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Infection and Disease
Pathology, Infection and Disease
• Pathology: scientific study of a disease
• Etiology: cause/ origin of a disease
• Patho...
Pathology, Infection and Disease
• Infection: invasion or colonization of body by
pathogenic bacteria
– Also presence of b...
Normal Microbiota
• Normal Microbiota
– Normal flora
– Permanent residents
– Don’t normally cause disease
• Transient Micr...
Normal Microbiota
• Skin
– Staphylococcus, Micrococcus,
Candida (fungus)
– Salt and low pH inhibitory for
others
• Eyes
– ...
Normal Microbiota
• Nose & Throat
– S. aureus, S. epidermidis, Haemophilus
– Mucus & cilia remove/inhibit most microbes
• ...
Normal Microbiota
• Large intestine
– E. coli, Lactobaccillus, Enterobacter, Candida (fungus),
Enterococcus
– Largest numb...
Factors Affecting Distribution and
Composition of Microbiome
• Nutrients
• Temperature
• pH
• Oxygen
• Salinity
• Sunlight...
Normal Microbiota: Host Relationship
• Microbial Antagonism/Competitive Exclusion
– Prevent growth of other (pathogenic) m...
Normal Microbiota: Host Relationship
• Symbiosis: relationship between two
organisms with at least one dependent on the
ot...
Normal Microbiota: Host Relationship
• Opportunistic Pathogens
– Normal Flora: don’t cause disease in their specific
niche...
Koch’s Postulates: Etiology of a Disease
• Robert Koch: 1877
– Experimental Requirements to determine the
microbial cause ...
Koch’s Postulates
Koch’s Postulates: Exceptions
• Cannot satisfy Postulate 2
– Some pathogens cannot be cultured on artificial media
• Virus...
Disease Classification
• Communicable Disease: spreads from host to host
(directly/ indirectly)
• Contagious Disease: easi...
Disease Occurence
• Incidence: number of people that develop a
disease in a given time period
– Indicates the rate of dise...
Disease Occurence
• Sporadic: occurs only occasionally in given population
– Typhoid fever
• Endemic: constantly present i...
Disease Severity/ Duration
• Acute: rapid but short time
– Influenza
• Chronic: slow progression, long duration
– Mononucl...
Extent of host involvement
• Classify infections based on the affect on host
– Local infection: relatively small area
• Ab...
Extent of host involvement
• Sepsis: whole body inflammation by microbial
spread
• Septicemia: blood poisoning
– Systemic ...
Steps in disease development
• Incubation Period
– Before signs and symptoms appear
• Prodromal period
– Early, mild, non-...
Patterns of disease
For disease to occur, the following conditions need
to be met:
 Reservoir of infection
 Source of pa...
Reservoirs of infection
• Human
– Lacking disease symptoms
• Carriers
• Animal reservoirs
– Zoonoses
• Animal diseases tra...
Reservoirs of infection: Carriers
Typhoid fever = infection of Salmonella typhi characterized by
high fever, headache and ...
Transmission of infection: Contact
• Direct
• Indirect (fomites: inanimate objects)
• Droplet (mucus; travel < 1m)
Transmission of infection: Vehicles
• Waterborne
– Contaminated with feces
• Foodborne
– Improperly cooked/ stored/ prepar...
Transmission of infection: Vectors
• Mechanical
– Flies sit on feces, sit on food
– Pathogens ingested
• Biological
– Inse...
Nosocomial Infections
• Direct Contact
– Staff to patient
– Patient to patient
• Indirect Contact
– Fomites (Catheters, ne...
Transmission in hospitals
Nosocomial infections in the United States
• Eighth leading cause of death
• Occur because of th...
Nosocomial infections: most common sites
Invasion and Pathogenesis
• Host v/s pathogen
– Host defenses prevent invasion by pathogen
• No disease
– Pathogen outwits...
Predisposing Factors
• Alter disease susceptibility
• Alter disease course
• Genetics
– Sickle cell disease
• Heterozygous...
Predisposing Factors
Genetic predisposing factors continued
Malaria = infectious disease caused by the proliferation of
th...
Predisposing Factors
Other predisposing factors:
• Environment (nutrition, occupation, lifestyle, climate)
• Age
• Immunit...
