DMT1104

Some

diseases-such as polio, Lyme disease, and tuberculosis have a well-known etiology. Some have an etiology that is not completely understood
E.g. the relationship between certain viruses and cancer.
For

still others, such as Alzheimer disease, the etiology is unknown.

 Koch

showed that a specific infectious disease (anthrax) is caused by a specific microorganism (B. anthracis) that can be isolated and cultured on artificial media. He later used the same methods to show that the bacterium Mycobacterium tuberculosis is the causative agent of tuberculosis.

 Koch's

research provides a framework for the study of the etiology of any infectious disease. Koch's postulates
The same pathogen must be present in every case of the

disease. The pathogen must be isolated from the diseased host and grown in pure culture. The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible laboratory animal. The pathogen must be isolated from the inoculated animal and must be shown to be the original organism.

 Exceptions
For

to Kochs Postulates

example, some microbes have unique culture requirements.

The bacterium Treponema pallidum is known to cause

syphilis, but virulent strains have never been cultured on artificial media. The causative agent of leprosy, Mycobacterium leprae, has also never been grown on artificial media. Moreover, many rickettsial and viral pathogens cannot be cultured on artificial media because they multiply only within cells

 Modifications

to Koch's postulates and use of alternative methods of culturing and detecting certain microbes.
For example, when researchers looking for the

microbial cause of legionellosis ( Legionnaires disease) were unable to isolate the microbe directly from a victim, they took the alternative step of inoculating a victim's lung tissue into guinea pigs.

 In

a number of situations, a human host exhibits certain signs and symptoms that are associated only with a certain pathogen and its disease. But some infectious diseases are not as clearcut and provide another exception to Koch's postulates.

 For

a disease to perpetuate itself, there must be a continual source of the disease organisms. This source can be either a living organism or an inanimate object that provides a pathogen with adequate conditions for survival and multiplication and an opportunity for transmission. Such a source is called a reservoir of infection.

 Human

reservoirs

Many people harbor pathogens and transmit them

directly or indirectly to others. People with signs and symptoms of a disease may transmit the disease Then there are those that do that present with any signs----these are called carriers

 Human

carriers play an important role in the spread of such diseases as AIDS, diphtheria, typhoid fever, hepatitis, gonorrhea, amoebic dysentery, and streptococcal infections.

 Animal

Reservoirs

Both wild and domestic animals are living reservoirs of

microorganisms that can cause human diseases. Diseases that occur primarily in wild and domestic animals and can be transmitted to humans are called zoonoses

Disease Viral Influenza West Nile encephalitis

Causative agent

Reservoir

Transmission due to

Influenzavirus Lyssavirus Flavivirus

Swine, birds Bats, skunks, dogs Horse, birds

Direct contact Direct contact (bite) Aedes and Culex mosquito

Hanta pulmonary syndrome

Bacterial Plague Cat-scratch disease Rocky Mountain spotted fever Salmonellosis

Hantavirus

Rodents(deer mice)

Direct contact with rodent saliva, urine, feces

Yersinia pestis Bartonella henselae Rickettsia enterica Salmonella enterica

Rodents Domestic cats Rodents Poulttry, reptiles

Flea bites Direct contact Tick bites Ingestion of contaminated food and/or water

Disease Edemic typhus Fungal Ringworm

Causative agent Rickettsai typhi

Reservoir Rodents

Transmission due to Flea bites

Trichophyton Microsprum Epidermophyton

Domestic mammals

Direct contact; fomites (nonliving objects)

Protozoan
Malaria Plasmodium spp. Monkeys Anopheles mosquito bite

Toxoplasmosis

Toxoplasma gondii

Cat and other mammals

Ingestion of contaminated meat or by direct contact with infected tissues or fecal matter
Ingestion of uncooked contaminated pork

Helmintic Tapeworm (pork)

Taenia solium

Pigs

 Nonliving

Reservoirs

The two major nonliving reservoirs of infectious disease are

soil and water. Soil harbors such pathogens as fungi, which cause mycoses such as ringworm and systemic infections; Clostridium botulinum, the bacterium that causes botulism; and C. tetani, the bacterium that causes tetanus. Because both species of clostridia are part of the normal intestinal microbiota of horses and cattle, the bacteria are found especially in soil where animal feces are used as fertilizer.

 Water that has been contaminated by the feces of

humans and other animals is a reservoir for several pathogens, notably those responsible for gastrointestinal diseases.

 The

causative agents of disease can be transmitted from the reservoir of infection to a susceptible host by three principal routes:
Contact Vehicles, and Vectors

 Spread

of an agent of disease by direct contact, indirect contact, or droplet transmission.

