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Microbe-Human Interactions: Infection and Disease Chapter 13 Adapted from McGraw Hill by Dr. G Cornwall 13.1 The Human Host • Contact, Infection, Disease- A Continuum • Body surfaces are constantly exposed to microbes • Inevitably leads to infection: pathogenic microorganisms penetrate the host defenses, enter the tissues, and multiply • Pathologic state that results when the infection damages or disrupts tissues and organs = disease • Infectious disease: the disruption of a tissue or organ caused by microbes or their products • Host-Parasite relationship • contact - not all contacts lead to colonization • progress to infection • disease Resident Biota • Resident Biota: The Human as a Habitat • Cell for cell, microbes on the human body outnumber human cells at least ten to one • Human cells in an adult is about 10 trillion • Bacteria in and on an adult is about 100 trillion • Normal (resident) biota - adapted to live here on us • Metagenomics being used to identify the microbial profile inside and on humans • Human Microbiome Project • Acquiring Resident Biota • The body provides a wide range of habitats and supports a wide range of microbes Normal Microbiota • Resident Microbes • each site has particular populations • changes over time • Transient Microbes • do not normally reside, just passing through • most are harmless, some pathogens • Opportunists • cause disease when given opportunity • breakdown in immunity • certain medical treatments • implantation of devices Sites Thought to be Sterile Impact of the Normal Flora • Organ Development is influenced by presence of resident biota • Prevent overgrowth of harmful microbes (e.g lactobacilli & yeasts in vagina) • Microbial antagonism: antagonism of “good” microbes against intruders • residents are unlikely to be displaced by intruders • production of a chemical or physiological environment that in unfavorable to intruders • Composition of intestinal biota may influence your tendency to be overweight • obese humans have more firmicutes, and less bacteroidetes • firmicutes may draw more calories out of food • Whether we can call a microbe beneficial depends on an individuals good health and fully functional immune system • disease could easily be caused by previously normal biota • Endogenous Infections - caused by endogenous biota (AIDS, or introduction in to sterile organ - Bladder infection) • What about Viruses as normal Biota? • now finding that some may have coevolved with us to be beneficial • ERV’s are vital to healthy placental development in sheep • T-lymphotrophic virus = lower incidence of stomach cancer (mutualistic and protective role) Initial Colonization of a Newborn • Birth canal - vaginal biota are the first to colonize when membranes break • C-section means skin biota are first • either way mostly from mother • Food - breast or Bottle (formula) makes a HUGE difference • Breathing • Healthcare professionals Concept Check Which of the following do not normally contain microbiota? A. Skin B. Liver and kidneys C. Vagina D. Upper respiratory system 13.2 The Progress of an Infection • Pathogen: a microbe whose relationship with its host is parasitic and results in infection and disease • True vs Opportunistic • Type and severity of infection depend on pathogenicity of the organism and the condition of its host • Opportunistic Pathogens cause disease when hosts defenses are compromised Virulence • The degree of pathogenicity • Determined by its ability to • Establish itself in the host • Cause damage • Virulence factor: any characteristic or structure of the microbe that contributes to its virulence • Different healthy individuals have widely varying responses to the same microorganism: hosts evolve Becoming Established: Step OnePortals of Entry • Microbe enters the tissues of the body by a portal of entry • Usually a cutaneous or membranous boundary • Exogenous or Endogenous Sources • Normally the same anatomical regions that support normal biota: Skin, GI tract, Respiratory tract, and urogenital tract • the majority of pathogens have adapted to a specific portal of entry, although some are adapted to several Infectious Agents that Enter the Skin • Nicks, abrasions, and punctures • Intact skin is very tough- few microbes can penetrate • Some create their own passageways using digestive enzymes or bites • certain helminth worms • bites from insects or other animals carrying microbes • contaminated needles - HIV, hepatitis, tetanus • Examples • Staphylococcus aureus (boils) • Streptococcus pyogenes (impetigo) • Haemophilus aegyptius (pink eye) • Chalmydia