Microbe-Human Interactions: Infection & Disease I. Introduction A. Recall _______ Koch’s Postulates (experimental steps to establish the microbe that causes a disease) 1. isolate a pathogen from a diseased host & grow pathogen in pure culture 2. inoculate a healthy organism with the cultured pathogen 3. organism must get the same disease 4. isolate the same pathogen from the new host B. Exceptions to Koch’s postulates 1. Microbes that can’t be grown on artificial media examples: Viruses Rickettsia Treponema 2. More than one microbe produces the same disease examples: meningitis pneumonia 3. One microbe that causes multiple diseases examples: Streptococcus pyogenes 4. Strictly human diseases with no animal model examples: Rubella (German measles) Strep throat Scarlet fever smallpox Normal Flora (microbes that normally live in/on the body w/o harm) II. ____________ A. _______ Resident vs _________ Transient flora (always there) (only present for a short time or on and off) Colonization B. Establishment of Normal Flora = __________ 1. Newborns are free of flora, but established as infant is exposed to organisms from _______, food etc. vagina _____, air ______ 2. Colonization is a selective process due to physiological conditions in the body such as _____, O2 ________, temperature ____, nutrients etc. pH ___________, 12-18 months to fully establish normal flora 3. Takes about ____________ Symbioses (different organisms living together) C. __________ 1. __________ Mutualism (both partners benefit) bacteriocins E. coli: produces vitamins K & some B, and ___________ (chemicals that ward off harmful species) Commensalism (one partner benefits, other is neutral) 2. ___________ skin organisms live off of secretions/sloughed cells Parasitism (one partner benefits while the other is harmed) many 3. _________ bacteria, fungi, protozoans, worms and even viruses parasite host D. Opportunistic ____________ organisms (organisms that are usually nonpathogenic, but that can become pathogenic under certain circumstances) 1. when host health is compromised 2. when there is a reduction of normal flora habitat (part of the body) 3. if an organism gets in a different_______ E. coli from gut to urinary tract Klebsiella pneumoniae from gut to respiratory Pathogenesis (disease development) III. Mechanisms of ____________ A. Production of disease is actually a process of steps Transmission to a susceptible host 1. ____________ Adherence to appropriate target tissue(s) 2. ___________ Invasion 3. ________ Colonization 4. __________ Damage to host while evading defenses 5. ________ Exit from body 6. _____ Survival outside long enough to be transmitted to another host 7. _________ B. Transmission must be to the correct “portal of entry” mucous 1. typically to exposed surfaces such as ______ skin or _______ membranes (which is not an easy thing to do!) punctures bites cuts abrasions _________etc. 2. entry aided by _____, ____, ________, food water a. Gastrointestinal tract (via ______, _____) bacteria, especially Gram- _______ enteric bacilli viruses such as polio and Hepatitis A protozoans such as Entamoeba and Giardia b. Respiratory tract (via ____) air bacteria that cause strep throat, diphtheria, pertussis viruses such as influenza, measles, mumps, rubella, chickenpox and the common cold fungi such as Histoplasma and Pneumocystis c. Urogenital tract (most are _____) STDs (or misplaced opportunists) bacteria such as Neisseria, Treponema, and Chlamydia viruses such as papilloma and herpes protozoans such as Trichomonas fungi such as Candida 3. Infectious ________ ____ dose = minimum number of microbes necessary to insure infection (ex: only 10-100 Shigella but 1,000,000 Salmonella) C. Adherence (attachment) Ligands (projections of microbe that match host receptors) _________ 1. pili tips, surface proteins, etc. (can change b/c of mutations so previous Ab don’t recognize them!) 2. same organism can have different ligands to adhere to different Pink eye parts of the body (ex: Haemophilus influenzae) Middle ear 3. some ligand genes on plasmids can spread like antibiotic resistance! 4. why people don’t get a lot of other animal diseases and vice versa D. Invasion (in order to establish infection) 1. high concentrations, more likely to invade successfully Bacteremia = presence of bacteria in the blood 2. ___________ Viremia = presence of viruses in the blood ________ E. Colonization (when conditions are such that invading microbes are reproduce successful enough to _________) Septicemia = blood infection where bacteria are reproducing __________ phagocytosis F. Evade host defenses (mainly by avoiding ____________) 1. Capsules ________ (Streptococcus, Salmonella, Neisseria) Leukocidins are substances that are toxic to WBCs 2. __________ 3. _________ Catalase breaks down H2O2 produced by phagocytes, preventing digestion of the engulfed microbe & Cause Damage/Disease