Microbe Human Interactions: Contact, Infection and Disease Host Microbe Relationships Host Any organism that harbors another organism or particle (virus, prion) Symbiosis An association between 2 species ( living together ) Mutualism Parasitism Commensalism Host-Microbe Relationships: Symbiosis Mutualism Both members benefit from relationship E. coli produce useful products (Vit K) in our large intestine Parasitism One member benefits, one member is harmed Commensalism One member benefits, one member is not benefited nor harmed Microbes on our skin utilize skin products E. Coli in Lg. intestines Giardia in intestines Resident Microflora Adult human body consists of: 10 trillion (10 13 ) eukaryotic cells Human cells 100 trillion (10 14 ) prokaryotic cells Bacteria cells We have 10 times as many prokaryotic cells vs. our own cells!! How is this possible? Demodex folliculorum in hair follicle Resident Microflora Resident Microflora Resident Microflora Microbes always present on or in the body Transient Microflora Microbes present for shorter periods of time (minutes to months) Which areas harbor microflora? What are some types of normal microflora? Which body tissues, organs and fluids are usually microbe free? 1
Types of microbes and the anatomic sites they occupy The Absence of Resident Microflora can have Harmful Effects Enlargement of cecum Vitamin deficiency Underdeveloped immune system Resident Microbial Antagonism normal biota are unlikely to be displaced by incoming microbes limited number of attachment sites chemical or physiological environment created by resident biota is hostile to other microbes Normal biota is beneficial, or at worst, commensal to the host in good health with a functioning immune system First Acquiring Resident Microflora Mother s birth canal Mother s breast milk Bottle feeding People Air Surfaces The only time that humans are sterile is when they are in the womb (in utero) Contamination, Infection and Disease Invasion of normally sterile regions of the body can result in infection and disease. Contamination: Microbes are present Infection (Infestation larger parasites) Multiplication of microbes (Microbes penetrate host defenses, enter tissue and MULTIPLY) Disease Disturbance in normal homeostasis 2
Factors that weaken host defenses and increase susceptibility to infection old age and extreme youth (infancy, prematurity) genetic defects in immunity and acquired defects in immunity (AIDS) surgery and organ transplants underlying disease: cancer, liver malfunction, diabetes chemotherapy/immunosuppressive drugs physical and mental stress pregnancy other infections True vs. Opportunistic Pathogen True pathogen Cause disease in healthy individuals Associated with a specific and recognizable disease Opportunistic pathogen Cause disease in immune compromised host Gain access (injury) to sterile regions Vibrio cholerae Staphylococcus aureus Opportunistic microbes Pathogens, Pathogenicity and Virulence Opportunists usually do not cause disease unless the opportunity arises. Conditions that opportunists can flourish: Failure of the host s normal defenses Immunocompromised populations Intro of the organism into unusual body sites E. coli normal in gut but not urinary tract Disturbances in normal microflora Yeast infection after antibiotic use. Why? Pathogen Disease causing agent Pathogenicity The ability to cause disease Virulence The degree of pathogenicity Influenza E. coli The Progress of an Infection The Progress of an Infection Pathogen needs to become established by being successful at the following: 1. Portals of entry 2. Attachment 3. Surviving host defenses 4. Causing disease 5. Portals of exit Virulence of a microbe is determined by its ability to - establish itself in a host - cause damage Virulence factor: any characteristic or structure of the microbe contributes to its ability to establish itself in the host and cause damage 3
1. Portal of Entry Portal of entry: the route that a microbe takes to enter the tissues of the body to initiate an infection Exogenous: microbe originating from a source outside the body from the environment or another person or animal Endogenous: microbe already existing on or in the body normal biota or a previously silent infection 1. Portals of Entry The majority of pathogens have adapted to a specific portal of entry if certain pathogens enter the wrong portal, they will not be infectious inoculation of the nasal mucosa with the influenza virus will result in infection, but if the virus contacts the skin, no infection occurs 1. Portals of Entry Occasionally, an infectious agent can enter by more than one portal Mycobacterium tuberculosis can enter through both the respiratory and gastrointestinal tracts Streptococcus and Staphylococcus can enter through the skin, urogenital tract, and the respiratory tract 1. Portals of Entry The Size of the Inoculum Infectious dose (ID) - the minimum number of