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

* 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

• Pathogenicity - The ability of an organism to cause a disease. A taxonomically significant attribute generally ascribed to a species.


Generally organisms referred to as pathogens have a high probability of causing an infection (and more reasonably should be called frank pathogens!), but under unusual circumstances any microorganism, even a non-pathogen, might be capable of causing an infection.
Virulence - The degree of pathogenicity. An attribute generally ascribed to a strain.

* 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.

• Leukocidins -- destroy phagocytic leukocytes, which then release their own digestive enzymes onto tissues. S. aureus and S. pyogenes.
• Hemolysins -- destroy RBC'S -- S. aureus, S. pyogenes and C. perfringes
• Coagulase -- makes a fibrin clot around the organism. -- S. aureus
• Bacteria kinases -- digest fibrin clots -- streptokinase and staphylokinase. can be used therapeutically to dissolve blood clots.
• Hyaluronidase -- dissolves hyaluronic acid
• Collagenase (gelatinase) -- dissolves collagen -- C. perfringes
• Siderophores -- scavenge iron

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

• Can be classified as CYTOTOXINS, NEUROTOXINS, ENTEROTOXINS.
• Diptheria toxin -- phage with TOX gene. Toxin inhibits protein synthesis in eukaryotic cells
• Erythrogenic toxin -- This is a SUPERANTIGEN -- host response causes fever and rash and damage to capillaries.
• Botulinum toxin -- hits the neuromuscular junction - No acetylcholine release - flaccid paralysis.
• Tetanus toxin (tetanospasm) -- hits the central nervous system - Inhibits the firing of the inhibitory motor neurons - Spastic paralysis.
• Cholera toxin (choleragen) -- Stimulates adenyl cyclase in the enterocytes - which then dump water and electrolytes into the small intestine.
• E. coli enterotoxin -- very similar to cholera toxin
• S. aureus enterotoxin -- has cholera like activity but is also a superantigen -- Activates T-cells to release a lot of interleukin-2 (IL-2) and Tumor necrosis factor (TNF).