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BIOL 444
Christine Dupont

BIOL444 – Microorganisms & Disease Fall 2012 Set 01 – Koch’s Postulates Medical Microbiology: Study of interactions b/w animals (humans) & microorganisms (pathogens) w.r.t disease - Germ Theory of Disease (Pasteur 19 century): o Argued microbes were responsible for diseases, food spoilage & fermentations o Developed vaccine for Rabies o Jenner (1796): Cowpox derived smallpox vaccine (Milkmaids’ Complexion) - Microbial caused diseases have influenced history o Rats, Lice & History – Hans Zinsser – typhus 1935 (Rickettsia prowazeki)  Diseases ended up deciding the winning side of war - Hippocrates (350 BC): Disease comes from within – Divine Retribution o Phlegm (Lung & brain), Blood (Liver), Black Bile (Spleen) & Yellow Bile (Gall Bladder) o Balance: Disease was an upset of the natural balance of the body (Balance must be stored) Koch’s Postulates (1882): The golden standard for proving causal relationship b/w microorganism & specific disease - Microorganism must be present at the site of infection in every case of the disease but absent from healthy individuals o Asymptomatic “carrier”: Individual that carries pathogen but do not exhibit symptoms of disease  Can transmit the pathogens to others that then may become diseased o Opportunistic Pathogens: Cause disease only when the person is compromised  E.g. HIV – Die from common infections due to compromised immune system; Hospital secondary infections; Skin lesions  E.g. S. pneumoniae (30% naturally infected), healthy until another infection → Influenza - Microorganism/viruses must be isolated from the infected host & grown in pure culture o Some microorganisms are very difficult to grow in-vitro (in the laboratory – pure artificial media) hence they are grown in cell cultures, small animals (culture vessel) or tissue cultures/eggs o E.g. Microorganisms: Chlamydia, M. leprae & T. pallidum & Toxins: tetanus, botulism o Isolation can be done with PCR (Gene) & Immunohistochemistry (Antibody) - Pure culture, must produce the same disease if inoculated into healthy susceptible host o Ethical considerations limits the use of laboratory humans & animals o Many pathogens are species-specific, animals susceptible to human pathogens often do not reproduce the same disease characteristics  E.g. Robin Warren & Barry Marshall (2005 Nobel Prize) – Bacterium H. pylori is the cause of most peptic ulcers leading to stomach cancers  E.g. Tamiflu (Anti-Influenza Drug) Speed-up recovery, tested on humans before put in use  E.g. Tuskegee syphilis experiment – Infamous (Bad Reputation) 40 year study  Untreated syphilis – withholding penicillin from patients - Same microorganism must be re-isolated in pure culture from experimentally infected host o Must be isolated from disease lesion to show it is the direct cause of the disease  Many diseases occur due to a change in normal microbial populations (Multifactorial)  E.g. Crohn’s disease – Common Ongoing Inflammatory Disease with unknown causes - Terminology: o Infection: Successful colonization (not just exposure) of the body by microbe capable of causing damages. Hard for most pathogen to colonize, so they usually invade tissues & cells. o Disease: Change away from normal state of health to abnormal state, can be asymptomatic or can cause clinical signs or clinical symptoms  Clinical Signs: Directly observable & measurable (e.g. Fever) ← Commonly Used.  Clinical Symptoms: Experienced by the patient, not measurable or observable. o Parasite (Multicellular): Organism that are capable of routinely causing disease  E.g. Nematode worms o Pathogen (Single Cell Parasite): Microbe that are capable of routinely causing disease  E.g. Bacterium, fungus, virus, protozoan BIOL444 – Microorganisms & Disease Fall 2012  Obligate (Primary) Pathogen: Can directly cause disease among non-compromised population, does not require compromising conditions to cause damage  E.g. Mycobacterium tuberculosis → Tuberculosis (TB)  Opportunistic Pathogen: Capable of infection only when host defenses are compromised or if the microbes get misplaced  E.g. Pseudomonas aeruginosa → Cystic Fibrosis; Enterococcus infections after intestinal surgery → Body Cavity Systematic Infection  Secondary Pathogen: Opportunistic pathogen that causes disease due to an underlying primary infection (already compromised) o E.g. Rhodococcus equi in AIDS patients ← Already compromised o Nosocomial Infection “Health-care Associated”: Hospital/Institution acquired infection o Pyogenic/Purulent Strains: Produces pus (Leukocyte-released Peroxidase) o Pyrogenic Strains: Causes fever (local ↑ in temperature) to ↓ optimal growth of microbes  Cytokine IL-1: Fever producing cytokine during inflammatory responses o Pathogenicity: Relative ability of microorganisms to cause disease (# of ppl infected)  Dose-related  E.g. 10,000 Salmonella (Low) vs. 10 Shigella (High) required to cause illness o Virulence: The intensity/severity of disease produced (# of ppl dead)  E.g. ribes virus – 100% mortality (High) vs. variola virus – 50% (Moderate)  Virulence factor: Products (excretions) of microbe that enhances its ability to cause disease. (Must be found only in virulent strains, disruption must result in reduced virulence or introduction into an avirulent must render the strain virulent & the gene must be expressed in host during infection) - Classic, Emerging, Re-emerging Infectious Disease o Historical factors:  ↑ Human population: Critical mass needed to spread disease  Poverty, crowding, competition for food: Compromisation  Domestication of animals: Zoonoses disease that came from domesticated animals o Recent factors:  ↑ Hygienic practices & Medical advances: Puerperal Fever (Maternity wards) – Anti- septic Hand-washing Solution (Dr. Ignaz Semmellweis)  Water & sewage treatment, antimicrobials, vaccines  ↑ Nutrition, ↓ Crowding, social safety net  ↑ Proportion of elderly population: Immuno-compromised @ late 20s  Global community – Travel ↑ spread of disease: SARs from HK & Swine Flu from Mexico  Human encroa
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