Direct contact Person-to-person Direct transmission of an agent by physical contact between its source and a susceptible host; no intermediate object is involved
E.g. viral respiratory diseases

The most common forms of direct contact transmission are touching, kissing, and sexual intercourse.

 Indirect

contact transmission

Occurs when the agent of disease is transmitted from its

reservoir to a susceptible host by means of a nonliving object. The general term for any nonliving object involved in the spread of an infection is a fomite. Examples of fomites are tissues, handkerchiefs, towels, bedding, diapers, drinking cups, eating utensils, toys, money, and thermometers

 Droplet

transmission

Microbes are spread in droplet nuclei (mucus droplets)

that travel only short distances. These droplets are discharged into the air by coughing, sneezing, laughing, or talking and travel less than 1 meter from the reservoir to the host. One sneeze may produce 20,000 droplets. Examples of diseases spread by droplet transmission are influenza, pneumonia, and pertussis (whooping cough).

 The

transmission of disease agents by a medium, such as water, food, or air.

Other media include blood and other body fluids,

drugs, and intravenous fluids.

In

waterborne transmission, pathogens are usually spread by water contaminated with untreated or poorly treated sewage. Diseases transmitted via this route include cholera, waterborne shigellosis, and leptospirosis.

 In

food borne transmission, pathogens are generally transmitted in foods that are incompletely cooked, poorly refrigerated, or prepared under unsanitary conditions. Foodborne pathogens cause diseases such as food poisoning and tapeworm infestation.

 Airborne

transmission refers to the spread of agents of infection by droplet nuclei in dust that travel more than 1 meter from the reservoir to the host. For example, microbes are spread by droplets, which may be discharged in a fine spray from the mouth and nose during coughing and sneezing
These droplets are small enough to remain airborne for

prolonged periods.

 The

virus that causes measles and the bacterium that causes tuberculosis can be transmitted via airborne droplets. Dust particles can harbor various pathogens.
Staphylococci and streptococci can survive on dust and be

transmitted by the airborne route.

Spores

produced by certain fungi are also transmitted by the airborne route and can cause such diseases as histoplasmosis, coccidioidomycosis, and blastomycosis

 Arthropods

are the most important group of disease vectors-animals that carry pathogens fro m one host to another. Arthropod vectors transmit disease by two general methods. Mechanical transmission is the passive transport of the pathogens on the insect's feet or other body parts

 If

the insect makes contact with a host's food, pathogens can be transferred to the food and later swallowed by the host. Houseflies, for instance, can transfer the pathogens of typhoid fever and bacillary dysentery (shigellosis) from the feces of infected people to food.

 Biological

transmission is an active process and is more complex.

The arthropod bites an infected person or animal and

ingests some of the infected blood The pathogens then reproduce in the vector, and the increase in the number of pathogens increases the possibility that they will be transmitted to another host.

 Some

parasites reproduce in the gut of the arthropod; these can be passed with feces.
If the arthropod defecates or vomits while biting a potential

host, the parasite can enter the wound.

Other

parasites reproduce in the vector's gut and migrate to the salivary gland; these are directly injected into a bite. Some protozoan and helminthic parasites use the vector as a host for a developmental stage in their life cycle.

 To

cause disease, most pathogens must gain access to the host, adhere to host tissues, penetrate or evade host defenses and damage the host tissues. microbes do not cause disease by directly damaging host tissue but instead, disease is due to the accumulation of microbial waste products

Some

 Some

microbes, such as those that cause dental caries and acne, can cause disease without penetrating the body.
can gain entrance to the human body and other hosts through what are called portals of entry.
The portals of entry for pathogens are mucous

Pathogens

membranes, skin, and direct deposition beneath the skin or membranes (the parenteral route).

 The

majority of bacteria and viruses gain access to the body by penetrating mucous membranes lining the respiratory tract, gastrointestinal tract, genitourinary tract, and conjunctiva
pathogens enter through the mucous membranes of the gastrointestinal and respiratory tracts.

Most

Microorganisms can gain access to the gastrointestinal tract in food and water and via contaminated fingers.
Most microbes that enter the body in these ways are destroyed by hydrochloric acid (HCL) and enzymes in the stomach or by bile and enzymes in the small intestine.

Microbes in the gastrointestinal tract can cause poliomyelitis, hepatitis A, typhoid fever, amoebic dysentery, giardiasis, shigellosis (bacillary dysentery), and cholera.

 The

genitourinary tract is a portal of entry for pathogens that are contracted sexually. microbes that cause sexually transmitted infections (STls) may penetrate an unbroken mucous membrane. require a cut or abrasion of some type.

Some

Others

Examples

of STIs are HlV infection, genital warts, chlamydia, herpes, syphilis, and gonorrhea.

