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Microbial Agents of Infectious Diseases. ENVR 412 – Ecological Microbiology 04/09/09. Human-Microbial Interactions. Microbes colonize and inhabit humans and other living things.
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Microbial Agents of Infectious Diseases ENVR 412 – Ecological Microbiology 04/09/09
Human-Microbial Interactions • Microbes colonize and inhabit humans and other living things. • So-called “Normal Flora” colonize the skin, the oral cavity, the gastrointestinal tract, the upper respiratory tract (e.g. nasopharynx), and parts of genitourinary tract (urethra and vagina). • Colonization by normal flora is either neutral or beneficial. • “Pathogens” are microorganisms that colonize, invade and damage the body. Pathogens cause disease.
Deaths due to infectious diseasein the United States (1918 flu pandemic)
Africa • 10.7 million deaths • 6.7 million (63%) due to infectious disease • Americas • 6.0 million deaths • 623,000 (10%) due to infectious disease
Sanitation Global Water Supply and Sanitation Assessment (2000) • 2.4 billion people have inadequate sanitation • 1.1 billion people have inadequate or unsafe water • 4 billion cases of diarrhea every year • 2.2 million deaths from diarrheal disease every year • Most illness and death in children <5 years old • Less services in rural than in urban areas • Urban settlement/slums remain a problem • In the developing world wastewater treatment is rare Infectious disease risks from water, poor sanitation and hygiene, food and air are still with us the developed and developing world
Outline • Short history of public health microbiology • Types of pathogens • Infection dynamics • Host-pathogen interactions • Routes of transmission • Indicators of water quality
Early History of Public Health • The first recording of laws concerning public health appears in the Book of Leviticus in The Bible, • the Hebrew people were told to practice personal hygiene by washing and keeping clean. • they were instructed to bury their waste materials away from their camp sites, to isolate those who were sick and to burn soiled dressings. • they were prohibited from eating animals that had died of natural causes. • the procedure for killing animals was described and the edible parts were designated.
Early History of Public Health • During Middle Ages, most of the knowledge about sanitation and public health was lost and there was a general stagnation of culture for almost 1,000 years. • However, during Renaissance, wide spread epidemics of small pox, syphilis, rabies and other diseases prompted people to search for explanations as to how diseases were contracted and transmitted. • Most of the people believed that diseases were caused by the curse of Gods and as a result many bizarre treatments were used to drive away the devils or evil spirits and relieve symptoms.
Detail from Peter S. Bregel painting shows rich man standing near an outhouse which empties directly into the river. In Middle Ages, people used to throw excreta from their houses on the roads below.
Early History of Public Health • Outbreaks commonly decimated the populations of cities and countrysides • Plague • Syphilis • Cholera • Smallpox • By the middle of the 1800s, the new industrial cities were not only jam-packed, they were filthy, and full of garbage, dead animals, and sick people
John Snow (1854) • Proved cholera is waterborne • Fathered modern epidemiology • Provided basis of public sanitation movement
1840s • Public health began to slowly be redefined from a moral problem to an engineering and social reform problem • Chadwick Report (1842) – “The Sanitary Conditions of the Labouring Population” • John H. Griscom (1845) – “The Sanitary conditions of the Laboring Population of New York”
Sanitation Movement(1850s – 1900) “Our safety depends upon official vigilance” The Angel of Cleanliness bars the gate to cholera, yellow fever and smallpox. Harpers Weekly 1885, National Library of Medicine
Institutionalization of solid waste management in the U.S. late 1700s early 1800s Urban populations explode due to immigration and industrialization Water piped in (fire protection) then contaminated water sent to streets, rivers Poor sanitation leads to disease outbreaks, high rates of mortality and morbidity 1890s 1920s 1950s treatment of public (drinking) water supplies cities take responsibility for waste management, water supplies, etc. Federal subsidies for wastewater treatment 1980s 1980s Federal support switches from subsidies to loans Federal government begins requiring water treatment
Antony Van Leeuwenhoek (1685) • First to observe live microorganisms, using a simple microscope
Louis PasteurFather of Microbiology • Disproved the theory of spontaneous generation (1861).
