Disease

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Lecture 25

• Disease

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Health

• a state of complete physical, mental and social
  well being ..World Health Organisation (WHO)

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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.

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Infection

• The successful invasion, establishment and
  growth of microorganisms in the tissues of the
  host.

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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.

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Terminology

• Disease state of being not in good health (not
  at ease, "dis-ease").
• 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.

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Terminology

• 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

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Koch's Postulates

• 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

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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

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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.)

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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.

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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

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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.

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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

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Virulence Factors

• Virulence Factors are specific adaptations that
  allow pathogen to
• Attach selectively to host tissues.
• Gain access to nutrients by invading or
  destroying
• host tissues.
• 3. Avoid host defences.
• 4. Toxins exotoxins and endotoxins.
• 5. Siderophores.

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1. Specific attachment entry factors

• 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.

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2. Invasive enzymes

• 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 ---gt 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".

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3. Tricks to avoid host defenses

• 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.

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4. Exotoxins

• 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

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4. Exotoxins

• 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.

• 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 ---gt flaccid paralysis.
• Occurs most typically in improperly canned

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4. Exotoxins

• 3. Tetanus toxin, another neurotoxin.
• 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).

• 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, lt1. Prevention clean drinking
  water.

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4. Endotoxins

• 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.

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5. Siderophores

• 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.

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Common Infections
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Diseases of Developing Countries
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Controlling Infectious Diseases

• Treatment prophylaxis such as antibiotics,
  antiviral drugs.
• Prevention hygiene, disinfectants,
  sterilization, antiseptics and vaccination.

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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.

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Sterilisation

• Removal of any living organisms from a non-living
  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.

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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

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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.

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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.

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Assignment 8Common 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