microbes necessary to cause an infection to proceed - microorganisms with smaller infectious doses have greater virulence - ID for rickettsia is a single cell - ID for tuberculosis and beaver fever is about 10 cells - ID for gonorrhea is 1,000 cells - ID for typhoid fever is 10,000 cells - ID for cholera is 1,000,000,000 cells 2. Attachment/Adhesion - gain a stable foothold on host tissues - dependent on binding between specific molecules on both the host and pathogen - pathogen is limited to only those cells (and organisms) to which it can bind - firm attachment is almost always a prerequisite for causing disease since the body has so many mechanisms for flushing microbes from tissues Structures Capsules Pili or fimbriae Hooks 2. Attachment/Adhesion 4
2. Attachment/Adhesion 3. Surviving Host Defenses Example of how fimbriae and capsules are used to adhere to the host cell. Microbes not established as normal biota will likely encounter the host immune defenses when first entering Phagocytes: cells that engulf and destroy host pathogens by means of enzymes and antimicrobial chemicals WBC engulfing S. cerevisiae 3. Surviving Host Defenses Antiphagocytic factors: - Virulence factors that help pathogens to avoid phagocytes - Leukocidins: kill phagocytes; Streptococcus and Staphylococcus - Slime or capsule: makes it difficult for the phagocyte to engulf the pathogen; Streptococcus pneumoniae and Salmonella typhi - Some bacteria survive inside the phagocyte; Legionella, Mycobacterium 3. Surviving Host Defenses Humans have known for centuries that copper is a potent weapon against infection. New research shows that the bacteria that cause serious urinary tract infections steals copper from immune cells to prevent the metal from being used against them. Nature Chemical Biology (July 8, 2012) 4. Causing Disease 4. Causing Disease Enzymes Virulence factors are simply adaptations a microbe uses to establish itself in a host Three ways that microorganisms cause damage to their host A. directly through the action of enzymes B. directly through the action of toxins (both endotoxins and exotoxins) C. indirectly by inducing the host s defenses to respond excessively or inappropriately Exoenzymes - enzymes secreted by microbes that break down and inflict damage on tissues - dissolve the host s defense barriers to promote the spread of disease to other tissues Examples of exoenzymes - hyaluronidase: digests the ground substance that cements animal cells together - coagulase: causes clotting of blood or plasma 5
4. Causing Disease Exoenzymes 4. Causing Disease Toxins Toxin: a specific chemical product of microbes, plants, and some animals that causes cellular damage in other organisms Toxins are named according to their target - neurotoxins act on the nervous system - enterotoxins act on the intestines - hemotoxins lyse red blood cells - nephrotoxins damage the kidneys Two types of toxins in pathogenic bacteria Exotoxin Endotoxin 4. Causing Disease Exotoxins Exotoxins - proteins that targets a specific cell type - affect cells by damaging the cell membrane and initiating lysis Hemolysins - disrupt the membrane of red blood cells to release hemoglobin 4. Causing Disease Endotoxins Endotoxin - lipopolysaccharide (LPS), part of the outer membrane of gram negative cell walls - Released when cells die - has a variety of systemic effects on tissues and organs - causes fever, inflammation, hemorrhage, and diarrhea - Ex. Streptococcus pyogenes and Staphylococcus aureus 4. Causing Disease Endotoxins Some endotoxins are pyrogenic 5. Portal of Exit Enables pathogen to spread to other hosts Respiratory Salivary Skin Fecal Urogenital Blood 6
5. Portal of Exit - specific avenue by which pathogens exit - shed through secretion, excretion, discharge, or sloughed tissue - high number of microbes in these materials increases the likelihood that the pathogen will reach other hosts - portal of exit is usually the same as the portal of entry, but some pathogens use a different route Establishment, Spread, and Pathologic Effects Microbes eventually settle in a particular target organ and cause damage at the site - host tissues are weakened as a result of the multiplication of the pathogen - pathogens obstruct tubular structures such as blood vessels, lymphatic channels, fallopian tubes, and bile ducts - necrosis: accumulated damage due to pathogens leading to cell and tissue death The Steps Involved When a Microbe Causes Disease in a Host Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pathogenicity: The ability to cause disease Depends on a pathogen s ability to: Finding a Portal of Entry Skin GI tract Respiratory tract Urogenital tract Endogenous biota Attaching Firmly Fimbriae Capsules Surface proteins Viral spikes Surviving Host Defenses Avoiding phagocytosis Avoiding death inside phagocyte Absence of specific immunity Causing Damage (disease) Direct damage Toxins and/or enzymes Indirect damage Inducing inappropriate, excessive host response Exiting Host Portals of exit Respiratory tract, salivary glands Skin cells Fecal matter Urogenital tract Blood 1. Enter 2. Attach 3. Survive host defenses 4. Cause disease 5. Exit Look familiar? Virulence: The degree of pathogenicity Intensity of disease produced Virulence can be decreased as a pathogen is subcultured time after time Many virulence factors (weapons) exist to increase a pathogen s ability to: 1. Enter 2. Attach 3. Survive host defenses 4. Cause disease 5. Exit Establishment of Infections Localized infection: An infection that is limited to a specific part of the body and has local symptoms Systemic infection: pathogen is distributed throughout the body 7