Predisposing Factors
Ex) Climate & weather
• Increased respiratory diseases in winter
• Proximity to others while confined...
Invasion
• Portals of Entry: mucous membrane
– Conjunctiva: mucous membrane of eyelid and eyeball
– Respiratory tract
• Mo...
Invasion
• Portal of Entry: Skin
– Impenetrable by microbes
• Unless broken
– Penetrate through hair follicles, sweat duct...
Invasion
• Portal of Entry: Parenteral
– Deposited under skin or mucous membrane if
barrier broken/penetrated
– Cuts, burn...
Invasion
• Size Matters!
– Larger the “inoculum” more likely the chance to cause disease
– Harder to overcome host defense...
Invasion
• Adherence
– Adhesins on microbe to bind to cell receptors
– Primarily glycoproteins and lipoproteins
• Bind hos...
Need to avoid host defenses to survive
• Antiphagocytic factors
– Capsules, cell wall proteins (M-proteins)
– coagulase (w...
How do bacteria damage the host?
• Endotoxin
• Exotoxins
– Toxins acting on cell membranes
– Toxins active inside cells
– ...
Exotoxins
– Proteins expressed by bacteria during replication
– Secreted into media or released on lysis
– Made by some gr...
Endotoxins
• Part of bacterial cell wall
– Outer membrane of gram (-)
– Lipid A of LPS
– Released on cell death
– Symptoms...
Exotoxins & Endotoxins Compared
Signs and Symptoms
Signs: Objective findings observed by
healthcare worker
Symptoms: patient complains in own words
Epidemiological Triad
The traditional model of infectious disease causation. Includes three components: an
external agent,...
Definitions
• Epidemiology
– is the study of the behavior of disease in a community
rather than individual patients. Its i...
Types of studies: Descriptive
1. Retrospective
• Determine the source/ cause of infection
after the fact
• Cholera outbrea...
Types of Study:
Analytical Epidemiology
Analyze particular disease to determine cause
1.Cohort
– Two populations
• One who...
Experimental Epidemiology
• Hypothesis
• Experiments to test hypothesis
• Drug Effectiveness
– Select infected people
– Ra...
12 - Infection and Disease
12 - Infection and Disease
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12 - Infection and Disease

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Transcript of "12 - Infection and Disease"

  1. 1. Infection and Disease
  2. 2. Pathology, Infection and Disease • Pathology: scientific study of a disease • Etiology: cause/ origin of a disease • Pathogenesis: mechanism by which a disease develops Pathologists are concerned with etiology and pathogenesis of disease and effect of disease on human body.
  3. 3. Pathology, Infection and Disease • Infection: invasion or colonization of body by pathogenic bacteria – Also presence of bacteria where they do not belong • E. coli in urinary tract • Disease: change of state of health resulting from an infection – Abnormal state – Part of whole body is incapable of performing normal function
  4. 4. Normal Microbiota • Normal Microbiota – Normal flora – Permanent residents – Don’t normally cause disease • Transient Microbiota – Present for days/months/years then disappear Only certain body areas are colonized: Nasal epithelium Stomach lining Large intestine
  5. 5. Normal Microbiota • Skin – Staphylococcus, Micrococcus, Candida (fungus) – Salt and low pH inhibitory for others • Eyes – Similar to those on skin – Tears and blinking • Prevent others from colonization Staph epidermis SEM
  6. 6. Normal Microbiota • Nose & Throat – S. aureus, S. epidermidis, Haemophilus – Mucus & cilia remove/inhibit most microbes • Mouth – Streptococcus, Staphylococcus, Lactobacillus – Warm moist environment, food particles as nutrients SEM of bacteria on the human tongue, most of which are harmless or even beneficial
  7. 7. Normal Microbiota • Large intestine – E. coli, Lactobaccillus, Enterobacter, Candida (fungus), Enterococcus – Largest numbers • Moisture and nutrients • Urogenital system – Lactobacillus, Staphylococcus, Micrococcus, Enterococcus, Pseudomonas – Urine flushes out microbes – Low pH inhibits microbes
  8. 8. Factors Affecting Distribution and Composition of Microbiome • Nutrients • Temperature • pH • Oxygen • Salinity • Sunlight • Host Defenses • Individual Criteria – Age, Diet, Geography, Health, Stress
