THIS WEEK IN ENVIRONMENTAL HEALTH

WEEK 3: SEPTEMBER 15 - 19, 1998

At the conclusion of today's session, you should:

1. Gain an appreciation for the impact that infectious disease has had on the history of the human race.

2. Know the importance of "new" infectious diseases.

3. Learn how microorganisms gain entrance into a host to cause disease.

4. Understand the mechanisms involved in order for microorganisms to cause disease.

5. Understand the cycle of a disease within a host, and its importance in the transmission of a disease.

pathogenicity --- the ability of a microorganism to harm the host by causing a disease.

infectivity --- a pathogen�s ability to establish infection in a host�s epithelial cells.

virulence --- the degree or intensity of pathogenicity

invasiveness --- the ability of a microorganism to establish residency in a host

portal of entry --- avenue by which a microorganism gains access to the body.

intracellular --- within a cell

extracellular --- outside of a cell

attachment (of a microorganism) --- process by which a microorganism adheres itself to a host cell in order to begin the disease process.

capsule --- a layer (usually made up of complexes of fatty acids and carbohydrates) on the outside of a bacterial cell wall that enables the microbe to withstand a host�s defenses.

enzyme --- a protein that enables a chemical action to occur more efficiently in a living organism.

leukocidin --- a bacterial enzyme that has the ability to kill certain white blood cells (WBCs) --- leukocytes.

hemolysin --- a bacterial enzyme that causes the disintegration of red blood cells (RBCs).

coagulase --- a bacterial enzyme that aids in clotting blood.

kinase --- a bacterial enzyme that breaks down protective blood clots in the healing process.

toxin --- a poisonous substance produced by a microorganism.

exotoxin --- protein toxin released from bacterial cells into the surrounding medium.

endotoxin --- part of the cell membrane of a bacterium, which, when released in a host, can cause disease.

reservoir (of infection) --- something that is a continual source of an agent of infection.

1. Match up the word with its correct definition:

_____ pathogenicity

_____ virulence

_____ invasiveness

a. the ability of a microorganism to establish residency in a host
b. the degree or intensity of pathogenicity
c. the ability of a microorganism to harm the host by causing a disease

2. Which of the following sequences represents the most common portals of entry into the body by microorganisms, causing disease in humans?

• a. The respiratory tract and parenteral routes
  
• b. The genitourinary tract and the gastrointestinal tract
  
• c. The respiratory tract and the gastrointestinal tract
  
• d. Parenteral routes and the genitourinary tract

3. T or F: Viruses are intracellular pathogens. (Why?)

4. Which group of the following "normal flora" bacteria of the human body are considered transient? Why?

• a. Normal flora of the large intestine
  
• b. Normal flora of the mouth
  
• c. Normal flora of the skin

5. In order for a bacterium to begin the disease process, it must first __________ itself to an epithelial cell in or on the body.

6. Bacteria can use which of the following bacterial cell products to cause disease and evade a host�s defenses (circle as many as needed):

• a. Capsule
  
• b. Enzymes
  
• c. Toxins
  
• d. Cytoplasm
  
• e. Pigments

7. Match up the following steps in the pattern (cycle) of a disease with its correct definition:

__________ Period of incubation
__________ Prodromal period
__________ Period of illness
__________ Period of decline
__________ Period of convalescence

a. Disease is most acute during this time
b. Body returns to its pre-disease state
c. Fever declines, and symptoms subside
d. Interval between actual infection and first symptoms
e. Shortest period of the cycle; may not be present in some diseases

8. Indicate which of the following properties best define exotoxins and which ones best define endotoxins. Place an "X" by an exotoxin characteristic, and an "O" by those that better describe an endotoxin.

_____ Is a protein.
_____ Produced almost always by Gram negative bacteria
_____ Can withstand heat
_____ Can produce a disease with very few bacteria
_____ Is considered to be the more potent (stronger) toxin of the two

9. List three diseases that can be considered "new" diseases within the last 30 years.

10. Identify three reasons why we still have epidemics today.

Preview/Review: The Role of Normal flora

Last time, we looked at microorganisms that are normally found on different surfaces of the body, both external and internal, and examined how they provide a primary defense against pathogens, or disease causing microorganisms.

These microbes can be transitory, as is the case with those found on the skin, when they are constantly being shed and are subjected to perspiration and body oils that are inhospitable to them.

Or, normal flora can become resident, forming a colonization, such as the organisms that are found in the mouth or large intestines.

So... what happens when a pathogen does break through this first line of defense with the body? How do they gain access to areas to infect, and how do they produce disease? This is what we will examine today.

We have seen how important microorganisms have been ... and still are... in the structure and function of both our physical and natural environments from the formation of the Earth. In recent history, i.e., the history of our species, the microbes are constantly proving a challenge to us. A prominent microbiology educator (Tom Terry, Uconn) has stated that: "Every disease is a race between a pathogen trying to gain a foothold and host defenses trying to prevent [disaster] from that pathogen."

