CHAPTER 14: HOST PARASITE RELATIONSHIPS

INTRODUCTION:
a) Healthy individuals are INFECTED and are being infected anew constantly.

b) Some of these organisms maybe PATHOGENS (more frequently among the transient flora group).
    Some among the normal flora may be OPPORTUNISTS.

c) Our relationship with microbes is very dynamic:
    THERE IS A BALANCE BETWEEN:
     The disease causing properties of the microbes <<--->> and the antimicrobial defenses of
     the host.

d) INFECTIOUS DISEASE is disease caused by pathogenic microorganisms.
    Pathogenic = disease causing}
    Virulence = degree or intensity of pathogenicity
    Disease = abnormal state, deviation from a state of wellness or health
    Contamination means that microorganisms are present.
    Infection, when parasitic microorganisms increase in number either within or on the body of the
                    host.

e) Whether or not you will catch a disease depends on:
        (1) YOU: your health, nutrition, immune status.
        (2) The pathogen's VIRULENCE
                (A) How TOXIC the organism is
                (B) How INVASIVE the organism is 


II. THE NORMAL FLORA
* The human adult is estimated to have 1013 human cells and 1014 bacterial cells.
* SEE your book for diagram of human body sites and chart of normal human flora organisms and their
    locations.
* In all honesty, we are a cylinder with a hole through the center. Just about every surface is colonized.
    There are aparse areas:

     - THE STOMACH - was thought to be free of organisms -- but recently shown that some
        organisms can survive --- Helicobacter pylori---- This is probably not considered normal flora
        since it is now known to cause ulcers.
    - THE BLADDER and the LOWER REACHES OF THE RESPIRATORY TRACT. These
        areas can be transiently infected but normal clearance mechanisms exist to get rid of the
        intruders.
    - We are colonized at birth with Lactobacillus.
    - Over time we acquire and establish populations of:
         * COLIFORMS - (Escherichia coli and other enteric gram negative rods) - intestines
         * Staphylococcus aureus, Staphylococcus epidermidis, Proprionibacterium acnes and
            other diptheroids - skin
         * Streptococci (viridans and pneumoniae) as well as some anaerobes - mouth
         * Lactobacilli - vagina

III. BENEFICIAL EFFECTS OF THE NORMAL FLORA
    1) Antagonism
        * Competition and the production of inhibitors (bacteriocins)
        * If normal flora is destroyed ex.:
            - Sthaphilococcal enteritis - S. aureus
            - Pseudomembrane colitis - Clostridium difficile
            - Candida infections - Thrush, vaginitis caused by antibiotics, douches and deodorants;

   2) Production of nutrients- Vitamins B and K in the intestines by E. coli
   3) Stimulate maturation of the immune system

    Note: The above are examples of mutualism
 

IV. REVIEW SYMBIOSIS, COMMENSALISM, MUTUALISM, PARASITISM

  • Mutualism is a symbiosis in which both members benefit from the relationship.
  • -Parasitisms are those relationships in which one member benefits, and the other one is harmed in

  •      some way.
      -Commensalism is a relationship in which one member benefits, and the other one neither benefits
        nor is harmed.

    * Imposed on the the idea of opportunism

        OPPORTUNISTS - These are organisms that normally don't cause disease but will if given an
            opportunity:
                - As in secondary infections
                - If resistance is low: - Pneumocystis carinii - pneumonia in immunocompromised
                     individuals. Neisseria miningitidis - meningitis in children, 5-15% carriage rate in
                     apparently healthy people.
                - If they get into the wrong place. Ex:  E. coli - Normally in the intestine, but if in the bladder
                    or peritoneal cavity - Big problem!. Susch as when one sees peritonitis after a ruptured
                    appendix. Also with E. coli one has different pathogenic variants such as  O157:H7 - This
                    is EHEC or enterohemorrhagic E. coli which produces powerful toxins responsible for
                    hemolytic uremic syndrome.

                - Streptococcus pneumoniae - Pneumonia after influenza or other respiratory tract infection
                    particularly  in the elderly people.
                - Candida albicans - Vaginitis and thrush
                - Pseudomonas aeruginosa - Infections of burns and infections of the lungs in cystic fibrosis
                - Staphilococcus aureus - Skin infection and toxic shock syndrome


    HOW TO DETERMINE IF AN ORGANISM IS THE ETIOLOGIC AGENT OF DISEASE

        REVIEW KOCH'S POSTULATES:
    1. The agent must be observed in every case of the disease.
    2. The agent must be isolated from a diseased host and grown in pure culture.
    3. When purified agent is inoculated into a healthy but susceptible host, it must cause the same
        disease.
    4. The agent must be reisolated from the newly infected, diseased host, and be identical to the
        previously identified causative agent.

