Supplemental Lecture (98/05/09 update) by Stephen T. Abedon (abedon.1@osu.edu)

  1. Chapter title: Principles of Disease
    1. A list of vocabulary words is found toward the end of this document
    2. "A rather delicate balance exists between our defenses and the disease-producing mechanisms of microorganisms. When our defenses resist these disease-producing capabilities, we maintain our health. But when the disease-producing capability overcomes our defenses, disease results. After the disease has become established, an infected person may recover completely, suffer temporary or permanent damage, or die." (p. 366, Tortora et al., 1995)
  2. Disease
    1. A change away from a normal state of health to an abnormal state in which health is diminished.
  3. Sign
    1. A sign is an objective change in body function (e.g., health) that may be observed and measured by an individual in addition to the patient.
    2. Contrast with symptom.
  4. Symptom
    1. A symptom is a changes in body function felt by the patient.
    2. Symptoms are not measurable by a physician.
    3. Contrast with sign.
  5. Sequelae
    1. Residual effects of the disease process. Essentially the unrepaired wear and tear caused by a disease.
  6. Syndrome
    1. A collection of Error! Hyperlink reference not valid. and Error! Hyperlink reference not valid. that are characteristic of a disease or abnormality.
  7. Pathogen [parasite, pathogenesis, pathogenicity, pathology]
    1. Harmful symbiont:
      1. A pathogen is a symbiont that does more harm then good.
      2. A pathogen also may be described as a parasite.
    2. Pathogens are the cause of microbial (i.e., infectious) disease.
    3. Pathogenesis is the course of disease.
    4. Pathogencity is the degree to which a pathogen is capable of causing disease.
    5. Pathology is the study of disease.
  8. Koch's postulates
    1. Demonstrates pathogen causes disease:
      1. Koch's postulates were established by Koch in the late 1800s.
      2. They are also a means by which microorganisms may be established directly as causes of diseases in general (aseptic technique as a means of disease prevention is only circumstantial evidence that microorganisms cause disease).
      3. Koch's postulates are used particularly for demonstration that a specific pathogen is the cause of a specific disease.
    2. Koch's postulates:
      1. The following criteria must hold for a given microorganism to be considered the cause of a disease:
        1. the pathogen must be present in all hosts diagnosed with the disease
        2. the pathogen must be isolatable from the diseased host
        3. the pathogen must be purifiable
        4. the purified pathogen must cause the specific disease
        5. the pathogen must be isolated from the host used in step 4
        6. the pathogen in step 5 must be shown to be the same pathogen purified in step 3
  9. Problems with Koch's postulates
    1. There are a number of infectious diseases which adhere to the spirit of Koch's postulates but for which Koch's postulates, applied strictly, do not hold.
    2. The most common exceptions have to do with:
      1. an inability to culture the pathogen outside of the normal host
      2. a lack of suitable, especially non-human hosts that display the same symptoms
  10. Etiology of disease [etiologic agent]
    1. The etiology of a disease is a description of the cause of that disease (e.g., as addressed by Koch's postulates).
    2. Etiological agent:
      1. The agent responsible for the occurrence of a of microbial disease.
      2. Pathogens are the etiological agents of microbial disease.
  11. Infection [colonization]
    1. Body colonization:
      1. Infection is typically considered in terms of the colonization of the body by a disease-causing microorganism.
      2. (Note, however, that the term colonization actually has a specific meaning, i.e., the microorganism growth on epithelial tissues, and most pathogens cause disease by invading tissues, rather than growing on their surfaces.)
      3. "Infection refers to the multiplication of any parasitic organism within or upon the host's body. (Sometimes the term infestation is used to refer to the presence of larger parasites, such as worms or arthropods, in or on the body.) If an infection disrupts the normal functioning of the host, disease occurs." (p. 394, Black, 1996)
    2. However, there actually exist numerous variations on this infection theme including:
      1. symptomatic infection
      2. asymptomatic infection
      3. subclinical infection
      4. inapparent infection
      5. opportunistic infection
      6. local infection
      7. systemic infection
      8. focal infection
      9. primary infection
      10. secondary infection
      11. mixed infection
      12. acute infection
      13. chronic infection
      14. subacute infection
      15. latent infection
      16. bacteremia
      17. septicemia
      18. viremia
      19. intracellular infection
  12. Symptomatic infection
    1. Disease symptoms:
      1. An infection by a microorganism which results in some sort of expression of lack of health (i.e., disease) may be described as a symptomatic infection.
