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THE PROCESS OF INFECTION • The growth/multiplication of a microbe in a host • Infection does not always result in injury of the host (disease) • Two main classes of infection by site: – localized – generalized (disseminated; systemic) Localized Infections • Organism enters the body and reaches target site of infection • Organism adheres to or enters host cells and multiplies at site of infection • Infection spreads within the site (e.g., respiratory tract; intestines) • Symptoms of illness appear • Organism does not spread through the lymphatic system or reach the bloodstream • Infection subsides due to host defenses (e.g., immunity) • Agent eliminated from the body; infected cells replaced; "cure" Generalized Infections • Organism enters the body and reaches target site of initial infection • Organism adheres to or enters host cells and multiplies at initial site of infection • Infection spreads within site and to other sites via tissues, lymphatic system, bloodstream (bacteremia, viremia, etc.) and possibly other routes • Symptoms of illness may appear • Organisms infect other organs, tissues and cells; more spread via bloodstream • Symptoms of illness become severe • Host defenses eliminate organisms leading to cure or disease continues, possibly leading to irreversible damage or death FACTORS INFLUENCING EXPOSURE AND INFECTION: Agent Factors Sources, Reservoirs, Transport and Persistence (in the Environment) Ability to Enter a Portal in the Human or Other Host Ability to Reach and Proliferate at Site(s) of Infection in the Host Excretion of the Agent from the Host Quantity and "Quality" (including virulence) of the Infectious Factors Influencing Exposure and Infection: Environmental Factors • Reservoirs: where organisms can live, accumulate or persist outside of the host of interest; could be another organism or the inanimate environment. • Vehicles: inanimate objects/materials by which organisms get from one host to another; includes water, food, objects (called fomites) and biological products (e.g., blood). • Amplifiers: Types of reservoirs where organisms proliferate; often applied to organisms transmitted by the airborne route. • Vectors: Living organisms bringing infectious organisms to a host. – Mechanical vectors: Microbes do not multiply in the vector • ex: biting insects infected with the infectious organism – Biological vectors: Microbes must propagate in the vector before they can be transmitted to a host. Environmental Factors Influencing Survival or Proliferation of Infectious Agents • Physical: temperature, relative humidity, sunlight, moisture content or water activity, climate and weather, etc. • Chemical and Nutritional: Antimicrobial chemicals, nutrients for microbial proliferation. • Biological: Antagonistic activity by other organisms: antimicrobial agents, parasitism, etc.; presence and state of a vector Factors Influencing Exposure and Infection: Host Factors and Host Susceptibility • Opportunities for host exposure – transmission routes – host availability • Susceptibility factors – Dosage (quantity) and "quality" of infectious organisms, including their "virulence"; – age – immunity – nutritional status – immunocompetence and health status, – genetics – behavior (personal habits) of host. Infectivity of Pathogenic Microorganisms and Risk of Infection, Illness and Death Infection Illness Sequelae Death Secondary Spread Infectious Dose • Microbes differ in their infectious dose. • Enteric and respiratory viruses are infectious at very low doses – as little as one cell culture infectious dose has a high probability of infecting an exposed human. – But, this may still require exposure to many virus particles. • Most enteric bacteria are infectious at moderate (10s-100s of cells) to high (1,000 cells) doses. • Protozoan cysts may be infectious at low doses – A few as 1-10 cysts of Giardia lamblia) or oocysts of Cryptosporidium parvum Outcomes of Infection Microbes differ in their ability to produce the different outcomes of infection: • (i) infection without illness; • (ii) infection with illness; (with or without long-term sequelae) and • (iii) infection, illness and then