Just how disastrous have microorganisms been throughout recorded history? Let�s take a look at this listing of a few selected ones from the Christian era....

(overhead & handout... "Plagues & Epidemics... ADD HANTAVIRUS (96) AND RESURGENT TB --- 1990�S)

When microorganisms cause disease conditions, the ability to harm the host by causing disease referred to as pathogenicity of a microorganism. Pathogenicity includes describing an organism�s infectivity (a pathogen�s ability to establish infection in a host); invasiveness (an organism�s ability to spread to other tissues in the body); and its virulence (the degree or intensity of pathogenicity). The invasiveness of a microbe is its ability to establish residence in a host, and as a result of metabolism and multiplication, causes structural damage to a host�s cells and metabolic reactions.

Please take a look at the diagram in your handout, "CYCLES OF INFECTION". We will be referring back to this throughout today�s lecture. As with any good story, there are always two sides to be presented, and we be looking at two sides to this saga --- one as seen by the microbe, and the other as viewed by the host.

1. Portals of Entry (Overview & Handout)

A portal of entry is the avenue by which a microbe gains access to the body. There are four that we will be looking at today:

a. The respiratory tract: This is the easiest and most frequently traveled access route for infectious organisms. Microbes are taken into the nose or mouth by the inhalation of drops of moisture and dust particles that contain them. Some diseases contracted via the respiratory tract are: the common cold; chicken pox; pneumonia, TB; influenza; and measles.

b. The gastrointestinal tract: Another easy way. Enter via ingestion of food, water, milk, and fingers. Most microbes are destroyed by acid and enzymes in the stomach, and bile and enzymes in the small intestine. However, those that do survive can cause such diseases as polio; hepatitis; typhoid fever; amebic dysentery; and cholera. These pathogens are eliminated through the feces, and may begin the cycle again in water, food or milk with which they come into contact.

c. Skin and mucous membranes: The majority of microorganisms cannot penetrate unbroken skin. (Exceptions: hookworm and Brucella), although some do infect the skin itself (ringworm). Microbes can gain access through hair follicles or sweat ducts, but this is rare. (Why? sweat and oil....)

However, bacteria and viruses can enter the body by penetrating the mucous membranes lining such areas as the conjunctiva, nose and mouth. However, in order to penetrate these surfaces, the microbes must first adhere themselves to the membranes. (We�ll discuss this process in a moment.) An important pathogen in this category is Treponema pallidum, the causative agent of syphilis.

d. The parental route: Access to the body by means of something puncturing the skin or membranes and depositing the microbes directly into tissue. This form of introduction is caused by punctures, injections, bites, cuts, wounds, surgery, indwelling instrumentation, or splitting due to swelling or drying.

It is an interesting fact that most organisms have a preferred route of entry, as Salmonella through the GI tract but not the respiratory; strep via respiratory, not GI. Some --- many ways. EX --- Plague (skin & respira) staph (respir, skin, GI)

2. Mechanisms of Disease

Most pathogens have evolved to live either inside or outside of the cells of the host; rarely, if ever, do they live in both habitats.

Intracellular pathogens -- This group includes all viruses and a few bacteria, as brucella or chlamydia or TB; some parasites, as malaria and pneumocystis; and a few fungi as histoplasma.

Problems for host --- Why it is difficult to fight off these pathogens:

� a. Host can�t readily attack the organism without doing damage to itself.

b. WBC�s --- a main line of defense in the host --- are frequently the very cells infected

Problems for pathogen ---

� a. In order to survive, must leave cells & host at some point... run risk of not having an available new host
b. Some can�t survive at all outside of host cells... must rely of some form of mechanical transfer by host (ex... anima bites; sexual contact)

� Extracellular pathogens --- Problems that exist....

Problems for pathogen ---

Constantly having to deal with defense mechanisms of host: WBC�s, immune system, etc.

� Problem for host ---

� More opportunities for organism to grow, reproduce, and spread
Organisms can rapidly colonize an area of the body. EX- cholera invades intestine, quickly multiples and covers a large surface area.

� a. Invasiveness of microorganisms

1. Attachment --- in order to invade a host (or cells within the host) a microorganism must bind itself to some receptor molecule on the host cell surface, and ligand, or adhesive substance, from the microbe itself. These receptors and ligands are very specific. for example, the HIV virus attaches itself only to the CD4 receptor on certain WBCs.