      2. Typically an infection is only apparent symptomatically if noticeable disease results.
      3. A symptomatic infection may lead to an asymptomatic infection or to a lack of infection.
  13. Asymptomatic infection
    1. No disease, yet:
      1. Colonization of the body by a microorganism that does not cause symptoms may be described as an asymptomatic infection.
      2. An asymptomatic infection may lead to a symptomatic infection or to a lack of infection.
      3. If the asymptomatic infection does not change in status over time, the microorganisms involved essentially have taken on a role of normal flora.
  14. Subclinical [inapparent] infection
    1. Subclinical or inapparent infections are simply asymptomatic infection by different names.
  15. Opportunistic infection
    1. Misplaced microorganism:
      1. An opportunistic infection involves the pathogenic colonization of one part of the body with a normally benign microorganism that usually resides in a different part of the body.
      2. See disease caused by opportunists below.
    2. septicemia may be caused by a bacterium that normally resides, for example, benignly in the large intestine or on the skin.
  16. Local infection
    1. A local infection is an infection that is limited to a small area of the body.
  17. Systemic infection
    1. A systemic infection is an infection that is found throughout the body.
  18. Focal infection
    1. Systemic infection/local origin:
      1. A focal infection is a systemic infection that originates from a local infection.
      2. In one sense, all systemic infections are focal infections since they have to start somewhere.
      3. However, focal infection implies some amount of temporal difference between the start of the local and the systemic infections.
    2. Local infection/global symptoms:
      1. Focal infection is also another way of saying that a local infection is responsible for symptoms occurring in some other locality in the body.
      2. For example, tetanus is caused by the release of exotoxin from a local infection.
  19. Primary infection
    1. One infecting microorganism might sufficiently weaken a host that the host is consequently susceptible to infection by additional microorganisms (e.g., opportunistic infection).
    2. The originally infecting microorganism in such a circumstance would be described as the etiological agent of the initial (i.e., primary) infection.
    3. Typically the primary infection is also an acute infection.
  20. Secondary infection
    1. Secondary infection is an infection that occurs because some initial (primary) infection has weakened the host.
  21. Mixed infection
    1. Some diseases are caused by the infection by more than one type of organism simultaneously. Such infections are called mixed infections.
  22. Acute infection
    1. An acute infection is an infection that develops rapidly and only lasts a short time.
  23. Chronic infection
    1. A chronic infection is an infection that develops slowly and lasts a long time.
  24. Subacute infection
    1. A subacute infection is an infection intermediate to acute and chronic.
  25. Latent infection
    1. Inactive infection:
      1. A latent infection is inactive though continuing to infect, and which remains capable of producing symptoms.
      2. "A latent disease is characterized by periods of inactivity either before signs and symptoms appear or between attacks." (p. 407, Black, 1996)
    2. Herpes viruses are examples of pathogens which readily enter a latent stage during which symptoms disappear, only to reappear at a later time upon the reactivation of the latent infection.
  26. Bacteremia
    1. Bacteremia refers to the presence of bacteria in the blood.
  27. Septicemia
    1. Septicemia refers to the presence of replicating bacteria in the blood.
  28. Viremia
    1. Viremia refers to the presence of viruses in the blood.
    2. Note that since viruses are obligate intracellular pathogents, it is often possible for viruses which do not infect blood cells to be present in the blood, but not actively replicating.
  29. Intracellular infection
    1. The word infection also refers to the colonization of individual cells, e.g., a viral infection of an individual cell refers to a virus replicating intracellularly (or at least having that potential).
  30. Types of microbial diseases
    1. Microbes can cause a number of different types of infections as outlined above.
    2. Microbes can also cause a number of categorically distinct (though not necessarily non-overlapping) types of diseases including:
      1. infectious disease
      2. communicable disease
      3. contagious disease
      4. noncommunicable disease
      5. disease caused by opportunists
  31. Infectious disease
    1. An infectious disease is a disease caused by a microorganism and therefore potentially infinitely transferable to new individuals.
    2. Note that the reason for my using the qualifier infinitely is that organisms are different from inanimate entities, such as poisons, because they have a way of fighting off dilution: they replicate.