Louis Pasteur The Germ Theory of Disease • Contributed to the understanding of fermentation (1858). • Developed techniques for selective destruction of microorganisms (pasteurization) (1866). • Attenuated vaccines for chicken cholera (1881). • Immunization against rabies (1885).
Ignaz Swmmelweis (1850) • Advocated hand washing to stop the spread of “child bed fever” • Fired twice and generally ridiculed for his ideas, despite drop in mortality rates
Robert Koch The Germ Theoryof Disease • discovered anthrax bacilli (1876). • developed solid culture media (1882). • discovered organisms causing tuberculosis (1882).
Koch’s Postulates (1884)The Germ Theory of Disease • Isolate the suspected agent from a disease victim. • Grow the agent in pure culture. • Infect a healthy host and show that the organism produces the classical clinical disease. • Isolate the "same" organism from the new victim.
Golden Age of Microbiology1850-1920 • Advances led to the development of new branches of microbiology such as immunology and virology. • 1915 M. H. McCrady establishes a quantitative approach for analyzing water samples using the most probable number, multiple-tube fermentation test.
What causes infectious diseases? Pathogens: disease causing organisms • Human pathogens include: • bacteria • viruses • fungi • protozoa • Disease requires: • an infectious pathogen • a susceptible host • a suitable environment E. coli Hepatitis A Virus Giardia lamblia
Classes or Categories of Pathogenic Microorganisms Viruses: smallest (0.02-0.3 µm diameter); simplest: nucleic acid + protein coat (+ lipoprotein envelope) Bacteria: 0.5-2.0 µm diameter; prokaryotes; cellular; simple internal organization; binary fission Protozoa: most >2 µm- 2 mm; eukaryotic; uni-cellular; non-photosynthetic; flexible cell membrane; no cell wall; wide range of sizes and shapes; hardy cysts Groups: flagellates, amoebae, ciliates, sporozoans (complex life cycle) and microsporidia. Helminths (Worms): multicellular animals; some are parasites; eggs are small enough (25-150 µm) to pose health risks from human and animal wastes in water.
The Microbial World: Sizes of Microbes
Types of Pathogens: • Pathogen: a microorganism capable of causing disease. • True pathogen (frank pathogen): Presence is always considered abnormal (e.g. Mycobacterium tuberculosis, Yersinia pestis). Causes disease in hosts with normal immune defenses • Opportunistic pathogen: causes infection/disease in immuno-compromised hosts. May be member of host’s normal flora. Yersinia pestis Pseudomonas aeruginosa
Seven Capabilities of a Pathogen: 1. Maintain a reservoir 2. Be transmitted to and enter a host 3. Adhere to a body surface 4. Invade the body 5. Evade the Host’s Defenses 6. Multiply in the Host 7. Leave the Body
The Process of Infection • The presence of microbes in normally sterile sites is indicative of an infection • May involve normal flora or pathogens • Generally involves growth and multiplication of the microbe in a host • Infection does not always result in injury of the host (disease) • Two main classes of infection: • localized • generalized (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
Microbial Multiplication and Clinical Manifestation of Disease
Infection: Host-Pathogen Interaction Variables of the Host • Age • General health • Pregnancy • Medications--OTC or prescription • Metabolic disorders • Alcoholism, cirrhosis, hemochromatosis • Malignancy • Amount of food consumed • Gastric acidity variation: antacids, natural variation, achlorhydria • Genetic disturbances • Nutritional status • Immune competence • Surgical history • Occupation Variables of the Pathogen • Variability of gene expression of multiple pathogenic mechanism(s) • Potential for damage or stress of the microorganisms • Interaction of organism with food menstruum and environment • pH susceptibility of organism • Immunologic "uniqueness" of the organism • Interactions with other organisms
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 particles
Individuals at Increased Risk For Infections And Illness • Young • -immune systems not fully developed • Old • -immunosenescence (aging immunity) • Pregnant • Immunocompromised • -chemotherapy • -existing infection or • chronic medical • disorder (e.g., liver • disease) • Proper diet especially important for these individuals • Some of these individuals represent rapidly growing segments of the population
Virulence Virulence: A quantitative measure of the ability of a microorganism to cause disease (pathogenicity). LD50 (lethal dose 50%): The number of organisms needed to cause death in 50% of the infected hosts. ID50 (infectious dose 50): The number of organisms needed to cause an infection in 50% of the hosts.