Establishment of Infections Focal infection: A bacterial infection localized in a specific part of the body, that spreads to other parts of the body Mixed infection: Bacterial infection composed of different species of bacteria Establishment of Infections Primary and secondary infections: Illness caused by new microbe becoming established in the wake of an initial (primary) infection Acute: rapid onset of infection, short course of infection Chronic: Long duration of infection Infections That Go Unnoticed No noticeable symptoms are produced Microbe is present in host tissues Host does not seek medical attention These infections are known as asymptomatic or subclinical Signs, Symptoms and Syndromes Signs Objective/measurable (I.e., fever, inflammation) Symptoms Subjective (pain, tummy ache) Syndromes Combo of signs and symptoms that occur together How would you classify a sore throat? A red throat? A fever? Some commons signs and symptoms associated with infectious diseases Stages of an Infectious Disease 8
Incubation periods vary The Persistence of Microbes and Pathologic Conditions Recovery of the host does not always mean the microbe has been removed or destroyed by host defenses Latency: a dormant state of microbes in certain chronic infectious diseases - viral latency: herpes simplex, herpes zoster, hepatitis B, AIDS, Epstein Barr - bacterial/protozoan latency: syphilis, typhoid fever, tuberculosis, malaria The Persistence of Microbes and Pathologic Conditions Sequelae: long term or permanent damage to tissues or organs caused by infectious disease Epidemiology - meningitis: deafness - strep throat: rheumatic heart disease - Lyme disease: arthritis - polio: paralysis Epidemiology What is it? The study of disease within populations (human, plant, etc.) Why do we care? Helps us investigate the factors regarding a specific disease. what causes a disease how is it transmitted how do we prevent and treat it how many people are afflicted. Epidemiology Epidemiology allows us to take all we have learned about microbes and the diseases they cause and apply that knowledge to new situations. Involves many disciplines: microbiology, anatomy, physiology, immunology, medicine, psychology, sociology, ecology, and statistics 9
Epidemiology Terminology Epidemiologists disease detectives, scientists who study epidemiology Etiologic agent The cause of a disease Morbidity Illness Mortality Death Epidemiology Terminology Incidence Number of NEW cases within a period of time Prevalence TOTAL number of cases within a period of time Which one informs us if we have taken proper measures to halt disease transmission? Epidemiology Terminology Tracking Disease in the Population Reportable or notifiable diseases - certain diseases must be reported to authorities - other diseases are reported on a voluntary basis A network of agencies at the local, district, state, national, and international levels keeps track of infectious diseases Epidemiology Terminology Endemic Pathogen is continually present in population Sporadic occasional cases are reported at irregular intervals at random locales Epidemic An outbreak or higher than normal number of cases. Ie. prevalence of an endemic or sporadic disease is increasing beyond what is expected for a population Pandemic Spread of an epidemic across continents Epidemiology Terminology Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endemic Occurrence Epidemic Occurrence The incidence rate of chicken pox in the U.S. Cases (a) (c) Sporadic Occurrence Pandemic Occurrence Is this disease endemic, epidemic, pandemic or sporadic? (b) (d) 10
