1. 1 Host-Microbe Relationships and Disease Classical ecological definitions –Mutualism: organisms live together, both benefit E. coli in GI tract; we get Vitamin K, protection from pathogens, it gets warm wet place to live, lots to eat. –Commensalism: one organism benefits, the other is not particularly benefited or harmed; to eat at the same table Most GI tract microbes; we provide a warm wet place to live with food, we don’t get all that much in return. –Parasitism: one organism benefits at the other’s expense Disease-causing bacteria; to them, we’re dinner. Classically, a “parasite” lives in or on host.

2. 2 Terms, terms, and more terms Contamination: presence of microbes (where they don’t belong). Infection: multiplication of parasitic organisms in/on host. –Infestation: used to describe larger organisms, e.g. lice. Disease: malfunction in or damage to the host. –Many kinds of “disease”; here we discuss “infectious disease”. –Disease is a condition of the host, not an infectious microbe. Pathogen: a parasite capable of causing disease –Not all pathogens are equal as we will see.. Pathogenicity: ability of pathogen to cause disease

3. 3 Terms, terms, and more terms-2 Virulence: relative ability to cause disease. –Especially variations in pathogenicity w/in specific group –Can be weakened (attenuation) or increased (animal passage); Growing pathogens on agar attenuates them. Normal microbiota: the microbes normally found on the body. Since people are not “normally” sick, pathogens are not normally consider “normal microbiota”. “flora” is to be avoided as microbes are NOT plants! –Resident microbiota: always found on human tissues. –Transient microbiota: come and go, can include potential pathogens.

4. 4 Where do they live? Microbes live where it is “topologically outside” –We are a tube within a tube. We have sacs open to the outside. Respiratory tract: –nasal passages, sinuses, trachea, lungs. Lungs well protected, other areas more populated. GI tract: Crowded! –Mouth is full, fewer in esophagus and stomach; toward end of small intestine, numbers increase greatly. –Feces consist largely of bacteria. http://www.radiation-scott.org/deposition/respfig2.gif

5. 5 Where do they live?-2 Skin: largest organ in the body. –Colonized. Various factors keep the numbers down. Genito-urinary tract: –Female reproductive tract colonized, especially with Lactobacillus which is helpful and with yeast which is occasionally not helpful. –Lower portion of urethra contains some bacteria, but bladder, ureters, and kidneys normally sterile. All areas of the body have mechanisms for keeping us from being lunch; to be discussed soon.

6. 6 What determines whether we get sick? Inf Dis: the likelihood of contracting an infectious disease. N: the numbers of infecting organisms. V: the virulence of the organism. HF: host factors, including overall health, nutritional status, genetic background, age, immune status.

7. 7 How dangerous? Pathogen: causes disease. Opportunistic pathogen: can cause disease under the right circumstances –Dose in high numbers –Host is in a weakened state, e.g. HIV infection. –Organism gets where it doesn’t belong E. coli and urinary tract infections. –Lack of microbial antagonism, e.g. superinfection competition for space, nutrients; bacteriocins. Saprotroph: decompose dead stuff.

8. 8 Whether an organism will cause disease is not always a clear cut thing Not everything in biology can be neatly classified. There is a gradation from pathogen to opportunist to non-infectious, and what happens depends on the balance of these 3 factors.

9. 9 Types of disease Inherited diseases: caused by a faulty gene Congenital: due to damage during development. Degenerative diseases, due to age or lifestyle Nutritional, endocrine, mental, immunological, neoplastic (cancer), idiopathic; same caveat. Iatrogenic: caused by doctor. –Nosocomial infections: occur in hospital. Infectious disease: caused by infectious agents –Bacteria, viruses, fungi, etc. –Infectious agents may affect other types of disease

10. 10 Types of infectious diseases Communicable: can be spread from one person to another. –Example: tuberculosis, HIV Contagious: highly communicable, can easily be spread from one person to another. –Genital herpes, measles. Non-communicable: are not spread from one host to another. –Examples: your infected appendix bursts –You get tetanus from “rusty nail”

11. 11 How bacteria cause disease Bacteria can be invasive –Bacteria spread through tissues, usually using digestive enzymes which damage tissues, kill cells. Bacteria can be toxigenic (produce toxins) –Bacteria may not spread, but release soluble toxins which dissolve in body fluids, damaging cells. –Gram negatives contain endotoxin (LPS) Host processes –Host defenses, like inflammation, may over- respond, cause significant tissue damage.