Toxins (poisonous substances) (________ Toxemia when in the blood) 4. _______ Exo- toxic soluble proteins secreted (botulism, tetanus) a. _____: ___________ Hemolysins cause lysis of RBC’s b. Endo_____: cell wall components released when cell dies, toxic to host (lipopolysaccharides in Gram-negative cell walls) *Can lead to Septic shock 5. ____________ Exoenzymes (act on host cells/tissues) a. __________ Coagulase activates prothrombin to coagulate fibrinogen in plasma, forming a fibrin clot that “hides” the microbe from phagocytosis Fibrinase b. ___________ breaks down blood clots in order to spread Hyaluronidase “spreading factor” breaks down hyaluronic acid c. _____________ (loose connective tissue), allowing organism to invade tissues The effects of Hyaluronidase can be drastic! Late stage necrosis of epidermis, subcutaneous layers, fascia, and musculature of upper lateral leg. Necrosed peripheral nervous tissue results in no perception of pain at wound site! G. Development of Disease Incubation period (between infection and 1st signs/symptoms) 1. __________ Depends on dose of microbes, which microbes, virulence, host health a. typhoid fever 10-14 days b. AIDS 10 years! (allows more spreading!) Prodromal period of 1-2 days follows incubation in some (2). _________ malaise _______, fatigue diseases (= early, mild signs/symptoms such as _______, muscle aches etc. ) ____________, Death 3. Illness ______ period when the disease is acute and ______most likely Chills a. _______/______ Fever Leukocytes (> 10,000/ml) b. numbers of ___________ nodes c. swollen lymph _____ _____ d. Nausea/diarrhea ______________ Rashes/lesions e. ____________ pain f. severe ____ 4. Recovery Decline period (1-few days) when signs/symptoms are subsiding ________ BUT most susceptible to secondary, Opportunistic ___________ infections Convalescent period needed to regain strength ____________ H. Disease Terminology Local infection (limited to point of entry) 1. _____ boil wart Vs Focal infection (spreads to a new location) rabies Hepatitis A _____ Vs appendicitis tonsillitis Systemic ________ (infection that spreads to several sites and the blood) syphilis Acute diseases develop fast but for a short duration influenza 2. ______ cold Tooth abscess measles chickenpox Vs Chronic diseases develop slow but for a long duration TB leprosy _______ Vs ______ diseases may be inactive for long periods of time Cold sores Latent Genital herpes 3. Diagnosis ________ (identification) of a disease is dependent upon: Symptoms _________ of a disease are subjective changes in body function sore throat Vs pain aches malaise _____ of a disease are objective (measurable) changes Signs fever rash lesions edema inflammation A _________ Syndrome is a group of symptoms/signs characteristic of a certain disease. Rubella syndrome A Subclinical _________ infection is asymptomatic, but patient is still infectious (more common in children) I. Exit by means of 1. Sneeze ______/_______ Cough Insect bites Diarrhea 2. ________ 4. ____________ Sex! Pus /_______ 3. ____ 5. _____ Blood J. Survival outside long enough to gain entry into a new host 1. Some can also live in the environment Clostridium tetani 2. Some are hardy and can survive for as long as several weeks before a new host comes along Mycobacterium tuberculosis reservoirs Rabies, RMSF 3. Some hang out in animal__________ 4. Some require direct contact b/c they are fragile Treponema pallidum K. Pathogenesis depends on many factors 1. Genetics, both species and individual 2. state of host health 3. age (_______& less capable immune systems) Elderly Infants ________have 4. ________ Stress (causes corticosteroids that are immunosuppressive) Epidemiology: The study of Disease in Populations Epidemiology = study of frequency and distribution of disease in IV. ___________ order to set guidelines for disease prevention and control. = like detective work to determine the cause, reservoirs, transmission, portals of entry/exit, etc. Case reporting is essential to make predictions A. ____________ Centers for Disease Control & Prevention (CDC) 1. National ________________________ located in Atlanta, Georgia & Mortality Weekly Report (MMWR) tracks over 2. Morbidity _______________________________ 50 diseases carefully b/c hospitals, Drs., coroners, etc. REPORT them: AIDS, STDs (such as gonorrhea, syphilis, Herpes), measles, tetanus, TB, hepatitis, rabies, chicken pox, malaria, etc. www.cdc.gov/mmwr/ Health Organization (WHO) plans which diseases will 3. World _______________________ be targeted for eradication (such as smallpox, accomplished in 1979, and polio, targeted for 2009). B. Epidemiologic Statistics: Frequency of Cases 1. __________ Prevalence = total number of existing cases with respect to the entire population (usually expressed as a __________); percentage a “snapshot” to help assess the overall impact of a disease example: 100 