12 - Infection and Disease

1. Infection and Disease

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. 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. 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. 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. 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. 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. Factors Affecting Distribution and Composition of Microbiome Nutrients Temperature pH Oxygen Salinity Sunlight Host Defenses Individual Criteria Age, Diet, Geography, Health, Stress

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. 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. 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. Koch’s Postulates: Etiology of a Disease Robert Koch: 1877 Experimental Requirements to determine the microbial cause of a disease The same pathogen must be present in every case of the disease Pathogen must be isolated from diseased host and grown in pure culture Pathogen from pure culture must cause disease when inoculated into a healthy host Pathogen must be isolated from the new host and shown to be the same as the original organism

13. Koch’s Postulates

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. 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 t etani endospores

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. 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. 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. 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. 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. 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. 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. 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. 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. Transmission of infection: Contact Direct Indirect (fomites: inanimate objects) Droplet (mucus; travel < 1m)

26. Transmission of infection: Vehicles Waterborne Contaminated with feces Foodborne Improperly cooked/ stored/ prepared Airborne Travels > 1m to host Fungal spores, TB, measles

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. 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. 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. Nosocomial infections: most common sites

31. Invasion and Pathogenesis Host v/s pathogen Host defenses prevent invasion by pathogen No disease Pathogen outwits host defenses disease

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. 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. 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. 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. 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. 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. 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. Invasion Size Matters! Larger the “inoculum” more likely the chance to cause disease Harder to overcome host defenses ID 50 Infectious dose where 50% population is infected Compare relative virulence under experimental condition ID 50 of Bacillus anthracis through skin is 10-50 endospores, ID 50 through inhalation is 10,000-20,000 LD 50 lethal dose where 50% of population is killed Measure of potency of microbial toxin botulism toxin LD 50 = 0.03 ng /kg; Shiga toxin LD 50 = 250 ng /kg

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. 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. 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. 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. 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. Exotoxins & Endotoxins Compared

46. Signs and Symptoms Signs: Objective findings observed by healthcare worker Symptoms: patient complains in own words

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. 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. Types of studies: Descriptive Retrospective Determine the source/ cause of infection after the fact Cholera outbreak in Britain 1848-1849 SARS Prospective Follow a group of healthy people Study the effect of subsequent disease Salk polio vaccine UF Flu study

50. Types of Study: Analytical Epidemiology Analyze particular disease to determine cause Cohort Two populations One who had contact with disease Those that had blood transfusions v/s not Hep B association Case-control Identify factors that preceded disease Compare diseased v/s disease-free individuals Matched by sex, age, socioeconomic status, location

51. Experimental Epidemiology Hypothesis Experiments to test hypothesis Drug Effectiveness Select infected people Randomly select those that get drug v/s placebo Compare results