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Principles of Disease Microbiology 2314 • Every disease is a race between a pathogen trying to gain a foothold and the host defenses trying to prevent the pathogen from doing so. Disease • Is a Process • Is a State of Being Not In Good Health • Involves Many Factors - Age - Nutrition - Gender - Race • We tend to equate one pathogen with one disease, but it is more complicated than that. • It is actually much more complicated than that. Definitions: Parasite • Refers to Protozoans and Worms Definition: Pathogen • Refers to Bacteria / Virus / Fungus • An organism with the potential to cause disease. More Definitions: • Infection A pathogen growing in or on the host • Virulence The degree or intensity of pathogenicity • Invasiveness Ability to spread to other tissues • Infectivity Ability to secrete toxins • Septicemia Blood infection • Pathology Scientific study of disease • Etiology Cause of disease • Pathogenesis Development of disease • Host Organism that shelters and supports the growth of pathogens. Disease • An abnormal process in which part or all of the body is not properly adjusted or is incapable of performing normal functions often because of infection by pathogens. Relationships Between Microorganisms and Man Usually germ-free in utero Microorganisms begin colonization in and on the surface of the body during and after birth We require these organisms David Vetter the “Bubble Boy” Germ-free organisms are less healthy than organisms with normal microbiota Body Regions Have Characteristic Flora • Skin • Mouth • GI Tract 1012 1010 1014 Normal Flora Are Found Mostly – – – – – – – – • on the skin in the eyes in the nose in the mouth in the upper throat in the lower urethra in the lower intestine especially in the large intestine Note that this list basically includes all of the body surfaces exposed to the external environment. Microbial Antagonism • Normal Microbiota establish permanent colonies inside or on the body without producing disease • Symbiosis • Three Types 1. Commensalism 2. Mutualism 3. Parasitism • Transient microbiota are members of the normal flora that are not always present or are present for only a few days, weeks, or months before disappearing. Nitrogen Fixation -- Mutualism Ruminants and Resident Microbes – Mutualism Lichen Symbiosis -- Mutualism Ascaris Worms / Parasitism • The upper respiratory tract consists of the nostrils, nasal cavities and throat. It contains a number of commensalistic inhabitants including: Staphylococcus epidermidis. Out of all types of symbiotic bacteria, commemsalists are the least studied. The reason for this is simple; if a bacteria is not causing harm or benefit to a host there is simply not much reasons to studying it. Microbial Antagonism Microbial Antagonism or Colonization inhibition: A process by which pathogenic microorganisms are inhibited by normal flora from colonizing healthy organisms (a form of symbiosis) Antagonism between the fungus Paraconyothyrium variabile and Fusarium oxysporum • Mechanisms by which this inhibition occurs includes: 1. competing with pathogenic microorganisms for nutrients 2. competing with pathogenic microorganisms for space 3. producing toxins that are harmful to some pathogenic microorganisms Remember! • Categorizing symbiotic relationships is convenient, but keep in mind that under certain circumstances the relationship can change. Question? • A colonic microorganism which bores into its host and by doing so does it damage, competes with its host for nutrients, but is the sole supplier of an organic growth factor without which the host could not survive. This symbiotic relationship is an example of (chose the best answer): a. commensalism b. mutualism c. parasitism Question? • A colonic microorganism which bores into its host and by doing so does it damage, competes with its host for nutrients, and is the sole supplier of an organic growth factor without which the host could not survive. This symbiotic relationship is an example of (chose the best answer): a. commensalism b. mutualism c. parasitism Question? • A bacteria is attached to the intestinal wall via its pili, causes its host no harm, and secretes an antibacterial poison which limits colonization of the intestine by other, unrelated bacteria. With regard to the prevention of disease, what process specifically is this bacteria effecting? Microbial Antagonism Question? • Microbial antagonism (choose best answer) a. is a parasitic interaction between two organisms b. describes generally