trachomatis (trachoma - granular conjunctivitis) • Neisseria gonorrhoeae The Gastrointestinal Tract as Portal • Pathogens contained in food, drink, and other ingested substances • Adapted to survive digestive enzymes and pH changes • Examples • Salmonella, Shigella, Vibrio, Certain strains of Escherichia coli, Poliovirus, Hepatitis A virus, Echovirus, Rotavirus, Entamoeba histolytica, Giardia lamblia The Respiratory Portal of Entry • The portal of entry for the greatest number of pathogens • continuous membrane surface covering the upper respiratory tract, sinuses, and auditory tubes allows microbes to be transferred from one site to another • Examples • Streptococcal sore throat, Meningitis, Diphtheria, Whooping cough, Influenza, Measles, Mumps, Rubella, Chickenpox, Common cold • Bacteria and fungi can cause pneumonias when smaller pathogens that are inhaled into lower regions of respiratory tract Urogenital Portals of Entry • Sexually transmitted diseases (STDs) - 4% of infections worldwide - approximately 13 million new cases in the US each year • Enter skin or mucosa of penis, external genitalia, vagina, cervix, and urethra • Some can penetrate an unbroken surface • Examples • Syphilis • Genital warts • Chlamydia • Herpes • Trichomonas (a protozoan) • HIV, Hepatitis B • Not all urogenital infections are STD’s Pathogens that Infect During Pregnancy and Birth • Some microbes can cross the placenta (ex. the syphilis spirochete) • Other infections occur perinatally when the child is contaminated by the birth canal • TORCH (toxoplasmosis, other diseases, rubella, cytomegalovirus, and herpes simplex) The Size of the Inoculum: • The quantity of microbes in the inoculating dose • For most agents, infection only proceeds if the infectious dose (ID) is present • in general, microorganisms with smaller IDs have greater virulence • ID for causative agent of Q fever is 1 infectious cell • Only 10 infectious cells for tuberculosis • Gonorrhea ID = 1,000 • Cholera ID = 1,000,000,000 • Numbers below the ID will generally not cause infection, however if there is a much higher quantity then onset can be extremely rapid Becoming Established: Step TwoAttaching to the Host (Adhesion) Adhesion is a process by which microbes gain a more stable foothold • Bind with • Fimbriae (pili) • surface proteins, and adhesive slimes or capsules • viral envelope spikes • suckers, hooks, or barbs • pathogens are limited to only those cells to which it can bind Becoming Established: Step ThreeSurviving Host Defenses • Phagocytes -White blood cells that engulf and destroy pathogens • Antiphagocytic factors: used by some pathogens to avoid phagocytes • Leukocidins: toxic to white blood cells, produced by Streptococcus and Staphylococcus • Extracellular surface layer: makes it difficult for the phagocyte to engulf them, for example- Streptococcus pneumonia, Salmonella typhi, Neisseria meningitides, and Cryptococcus neoformans • Some can survive inside phagocytes after ingestion: Legionella, Mycobacterium, and many rickettsias Causing Disease: How Virulence Factors Contribute to Tissue Damage • virulence factors are adaptations used by microbes to invade and establish itself in the host • determine the degree of tissue damage • effect varies greatly • Microorganisms inflict damage by: • use of exoenzymes and toxins • cause damage indirectly - their presence causes an excessive or inappropriate response (most cases) Extracellular Enzymes • Break down and inflict damage on tissues or dissolve the host’s defense barriers • Examples • Mucinase • Keratinase • Collagenase • Hyaluronidase • Some react with components of the blood • Coagulase causes clotting of blood or plasma (staphylococci) • Kinases (streptokinase, and staphylokinase) do the opposite (dissolve fibrin clots to expedite invasion) Bacterial Toxins • Toxins are specific chemical products that are poisonous to other organisms • Toxigenicity: the power to produce toxins • Toxinoses: a variety of diseases caused by toxigenicity • Toxemias: the toxin is spread by the blood from the site of infection (tetanus and diphtheria) • Intoxications: ingestion of toxins (botulism) • Toxins are named according to the specific target of action (neurotoxin, enterotoxins, hemotoxins, nephrotoxins) Endotoxins and Exotoxins Toxins can also be classified according to their origins • Exotoxins are secreted by a living bacterial cell into the infected tissue • have highly specific targets, and physiological effects (many varieties) • Endotoxins are not actively secretes, but are shed from the outer membrane • given off when cell wall of gramnegative bacteria