  32. Communicable disease
    1. A communicable disease is an infectious disease that readily spreads from person to person.
    2. That is, just because a disease is infectious does not mean that it is easy to catch.
    3. A communicable disease is readily easily caught, especially from an infected person.
  33. Contagious disease
    1. A contagious disease is a very communicable disease, i.e., an infectious disease that very readily spreads from person to person.
  34. Noncommunicable disease
    1. Not typically spread from person to person:
      1. A noncommunicable disease is an infectious disease (i.e., with a microorganismal etiology) that is not typically spread from person to person.
      2. "Such diseases may result from (1) infections caused by an individual's normal microbiota, such as an inflammation of the abdominal cavity lining following rupture of the appendix; (2) poisoning following the ingestion of preformed toxins, such as staphylococcal enterotoxin, a common cause of food poisoning; and (3) infections caused by certain organisms found in the environment, such as tetanus, a bacterial infection resulting from spores in the soil gaining access to a wound." (p. 400, Black, 1996)
    2. A noncommunicable disease represents one end of the spectrum of communicability of infectious diseases.
    3. The distinction, not spread from person to person, is important since it implies not only that:
      1. individuals carrying the disease are not likely to spread the disease to others
      2. whatever led to the infection in such an individual likely did not include person to person contact
  35. Disease caused by opportunists
    1. Noncommunicable disease:
      1. A disease caused by an opportunistic infection is an example of a noncommunicable disease.
      2. Opportunist infections may be caused by pathogens that fail to cause disease when living in certain body sites in healthy individuals (i.e., are normal or transient flora), but can cause disease when located elsewhere on the body or under abnormal circumstances in their normal location.
    2. Immunocompromised = highly susceptible:
      1. Opportunists tend to cause disease especially in immunocompromised individuals.
      2. If the immunodepression is the result of an infectious disease then the infection by the opportunist would be called a secondary infection.
      3. Note that this overgrowth of opportunists in immunocompromised individuals suggests a role for the immune system in inhibiting the overgrowth of at least some normal flora.
  36. Periods of infectious disease
    1. Infectious disease tends to progress in broadly similar manners, passing through a number of roughly defined periods typically occurring in the following temporal order:
      1. period of incubation
      2. prodromal period/phase
      3. period of illness (illness phase)
      4. acme
      5. period of decline (decline phase)
      6. period of convalescence
    2. Expression of these periods varies with patient and pathogen.
    3. Note that though this order is typical, it may be circumvented and/or derailed via either:
      1. medical intervention
      2. the occurrence of mortality
      3. as a consequence of an individuals immune response
  37. Period of incubation
    1. Start to symptoms:
      1. The period of incubation is the interval occurring between the start of an infection and the appearance of symptoms.
      2. The patient is infected but does not yet know it.
    2. The length of the period of incubation is dependent on various host and pathogen characteristics.
    3. For many pathogens an infected individual can spread disease to others prior to realizing that they are sick.
  38. Prodromal period (phase)
    1. Beginning of symptoms:
      1. The prodromal period is a short interval in some diseases following the period of incubation.
      2. It is the beginning of appearance of symptoms
      3. The patient is starting to get sick.
    2. Acquired immunity:
      1. Note that in the case of acquired immunity against a pathogen the progress of disease may end during the prodromal period as a consequence of the rapid immune system response to the infection.
      2. For example, acquired immunity might be as a consequence of vaccination or previous natural exposure to the pathogen.
  39. Period of illness [illness phase]
    1. The period of illness, of course, is the time of greatest symptomatic experience (the patient is sick).
  40. Acme
    1. The peak of illness intensity is called the acme.
  41. Period of decline [decline phase]
    1. The period of decline occurs as pathogen replication is brought under control either by host immune response or through outside intervention.
    2. A subsidence of symptoms is experienced during this period.
    3. That is, the patient is getting better.
  42. Period of convalescence
    1. With the period of convalescence the pathogen replication has been stopped.
    2. This cessation of pathogen replication occurs either by the killing of all pathogens present or by killing all actively replicating individuals (i.e., all but latently infecting in the latter case).