  9. 9. Normal Microbiota: Host Relationship • Microbial Antagonism/Competitive Exclusion – Prevent growth of other (pathogenic) microbes • E. coli bacteriocins kill others (Salmonella/ Shigella) – Alter environment • Lactobacillus lower vaginal/ intestinal pH – Less desirable for other microbes like Candida – Compete for nutrients • Growth of C. difficile is kept in check by intestinal microbiome
  10. 10. Normal Microbiota: Host Relationship • Symbiosis: relationship between two organisms with at least one dependent on the other – Commensalism: one benefitted, other unaffected • Corynebacteria: NF of eye, no damage/benefit to host – Mutualism: both benefit • E. coli in gut: nutrients used; synthesizes Vit. K/ B vitamins – Parasitism: one benefits at expense of other • Pathogenic microbes
  11. 11. Normal Microbiota: Host Relationship • Opportunistic Pathogens – Normal Flora: don’t cause disease in their specific niche – Infection when they access a different environment – Immune suppression – E. coli: mutualistic in large intestine – Pathogen • UTI • Wound abscess • meningitis
  12. 12. Koch’s Postulates: Etiology of a Disease • Robert Koch: 1877 – Experimental Requirements to determine the microbial cause of a disease 1. The same pathogen must be present in every case of the disease 2. Pathogen must be isolated from diseased host and grown in pure culture 3. Pathogen from pure culture must cause disease when inoculated into a healthy host 4. Pathogen must be isolated from the new host and shown to be the same as the original organism
  13. 13. Koch’s Postulates
  14. 14. Koch’s Postulates: Exceptions • Cannot satisfy Postulate 2 – Some pathogens cannot be cultured on artificial media • Viruses (and other oligate intracellular parasites) • Fastidious organisms (mycoplasma) • Some pathogens cause several different diseases – M. tuberculosis: lungs, bones, skin, internal organs – S. pyogenes • Some diseases caused by different pathogens – Nephritis (kidney inflammation) – Pneumonia, meningitis, peritonitis • Viruses that cause Cancer
  15. 15. Disease Classification • Communicable Disease: spreads from host to host (directly/ indirectly) • Contagious Disease: easily spread from host to host – Influenza • Non-communicable disease: not spread from one host to another – tetanus Rusty nails are a prime habitat for Clostridium tetani endospores
  16. 16. Disease Occurence • Incidence: number of people that develop a disease in a given time period – Indicates the rate of disease spread • Prevalence: TOTAL number of cases in a given population at a given time – Indicates how long disease affects population 2007: Incidence of AIDS in US: 56,300 Prevalence: 1, 185,000
  17. 17. Disease Occurence • Sporadic: occurs only occasionally in given population – Typhoid fever • Endemic: constantly present in population – Common cold • Epidemic: acquired by many people in a given area in a short time period – Influenza • Pandemic: worldwide epidemic – Some influenza epidemics (H1N1) – SARS – AIDS
  18. 18. Disease Severity/ Duration • Acute: rapid but short time – Influenza • Chronic: slow progression, long duration – Mononucleosis – Tuberculosis – Hepatitis B • Subacute: intermediate between acute and chronic – Subacute sclerosing panencephalitis • Latent: causative agent remains inactive, can reactivate to produce symptoms – Herpesvirus
  19. 19. Extent of host involvement • Classify infections based on the affect on host – Local infection: relatively small area • Abscess, boils – Systemic (generalized): spread through the body by blood/ lymph • Local infection can also get systemic • measles – Focal infection: start in one area but spread to another confined area via blood/ lumph • Dental plaque linked to heart disease
  20. 20. Extent of host involvement • Sepsis: whole body inflammation by microbial spread • Septicemia: blood poisoning – Systemic infection from pathogens multiplying in blood – Toxemia, Bacteremia, Viremia • Primary infection: acute infection causing initial illness • Secondary infection: opportunistic pathogen infection because of weakened immune system
  21. 21. Steps in disease development • Incubation Period – Before signs and symptoms appear • Prodromal period – Early, mild, non-specific symptoms appear • Period of illness – Disease specific symptoms – Symptoms most severe – Immune system overcomes pathogen OR patient dies • Period of decline – Symptoms subside – Vulnerable to secondary infections • Period of convalescence – Body returns to pre-diseased state Patient can be infectious at EVERY stage of disease