Diphtheria cases after the break up of the former Soviet Union. Epidemiology Terminology Point source epidemic: infectious agent came from a single source, and all of its victims were exposed to it from that source Common source epidemic: result from common exposure to a single source of infection over a period of time Propagated epidemic: results from an infectious agent that is communicable from person to person and is sustained over time in a population Is this disease endemic, epidemic, pandemic or sporadic? Statistical data can be represented graphically, and can be used to predict trends Commonly reported diseases that are tracked in the United States We can analyze the data according to year, ages affected, and geographic location to help us predict what diseases we need to watch out for and identify precautions to prevent them. (similar to Influenza H5N1) Epidemiologic Studies Epidemiologists collect data on diseases to help prevent outbreaks in the future. Three Types of Epidemiologic Studies: Descriptive Analytical Experimental First formal epidemiologic study performed by John Snow in 1854. He traced the source of a cholera epidemic to a certain water pump and proved that people became infected by fecally contaminated drinking water. 11
Descriptive Studies Concerned with the physical aspects of an existing disease and disease spread. Provides the what, who, when and where Records as many details as possible: Number of cases Populations affected Locations and time Age, gender, race, socioeconomic status, etc. Examples of Data from Descriptive Studies Analytical Studies Provides the why and how Studies determine causes and factors that influence the rate of disease. These factors include demographic, biological, behavioral, and environmental influences. Disease groups are compared to control groups and data is analyzed for similarities and differences. Example analytical question: in the hanta virus epidemic, did people get sick if they had been outside near mice habitats or if they had been cooped up in office buildings? Example of Data from Analytical Studies (red -> higher risk) Bovine brucellosis cumulative incidence, 1995 99 (red -> higher risk) Bovine tuberculosis cumulative incidence, 1995 99 Notice the similarity in the distribution of the high risk areas, suggesting that the two diseases are associated Experimental Studies Designs experiments to test a hypothesis. These are the cleanest types of studies and often considered the gold standard. Many experimental studies are performed for pharmaceutical ( clinical trials ) or other treatments. Example of Data from Experimental Studies Mice were infected for 24 hours with wild type P. aeruginosa strain or a P. aeruginosa flagellin deficient mutant Lung histology analysis of non infected, WT infected, and flagellindeficient mutant infected mice. Blue cells are mucus producing cells induced by P. aeruginosa. Non infected mice Infected with +flagella P. aeruginosa Infected with flagella P. aeruginosa Mucus cells 10 3 /µm 2 Conclusion: flagella are needed for P. aeruginosa to induce mucus producing cells Disease Transmission Disease transmission is affected by: Reservoirs of infection Portals of Entry and Exit Mechanisms of Transmission We will investigate all three in order to understand how to break the chain of disease transmission. You can break it at just one site to stop transmission. Disease Transmission: Source of Infection Reservoir The natural host or habitat (living or nonliving) of a pathogen Source The person or item from which an infection is DIRECTLY acquired Carrier vs. Asymptomatic Carrier An organism that harbors infections and can spread them to others. They may show symptoms or not. 12
Disease Transmission: Source of Infection Biological vector An organism which not only TRANSPORTS a pathogen but ALSO plays a role in the LIFE CYCLE of the pathogen (virus inside of mosquito, bacteria inside of tick) Mechanical vector An organism which ONLY TRANSPORTS a pathogen (fly) Disease Transmission: Source of Infection Zoonosis An infectious disease indigenous to ANIMALS that humans CAN acquire through direct or indirect contact. (rabies) make up a full 70% of all new emerging diseases worldwide impossible to eradicate without also eradicating the animal reservoir attempts have been made to eradicate mosquitoes and certain rodents Zoonotic infections are caused by vectors and animal reservoirs spreading their own infections to humans Disease Transmission: Source of Infection Human Reservoirs Asymptomatic Carrier Symptomatic Carriers Animal Reservoirs Wild animals (Rabies) Deer mice (hanta virus) Nonliving Reservoirs Soil (Clostridium tetani, Bacillus anthracis) Water (Cholera, Giardia) Food (E. coli, Salmonella, Listeria) Disease Transmission: Source of Infection Some diseases are communicable but others are not Communicable Infected host transmits an infectious agent to another host Receiving host must become infected Non communicable Host acquires infectious agent but can t transmit it to another From self (compromised individual) microflora Nonliving reservoir soil (tetanus) Disease Transmission: Source of Infection Communicable Disease spread from one host to another I.e., cold, meningitis Contagious EASILY communicable I.e. measles, influenza Are all communicable diseases contagious? Are all contagious disease communicable? 13
