Transcript Lecture #25 - Suraj @ LUMS

Lecture 25
Disease
Health
“ a state of complete physical, mental and
social well being” …..World Health
Organisation (WHO)
Disease
• Infectious or communicable diseases –
diseases caused by other living organisms,
they can be transmitted from one person to
another.
• Non infectious diseases – social, deficiency,
genetic or congenital (present at birth),
ageing and degenerative, mental illness.
These are not transmitted by contact.
Infection
“The successful invasion, establishment
and growth of microorganisms in the
tissues of the host”.
Association Between Microbe
and Man
• Parasitic – one benefits at the expense of the
other.
• Symbiotic – mutual benefit.
• Commensalism – one organism derives
benefit by living near on on its surface
without causing any damage.
Terminology
• Disease = state of being not in good health (not at ease, "disease").
• Every disease is a race between pathogen trying to gain a
foothold and host defences trying to prevent pathogen. Many
factors involved: virulence and numbers of pathogen, health
and age of host, etc.
• Wrong to equate "one pathogen" = disease. Much more
complex.
• Parasite often used to refer to protozoans or worms; the term
"Pathogen" is typically used when referring to bacteria,
virus, or fungus that causes disease. All are parasitic.
Terminology
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Pathogen = organism with potential to cause disease
Infection = pathogen is growing in or on host
Virulence = degree or intensity of pathogenicity
Invasiveness = ability of pathogen to spread to other
tissues in body
• Infectivity = ability of pathogen to establish infection
• Toxigenicity = ability of pathogen to secrete toxins
• Septicemia = infection in which pathogen grows massively
in the body, being found in blood and throughout organs.
Usually leads to death
Koch's Postulates
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2.
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4.
Developed in late 1800's , provide basic logical proof that
disease is caused by a microbe
Microbe must be present in every case of disease, but
absent from healthy individuals.
Suspected microbe must be isolated from diseased host
and grown in culture.
Same disease must result when isolated microbe is
introduced into healthy host.
Same microbe must be isolated again from second
diseased host
Epidemiology
• Tracking the incidence and patterns of disease.
• Depends critically on data. Accuracy much better
in developed countries than in most developing
countries.
• Global: World Health Organization (WHO) in
Geneva maintains records on health statistics,
infection rates, epidemics in most of World. View
The World Health Report 2001
Epidemiology
• U. S.: Centers for Disease Control and Prevention (CDC)
maintains records on health statistics, infection rates,
epidemics in U. S.
• Every licensed clinic, physician, hospital must submit
weekly reports of every instance of reportable diseases
(about 50 on current list) to state public health office,
which forwards this information to CDC.
• CDC publishes weekly reports (now available on Web and
via e-mail): Morbidity & Mortality Weekly Reports.
• View Morbidity & Mortality Weekly Report summary
from CDC (Centers for Disease Control)
• U.S. and other countries in developed world have cut many
diseases by sanitation, public health (vaccines, etc.)
Spread of Infection
• Multiply within host
• Spread from one host to another – two types of
transfer horizontal and vertical.
• Horizontal spread – polio, influenza, thyphoid.
Spread by infected air, water, food or by insect
vectors.
• Vertical spread – parent to offspring congenital
rubella, leukemia viruses.
• Zoonoses – spread of infection from one species to
another.
Intracellular vs Extracellular
Pathogens
• Most pathogens have evolved to live either inside
or outside of host cells, rarely if ever in both
habitats.
• Inside the cell – intracellular
• Outside the cell - extracellular
Intracellular Life
• Poses special problems for host.
• Can't easily attack pathogen without harming its own tissues.
Many pathogens are adapted for intracellular life, including all
viruses, certain bacteria (e.g. TB, plague),
• Since white blood cells (macrophages, lymphocytes) are major
components of defence system, many successful pathogens
target these cells specifically for intracellular growth.
• Problem: to be successful, pathogen at some point must leave
cells, exit host. Best chance to prevent infection is sometime
during exit -- transmission -- entry to new host, before it has a
chance to hide in new cells.
• Some intracellular parasites are so highly evolved that they
can't survive at all outside their host's cells. Ex: Chlamydia,
Rickettsia. To be successful, these must rely on mechanisms
such as sexual contact or animal bites to transmit them to new
hosts.
Extracellular Life
• Pathogen must deal with host's defensive
strategies: white blood cells, immune system, etc.
