Infection and Disease.pdf

7/30/2019 Infection and Disease.pdf

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DMT1104


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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.


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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 bacteriumMycobacterium tuberculosis is

the causative agent of tuberculosis.


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Koch's research provides a framework for thestudy of the etiology of any infectious disease.

Koch's postulates

The same pathogen must be present in every case of thedisease.

The pathogen must be isolated from the diseased host andgrown in pure culture.

The pathogen from the pure culture must cause the disease

when it is inoculated into a healthy, susceptible laboratoryanimal.

The pathogen must be isolated from the inoculated animaland must be shown to be the original organism.


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Exceptions to Kochs Postulates

For example, some microbes have unique culture

requirements. The bacterium Treponema pallidum is known to cause

syphilis, but virulent strains have never been cultured onartificial media.

The causative agent of leprosy,Mycobacterium leprae, hasalso never been grown on artificial media.

Moreover, many rickettsial and viral pathogens cannot becultured on artificial media because they multiply onlywithin cells


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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.


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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 clear-

cut and provide another exception to Koch's

postulates.


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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.


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Human reservoirs

Many people harbor pathogens and transmit them

directly or indirectly to others.

People with signs and symptoms of a disease maytransmit the disease

Then there are those that do that present with any signs-

----these are called carriers


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Human carriers play an important role in the

spread of such diseases as AIDS, diphtheria,

typhoid fever, hepatitis, gonorrhea, amoebic

dysentery, and streptococcal infections.


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Animal Reservoirs

Both wild and domestic animals are living reservoirs of

microorganisms that can cause human diseases.

Diseases that occur primarily in wild and domesticanimals and can be transmitted to humans are called

zoonoses


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Disease Causative agent Reservoir Transmission due to

Viral

Influenza InfluenzavirusLyssavirus

Swine, birdsBats, skunks, dogs

Direct contactDirect contact (bite)

West Nile

encephalitis

Flavivirus Horse, birds Aedes and Culex

mosquito

Hanta pulmonary

syndrome

Hantavirus Rodents(deer mice) Direct contact with

rodent saliva, urine,

feces

Bacterial

Plague Yersinia pestis Rodents Flea bites

Cat-scratch disease Bartonella henselae Domestic cats Direct contact

Rocky Mountain

spotted fever

Rickettsia enterica Rodents Tick bites

Salmonellosis Salmonella enterica Poulttry, reptiles Ingestion of

contaminated food

and/or water


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Disease Causative agent Reservoir Transmission due

to

Edemic typhus Rickettsai typhi Rodents Flea bites

Fungal

Ringworm 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 meator by direct contact

with infected tissues

or fecal matter

Helmintic

Tapeworm (pork) Taenia solium Pigs

Ingestion of

uncooked

contaminated pork


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Nonliving Reservoirs

The two major nonliving reservoirs of infectious disease are

soil and water.

Soil harbors such pathogens as fungi, which cause mycosessuch 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 normalintestinal microbiota of horses and cattle, the bacteria are

found especially in soil where animal feces are used as

fertilizer.


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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.


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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


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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.


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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


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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).


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The transmission of disease agents by amedium, 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 withuntreated or poorly treated sewage.

Diseases transmitted via this route includecholera, waterborne shigellosis, andleptospirosis.


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Infood 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.


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Airborne transmission refers to the spread ofagents of infection by droplet nuclei in dustthat 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 fromthe mouth and nose during coughing and

sneezing These droplets are small enough to remain airborne for

prolonged periods.


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The virus that causes measles and the bacteriumthat causes tuberculosis can be transmitted viaairborne droplets.

Dust particles can harbor various pathogens. Staphylococci and streptococci can survive on dust and betransmitted by the airborne route.

Spores produced by certain fungi are alsotransmitted by the airborne route and can causesuch diseases as histoplasmosis,coccidioidomycosis, and blastomycosis


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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 feetor other body parts


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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.


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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.


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Some parasites reproduce in the gut of thearthropod; 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 andmigrate to the salivary gland; these are directlyinjected into a bite.

Some protozoan and helminthic parasites use thevector as a host for a developmental stage in theirlife cycle.


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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.

Some microbes do not cause disease by

directly damaging host tissue but instead,disease is due to the accumulation of microbial

waste products


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Some microbes, such as those that cause dentalcaries and acne, can cause disease withoutpenetrating the body.

Pathogens can gain entrance to the humanbody and other hosts through what are calledportals of entry.

The portals of entry for pathogens are mucousmembranes, skin, and direct deposition beneath the skinor membranes (the parenteral route).


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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

Most pathogens enter through the mucousmembranes of the gastrointestinal and

respiratory tracts.


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Microorganisms can gain access to the gastrointestinaltract 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 inthe stomach or by bile and enzymes in the smallintestine.

Microbes in the gastrointestinal tract can cause

poliomyelitis, hepatitis A, typhoid fever, amoebicdysentery, giardiasis, shigellosis (bacillary dysentery),and cholera.


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The genitourinary tract is a portal of entry forpathogens that are contracted sexually.

Some microbes that cause sexually transmitted

infections (STls) may penetrate an unbrokenmucous membrane.

Others require a cut or abrasion of some type.

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


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The skin is the largest organ of the body in terms ofsurface area and weight and is an important defenseagainst disease.