2. Capsules --- Some microorganisms form capsules outside of their cell walls. A capsule on a microorganism resists the host�s defenses to destroy it (specifically WBCs) by not allowing the WBC to adhere to the bacterial cell. EX-- Strep. pneumoniae, Hemophilus influenzae, Ps. aeruginosa)

3. Enzymes --- Some microorganisms produce enzymes (protein that catalyzes chemical reaction in a living organism) have the ability to alter the cells of the host, making the host more susceptible to infection. Some of these enzymes are:

� Leukocidins --- substances that have the ability to destroy certain types of WBCs, preventing the WBCs from "killing" the invading microbes. Some actually "kill" the WBC. EX --- Staph, strep
� Hemolysins --- Cause the lysis (breakage) of RBCs. EX -- Strep, staph. Cl. perfringens.
� Coagulases --- coagulate (clot) the blood. EX -- Some Staph.
� Kinases --- Opposite of above --- break down clots that the body has formed to help ward off the infection. EX -- strep, staph

b. Toxins --- In addition to invasiveness, many microbes produce toxins, substances which may be poisonous to their hosts. The capacity for microorganisms to produce toxins is called toxigenicity. Toxins can be transported by the blood or through the lymph system, and can cause serious, and sometimes fatal results. Some toxins produce fever, circulatory disturbances, diarrhea and shock. Toxins can inhibit protein synthesis; destroy blood cells and blood vessels and disrupt the nervous system by causing spasms and/or paralysis. There are two major types of toxins: exotoxins and endotoxins

(Overhead and handout --- toxins)

1. Exotoxins --- Produced by some bacteria as part of growth and metabolism, and are released into the surrounding medium (tissue, cells, etc.) Most bacteria that produce exotoxins are Gram positive. Most are proteins, can be destroyed by heat. Only a few organisms necessary to produce enough toxin to cause disease. (Botulinum == 1 pound purified can kill the world.) Diseases caused by these bacteria --- not the organism itself, but its toxin. High fatality rate, due to spasms and convulsions and paralysis and lysis. Protection can be produced in the form of antitoxins and toxoids.

Staph enterotoxin --- really a form of exotoxin, causes intestinal pathology, by not allowing absorption from the intestine = diarrhea, vomiting

2. Endotoxins --- Are usually part of the cell wall of Gram negative organisms. They are usually heat resistant, and require large numbers of organisms to be present to cause disease. Lower fatality rate than exotoxins. Most important clinical problems: fever and shock.

Cholera enterotoxin --- similar to staph, but need larger numbers to produce disease.

Other microorganisms, as viruses and fungi, cause disease in many different ways, depending upon the specific microorganism. To identify its means of pathogenicity, you would have to study each organism individually to understand the sequence of events leading up to the actual disease.

3. Pattern of Infection

A definite sequence of events occurs during infection and disease. First, there must be a reservoir for the infection. A reservoir is something that is a continual source of the agent of a particular infection, such as a contaminated water supply. Next, there must be transmission of the pathogen... either by direct or indirect contact. We have just discussed how a pathogen invades a host and begins an infection by causing some sort of injury to the host and evades defense mechanisms of the host.

All diseases follow a similar pattern of progress. The stages of this pattern include the following stages:

(Overhead --- )

Period of incubation --- (Refer back to earlier one) This is the time interval between the actual infection and the first appearance of any signs or symptoms. The incubation period in some diseases is constant; in others it is quite variable. The time of incubation depends on the specific microorganism involved, the virulence of the microorganism, the number of infecting microorganisms, and the resistance of the host.

� Prodromal period --- This is a relatively short period that sometimes follows the incubation period. During this time, a person might "just not fell well", due to general symptoms, as being tired; having a headache; general aches. Or, the symptoms can be specific, as a runny nose; sneezing.

� Period of illness --- During this time, the disease is most acute. The person exhibits overt signs and symptoms of the disease, such as high fever, chills, muscle pains, sore throat, lymph node enlargement, rash, gastrointestinal symptoms. It is during this period that increases/decrease of WBCs occur.

� Period of decline --- During the period of decline, the signs and symptoms subside. The fever decreases, and the person starts to feel less tired and "achy". If the period of decline is rapid, such as within 24 hours, it is said to occur by crisis. If it takes several days, with the fever decreasing a little each day until it returns to normal, then the period of decline is said to occur by lysis.

� Period of convalescence --- This is the period in which an individual regains strength and the body returns to its pre-disease state. Recovery has occurred.

� 4. Portals of Exit

In order to spread a disease among a population, a pathogen must exit the body. Just as pathogens have preferred portals of entry, they also have dentine routes of exit, called portals of exit . Usually these exit sites are related to the part of the body that has been infected.

Most common exits: respiratory and GI tracts. EX: From respiratory tract = coughs, sneezes. GI tract: saliva feces.

Also --- genital tract (STDs), urine (typhoid fever, paratyphoid fever, undulating fever); blood (HIV; hepatitis B & C)

Fomites and vectors --- wound infections; yellow fever and malaria; typhus.

Dr. Howard will later discuss the different ways in which the body protects itself against these microbes.

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