people have a disease………….. a. out of 500,000 people (0.02%) not a big deal, but b. out of 500 people (20%) is a big deal Incidence # of ____ new cases in a specific time period compared 2. _________ with the general healthy population (usually expressed as # cases per 100,000 people) risk of infection a. indicates both the _____ rate and ____ Disease rate Morbidity rate or ________ b. also called the__________ A class of 50 students w/o influenza (P & I both 0 because 0/50 have influenza) becomes exposed to influenza 1st week, 5 students become ill. 2nd week 5 more students become ill 2nd week 5 more students become ill w/ 1st 5 students recovered 1 in 10 % and I = __ P = 10 ____ 1 in 10 20% and I = __ P = ____ 1 in 10 10% and I = __ P = ____ Incidence of pneumococcal disease (per 100,000 people) 3. _________ Mortality rate = percentage of people who die from a disease 4. Terms that describe disease frequency Endemic = a disease that is always present in a population a. _________ (steady frequency) common cold b. Sporadic ________ = a disease that only pops up occasionally at irregular intervals in random locales Typhoid fever diphtheria Epidemic = a lot of people get a disease in a short time c. _________ (increasing frequency) Chlamydia Gonorrhea Pandemic = a worldwide epidemic influenza AIDS d. _________ C. Investigative Strategies of the Epidemiologist 1. Determining Reservoirs ________ (= continual ______ source of infectious organisms) a.Carriers ________ are asymptomatic people that can spread disease Gonorrhea (50% of infected females are asymptomatic!) (1). _________ Typhoid Mary (2). ________ *precautions can be taken: *if humans are the only reservoir, it should be easier to control 3. _________ Mortality rate = percentage of people who die from a disease 4. Terms that describe disease frequency Endemic = a disease that is always present in a population a. _________ (steady frequency) common cold b. Sporadic ________ = a disease that only pops up occasionally at irregular intervals in random locales Typhoid fever diphtheria Epidemic = a lot of people get a disease in a short time c. _________ (increasing frequency) Chlamydia Gonorrhea Pandemic = a worldwide epidemic influenza AIDS d. _________ C. Investigative Strategies of the Epidemiologist 1. Determining Reservoirs ________ (= continual ______ source of infectious organisms) Carriers are asymptomatic people that can spread disease a. ________ Gonorrhea (50% of infected females are asymptomatic!) (1). _________ Typhoid Mary (2). ________ *precautions can be taken: Don’t go out Don’t kiss Don’t drink after Don’t have sex! *if humans are the only reservoir, it should be easier to control b. Nonhuman animals biological vector (part of the pathogen’s life cycle) mosquitoes (1) ________ mechanical vector (just carriers) cockroaches (2) _________ houseflies Zoonosis = an animal disease we can get (3) _________ rabies anthrax plague RMSF A fly walked on the agar surface! Environmental (soil, water, food) c. ____________ tetanus cholera Salmonella 2. Terms for transmission of infectious agents a. Communicable ___________ diseases are spread from one person to another Herpes measles Common cold Contagious if easily spread b. Communicable diseases are called _________ Chickenpox c. Noncommunicable ______________ diseases (you cannot get them from another person) tetanus botulism 3. Patterns of communicable disease transmission Direct a. _______(Physical, person-to-person) “A portal of exit meets a portal of entry!” touch kiss sex Respiratory droplets/sneeze, 1 meter (close proximity) common in crowds, elevators cough Vertical spread (mother to fetus/infant) Rubella, STDs (1) _______ Horizontal spread (anybody else to anybody else) (2) _________ Indirect b. ________ Fomites (inanimate objects) toys (1) _______ used kleenex eating utensils needles Door knobs Toilet seats food (2) ______/______ water (especially GI parasites) (This transmission Preparation fecal-oral) Source or from __________; can be from the ________ Salmonella eggs/chicken Typhoid Mary (3) _______ Droplet nuclei (small, dried up on dust, carried by air currents) * * * * good ventilation helpful (dilutes) air filters help trap pressurized air (out of operating rooms) damp mops better than brooms D. Areas of Epidemiology 1. _________ Descriptive epidemiology occurs after disease outbreak and describes the characteristics of ill people age a. ____ sex b. _____ race c. ____ d. _________ occupation lifestyle Smoker? Drug use? Sexual activity? e. ________ Home location (to help figure out reservoirs) f. ___________ Timing g. ______ # # * Common Source Epidemic * Propagated Epidemic c a s e s time c a s e s time Analytical epidemiology then determines which risk factors 2. _________ [identified by descriptive studies] are actually relevant by comparing those with the disease to those without the disease _________