  22. 22. Patterns of disease For disease to occur, the following conditions need to be met:  Reservoir of infection  Source of pathogens  Transmission  Route from reservoir to host  Invasion  Pathogen enters host and multiplies  Pathogenesis  Causes damage to host
  23. 23. Reservoirs of infection • Human – Lacking disease symptoms • Carriers • Animal reservoirs – Zoonoses • Animal diseases transmitted to humans • Rabies, Lyme disease • Non-living reservoir – Contaminated water • Vibrio, Salmonella – Soil • Clostridium • Fungi (ringworm)
  24. 24. Reservoirs of infection: Carriers Typhoid fever = infection of Salmonella typhi characterized by high fever, headache and diarrhea • Spread only through human feces Chronic carriers: recovered patients that harbor S. typhi in gall bladder – may shed bacteria indefinitely “Typhoid Mary” Mallon • Early 1900s – worked as a cook in NY • Linked to several typhoid outbreaks and deaths • Numerous attempts to restrain her from food industry
  25. 25. Transmission of infection: Contact • Direct • Indirect (fomites: inanimate objects) • Droplet (mucus; travel < 1m)
  26. 26. Transmission of infection: Vehicles • Waterborne – Contaminated with feces • Foodborne – Improperly cooked/ stored/ prepared • Airborne – Travels > 1m to host – Fungal spores, TB, measles
  27. 27. Transmission of infection: Vectors • Mechanical – Flies sit on feces, sit on food – Pathogens ingested • Biological – Insect bites infected host – Pathogen replicates in insect – Insect bites uninfected host and transmits pathogen – Lyme disease, Dengue, plague, malaria
  28. 28. Nosocomial Infections • Direct Contact – Staff to patient – Patient to patient • Indirect Contact – Fomites (Catheters, needles) – Airborne (ventilation system) Prevention of transmission • Aseptic Technique/ Sterilization of equipment • Hand washing • Proper handling/ disposal of contaminated material
  29. 29. Transmission in hospitals Nosocomial infections in the United States • Eighth leading cause of death • Occur because of three factors:  Presence of pathogens  Chain of transmission  Immune compromised host
  30. 30. Nosocomial infections: most common sites
  31. 31. Invasion and Pathogenesis • Host v/s pathogen – Host defenses prevent invasion by pathogen • No disease – Pathogen outwits host defenses • disease
  32. 32. Predisposing Factors • Alter disease susceptibility • Alter disease course • Genetics – Sickle cell disease • Heterozygous: sickle cell trait • Homozygous: sickle cell disease – Deliver less oxygen – Stuck in capillaries – Anemia, organ failure – Highest prevalence in West Africa – Confers resistance to MALARIA
  33. 33. Predisposing Factors Genetic predisposing factors continued Malaria = infectious disease caused by the proliferation of the eukaryotic parasite plasmodium in RBCs • Vector = mosquito • plasmodium can’t multiply in sickled cells So…  While sickle cell disease is very unfavorable,  sickle cell trait provides heightened survival in malaria prone areas • ensures retention of sickle cell gene
  34. 34. Predisposing Factors Other predisposing factors: • Environment (nutrition, occupation, lifestyle, climate) • Age • Immunity • Gender Above: Bear Grylls is environmentally predisposed to all sorts of diseases
  35. 35. Predisposing Factors Ex) Climate & weather • Increased respiratory diseases in winter • Proximity to others while confined indoors & poor ventilation • Breathing cold air  cough, sneeze, runny nose  transmits pathogens
  36. 36. Invasion • Portals of Entry: mucous membrane – Conjunctiva: mucous membrane of eyelid and eyeball – Respiratory tract • Most frequently used portal • Moisture and dust inhaled through nose and mouth • Pneumonia, tuberculosis, influenza – GI tract • Contaminated food and water • Must survive stomach acid, bile in small intestine • Eliminated in feces: can further contaminate
  37. 37. Invasion • Portal of Entry: Skin – Impenetrable by microbes • Unless broken – Penetrate through hair follicles, sweat ducts – Some fungi and eukaryotic parasites • Infect unbroken skin • Penetrate intact skin (ex. Hookworm)