Unbroken skin is impenetrable by mostmicroorganisms.

Some microbes gain access to the body through

openings in the skin, such as hair follicles and sweatgland ducts. Larvae of the hookworm actually bore through intact skin, and

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


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The conjunctiva is a delicate mucous

membrane that lines the eyelids and covers the

white of the eyeballs.

Although it is a relatively effective barrier

against infection, certain diseases such as

conjunctivitis, trachoma, and ophthalmianeonatorium are acquired through the

conjunctiva.


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Mos gain access to the body when they are depositeddirectly into the tissues beneath the skin or into mucousmembranes when these barriers are penetrated orinjured.

Punctures, injections, bites, cuts, wounds, surgery, andsplitting of the skin or mucous membrane due toswelling or drying can all establish parenteral routes.

HIV, the hepatitis viruses and bacteria that cause tetanusand gangrene can be transmitted parenterally.


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If only 3 few microbes enter the body, they will

probably be overcome by the host's defenses.

However, if large numbers of microbes gain

entry, the stage is probably set for disease.

Thus, the likelihood of disease increasesproportional to the number of pathogens.


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This relates to the virulence of the mo

The virulence of a microbe is often expressed

as the ID50 (infectious dose for 50% of a

sample population).

The 50 is not an absolute value; rather, it isused to compare relative virulence under

experimental conditions.


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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.


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The potency of a toxin is often expressed as the

LD50 (lethal dose for 50% of a sample

population ).

For 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.


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Almost all pathogens have some means ofattaching themselves to host tissues at theirportal of entry.

For most pathogens, this attachment, calledadherence

This adherence is accomplished throught theuse of Adhesins or ligands Bind specifically to complementary surface receptors on the

cells of certain host tissues


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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 theglycocalyx of S. mutans. The combination of S. mutans,

Actinomyces, and dextran make up dental plaque and

contribute to dental caries


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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 ofStreptococcus

pneumoniae, the causative agent of pneumococcalpneumonia, allows this bacterium to exert its virulence

Other bacteria that produce capsules related to

virulence are Klebsiella pneumoniae, a causativeagent of bacterial pneumonia


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Haemophilus influenzae, a cause of pneumonia and

meningitis in children;

Bacillus anthracis, the cause of anthrax; and

Yersinia pestis, the causative agent of plague.


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Cell wall components

The cell walls of certain bacteria contain chemical

substances that contribute to virulence

For example, Streptococcus pyogenes produces a heat-resistant 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.


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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 ofMycobacterium tuberculosis also increases

virulence by resisting digestion by phagocytes, and caneven multiply inside phagocytes.


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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) thefibrinogen in blood, e.g. staphylococci


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

streptococci such as Streptococcus pyogenes; andstaphylokinase.

Hyaluronidase is another enzyme secreted bycertain bacteria, such as streptococci. It hydrolyzes hyaluronic acid, a type of polysaccharide that

holds together certain cells of the body, particularly cells inconnective tissue.


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Another enzyme, collagenase produced by

several species ofClostridium, 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.


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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.


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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 andbetween host cells.


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If a pathogen overcomes the host's defense, thenthe microorganism can damage host cells in fourbasic ways:

1.

By using the host's nutrients;2. By causing direct damage in the immediatevicinity of the invasion;

3. By producing toxins, transported by blood and

lymph, that damage sites far removed from theoriginal site of invasion;4. By inducing hypersensitivity reactions.


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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 moretightly.

Once the iron-siderophore complex is formed, it is

taken up by siderophore receptors on the bacterial

surface.


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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, andNeisseria gonorrhoeae, can induce host epithelial cells to

engulf them by a process that resembles phagocytosis.


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Production of Toxins Toxins are poisonous substances that are produced

by certain microorganisms

The capacity of microorganisms to produce toxinsis called toxigenicity.

Toxins transported by the blood or lymph can cause

serious, and sometimes fatal, effects.


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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


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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 bodyto produce antitoxins.


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Diphtheria Toxin Corynebacterium diphtheriae produces the diphtheria toxin

only when it is infected by a lysogenic phage carrying thetox 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 namedfor this characteristic rash.


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Botulinum Toxin

It is produced by Clostridium botulinum

Although toxin production is associated with the

germination of endospores and the growth of vegetativecells, 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 thetransmission of impulses from the nerve cell to the

muscle.


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Tetanus Toxin

Clostridium tetani produces tetanus neurotoxin, also

known as tetanospasmin.

This A-B toxin reaches the central nervous system andbinds to nerve cells that control the contraction of

various skeletal muscles

The result is uncontrollable muscle contractions,

producing the convulsive symptoms (spasmodiccontractions) of tetanus, or "lockjaw."


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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 bacterialmultiplication


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Endotoxins do not promote the formation ofeffective antitoxins against the carbohydratecomponent of an endotoxin. Antibodies are produced, but they tend not to counter the

effect of the toxin; sometimes, in fact, they actually enhanceits effect

Representative mos that produce endotoxins are Salmonella typhi (the causative agent of typhoid fever),

Proteus spp. (frequently the causative agents of urinary tractinfections),

Neisseria meningitidis (the causative agent ofmeningococcal meningitis)

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Infection and Disease.pdf