The skin is the largest organ of the body in terms of surface area and weight and is an important defense against disease.
Unbroken skin is impenetrable by most microorganisms.

Some microbes gain access to the body through openings in the skin, such as hair follicles and sweat gland ducts.
Larvae of the hookworm actually bore through intact skin, and

some fungi grow on the keratin in skin or infect the skin itself.

 The

conjunctiva is a delicate mucous membrane that lines the eyelids and covers the white of the eyeballs.
it is a relatively effective barrier against infection, certain diseases such as conjunctivitis, trachoma, and ophthalmia neonatorium are acquired through the conjunctiva.

Although

Mos gain access to the body when they are deposited directly into the tissues beneath the skin or into mucous membranes when these barriers are penetrated or injured.
Punctures, injections, bites, cuts, wounds, surgery, and splitting of the skin or mucous membrane due to swelling or drying can all establish parenteral routes. HIV, the hepatitis viruses and bacteria that cause tetanus and gangrene can be transmitted parenterally.

 If

only 3 few microbes enter the body, they will probably be overcome by the host's defenses.
if large numbers of microbes gain entry, the stage is probably set for disease. the likelihood of disease increases proportional to the number of pathogens.

However,

Thus,

 This
The

relates to the virulence of the mo

virulence of a microbe is often expressed as the ID50 (infectious dose for 50% of a sample population). 50 is not an absolute value; rather, it is used to compare relative virulence under experimental conditions.

The

 Bacillus

anthracis can cause infection via three different portals of entry.

The ID50 through the skin (cutaneous anthrax) is 10 to

50 endospores; The ID50 for inhalation anthrax is inhalation of 10,000 to 20,000 endospores; The ID50 for gastrointestinal anthrax is ingestion of 250,000 to 1,000,000 endospores.

 The

potency of a toxin is often expressed as the LD50 (lethal dose for 50% of a sample population ).
example, the LD50 for botulinum toxin in mice is 0.03 ng/kg; for Shiga toxin, 250 ng/kg; and staphylococcal enterotoxin, 1350 ng/kg.

For

 Almost

all pathogens have some means of attaching themselves to host tissues at their portal of entry. For most pathogens, this attachment, called adherence This adherence is accomplished throught the use of
Adhesins or ligands Bind specifically to complementary surface receptors on the cells of certain host tissues

 Examples:

Streptococcus mutans, a bacterium that plays a key role

in tooth decay, attaches to the surface of teeth by its glycocalyx.

An enzyme produced by S. mutans, called glucosyltransferase, converts glucose into a sticky polysaccharide called dextran, which forms the glycocalyx. Actinomyces bacterial cells have fimbriae that adhere to the glycocalyx of S. mutans. The combination of S. mutans, Actinomyces, and dextran make up dental plaque and contribute to dental caries

 Capsules

The capsule resists the host's defenses by impairing

phagocytosis, the process by which certain cells of the body engulf and destroy microbes E.g. the polysaccharide capsule of Streptococcus pneumoniae, the causative agent of pneumococcal pneumonia, allows this bacterium to exert its virulence Other bacteria that produce capsules related to virulence are Klebsiella pneumoniae, a causative agent of bacterial pneumonia

 Haemophilus influenzae, a cause of pneumonia and

meningitis in children; Bacillus anthracis, the cause of anthrax; and Yersinia pestis, the causative agent of plague.

 Cell

wall components

The cell walls of certain bacteria contain chemical

substances that contribute to virulence For example, Streptococcus pyogenes produces a heatresistant and acid-resistant protein called M protein The M protein mediates attachment of the bacterium to epithelial cells of the host and helps the bacterium resist phagocytosis by white blood cells.

 Neisseria gonorrhoeae grows inside human epithelial

cells and leukocytes. These bacteria use fimbriae and an outer membrane protein called OpA to attach to host cells.
The waxy lipid (mycolic acid) that makes up the cell

wall of Mycobacterium tuberculosis also increases virulence by resisting digestion by phagocytes, and can even multiply inside phagocytes.

 Enzymes

The virulence of some bacteria is thought to be aided

by the production of extracellular enzymes (exoenzymes) and related substances. These chemicals can digest materials between cells and form or digest blood clots, among other functions. Examples of enzymes produced by mos
Coagulases are bacterial enzymes that coagulate (clot) the fibrinogen in blood, e.g. staphylococci

 Bacterial

kinases are bacterial enzymes that break down fibrin and thus digest clots formed by the body to isolate the infection .
E.g. Fibrinolysin (a streptokinase) produced by

streptococci such as Streptococcus pyogenes; and staphylokinase.

Hyaluronidase

is another enzyme secreted by certain bacteria, such as streptococci.