    3. The body regains its pre-illness strength.
  43. Vocabulary
    1. Acme
    2. Acute infection
    3. Bacteremia
    4. Chronic infection
    5. Communicable disease
    6. Disease
    7. Etiology of disease
    8. Infection
    9. Infectious disease
    10. Focal infection
    11. Koch's postulates
    12. Latent infection
    13. Local infection
    14. Mixed infection
    15. Noncommunicable disease
    16. Opportunist
    17. Opportunistic infection
    18. Pathogenesis
    19. Pathogenicity
    20. Pathogen
    21. Pathology
    22. Period of convalescence
    23. Period of decline
    24. Period of illness
    25. Period of incubation
    26. Problems with Koch's postulates
    27. Prodromal period
    28. Secondary infection
    29. Septicemia
    30. Subacute infection
    31. Subclinical infection
    32. Systemic infection
    33. Viremia
  44. Practice questions
    1. Measles is an example of a disease which herd immunity (i.e., protection of a population against the epidemic spread of a disease as a consequence of the fraction of susceptible hosts being sufficiently small) has little effect. This implies that the ability of the measles virus to be transmitted from one host to another is very high. Measles especially is therefore an example of a (circle best answer) [PEEK]
      1. contagious disease
      2. communicable disease
      3. noncommunicable disease
      4. viremia
      5. all of the above
      6. none of the above
    2. A microorganism is isolated from a sick animal. The microorganism is grown in the laboratory. The same microorganism is subsequently isolated from two additional animals displaying the similar symptoms. Is this microorganism the cause of the disease afflicting these animals? Why? [PEEK]
    3. Give me an example of a circumstance that would cause problems for the successful application of Koch's postulates.[PEEK]
    4. A disease which is not spread from person to person but nevertheless is caused by a microbe is __________.[PEEK]
    5. A communicable disease that develops rapidly and just as quickly subsides could be called __________.[PEEK]
    6. During which of the following would you expect the host to appear most healthy? (choose best answer) [PEEK]
      1. period of convalescence
      2. prodromal period
      3. period of incubation
      4. period of illness
      5. period of decline
    7. In what way does septicemia differ from both bacteremia and viremia?[PEEK]
    8. In terms of your appearance of health, which of the following would most likely have the least impact? (choose best answer) [PEEK]
      1. an acute infection
      2. a chronic infection
      3. a subacute infection
      4. a subclinical infection
      5. any of the above
    9. Clostridium tetani is replicating within a deep puncture wound. Some exotoxin but no bacteria are entering the blood or lymph. Which of the following best describes this situation? (circle only one correct answer) [PEEK]
      1. secondary infection
      2. septicemia
      3. focal infection
      4. local infection
      5. all of the above
      6. none of the above
    10. Starting with two animals, one healthy and one sick with anthrax, tell me the steps you would have to go through in order to duplicate, in spirit at least, what Koch went through to prove that Bacillus anthracis is the anthrax etiology. [PEEK]
    11. Matching: Place letter in the appropriate blank: [PEEK]
      1. symptomatic infection
      2. primary infection
      3. period of incubation
      4. secondary infection
      5. focal infection
      6. chronic infection
      7. period of convalescence
      8. latent infection
      9. period of decline
      10. period of illness
      11. subclinical infection
      12. inapparent infection
      13. secondary infection
      14. noncommunicable disease
      15. acute infection
      16. opportunistic infection
      17. bacteremia
      18. septicemia
      19. local infection
      20. communicable disease
      21. subacute infection
      22. infectious disease
      23. contagious disease
      24. viremia
      25. asymptomatic infection
      26. prodromal period
  45. arises and subsides rapidly: __________.
  46. lack of health caused by microorganism which is poorly transmitted from person to person: __________.
  47. presence and replication of cellular microorganism in blood: __________.
  48. opportunistic infection of individual immunodepressed due to effects of additional infection: __________.
  49. synonymous with asymptomatic infection and inapparent infection: __________.
  50. infection very easily spread from person to person: __________.
  51. period during which microorganism replication has just begun but individual is not yet sick or showing symptoms: __________.
  52. an infection which comes on fast but seems to take forever to go away: __________.
  53. presence of acellular microorganism in blood: __________.