disintegrates (lipopolysaccharide / LPS) • has more generalized physiological effects Concept Check Which of the following is not an exoenzyme? A. Botulism toxin B. Keratinase C. Mucinase D. Collagenase The Process of Infection and Disease • Establishment, Spread, and Pathologic Effects • Microbes eventually settle in a particular target organ and continue to cause damage at the site • In addition to the effects of enzymes and toxins, multiplication of the pathogen frequently weakens host tissues • Pathogens can obstruct tubular structures (blood vessels, lymphatic vessels, and fallopian tubes, bile ducts) • Necrosis: accumulated damage leads to cell and tissue death • Viruses do not produce toxins or exoenzymes • multiply and lyse cells • many cytopathic effects from impaired metabolism and death of cells Progression of Infection • Incubation period • Prodromal • Invasion • Convalescence Patterns of Infection • Localized: pathogen is restricted to a specific site • Systemic: pathogen spreads through circulation to many sites • Focal Infection: initially a local infection, but circumstances cause the pathogen to be carried to many other sites • Mixed Infection: same site infected with multiple microbes • Primary- Secondary: initial infection is complicated by a second one in same or different location • Acute vs Chronic Stages in Infections Signs and Symptoms: Warning Signals of Disease • Sign: any objective evidence of disease as noted by an observer • Symptom: the subjective evidence of disease as sensed by the patient • Syndrome: when a disease can be identified or defined by a certain complex of signs and symptoms Signs and Symptoms of Inflammation • Fever, pain, soreness, swelling • Edema • Granulomas and abscesses • Lymphadenitis • Lesion: the site of infection or disease including rashes or other skin eruptions Signs of Infection in the Blood • Changes in the number of circulating white blood cells are considered to be signs of possible infection • Leukocytosis = increase in level of WBC’s • Leukopenia = a decrease in WBC’s • Other signs of infection include presence of a microbe, or its products in the blood • Septicemia: general state in which microorganisms are multiplying in the blood and are present in large numbers • Bacteremia or viremia: microbes are present in the blood but are not necessarily multiplying • Immune response (antibodies in serum) • basis of several serological tests • Asymptomatic or Subclinical = unnoticed infections Exit Portals In most cases the pathogen is released from the body through secretions, excretion, discharge or sloughed tissue • Respiratory and Salivary Portals • Coughing and sneezing • Talking and laughing • Skin Scales • Fecal Exit • Urogenital Tract • Removal of Blood or Bleeding The Persistence of Microbes and Pathologic Conditions • Latency: a dormant state • The microbe can periodically become active and produce a recurrent disease • microbe may or may not be shed during latency • Examples of persistent infectious agents • Herpes simplex, Herpes Zoster • Hepatitis B • AIDS • Epstein-Barr • Sequelae: long-term or permanent damage to tissues or organs Reservoirs: Where Pathogens Persist • Reservoir: the primary habitat in the natural world from which a pathogen originates • Source: the individual or object from which an infection is actually acquired • Living Reservoirs • Carrier: an individual who inconspicuously shelters a pathogen and spreads it to others without any notice • Asymptomatic carriers • Incubation carriers • Convalescent carriers • Chronic carrier • Passive carrier Animals as Reservoirs and Sources • Vector: a live animal that transmits an infectious agent from one host to another • Majority are arthropods • Larger animals can also be vectors • Biological vector: actively participates in a pathogen’s life cycle • Mechanical vectors: transport the infectious agent without being infected • Zoonosis: an infection indigenous to animals but naturally transmissible to humans • People in animal oriented outdoor professions are at the greatest risk • At least 150 worldwide • make up 70% or emerging diseases worldwide • mostly due to environmental destruction (deforestation, urban sprawl) - animals have to find new habitat Nonliving Reservoirs • Microorganisms have adapted to nearly every habitat in the biosphere • they thrive in soil and water • most are saprobic, and of benefit to us • Human hosts in regular contact with environmental sources Concept Check Which of the following is a symptom? A. Elevated white blood cell count B.Fever C. Nausea D. Swollen lymph nodes Acquisition and Transmission of Infectious Agents • Communicable disease: when an infected host can transmit the infectious agent to another host and establish infection in that host • Transmission can be direct or indirect • If the agent is highly communicable, it s considered Contagious • Noncommunicable disease: does not arise through transmission of the infectious agent from host to host • Acquired through some other, special circumstance • Compromised person invaded by his or her own microbiota • Individual has accidental contact with a microbe in a nonliving reservoir (tetanus) Transmission Direct (Contact) transmission • Touching • Kissing • Sexual Intercourse • Bites by biological vectors • Vertical transmission • prenatal -- across placenta • perinatal -- during or shortly after birth • Droplet contact - spray from sneezing or coughing Indirect transmission • Vehicle: any inanimate material commonly used by humans that can transmit infectious agents (food, water, biological products, fomites) • Fomites: Contaminated objects (doorknobs, telephones, remote controls, faucets etc.) • Food poisoning (soil, handler, mechanical vector) • Oral-fecal route (contaminated toys, handler with inadequate personal hygiene) • Air as a vehicle • Indoor air • Droplet nuclei • Aerosols Nosocomial Infections: The Hospital as a Source of Disease • Nosocomial infections: infectious diseases that are acquired or develop during a hospital stay • 2-4 million cases a year, resulting in nearly 90,000 deaths • Most common = urinary tract, respiratory tract and surgical site infections • The importance of medical asepsis Universal Blood and Body Fluid Precautions • Universal precautions (UPs): guidelines from the Centers for Disease Control and Prevention • Assume that all patient specimens could harbor infectious agents • Include body substance isolation (BSI)techniques to be used in known cases of infection • precautions designed to protect ALL individuals in clinical settings (patients, workers, and public) Which Agent is the Cause? Using Koch’s Postulates to Determine Etiology • Etiologic agent: the causative agent • Robert Koch: developed a standard for determining causation that would stand the test of scientific scrutiny • Koch’s Postulates • Find evidence of a particular microbe in every case of a disease • Isolate that microbe from an infected subject and cultivate it in pure culture in the laboratory • Inoculate a susceptible healthy subject with the laboratory isolate and observe the same resultant disease • Re-isolate the agent from this subject 13.3 Epidemiology: The Study of Disease in Populations • Epidemiology: the study of the frequency and distribution of disease and other health-related factors in defined human populations • Involves not only microbiology but also anatomy, physiology, immunology, medicine, psychology, sociology, ecology, and statistics Who, When, and Where? Tracking Disease in the Population • Epidemiologists concerned with virulence, portals of entry and exit, and the course of the disease • Also interested in surveillance - collection and analysis of data on rates of occurrence, mortality, morbidity, and transmission • Reportable diseases: by law, must be reported to authorities (specified diseases) • Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia • Weekly notice: the Morbidity and Mortality Report • Shares statistics with the World Health Organization (WHO) Epidemiological Statistics • Prevalence rate: total number of existing cases with respect to the entire population • Incidence rate: the number of new cases over a certain period of time (case or morbidity rate) • of particular interest are statistics on sex, race, or geographic region • Mortality rate: total number of deaths in a population due to certain disease Examination of epidemic curve (incidence rate over time) can determine if infection is: • point-source - all victims exposed from a single source (contaminated food item at potluck) • common-source - common exposure to a single source over time (contaminated water source) • propagated epidemic communicable infectious agent (influenza) • Index case - the first patient found in epidemiological investigation Epidemiology is the Study of occurrence of disease • When, where, and how is it transmitted? • Endemic • Chronic occurrence in a geographical region • Sporadic • Random small outbreaks • Epidemic • Sudden acute disease outbreak affecting many people • Pandemic • A worldwide epidemic (across geopolitical boundaries) Concept Check What term refers to the rapid increase in the incidence of a disease in a localized geographical region? A.Endemic B.Pandemic C.Sporadic D.Epidemic