    Note: Identification of disease agents, according to the postulates requires growing the organism; this can be difficult or impossible for some: Treponema pallidum, Mycobacterium leprae, and so this cannot be an inflexible approach.


    CLASSIFYING INFECTIOUS DISEASES.

    How they behave within a population?
    I. Spread within a population
    1) COMMUNICABLE DISEASES = CONTAGIOUS, easily spread from host to another either
        directly or indirectly, ex.: influenza, common cold, tuberculosis, chicken pox, measles, genital
        Herpes. Note: NOT all communicable diseases are equally contagious).  Contagiousness depends
        on several factors.

    2) NON-COMMUNICABLE DISEASES a disease that is not spread from one host to another.
    ex.: tetanus, food poisoning, subacute bacterial endocarditis, etc.

    II) Frequency in a population:
    a) Epidemiology: study of factors and mechanisms governing spread of disease within a population,
        incidence, spread, control, prevention. (what, how, when).

    Diseases in a population:
    a) Sporadic disease: outbreak occurs in population occasionally and at irregular intervals eg, many
        gastrointestinal diseases from contaminated food. (Typhoid fever)
    b) Endemic disease: constantly present at low level eg, colds
    c) Epidemic disease: outbreak occurs in unusually high numbers in a population eg, mumps in
        elementary schools, influenza.
    d) Pandemic disease: epidemic over a large geographical area (such as the world). eg, worldwide
        influenza outbreak in 60s; AIDS.

    TERMS TO DEFINE DISEASE IN A POPULATION.
    a) Incidence: # of people in a population with new cases over a specific period of time. This term
        reflects the spread of the disease. (1992 AIDS had a 8% incidence)
    b) Prevalence: Total # of cases of disease in a population at any given time.  This term reflects how
        sick the population is. (1992 AIDS prevalence was 19%).
    c) Morbidity: Occurrence of a disease in a population over a defined period of time. Expressed as a
        rate # new cases in population in a period / total population.600 in 10,000 = 6%.

    SEVERETY OR DURATION OF DISEASE:
    a) Duration:
    1) Acute disease develops rapidly but ends shortly (influenza, herpes)
    2) Chronic disease slow development but continuous for long period of time (TB, infectious
        mononucleosis [EBV], hepatitis B
    3) Latent disease agent remains inactive then reactivates (TB, toxoplasmosis, shingles [VZV])

    b) Severity:
    1) Local VS systemic infectious agent remain in one area in the body (abscesses in teeth, skin
        infections) or they can be spread through the body by the blood (measles, chicken pox).
    2) Primary vs secondary acute infection that causes initial illness or caused by an opportunistic
        pathogen after body weakened by initial infection.
    3) Bacteremia vs septicemia bacteria are present in the blood. When bacteria are actually growing
        and dividing in the blood.

    DISEASE PRESENTATION:
    a) Symptoms (subjective) pain, dizziness, aches, etc. Commonly felt by the patient.
    b) Signs (objective) fever, swelling, paralysis, vomiting, etc.  Commonly observed by a physician.
    c) Syndrome a combination of both symptoms and signs.
     

    HOSPITAL ACQUIRED INFECTIONS
        * 5-15% of all patients will suffer these
        * Most common organisms: E. coli, Klebsiella, Proteus, and S. aureus.

    Nosocomial infections -- Hospital acquired infections are especially fearsome because:
            - Many hospital organisms are resistant to antibiotics
            - Patients are immuno compromised  (By disease, injury, or chemotherapy)
            - There are many invasive procedures
            - Chain of transmission

    THE DEVELOPMENT OF DISEASE:
    1. The incubation period - initial infection and the first appearance of signs or symptoms.
    2. The prodromal period -short duration. Period of initial mild sign or symptoms.
    3. The period of illness -period of maximum presentation of signs and symptoms.
    4. The period of decline -signs and symptoms start to decline.
    5. The period of convalescence - regain strength


    SPREAD OF INFECTION IN A POPULATION
    * Need to know the reservoir and mode of trasnmission

    a) RESERVOIR - Can think of the reservoir as the source of the organism
        1) Human source:
             Sick human -- Acute illness (rapidly developing and often rapid resolution -  get better or die.
                                   Ex:  influenza, chicken pox, cholera, strep throat.

             Carrier human -- Inapparent infections, subclinical infection, chronic infection. Ex: tuberculosis,
                                    Epstein-Barr infection (mononucleosis), syphilis, HIV infection, Hepatitis B

        2) Animal source: wild animal (sylvatic)? domestic?
              Zoonosis -- primarily an animal disease and then spread to humans. Examples of diseases with
                                a significant animal reservoir: rabies, plague, leptospirosis, lyme disease,
                                Toxoplasmosis, psittacosis, salmonella food poisoning

        3) Non-living source:
             - a) Soil harbors organisms that cause a variety of infectious diseases. Ex: tetanus, botulism,
                anthrax, Pseudomonas infections, a variety of fungi.
             - Water is often contaminated and can serve as a vehicle of infection. Ex. giardiasis, typhoid
                fever, amebiasis, leptospirosis -- note that water is easily contaminated by human and animal
                feces.