    1. Distinguish sign from symptom. [PEEK]
    2. Define focal infection. [PEEK]
    3. Is an acute infection necessarily a contagious disease? Why or why not? [PEEK]
    4. Describe a typical infectious diseases (from which the host recovers) in terms of its phases or periods, defining each period (or phase) as a function of degree of symptoms experienced and relative numbers of replicating microorganisms. [PEEK]
    5. Define acme. [PEEK]
    6. What is the name of the formal mechanism that would typically be employed to establish the etiology of a novel infectious disease? [PEEK]
    7. You feel sick so you go to a doctor. She tells you that you are sick because one microbe that normally lives in one location in your body (e.g., your large intestine), but does not cause disease there, is now growing in another location within your body and there is causing disease. Which is the best description of this disease? [PEEK]
      1. subclinical infection
      2. inapparent infection
      3. asymptomatic infection
      4. opportunistic infection
      5. systemic infection
    8. Contrast "period of incubation" with "prodromal period/phase," other than in terms of the order in which they tend to occur. [PEEK]
    9. A pimple is to septicemia as a local infection is to a(n) __________ infection. [PEEK]
    10. A(n) __________ infection is an infection that develops slowly and then lasts a long time. [PEEK]
    11. Distinguish mixed infection from secondary infection. [PEEK]
  54. Practice question answers
    1. i, contagious disease
    2. No, or, at least, not necessarily. Just because a microorganism may be isolated from a number of sick animals has little bearing on whether that microorganism is the etiological agent unless and until it can be demonstrated that that microorganism causes the disease by Koch's postulates. As far as we can tell, that hasn't been attempted in the example. For all we know, given the information provided, the microorganism isolated is a nonpathogenic member of the animal's normal flora.
    3. disease only affects humans, or microbes that can't be cultured in vitro.
    4. a noncommunicable disease
    5. an acute infection
    6. iii, period of incubation since by definition the host does not display any signs or symptoms of the infection, i.e., they are healthy.
    7. Septicemia refers to pathogen replication in the blood while the latter two refer only to the presence of the pathogen in the blood.
    8. iv, a subclinical infection since this by definition shows only minimal symptoms.
    9. iii, focal infection. This is a local infection the effects of which are manifest in other locations within the body (i.e., tetanus)
    10. (i) Isolate microbe from sick animal, (ii) purify microbe, (iii) identify characteristics associated with the purified microbe, (iv) infect healthy animal with purified microbe, (v) if animal gets sick (i.e., same disease), attempt to isolate and purify the same microbe from this second animal. If it is the same microbe as was purified and identified in steps (ii) and (iii), then you have successfully identified and purified the anthrax etiology. Basically this works out making sure that there exists a single organism, which you can isolate, identify, and then show that it not only can make a second animal sick with the same disease, but can also show that this same organism has replicated and/or is still present in the second animal.
    11. xv, xiv, , xviii, xiii, xi, xxiii, iii, xxi, xxiv.
    12. A sign can be measured by a physician while a symptom can be felt only by a patient, i.e., not measured by a physician.
    13. A local---i.e., contained, infection---which becomes systemic---i.e., enters the blood or lymph, either as a toxin or as a whole organism. In less technical terms, a local infection gone very bad.
    14. No! An acute infection is one which comes on fast and subsides, also rapidly. It need not be caused by a contagious pathogen. Indeed, it need not be a communicable disease since these terms concern only how the disease is acquired and not its time course.
    15. Period of incubation: relatively small numbers of replicating microorganisms and no symptoms; Prodromal period: more replicating microorganisms and some symptoms; Period of illness: Increasing numbers of replicating microorganisms, reaching a peak called the acme; Period of decline: decline in numbers of replicating microorganisms, decline in the symptomatic expression of the illness; Period of convalescence: no replicating microorganism, recovery from symptoms to state of health.
    16. The point of maximum symptomatic expression of a disease.
    17. Koch's postulates
    18. iv, opportunistic infection
    19. symptoms are lacking during the period of incubation but are present, to some extent at least, during the prodromal period
    20. systemic
    21. chronic
    22. A mixed infection is a disease caused by two microorganisms simultaneously infecting, for example, the vaginitis caused, in part, by Gardnerella vaginalis. A secondary infection is a second disease caused by a second microorganism.
  55. References
    1. Black, J.G. (1996). Microbiology. Principles and Applications. Third Edition. Prentice Hall. Upper Saddle River, New Jersey. pp. 392-412.
    2. Tortora, G.J., Funke, B.R., Case, C.L. (1995). Microbiology. An Introduction. Fifth Edition. The Benjamin/Cummings Publishing, Co., Inc., Redwood City, CA, pp. 369-373.