It hydrolyzes hyaluronic acid, a type of polysaccharide that

holds together certain cells of the body, particularly cells in connective tissue.

 Another

enzyme, collagenase produced by several species of Clostridium, facilitates the spread of gas gangrene.
Collagenase breaks down the protein collagen, which

forms the connective tissue of muscles and other body organs and tissues.

 Antigenic

Variation

In the presence of antigens the body produces proteins

called antibodies, which bind to the antigens and inactivate or destroy them. However, some pathogens can alter their surface antigens, by a process called antigenic variation.

 Penetration

into host cytoskeleton

A major component of the cytoskeleton is a protein

called actin, which is used by some microbes to penetrate host cells and by others to move through and between host cells.

 If

a pathogen overcomes the host's defense, then the microorganism can damage host cells in four basic ways: 1. By using the host's nutrients; 2. By causing direct damage in the immediate vicinity of the invasion; 3. By producing toxins, transported by blood and lymph, that damage sites far removed from the original site of invasion; 4. By inducing hypersensitivity reactions.

 Using

Host Nutrients

When a pathogen needs iron, siderophores are released

into the medium where they take the iron away from iron-transport proteins by binding the iron even more tightly. Once the iron-siderophore complex is formed, it is taken up by siderophore receptors on the bacterial surface.

 Direct

Damage

Once pathogens attach to host cells, they can cause direct

damage as the pathogens use the host cell for nutrients and produce waste products. As pathogens metabolize and multiply in cells, the cells usually rupture.
Many viruses and some intracellular bacteria and protozoa that grow in host cells are released when the host cell ruptures.

Some bacteria, such as E. coli, Shigella, Salmonella, and

Neisseria gonorrhoeae, can induce host epithelial cells to engulf them by a process that resembles phagocytosis.

Production

of Toxins

Toxins are poisonous substances that are produced

by certain microorganisms The capacity of microorganisms to produce toxins is called toxigenicity. Toxins transported by the blood or lymph can cause serious, and sometimes fatal, effects.

 Toxins can produce fever, cardiovascular disturbances,

diarrhea, and shock, inhibit protein synthesis, destroy blood cells and blood vessels, and disrupt the nervous system by causing spasms
Exotoxins

Produced inside some bacteria as part of their growth

and metabolism and are secreted by the bacterium into the surrounding medium or released following lysis Produced by either Gram-positive or Gram-negative bacteria

 Exotoxins work by destroying particular parts of the

host's cells or by inhibiting certain metabolic functions. Diseases caused by bacteria that produce exotoxins are often caused by minute amounts of exotoxins, not by the bacteria themselves When exotoxins are inactivated by heat or by formaldehyde, iodine, or other chemicals, they no longer cause the disease but can still stimulate the body to produce antitoxins.

 Diphtheria Toxin Corynebacterium diphtheriae produces the diphtheria toxin

only when it is infected by a lysogenic phage carrying the tox gene. This cytotoxin inhibits protein synthesis in eukaryotic cells.
Erythrogenic Toxins Streptococcus pyogenes has the genetic material to

synthesize three types of cytotoxins, designated A, B, and C. These are superantigens that damage the PM of blood capillaries under the skin and produce a red skin rash. Scarlet fever, caused by S. pyogenes exotoxins, is named for this characteristic rash.

 Botulinum

Toxin

It is produced by Clostridium botulinum Although toxin production is associated with the

germination of endospores and the growth of vegetative cells, little of the toxin appears in the medium until it is released by lysis late in growth. It acts at the neuromuscular junction (the junction between nerve cells and muscle cells) and prevents the transmission of impulses from the nerve cell to the muscle.

 Tetanus

Toxin

Clostridium tetani produces tetanus neurotoxin, also

known as tetanospasmin. This A-B toxin reaches the central nervous system and binds to nerve cells that control the contraction of various skeletal muscles The result is uncontrollable muscle contractions, producing the convulsive symptoms (spasmodic contractions) of tetanus, or "lockjaw."

 Endoloxins

differ from exotoxins in several

ways.
Endotoxins are part of the outer portion of the cell wall

of gram-negative bacteria Endotoxins are released when gram-negative bacteria die and their cell walls undergo lysis, thus liberating the endotoxin. Endotoxins are also released during bacterial multiplication

 Endotoxins

do not promote the formation of effective antitoxins against the carbohydrate component of an endotoxin.
Antibodies are produced, but they tend not to counter the

effect of the toxin; sometimes, in fact, they actually enhance its effect
Representative mos that produce endotoxins are Salmonella typhi (the causative agent of typhoid fever), Proteus spp. (frequently the causative agents of urinary tract

infections), Neisseria meningitidis (the causative agent of meningococcal meningitis)