infection and disease.pdf
TRANSCRIPT
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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)