the harm done by a microorganism to a host c. can be an example of mutualism d. can be an example of parasitism e. all of the above Ab. none of the above Question? • Microbial antagonism (choose best answer) a. is a parasitic interaction between two organisms b. describes generally the harm done by a microorganism to a host c. can be an example of mutualism d. can be an example of parasitism e. all of the above Ab. none of the above Question? • A colonic microorganism which bores into its host and by doing so does it damage. This organism has no additional redeeming characteristics. You would describe the symbiotic relationship it has with its host as an example of (choose the best answer): a. commensalism b. mutualism c. microbial antagonism d. parasitism e. none of the above Question? • A colonic microorganism which bores into its host and by doing so does it damage. This organism has no additional redeeming characteristics. You would describe the symbiotic relationship it has with its host as an example of (choose the best answer): a. commensalism b. mutualism c. an effector of microbial antagonism d. parasitism e. none of the above Question? • Which is not a member of the normal flora of a plant or an animal? (assume all are obligate colonizers of the plant or animal host organism) a. a bacterium b. a virus c. a fungus d. a protozoa e. all are equally likely to be members of normal flora Question? • Which is not a member of the normal flora of a plant or an animal? a. a bacterium b. a virus c. a fungus d. a protozoa e. all are equally likely to be members of normal flora Question? • Name a part of the body that you would not expect to have an associated normal flora. Stomach Kidney Liver Etc. Anything Basically That Is Internal Transient Microbiota • Transient microbiota are members of the normal flora that are not always present or are present for only a few days, weeks, or months before disappearing. Opportunistic Microorganisms • Do not cause disease under normal conditions but can cause disease under special conditions. Staph Infection Cooperation Among Microorganisms • One of the organizing principles of life on Earth is that cells cooperate. • This is evident in the case of multicellular organisms, from nematodes to humans, but it also appears to apply widely among single-celled organisms such as bacteria, fungi, and amoeba. • A well-studied example of intraspecies cooperation concerns the cyanobacterium Anabaena, which grows in long chains, in which approximately one cell out of ten differentiates into a heterocyst that provides fixed nitrogen for the neighboring cells This Cellular Cooperation Can Increase the Virulence of a Microorganism Example: Strep Infection Scarlet Fever Rheumatic Fever The Etiology of Infectious Disease Koch’s Postulates • Robert Koch played an important role in determining that specific microbes were associated with specific diseases. • Four Postulates 1. Same pathogen must be present in every case of the disease. 2. Pathogen must be isolated in pure culture. 3. Pathogen isolated from pure culture must cause the same disease in lab animal. 4. Pathogen must be re-isolated from inoculated lab animal. Exceptions to Koch’s Postulates • Inability to grow on artificial media (Syphilis) Exceptions to Koch’s Postulates • Unequivocal signs and symptoms (Tetanus) Exceptions to Koch’s Postulates • Diseases caused by variety of organisms (Pneumonia) • Pathogens causing variety of diseases (Streptococcus pyogenes) Exceptions to Koch’s Postulates • Diseases that occur in humans only (Smallpox) Classifying Infectious Diseases • Symptoms Subjective Changes Cannot Be Measured • Signs Objective Changes Measurable Changes Sign or Symptom? • • • • • • Pain Temperature Nausea Swelling Discomfort Blood Pressure Classifying Infectious Diseases • Syndrome A specific group of symptoms or signs that always accompany a specific disease. What is the Syndrome? • • • • • • • • Flu Measles Anthrax Legionnaires Mumps Carbuncles Smallpox West Nile Virus Communicable Diseases • Transmitted Directly or Indirectly From One Host to Another Host Chickenpox Measles Genital Herpes Contagious Diseases • A communicable disease that is spread easily from one individual to another Name a Communicable Disease that is Not Contagious. Noncontagious Diseases • Caused by microorganisms that normally grow outside the human body and are not transmitted from one host to another. Tetanus Anthrax The Occurrence of Disease • Incidence Number of New Cases of Disease in a Given Population. The Risk of