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 bacteriaare 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
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).
Factors Influencing Exposure and Infection: Environmental Factors • Amplifiers: Types of reservoirs where organisms proliferate; A host in which infectious agents multiply rapidly • 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 Penicillin
Disease Frequency • Sporadic • occurs occasionally in a population (tetanus) • Endemic • always present in a population at about the same level (gonorrhea) • Epidemic • outbreak that affects many members of a population in a short time (cholera, influenza) • Pandemic • An epidemic affecting a large geographical area; often on a global scale (HIV, influenza)
Transmission • Person-to-person microbial diseases • Airborne, direct contact & sexually transmitted diseases • Animal-transmitted diseases • Arthropod-transmitted diseases • Soilborne diseases • Waterborne diseases
Airborne Transmission • Bacterial and viral respiratory diseases are transmitted in air • Most respiratory pathogens are transferred from person to person via respiratory aerosols generated by coughing, sneezing, talking or breathing • A few respiratory pathogens can be transmitted by water or soil and do not require person-to-person propagation (e.g. Legionella pneumophila)
Airborne Transmission The upper and lower respiratory tracts offer different environments, favoring different microorganisms
Direct Contact Transmission • Diseases spread by direct contact with an infected person or by contact with blood or excreta from an infected person • Staphylococcal infections – acne, boils, pimples, impetigo, pneumonia, osteomyelitis, carditis, meningitis, and arthritis • Helicobacter pylori – gastric ulcers • Hepatitis viruses – hepatitis, cirrhosis
Sexually Transmitted Diseases • Caused by a wide variety of bacteria, viruses, protists and even fungi • WHO estimates 1 million new cases daily • About 60% of these infections occur in young people <25 years of age • Chlamydia is the most common bacterial STI in humans • HIV infection in humans is now pandemic, and has killed more than 25 million people since it was first recognized in 1981
Animal-Transmitted Pathogens • Zoonosis – animal disease transmissible to humans • Rabies – reservoirs in wild animals, primarily raccoons, skunks, coyotes, foxes and bats; a viral neuroinvasive disease that causes acute encephalitis (inflammation of the brain) • Hantavirus – reservoirs in rodents, primarily mice and rats; can cause several severe diseases including viral hemorrhagic fever
Vectorborne Pathogens • Pathogens spread from the bite of a pathogen-infected arthropod vector, such as ticks, mosquitoes and fleas • Humans can either be accidental hosts (e.g. rickettsias) or they can be required hosts in the life cycle of the pathogen (e.g. malaria)
Soilborne Pathogens • Accidential agents of infection, with no life cycle dependency on the accidental host • Soil is an unlimited reservoir of these pathogens, and so they cannot be eliminated • Includes fungi (e.g. ringworm) and bacteria (tetnus) • Overall incidence of serious infections from the soil is low, although certain superficial fungal infections are common
Protozoa 1Shigella dysenteriae 1Escherichia coli Giardia lamblia rod ~ 1.5 - 2 mm rod ~ 1.5 - 2 mm Caliciviruses Hepatitis A virion ~ 35 nm virion ~ 27 nm Waterborne Pathogens Bacteria Viruses trophozoite ~ 15 mm 1Copyright Dennis Kunkel Microscopy, Inc.; http://www.denniskunkel.com
Virulence properties ofEnteropathogenic E. coli • Enteroaggregative strains (EAEC) – adhere to enterocytes, causing cell death • Enterotoxigenic strains (ETEC) – enterotoxin secretions in small intestine, causing fluid loss and diarrhea; heat stable (ST) and heat labile (LT) toxins; stimulate guanylate or adenylate cyclase activity with fluid and electrolyte loss • Enterohemorrhagic strains (EHEC) – produce shigella-like toxins (large intestine), causing effacement of microvilli and cell death; watery and later bloody stools • Invasive strains (EIEC) – invasion and ability to grow in intestinal epithelium (large intestine), killing the cells