Disease Transmission: Portal of Exit and Entrance Respiratory pathogens are usually inhaled or enter via the eye. Digestive pathogens are usually ingested. (Can you get an E. coli infection by inhaling cow poop?) Disease Transmission: Patterns of Transmission Horizontal transmission Disease is spread through a population from one infected person to another Kissing, sneezing Vertical transmission The disease is transmitted from parent to offspring Ovum, sperm, placenta, milk Intact skin prevents many microbial invasions. Watch out for those paper cuts! Disease Transmission: Patterns of Transmission Direct (contact) Kissing, sex Droplets (sneezing, coughing directly upon a person within 3 feet) Vertical Vector Indirect Contaminated materials Vehicles=Food, water, biological products (blood, serum, tissue), FOMITE (door knobs, toilet seats, etc.) Fecal oral (aka oral fecal) Air (greater than 3 feet away) Droplet nuclei (dried microscopic residue) Aerosols (dust or moisture particles) A sneeze can release enormous amounts of moist droplets, and the dry droplets form droplet nuclei. (SO COVER YOUR MOUTH WITH YOUR ELBOW ) Disease Transmission: REVIEW Disease transmission is affected by: Reservoirs of infection Portals of Entry and Exit Mechanisms of Transmission You can break the transmission of disease at each of the above levels!! Disease Transmission: Prevention Sanitation What is the #1 way to stop disease? Immunization Isolation Quarantine Control vectors Education about prevention and treatment 14
Disease Transmission: Prevention Herd immunity is the proportion of people immune to a certain disease. Is it easier or more difficult to transmit disease when herd immunity is low? How do we acquire herd immunity? Disease Transmission: Prevention and Public Health Organizations Created to control disease They monitor NOTIFIABLE (reportable) DISEASES A list of notifiable diseases promotes cooperation between the different health agencies. These are diseases that are particularly harmful to humans and infectious and must be monitored to protect the population. Many levels: County Health Department State Health Department Centers for Disease Control and Prevention (CDC a federal health department) World Health Organization (WHO) Nosocomial Infections: The Hospital as Source of Disease An infection acquired in a hospital Nosocomial Infections Patient enters the hospital with tuberculosis. Is this a nosocomial infection? Patient enters hospital with a broken hip. After surgery and during recuperation, she acquires an urinary tract infection (UTI). Is this a nosocomial infection? Nosocomial Infections: The Hospital as Source of Disease About 2 4 million (5 20 percent) of admitted patients acquire a nosocomial infection 90, 000 die of nosocomial infections $5 10 billion per year to treat nosocomial infections Nosocomial Infections: Contributing Factors - compromised patients - collection point for pathogens - lowered defenses permit normal biota to enter the body - infections acquired directly or indirectly from fomites, medical equipment, other patients, medical personnel, visitors, air, and water 15
Epidemiology of Nosocomial Infections Epidemiology investigates: Sources of Infection Modes of Transmission Susceptibility to Infection Prevention Control Risk Factors Sites of Infection Nosocomial Infections: Source Exogenous Other patients Staff Visitors Insects (ants, roaches, flies) Fomites (floor, trash can, counters, catheters, bathroom fixtures, medical equipment like nebulizers and dialysis machines, tubing, syringes, needles) Endogenous Opportunists among patient s own normal microflora Nosocomial Infections: Source There are many possible sites of contamination that can lead to infection. Nosocomial Infections: Source Some common modes of transmission of nosocomial infections Common nosocomial pathogens The most common nosocomial infections 16
Nosocomial Infections: Prevention and Control Healthcare processes that lead to nosocomial infections: - treatments using reusable instruments such as respirators and thermometers - indwelling devices such as catheters, prosthetic heart valves, grafts, drainage tubes, and tracheostomy tubes form ready portals of entry - high proportion of the hospital population receives antimicrobial therapy, drug resistant microbes are selected for at a much higher rate Nosocomial Infections: Prevention and Control Recent evidence suggests that more than 1/3 of nosocomial infections could be avoided by consistent and rigorous infection control methods Use Universal Precautions (aka Standard Precautions) Assume all patients and fomites may harbor pathogens Use caution and compassion Nosocomial Infections: Prevention and Control To maintain accreditation by the American Hospital Association, all hospitals must have: Surveillance methods and data Microbiology laboratory Isolation procedures Standard operating procedures (SOPs) for equipment General sanitation procedures Disease education programs What is the single most important technique to prevent nosocomial infections? 17