death The Iceberg Concept: As Applied to Virus Infections Type of contact Inhalation Example Type of Agent Virus Source Ingestion Coccidiodo mycosis Typhoid fever Salmonella food poisoning Fungus Bacterium Bacterium Sexual contact Wound Gonorrhea Bacterium Surgical infections Bacterium Insect Bite Malaria Protozoan Difficult to avoid contact Lower infecting dose Lower infecting dose Person Social Avoid Behavior contact Normal flora Aseptic Avoid surroundin techniques contact gs Mosquito Insect Eliminate control vector Common cold Strategy for Preventive Prevention Aim None Difficult to avoid contact Aerosol from infected persons Soil None Water, food Sanitation Food Sanitation Examples of Encounters and Disease Prevention Type of contact Example Type of Agent Source Strategy for Preventive Aim Prevention Inhalation Common cold Virus None Difficult to avoid contact Ingestion Coccidiodomycosis Typhoid fever Salmonella food poisoning Gonorrhea Fungus Aerosol from infected persons Soil None Hard to avoid contact Lower infecting dose Surgical infections Bacterium Normal flora Aseptic Avoid contact surroundings techniques Sexual contact Wound Insect Bite Malaria Bacterium Water, food Bacterium Food Sanitation Sanitation Bacterium Person Social Behavior Protozoan Mosquito Insect control Avoid contact Eliminate vector Constitutive Defenses: Physical Barriers to Infection System or Organ Skin Mucous membranes Cell Type Squamous Columnar nonciliated (e.g., gastrointestinal tract) Columnar ciliated (e.g., trachea) Cuboidal ciliated (e.g., nasopharynx) Secretory Clearing Mechanism Desquamation Perstalsis Mucociliary movement Tears, saliva, mucus, sweat Flow of liquids Constitutive Defenses: Chemical Barriers to Infection System or Organ Source Skin Mucous membranes Sweat, sebaceous glands Parietal cells of stomach Secretions Neutrophils Lung A cells Salivary glands Neutrophils Small bowel and below Liver via biliary tree Gut flora Substances Organic acids Hydrochloric acid, Low pH Antimicrobial compounds Lysozyme, peroxidase, lactoferrin Pulmonary surfactant Thiocyanate Myeloperoxidase Cationic proteins Lactoferrin Lysozyme Bile acids Low molecular weight fatty acids Mortality Rates for Different Viruses in Healthy, Immunocompetent Humans (Rates Higher in the Immunocompromised) VIRUSES: • Adenovirus • Enteroviruses – Coxsackievirus B – Echoviruses • Hepatitis A virus • Norwalk virus • Rotavirus % Mortality 0.01% 0.001 (average) 0.59-0.94 0.28 0.3 0.0001 0.01 Mortality Rates for Different Pathogens in Healthy, Immunocompetent Humans (Rates Higher in the Immunocompromised) BACTERIA: • Campylobacter jejuni • E. coli • Salmonella spp. • Shigella spp. % Mortality 0.1 0.2 0.1 0.2 • PARASITES: • Giardia lamblia • Entamoeba histolytica 0.0001 0.3 Transmission Categories of WaterAssociated Diseases • Waterborne Microbial Diseases • Water-washed or Water Hygiene Diseases • Water Contact/Water Vector Habitat Diseases Transmission Categories of Water-Associated Diseases: Waterborne Microbial Diseases • Exposure mainly by ingestion of contaminated water • Primarily enteric diseases transmitted by the fecaloral route • Some are due to organisms that are not fecally associated and also proliferate in water – example: Legionella bacteria via aerosols and droplets Transmission Categories of Water-Associated Diseases: Water-washed or Water Hygiene Diseases • Diseases whose exposure is reduced by the use of water for personal and domestic hygiene: – washing: clothes, floors, other household chores – bathing and other personal hygiene – cleaning of cooking and eating utensils • Includes many enteric organisms as well as diseases of the skin and eyes (ex: trachoma) and insect infestations (ex: scabies caused by mites; pediculosis caused by lice). Transmission Categories of Water-Associated Diseases: Water Contact/Water Vector Habitat Diseases • Exposure by skin contact with infested water – example: schistosomiasis: the free-living larvae released from aquatic snails (the intermediate host) invade the skin. • Exposure to water habitat "insect vector" diseases – Insect vectors breed in or near water • examples: malaria (parasite) and yellow fever (virus) transmitted by mosquitoes