12. 12 Steps in an infectious disease-Overview Entry and attachment –Microbe needs to approach tissue, then attach to it. Deal with host defense –Successful parasite must infect, persist long enough to reproduce, then escape. Host defense seeks to kill it. Damage: if disease is involved, damage occurs. Escape: parasite must escape and spread to others. –Discussed in “Portals of exit” Virulence Factors: Things that bacteria have that improve their abilities to cause disease –Fimbriae, capsules, enzymes, toxins, all these things.

13. 13 Typical steps in a bacterial infection Attachment –Typical first step is attachment to tissues. Often a specific interaction takes place between molecules. –Fimbriae, capsules help in attachment. –Molecules that aid in attachment = adhesins. Deal with host defenses –A pathogen can defend, attack, or hide. Interfere with phagocytosis, have a capsule, etc. Produce leukocidins, etc. Switch surface antigens, hide inside WBC, etc.

14. 14 Step 3: Damage Damage occurs from combination of factors –Bacteria increase their growth by Releasing enzymes that break down host cell molecules, releasing nutrients or allowing spread. –Hemolysins release iron. Releasing toxins that kill cells or damage organ systems, eliminating host resistance. –Bacteria cause disease by Stimulating inflammation, leading to damage and discomfort Over-stimulating host defense, damaging cells and organ systems.

15. 15 Virulence factors: enzymes and toxins Enzymes –Coagulase, streptokinase. –Allow spread or hiding of pathogen. Toxins –Exotoxins, produced by G+ and G-, proteins, heat labile, released and affect different targets Enterotoxins, neurotoxins, general cytotoxins. –Endotoxin: LPS, especially Lipid A part Present only on Gram – Released when bacterium dies –Acts as Super antigen

16. 16 Hijacking host defenses Inflammation –A protective mechanism, but can cause local damage. Chronic inflammation results in loss of functional tissue, disease. Super antigens –Endotoxin, Toxic Shock Syndrome toxin, et al. Cause massive over response of WBCs –Fever, shock, intravascular coagulation, emesis Over-response followed by under-response

17. 17 Epidemiology and Disease terms Epidemiology is the study of disease: –the study of the factors involved in the frequency and spread of disease. Etiology –The study of the causes of disease Signs and symptoms –Signs are observable/measurable –Symptoms are experienced by patient Syndrome: collection of signs and symptoms

18. 18 More epidemiology definitions Incidence: # of new cases during a time period Prevalence: ongoing cases at any one time –Both often expressed per number of people at risk Mortality and morbidity rate: –Death and sickness per total population over a given period of time. –Many diseases have unique patterns, such as flu occurring during the winter months.

19. 19 The first epidemiological study John Snow, London, 1854 The cause of cholera wasn’t known, but Snow guessed it was spread by water. By mapping all the known cases and comparing them to the sources of water, he correctly identified the source of the problem. http://www.sfu.ca/gis/bguide/icons/figure1.4_snowmap.gif

20. Terms-1 Acute, subacute, chronic –Refers to how long the disease lasts –Acute is short lived, subacute longer,chronic longest Local, systemic –A local infection is in one specific place, systemic means throughout the body. Primary, secondary, superinfection –Primary: the first or main infection –Secondary: a second infection once weakened by a first one. –Second infection usually blamed on antibiotic Rx 20

21. Terms-2 Bacteremia, viremia vs. septicemia (blood poisoning) –Bacteremia is a clinical finding: bacteria in the blood –Septicemia is a disease condition, microbes actively growing in, infecting blood. –Viremia: viruses in the blood, common in systemic infections http://www.mansfield.ohio- state.edu/~sabedon/biol2040.htmhttp://www.mansfield.ohio- state.edu/~sabedon/biol2040.htm –Excellent web site with definition of many, many terms related to infection and disease. 21

22. 22 Susceptibility and transmission Exogenous vs. endogenous –Exogenous means infection comes from outside the host. Examples: common cold, STD. –Endogenous means host is original source of infection. Examples: boils on skin spread by fingers from Staph sinus infection; E. coli urinary tract infection. Compromised host –Weakened immune system, poor lung clearance from bed rest, surgical wounds, bedsores, etc.