    MODE OF TRANSMISSION

    1. CONTACT TRANSMISSION:
        a) Direct contact -- Touch, kiss, sex, animals
        b) Indirect: - Fomites (Inanimate objects that serve as means of spread) -- doorknobs, towels,
            phones, needles and other medical equipment.
        c) Droplet transmission: droplet nuclei - travel short distances - Important in many
                respiratory infections (see picture Tortora pg. 407)

    2. VEHICLE TRANSMISSION:
        a) Waterborne --  oral-fecal transmission
        b) Foodborne -- unproperly cooked, fecal contamination
        c) Airborne -- droplet nuclei in dust -- must travel more than 1 meter.

     3. Vector -- and infected animal (usually an insect) that transmits to humans
            - Biological transmission -- The animal host is needed by the microbe for some metabolic or
                other essential process. Ex.: malaria protozoan- mosquito; Lyme disease spirochete -- tick;
                sleeping sickness protozoan -- tsetse fly; the plague bacterium -- flea and rodent (rat)
            - Mechanical transmission -- the animal host host picks up the microbes and moves them
                around. Ex.: flies landing on feces or dead animals. cockroaches and lizards rats can do the
                same thing.


    THE VIRULENCE FACTORS OF MICROORGANISMS

        a) PATHOGENICITY vs. VIRULENCE
    * This involves INVASIVE FACTORS and TOXICITY FACTORS

    * Organisms have to get in first (How?) -- The portals of entry:
            - Mucous membranes - mouth, nose, eyes, respiratory tract, GI, GU.
            - Breaks in the skin
            - Breaks into the tissues below the skin into the tissues, veins, or arteries --PARENTERAL
     

    Development of disease:
    2) ORGANISMS HAVE TO ADHERE -- THEY HAVE ADHESINS

     CAPSULE -- HELPS TO ATTACH BUT ALSO IMPEDES PHAGOCYTOSIS.
        ex.:Streptococcus  pneumoniae, Klebsiella pneumoniae, Streptococcus mutans - dextran and
        tooth decay.

     FIMBRIAE (PILI) -- ARE OFTEN TISSUE SPECIFIC.  ex.: E. coli strain differences in tissue
        specificity due to different types of fimbriae - urinary tract strains differ from enteropathogenic
        strains in the type of pili they  make. Whooping cough bacterium - Bordetella pertusis attaches
        specifically to repiratory epithelium cilia.

     Neisseria gonorrhea - has pili and outer membrane proteins that allow it to stick to urethral and
        vaginal epithelium, non-ciliated fallopian tube cells, sperm cells and neutrophils; Streptococcus
        pyogenes - protein F attaches to pharyngeal epithelium, protein M attaches to keratinocytes in the
       skin both proteins are are part of the fimbriae of these organisms.

    THE CELL WALLS OF SOME BACTERIA HAVE VIRULENCE PROMOTING
        PROPERTIES.   ex.: Streptococcus pyogenes - protein G binds to the back end of antibodies
        preventing their normal function - this is a CLOAKING DEVICE for the bacterial cell and it helps
        the cell avoid phagocytosis. Staphylococcus aureus has protein A - which works the same way.
        Mycobacterium tuberculosis has wax D and sulfolipids which inhibit the killing mechanisms of
        phagocytes.

    The outer membrane of Gram negative organisms (endotoxin, LPS, contains lipid A). The structure
        is shed periodically but in large scale when the organism dies. Profound effect on humans: fever,
        weakness, aches, schock, hemorrhage,etc. These effects are caused by the release of interleukin
        (IL)-1 and tumor necrosic factor (TNF) by macrophages.
     

    BACTERIAL ENZYMES ASSOCIATED WITH VIRULENCE - many are exoenxymes or
        secreted enzymes.


    a) BACTERIAL TOXINS -- EXOTOXINS (many are enzymes)

    Some bacteria have enzymes and properties that allow them to survive inside phagocytic cells. These include Mycobacterium tuberculosis, Salmonella typhi, and Neisseria gonorrhea.

    b) The outer membrane of Gram negative organisms (endotoxin, LPS, contains lipid A). This structure is sloughed off during the life of the organism and is shed in large scale when the organism dies. Has profound toxic effects on the human. can result in fever, weakness, aches, shock, hemorrhage, miscarriage, disseminated intravascular coagulation. These effects are caused by the release of interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha  by macrophages in an apparent over-reaction. These are cytokines which affect many aspects of the inflammatory and immune responses.

    The landmark of endotoxemia are: 1) Fever and 2) Toxic shock.