• But does provide greater opportunities for grown,
reproduction, and spreading than living inside
cells.
• Can rapidly colonize a habitat; Ex. when cholera
invades intestine, can quickly multiply, spread to
cover large surface area
• Typical bacterial pathogens that act
extracellularly: E. coli, Pseudomonas sp., Vibrio
cholera
Virulence Factors
• Virulence Factors are specific adaptations that
allow pathogen to:
1. Attach selectively to host tissues.
2. Gain access to nutrients by invading or destroying
host tissues.
3. Avoid host defences.
4. Toxins – exotoxins and endotoxins.
5. Siderophores.
1. Specific attachment & entry factors
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Pathogen must be able to bind to some receptor
molecule on cell surfaces. These typically have
necessary functions for cell.
Most diseases are tissue specific, because only
certain tissues have receptor molecule needed.
Ex: HIV binds to cells that have CD4 receptor
(only certain lymphocytes).
Fimbriae or pili are used by some bacteria to
attach selectively to certain tissues. Ex:
Neisseria gonorrhaea binds to genital
epithelium by fimbriae. In mutant cells w/o
fimbriae, infectivity and pathogenicity are lost.
2. Invasive enzymes
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Many bacteria have specific enzymes that allow cells to
penetrate host tissues
Example 1: collagenase produced by Clostridium
perfringens. Enzyme degrades collagen, the primary
structural fibre of connective tissue (25% of body's
protein), allows penetration deeper into tissues --->
fulminating gangrene. Strictly anaerobic process, only
occurs when tissue is damaged so blood can't supply
oxygen (e.g. serious wounds, frostbite).
Example 2: hemolysin enzymes produced by
Streptococcus pyogenes dissolves cell membranes of
tissues, produces typical symptoms of "strep throat".
3. Tricks to avoid host defenses
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2.
Capsules - Many pathogens have thick extracellular
polysaccharide capsules. Capsules inhibit phagocytosis,
prevent quick disposal of bacterium by WBCs. Loss of
capsule typically causes loss of infectivity.
"Nasty Enzymes" Leukocidins - some pathogens
secrete chemicals that specifically kill WBCs. Eg:
Staphylococcus aureus. Accumulation of pus at infected
site is caused by dead WBCs. Coagulase - Staph.
aureus produces enzyme that coagulates blood. Result:
WBCs, other body defences can't reach site of infection.
Staph typically remains localized, "walled off" from
defenses, produces many nasty types of localized
infections such as boils, abcesses, etc.
4. Exotoxins
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Most exotoxins are proteins, secreted from cell, often
damaging tissues at some distance. Very potent, small
amounts are very toxic.
Often coded by plasmid DNA (ex. E. coli) or lysogenic
phage DNA (ex. botulism, diphtheria)
Almost always inactivated by heat. Most are good antigens
when inactive, can make toxoids (antigens without poison
activity) = strong immune response.
Visit cholera (Vibrio cholerae) web page from Bacteriology
330, by Kenneth Todar, University of Wisconsin Department
of Bacteriology
4. Exotoxins
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1. Diphtheria toxin.
Corynebacterium
diphtheriae.
Enters cell, inactivates
elongation factor needed
for protein synthesis.
Cell gradually loses ability
to make proteins (same
toxin molecule keeps
inactivating more and
more factors), shuts down.
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2. Botulin toxin, a neurotoxin
(attacks nervous system).
Clostridium botulinum,
anerobic soil bacterium.
Most potent toxin known- 1
gram could kill 10 million
people.
Toxin interferes with synaptic
transmission at nerve-muscle
junctions ---> flaccid paralysis.
Occurs most typically in
improperly canned
4. Exotoxins
3. Tetanus toxin, another
neurotoxin.
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Clostridium tetanus, anerobic
soil bacterium.
Blocks synaptic transmission
to inhibitory neurons, leads to
rigid paralysis.
Common from deep wounds,
pulled teeth.
Treatment: antitoxin.
Prevention: toxoid
immunization (lasts 5-10 yrs).
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4. Cholera toxin = an enterotoxin
(attacks enteric tract).
Vibrio cholerae. is free-living in
fresh water.
Binds to receptors on intestinal
cells, chemically alters molecule
involved in c-AMP production,
leaves cAMP stuck in the "on"
position.
Causes massive outflow of water
(chasing outflow of Na+/Cl-).