23. 23 Where germs live: reservoirs Humans –May be sick, may be carriers Animals –Many diseases are zoonotic but can also be caught by humans; animal may be healthy or not. Non-living –Soil, water are typical homes to microbes that can cause disease.

24. 24 The Ins and Outs of infections: Portals of entry and exit The successful parasite has to get in, multiply, then get out to spread to others. People have lots of entry points –Glands, follicles that open to outside –Larger openings: respiratory system, digestive system, genito-urinary tract –Cuts, bites, burns, surgical incisions –Crossing the placenta, infecting the fetus Pathogens have favored portals of entry –Some microbes aren’t harmful if portal is not optimal

25. 25 Exit The portal of exit is often the same or connected to a portal of entry –Coughing sneezing speaking: from mouth –Excretory systems: GI tract, in feces; in urine –From sex: vaginal fluid, semen –From blood: insect bites, shared needles http://www.humboldtredwoods.org/images/mosquito.jpg

26. 26 Transmission Microbe needs to get from reservoir to you. Contact –Direct contact: touching, kissing, sex, endogenous spread (one part of you to another) –“vertical”: mother to offspring, e.g. transovarian –Indirect contact, via fomites (inanimate objects) –Droplet transmission: less than 1 meter thru air http://students.washington.edu/grant/random /sneeze.jpg WASH YOUR HANDS!!!!

27. 27 Transmission-2 Vehicles –Water: various viruses, bacteria, protozoa, mostly that cause diarrhea and enter water supply. –Food: unpasteurized or contaminated food, either improperly grown, processed, or prepared. –Airborne: microbes attached to dust, skin flakes, dried mucus become aerosols, travel thru air. http://www.kennethkeith.com/milkgreeceb.JPG

28. 28 Transmission-3 Vectors –Typically arthropods (insects, ticks) –Mechanical vectors: simply spread disease, e.g. houseflies walking on feces, spread germs to humans. –Biological: pathogen goes through part of life cycle in vector Viruses or protozoa that reproduce within mosquito, e.g. Major method for spread of zoonoses. http://www.doktordoom.com/images/Tick.jpg

29. 29 Koch’s Postulates Historical context: –So many germs, so many diseases –Logical framework for matching them 1.Microbe must be found in every instance of the disease. 2.Obtain microbe in pure culture 3.Produce disease in susceptible host 4.Re-isolate original microbe http://www.nsc.gov.tw/files/popsc/2003_276/9208-13-04.jpg

30. 30 Stages of Disease Incubation Prodromal Illness ( acute/invasive) Decline Convalescent http://www.goshen.edu/bio/NaSc104/graphics/stages.jpg Stages for acute disease; chronic lasts longer.

31. 31 Distribution of diseases in time and space Some diseases, such as influenza, are seasonal. Some diseases are found only in some geographic areas http://www.phac- aspc.gc.ca/publicat/ccdr- rmtc/03vol29/images/2906f g3.gif http://whyfiles.org/016skeeter/images/malari a_distribution_2000.gif

32. 32 Frequency of disease terms Endemic: continually present in low numbers Epidemic: higher than normal occurrence Pandemic: epidemic spreads worldwide Sporadic: cases show up only occasionally http://www.cdc.gov/mmwr/preview/mmwrhtm l/figures/00000122.gif

33. 33 Herd Immunity Herd immunity: indirect protection from disease due to there being a high number of immune individuals in the population. The more immune individuals, the harder it is for the disease to be spread among many people; the cycle of transmission is broken. http://www- micro.msb.le.ac.uk/3035/3035pics/Herd.gif

34. 34 Notifiable diseases Notifiable disease: potentially harmful diseases which must be reported to the CDC or other Health Unit by physicians –Allows CDC to keep track and intervene. –Some examples listed by Arkansas Dept. of Health: Anthrax, Botulism, Hepatitis A, Pertussis, Plague, Q Fever, SARS, Smallpox, Tularemia, Typhus, Viral Hemorrhagic Fevers