an ____________ carrier. The spread of a pathogen in the air for a meter or more from the source is called ____________ ____________. The transmission of pathogens by a coming together or a touching of the source and the host is called ____________ transmission. Living transmitters of pathogens are called ____________, and this method of transmission is called __________ transmission. If the pathogen is carried within the transmitter’s body and does not undergo morphological or physiological changes, this is called ____________ transmission, and if the pathogen does undergo morphological or physiological changes, this is called ____________ transmission. MULTIPLE CHOICE For each of the questions below select the one best answer. 1. Which of the following has no effect on the outcome of the host-parasite relationship? a. the number of parasites on or in the host b. the virulence of the parasite c. the defenses of the host d. All of the above affect the outcome of the host-parasite relationship. 2. 3. 337 What is an organism that transmits a parasitic organism from one host to another called? a. fomite b. vector c. transmitter d. carrier Which of the following is a membranedisrupting exotoxin? a. b. c. d. e. 4. 5. 6. 7. leukocidin streptolysin-O streptolysin-S phospholipase All of the above are membranedisrupting exotoxins. Which of the following is a factor that helps determine the virulence of a pathogen? a. invasiveness b. infectivity c. pathogenic potential d. All of the above are correct. Which of the following is NOT a mode of action associated with endotoxins? a. shock b. paralysis c. diarrhea d. All of the above are modes of action associated with endotoxins. When is endotoxin released from a gramnegative bacterium? a. when the bacterium lyses b. when the bacterium reproduces c. Both (a) and (b) are correct. d. Neither (a) nor (b) is correct. Neisseria gonorrhoeae uses a mechanism called serum resistance to evade host defenses. Which host defense is evaded by this mechanism? a. formation of the membrane attack complex b. phagocytosis c. destruction within a phagosome d. the action of secretory IgA 8. Which of the following is a large segment of DNA that carries virulence genes acquired through gene transfer? a. fomite b. pathogenicity island c. peripheral transducer d. immune complex 9. Which term refers to carriers that harbor a pathogen for only a brief time (hours, days, or weeks)? a. casual carriers b. acute carriers c. transient carriers d. All of the above are this type of carrier. 10. Which of the following is NOT normally a way that humans or animals introduce airborne organisms into the air? a. sneezing b. evaporation of sweat c. coughing d. vocalization (talking) 11. Which of the following does NOT refer to inanimate objects involved in the transmission of disease-causing organisms? a. vectors b. vehicles c. fomites d. All of the above refer to inanimate objects involved in the transmission of disease-causing organisms. TRUE/FALSE ____ 1. ____ 2. Parasitic organisms are metabolically dependent on their hosts. Some pathogens have mechanisms that allow them to penetrate into host epithelial cells, while others can enter only if the epithelial cells have been damaged by other means (wounds, insect bites, etc). ____ 3. Generally, exotoxins tend to be more heat stable than endotoxins. ____ 4. A pathogen is generally found in the area of the host’s body that provides the most favorable conditions for its growth and reproduction. ____ 5. Endotoxin effects can be mediated by cytokines released from monocytes and macrophages to which the endotoxin has bound. ____ 6. Colonization specifically refers to the multiplication of a pathogen on or within a host. ____ 7. For most pathogenic bacteria, many clonal types exist in the environment. ____ 8. Genes for virulence are expressed constitutively. ____ 9. Exotoxins can cause disease only after the bacterium colonizes its host. ____ 10. Pathogens that are spread by direct contact tend to be more virulent than those that are vectorborne. ____ 11. Direct contact spread of a pathogen implies that there is actual physical contact between the current host and the new host. Therefore, transfer of a respiratory pathogen by a sneeze or a cough is not considered direct transmission. 338 ____ 12. In order to maintain its life cycle, a pathogen must escape from the host either passively (i.e., secreted out of the host in feces, urine, droplets, salvia, or desquamated cells) or actively (pathogen moves on its own to a portal of exit and then escapes). ____ 13. The manifestations of an infectious disease are the same in all hosts belonging to the same species. 339 TYPES OF INFECTIONS ASSOCIATED WITH PARASITIC ORGANISMS Using your own words, complete the following table by describing each type of infection. Type of Infection Description Acute Bacteremia Chronic Latent Localized Opportunistic Primary Secondary Sepsis Septicemia Septic shock Subclinical (unapparent or covert) Systemic Toxemia Zoonosis 340 CRITICAL THINKING 1. Compare and contrast exotoxins and endotoxins. Discuss the chemical and physiological characteristics of the molecules, as well as their mechanisms of pathogenesis. 2. Describe the different mechanisms by which pathogens can be transmitted. Which type of transmission seems the most effective in causing large outbreaks? Pathogens transmitted by which mechanism might be the most easily controlled and eliminated? ANSWER KEY Terms and Definitions 1. j, 2. cc, 3. w, 4. k, 5. l, 6. s, 7. u, 8. r, 9. ee, 10. o, 11. m, 12. t, 13. z, 14. dd, 15. v, 16. h, 17. a, 18. ff, 19. x, 20. c, 21. n, 22. aa, 23. y, 24. g, 25. b, 26. bb, 27. p, 28. i, 29. f, 30. d, 31. q, 32. e Fill in the Blank 1. parasitic; parasite 2. parasitism; ectoparasite; endoparasite 3. leukocidins 4. infectious; intoxication; toxemia 5. exotoxins; AB; neurotoxins; cytotoxins; enterotoxins; membrane-disrupting exotoxins 6. pathogenicity islands; secretion systems 7. viremia; tropisms 8. pathogenicity; virulence; LD50; ID50 9. hemolysins; beta hemolysis; alpha hemolysis 10. communicable disease; reservoir; source 11. carrier; active; convalescent; healthy; incubatory 12. airborne transmission 13. contact 14. vectors; vector-borne; harborage; biologic Multiple Choice 1. d, 2. b, 3. e, 4. d, 5. b, 6. c, 7. a, 8. b, 9. d, 10. b, 11. a True/False 1. T, 2. T, 3. F, 4. T, 5. T, 6. T, 7. F, 8. F, 9. F, 10. F, 11. F, 12. T, 13. F 341