Similar mode of action for other
enterotoxin.
Can be spread by drinking water,
food (shellfish common).
Untreated, mortality is ~50%.
With fluid replacement, <1%.
Prevention: clean drinking water.
4. Endotoxins
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Endotoxins are integral parts of Gram-negative outer
membrane (= LPS, lipolysaccharide).
Unlike Exotoxins, they are typically heat resistant, active
only in sizable amounts, and remain bound to cells.
Mechanism of action is very diverse. "When we sense
LPS, we are likely to turn on every defence at our
disposal" (Lewis Thomas), including fever, decrease in
iron, inflammation, blood clotting, reduced sugar in
blood, etc. Most important clinical problems are fever
and shock.
Typical scenario: Gram-negative bacteria (e.g. E. coli,
Pseudomonas) enter body via clinical procedure
(improperly sterilized kidney dialysis tubing, catheter,
etc.), cause sudden decrease in blood pressure
(hypotension) = "septic shock". Can be lethal.
5. Siderophores
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Iron plays special role in control of infection.
Most bacteria require iron to synthesize cytochromes.
Iron in human body is tightly bound, either in hemoglobin
(blood cells), on transferrin proteins (serum and lymph), or
lactoferrin (milk, tears, saliva, mucus, etc.).
Some bacteria (Streptococci) do not require iron -metabolism is strictly fermentative, no respiratory system.
But most bacteria have to find way to get iron or cannot
grow.
Siderophores = iron-binding factors that allow some
bacteria to compete with the host for iron. Ex:
Enterochelin produced by enteric bacteria (E. coli,
Salmonella). Mutants that cannot synthesize enterochelin
lose virulence. These mutants can regain virulence if pure
enterochelin is injected along with mutant bacteria.
Bio101 Infectious Disease Statistics
30
Hepatitis
Malaria
Chicken Pox
Measles
Mumps
Whooping Cough
No. of cases
25
20
15
10
5
0
1 to 5
5 to 10
10 to 15
Age (years)
15 to 20
Common Infections
Diseases of Developing
Countries
Controlling Infectious Diseases
• Treatment – prophylaxis such as antibiotics,
antiviral drugs.
• Prevention – hygiene, disinfectants,
sterilization, antiseptics and vaccination.
Antiseptics and Disinfectants
• Chemical substances that destroy microorganisms.
• Antiseptic can be applied safely to the body. e.g on
skin, ethanol and isopropanol.
• Disinfectants cannot be used on the body directly
but are used to clear work surfaces, crockery,
cutlery, instruments etc. e.g hypochlorites in
commercial disinfectants, phenol, aldehydes,
chlorxylenol (dettol) and iodine in more dilute
form can be used as antiseptics.
Sterilisation
• Removal of any living organisms from a nonliving object or material. E.g water, operating
theatre gowns.
• Heat – pasteurising milk , tinned food.
• Steam - autoclave where steam under pressure is
fed into a sealed chamber.
• Radiation – Longer wave lengths have no effect
shorter wavelength such as UV light results in
death.
Vaccination
• Giving antigens from a disease causing
organism, either by injection or orally.
• In order for the immune system to learn to
make antibodies against the organism.
• So that the body will be able to respond fast
enough to prevent the organism from
causing an infection.
• Artificial active immunity
Different Types of Vaccines
• Toxoid – detoxified yet antigenic property remains
and when used as a vaccine will elicit production
of antibodies in the host e.g tetanus toxoid
• Killed organisms – heat inactivated e.g flu vaccine
• Live organisms – attenuated e.g measles vaccine
• New vaccines – genetic engineering has enabled
antigens to be made in bacteria and isolated,
purified and used in a vaccine.
Infectious Diseases
• The spread of an infectious disease is critically influenced
by social, economic, and behavioral factors in the human
population.
• In infected populations, viruses and their hosts co-evolve,
with each influencing the other's destiny.
• Often the most successful pathogens evolve to avoid
killing their hosts.
• Infectious diseases will never be eradicated as a group, but
individual diseases can be controlled through public health
measures, vaccination, and specific therapy.
Assignment 8
Common Infections
What organisms cause the following infections?
Give details of symptoms and how are the infections are
treated.
• Measles
• Chicken Pox
• Hepatitis (Jaundice)
• Malaria
• Diarrhoeal diseases
• Mumps
• Throat Infections