Disease • Prevalence Number of Existing Cases of Disease in a Given Population at Any One Time The Burden of Disease Question? • Assume a classroom of 50 students exposed to a new strain of three-day influenza. • Before exposure, the prevalence and incidence in this population are both zero. • If within one week, 5 out of the 50 students contract the flu, what is the incidence? • What is the prevalence for that one week period? Continue? • If after one more week, 5 more students become infected, what is the point prevalence? • What is the overall prevalence? • What is the incidence? Trends • Changes in incidence and prevalence are usually followed over a seasonal, yearly, and long-term basis and are helpful in predicting trends. • Statistics of concern to epidemiologists are the rates of disease with regard to sex, race, and geographic region. What We See • Infectious Diseases High Incidence Low Prevalence • Chronic Diseases Low Incidence High Prevalence Classification of Disease • Sporadic Only an Occasional Case (Typhoid Fever) • Endemic Constantly Present at an Expected Level (Common Cold) • Epidemic Above the Normal Expected Frequency (Flu) • Pandemic World Wide Epidemic (AIDs) Scope of Disease • Acute Develops Rapidly Short Lifespan Usually Severe Symptoms Example: Flu, Measles • Chronic Develops Slowly Continual, Long Lasting, or Reoccurring Usually Less Severe Example: Osteoporosis • Latent Causative Agent Remains Inactive for a Time – Then Becomes Active and Produces Symptoms. Chicken Pox to Shingles HIV to AIDS Herd Immunity • The presence of immunity to a disease in most of the population. • Normally due to Vaccination. Herd Immunity is the Reason we Vaccinate! The way herd immunity works is by isolating potential hosts and reducing virus’ opportunities to be passed on. For herd immunity to be effective I need to vaccinate at least 90% of the susceptible population. If I drop below a 90% vaccination rate, the chances of passing infection increase and I get small clusters of disease occurring. Emerging Infectious Diseases • New diseases with increasing incidence. 1. SARS 2. Ebola 3. West Nile Virus 4. Bird Flu 5. Monkeypox Emerging Infectious Diseases EIDs • EIDs Can Result From 1. Overuse of Antibiotics 2. 3. 4. 5. Overuse of Pesticides Climatic Changes Travel Lack of Necessary Vaccinations The CDC, NIH and WHO are responsible for surveillance and responses to EIDs and the world’s health. Re-emerging Infectious Diseases RIDs • Old diseases that are occurring with increasing incidence. 1. Tuberculosis 2. Hantavirus 3. Plague The Extent of Host Involvement Local Infection • A local infection affects a small area of body • Boil or Acne Systemic Infection • Infection spread throughout the body via the circulatory system • Mumps • Systemic Infections often lead to Focal Infections. • What is a Focal Infection? Secondary Infection • After the host is weakened from a primary infection, it is easier for them to become infected with a secondary infection due to a compromised immune system. Unapparent or Subclinical Infection • An apparently healthy individual carries the disease organism and passes it on to others without expressing any symptoms of the illness. • Poliovirus • Hepatitis A • HIV Reservoirs of Infection For a disease to perpetuate itself, there must be continual organisms available and a source providing appropriate conditions. Birds are Reservoirs for WNV • Marine shellfish are the main reservoir of Cholera Zoonoses • Diseases that affect wild and domestic animals and can be transmitted to humans. • Lyme Disease • Rabies • Anthrax • West Nile Virus Transmission of Zoonoses • • • • • • Direct Contact with Infected Animals Direct Contact with Animal Waste Contamination of Food and Water Contaminated Hides, Fur, and Feathers Consuming Infected Animal Products Insect Vectors Some Diseases Result from Pathogenic Microorganisms Growing in or on Nonliving Reservoirs Such as Soil and Water or Objects • Ringworm • Botulism • Tetanus Transmission of Disease • Direct Transmission 1. Close Personal Contact 2. Touching, Kissing, etc. Indirect Transmission 1. 2. 3. 