  38. 38. Invasion • Portal of Entry: Parenteral – Deposited under skin or mucous membrane if barrier broken/penetrated – Cuts, burns, bites, wounds, injections – Tetanus from puncture wound – Malaria from mosquito bite – HepB/ HepC from injection
  39. 39. Invasion • Size Matters! – Larger the “inoculum” more likely the chance to cause disease – Harder to overcome host defenses • ID50 – Infectious dose where 50% population is infected – Compare relative virulence under experimental condition • ID50 of Bacillus anthracis through skin is 10-50 endospores, ID50 through inhalation is 10,000-20,000 • LD50 – lethal dose where 50% of population is killed – Measure of potency of microbial toxin • botulism toxin LD50 = 0.03 ng/kg; Shiga toxin LD50 = 250 ng/kg
  40. 40. Invasion • Adherence – Adhesins on microbe to bind to cell receptors – Primarily glycoproteins and lipoproteins • Bind host receptors: sugars (mannose) – Adhesins can bind other bacteria • Actinomyces bind glycocalyx of S. mutans on teeth – Biofilms • Microbes bind to living/non-living • Dental plaque, algae on swimming pool walls, scum on shower stalls • First microbes in biofilm usually bacteria • Can colonize heart valves, catheters, contact lens – Difficult to treat with antibiotics
  41. 41. Need to avoid host defenses to survive • Antiphagocytic factors – Capsules, cell wall proteins (M-proteins) – coagulase (walls off) – survival in WBC - intracellular parasites (mycobacteria, Listeria) • Opportunistic pathogens need compromised host • Antigenic Variation N. meningitidis crosses blood-brain barrier
  42. 42. How do bacteria damage the host? • Endotoxin • Exotoxins – Toxins acting on cell membranes – Toxins active inside cells – Superantigens –Non-specific proliferation of T-cells  cytokines
  43. 43. Exotoxins – Proteins expressed by bacteria during replication – Secreted into media or released on lysis – Made by some gram (+) and gram (-) bacteria – Water soluble, easily diffuse into lymph/ blood – Extremely lethal • Cholera Toxin – Causes cells to secrete fluids & electrolytes  diarrhea • Tetanus neurotoxin – Binds nerve cells, prevents muscle relaxation, causes convulsive muscle contractions
  44. 44. Endotoxins • Part of bacterial cell wall – Outer membrane of gram (-) – Lipid A of LPS – Released on cell death – Symptoms for all endotoxins same • Chills, fever, aches • Shock (decrease in BP) – S. typhi – typhoid fever – Neisseria meningitidis: meningococcal meningitis
  45. 45. Exotoxins & Endotoxins Compared
  46. 46. Signs and Symptoms Signs: Objective findings observed by healthcare worker Symptoms: patient complains in own words
  47. 47. Epidemiological Triad The traditional model of infectious disease causation. Includes three components: an external agent, a susceptible host, and an environment that brings the host and agent together, so that disease occurs. Science that evaluates the occurrence, determinants, distribution, and control of health and disease in a defined human population Epidemiology-
  48. 48. Definitions • Epidemiology – is the study of the behavior of disease in a community rather than individual patients. Its incidence and spread. – It includes the study of the reservoirs and sources of human diseases. • Epidemiologists – looks at the factors involved in the occurrence and spread of disease within populations of humans or animals. • AIM: – To understand the mode of transmission and what predispose a population to a particular agent
  49. 49. Types of studies: Descriptive 1. Retrospective • Determine the source/ cause of infection after the fact • Cholera outbreak in Britain 1848-1849 • SARS 2. Prospective • Follow a group of healthy people • Study the effect of subsequent disease • Salk polio vaccine • UF Flu study
  50. 50. Types of Study: Analytical Epidemiology Analyze particular disease to determine cause 1.Cohort – Two populations • One who had contact with disease • Those that had blood transfusions v/s not – Hep B association 2.Case-control – Identify factors that preceded disease • Compare diseased v/s disease-free individuals • Matched by sex, age, socioeconomic status, location
  51. 51. Experimental Epidemiology • Hypothesis • Experiments to test hypothesis • Drug Effectiveness – Select infected people – Randomly select those that get drug v/s placebo – Compare results
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