4. Fomites Droplets/Airborne Vehicles Vectors Direct Transmission 1. Personal Contact 2. Touching Kissing Sex Etc. Indirect Transmission • Fomites Inanimate Objects Tissues, Drinking Glasses, Needles AIDS, Hepatitis Indirect Transmission • Transmission by a Medium Water, Food, Air Plague, Cholera Indirect Transmission • Droplet Transmission Saliva and Mucus Coughing, Sneezing, Laughter Less than 1 Meter Indirect Transmission • Airborne Transmission Carried on Water/Mucus Droplets Greater than 1 Meter Indirect Transmission • Vectors (Often Arthropod) 1. Mechanical Means Passive Process Pathogens are on the body of the vector. Ex. Fly landing on food Can you name a Disease Transmitted by this Process? this Indirect Transmission • Vectors (Often Arthropod) 2. Biological Means Active Process Vector must bite or scratch or sting. Ex. Mosquito Bite Can you name a Disease Transmitted by this process? Routes of Transmission 1. Vertical Mother to Offspring - Transplacental: Rubella, Toxoplasma (Note: Humans only have two layers of separation) - Perinatal: Listeria, Gonorrhea, Chlamydia - Breastfeeding: HIV 2. Horizontal Person to Person - Contact Spread - Common Vehicle - Airborne - Vector-borne Portals of Exit (Preferred Ways to Leave the Body and Spread Infection) • Respiratory Tract (Coughing or Sneezing) • Gastrointestinal Tract (Saliva or Feces) • Urogenital Tract (Secretions from the Vagina or Penis) Arthropods and Syringes provide a portal of exit for microbes in blood. Nosocomial Infections • An infection that is acquired during the course of stay in a health facility. • 2 million NI Yearly • 5-15% of All Patients Acquire NI • 90,000 Die The Rate of Nosocomial Infections Is Increasing Trends in Nosocomial Infections • • • • • 1940’s – 1950’s 1970’s 1980’s 1990’s 2000’s Gram + S. aureus Gram – E. coli Gram + A.R. S. aureus Both No Relief in Sight Frequency of Nosocomial Infections Large Number of Skin Infections Due to Newborns The Compromised Host is Most at Risk 1. Burns (Broken Skin) 2. Surgical Wounds (Broken Skin) 3. Suppressed Immune Systems (Due to Ill Health) The Body Defends Us • Skin and Mucus Membranes • T-Lymphocytes Kill Pathogens • B-Lymphocytes Produce Antibodies • Their Effectiveness if Altered By Many Things - Drugs Radiation Steroids Burns Diabetes Stress Poor Nutrition Chain of Transmission: Nosocomial Infections Are Transmitted By Direct Contact Between Staff Members and Patients Fomites such as catheters, syringes, and respiratory devices can transmit nosocomial infections. Control of Nosocomial Infections 1. Handwashing #1 2. Disinfect Equipment 3. Necessary Antibiotics Only 4. Infection Control Team Could a copper door handle help to beat MRSA (2009 Study)? • Doorknobs, bath taps, toilet handles and 'grab rails' will be ripped out and replaced with copper versions at Birmingham's Selly Oak hospital in a bid to beat MRSA • MRSA has proven resistant to even the most powerful antibiotics. But hospital superbugs may finally have met their match - in copper door handles. • Copper, used in medicines for 4,000 years, has been shown to be highly effective in killing off pathogens such as MRSA. • In the trial study, copper grew 95% less bacteria. Predisposing Factors A Factor that Makes the Body More Susceptible to Disease or Alters the Course of an Illness. • • • • • • Gender Climate Age Fatigue Poor Nutrition Low Vitamin D Epidemiology • The study of the distribution and determination of health related events within a given population. • The study of the transmission, incidence, and frequency of disease 1. Descriptive Epidemiology 2. Analytical Epidemiology 3. Experimental Epidemiology Descriptive Epidemiology • Data about infected people are collected and analyzed in descriptive epidemiology. • Who, What, When, Where, How, etc. Analytical Epidemiology • A group of infected people is compared with an uninfected group. • Analytical epidemiology aims to research and study risk and protector factors of diseases. Relative Risk of Death on the Titanic Female Male Alive Dead 308 154 462 142 709 851 Female Male Alive Dead 308 154 462 142 709 851 Probability of Death for Females is 154 / 462 = .333 or 33% Probability of Death for Males is 709 / 851 =.833 or 83% RR = .833 / .333 = 2.5 There is a 2.5 greater probability of death for males than for females. Experimental Epidemiology • Use of controlled experiments designed to test hypotheses are performed in experimental epidemiology. • Example: In these studies normal guinea pigs were exposed to tuberculosis cage mates in two different degrees of crowding, some in ordinary cages, where the food became contaminated with the excreta, laden with tubercle bacilli, of the inoculated animals, and some in special cages with wire-mesh floors, where these excreta were largely excluded as a source of contagion. Clinical Trial History • John Snow • London Cholera Epidemic • Broadstreet Pump The CDC is the Main Source of Epidemiological Information in the United States