MIC 201 - Lecture Part II

MIC 201 - Lecture Part II - Infection and Disease INFECTION...

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Unformatted text preview: Infection and Disease INFECTION The body is invaded by a pathogenic microorganism. DISEASE Alteration from the normal state of health INFECTIOUS DISEASE Alteration from a normal state of health caused by a pathogenic microorganism. PATHOGEN An organism capable of infection and disease "species dependent" COMMENSALS Microorganisms getting benefit from growing in or on the body but not causing any damage. OPPORTUNISTS Organisms capable of producing disease under only the right set of circumstances. [usually a suppressed immune system of the host] VIRULENCE The degree of pathogenicity. {a quantitative measure} Progress of Disease 1. Incubation Period 1 day to 6 years: affected by generation time of microbe, virulence and host resistance 2. Prodromal symptoms malaise, nausea, headache, fever 3. Period of Acme body rash, lesions, jaundice, swollen glands {ACUTE} 4. Period of Decline of disease symptoms 5. Convalescence Return to a normal state of health EPIDEMIOLOGY ENDEMIC The disease is always present in the population at low incidence. EPIDEMIC A rapid spread of the disease through the population PANDEMIC A worldwide epidemic TYPES OF DISEASES ACUTE cholera, typhus CHRONIC brucellosis, tuberculosis PRIMARY Diseases that attack healthy persons (cholera) SECONDARY Diseases that require predisposing conditions (pneumonia) LOCAL pustule, abscess SYSTEMIC tuberculosis (all organs of the body) CARRIER A person having no symptoms of the disease carries the infectious agent and acts as a reservoir. {chronic, transient, incubatory} ESTABLISHMENT OF DISEASE 1. ENTRY May have one route or many 2. DOSE Shigella ID = 100; Salmonella ID = 1067; Yersinia pestis ID = 1 3. TISSUE PENETRATION (may or may not be involved) 4. VIRULENCE FACTORS: AGRESSINS VS. TOXINS Staphylococcal Coagulase boils, causes localization of infection Streptokinase dissolves fibrin clots (spreading factor) Lecithinase dissolves cell membranes " " Hyaluronidase " tissue cell cement " " Hemolysin lyses red blood cells Leukocidin kills white blood cells (phagocytic cells) capsules helps microbes avoid being eaten by phagocyte TOXINS EXOTOXINS Gram + & Gram bacteria Protein found in cytoplasm of cell usually heat labile highly toxic good antitoxins ENDOTOXINS only Gram bacteria Lipopolysaccharide (LPS) in cell envelope of Gram heat stable not as toxic, fever TOXOIDS alum or formalin treated exotoxins vaccines [DTP] NEUROTOXINS tetanus paralyzes the central nervous system (suppresses synaptic inhibition) botulism paralyzes peripheral nervous system (blocks acetyl choline release across myoneural junction) Diphtheria Toxin Inhibits protein synthesis; produces a pseudomembrane in the throat Cholera Toxin causes a fluid and electrolyte imbalance of intestines "massive diarrhea" Bordetella pertussis cause of whooping cough: destruction of ciliated epithelium of the trachea much coughing Endotoxins pyrogenic [actually trigger the release of pyrogens from PMNs and macrophages IL1 & TNF induce fever, activate complement, reduce platelet counts, increase vascular permeability.] May lead to shock and death by Disseminated Intravascular Coagulation (DIC). NORMAL FLORA found on skin, in throat, intestines, vagina: normally protective not normally found in blood and urine. [most organs generally sterile {spleen, kidneys, liver and lungs = filter organisms out of the blood}] Intact unbroken skin and mucous membranes are the 1st line of defense Resistance to Infection NONSPECIFIC RESISTANCE SPECIES RESISTANCE only humans get gonorrhea only hogs get hog cholera only humans get polio only humans get smallpox Different populations of humans are more or less susceptible to certain diseases (measles). MECHANICAL AND CHEMICAL BARRIERS Intact Skin & mucous membranes very important generally must have penetration for disease. Mucus traps cilia move on to stomach {acid kills microorganisms} Bile in the intestines (salts to dissolve fats) {kill certain bacteria} Lysozyme hydrolyzes peptidoglycan, especially in Gram + bacteria Acid pH of urine and the mucus found in the vagina Interferon (produced by lymphocytes) Active against viruses and intracellular parasitic bacteria HUMAN CIRCULATORY SYSTEM Plasma (fluid) clot the blood Serum pH 7.4 CELLS: 1. Erythrocytes (hemoglobin = O2) [5 billion per cc] 2. Leukocytes [59 million per cc] a. granulocytes PMN (2 week lifetime) {phagocytes} neutrophils, eosinophils, basophils b. monocytes macrophages c. lymphocytes (integral part of the immune system) [make immunoglobulins and confer CellMediatedImmunity] LYMPH NODES: Sites of filtering (phagocytes) and lymphocytes tonsils, peyers patches, adenoids, appendix, spleen {sites of action during infection} PHAGOCYTOSIS (VERY IMPORTANT) PMN neutrophils and macrophages (RES) Chemotaxis Opsonization Attachment Engulfment Phagosome Phagolysosome Destruction Egestion CHEMOTAXINS LPS + complement C5a + C3a Peptides (emitted by PMN or bacteria) OPSONINS Antibodies Complement C3b INFLAMMATION (Early defense response to invasion by foreign body) Dilation of blood vessels, increased capillary permeability, PMN adhere to the site to eliminate the irritant. Four Signs of Inflammation: Calor, Rubor, Dolor & Tumor Pus serum & dead tissue cells plus leukocytes and dead bacteria ABSCESS Pus + a fibrin clot that encapsulates the pus SPECIFIC RESISTANCE (Specificity, Memory, and Recognition of nonself) ANTIGENS Substances which elicit a response from the body's immune system. (generally protein or polysaccharide and > 10,000 daltons) HAPTEN A very small molecule that is antigenic when combined with a carrier protein or polysaccharide molecule. (penicillin, poison ivy) SPECIFIC IMMUNE TOLERANCE self antigen reacting cells (specific lymphocytes) are continually removed from service TYPES OF ANTIGENS: AUTOANTIGENS self tolerance breaks down leads to autoimmune disease(s) ALLOANTIGENS blood group and transplantation antigens HETEROPHILE shared antigens [rickettsia and proteus OX series] BCELLS = They produce specific antibodies (immunoglobulins = immune globular proteins) TCELLS = They are involved in processing of antigens, regulation of the immune response and cellmediated immunity (CMI) These lymphocytes are found in lymph tissue: lymph nodes, spleen, tonsils, etc. OPERATION OF THE IMMUNE SYSTEM The maternal antibodies function to protect the newborn for 36 months; during this period of time foreign antigens are phagocytosed by PMN, macrophages, monocytes and partially digested and processed, then passed to lymphoid tissue. Activated Tcells Activated Bcells produce effector and memory produce effector (plasma) cells cells and memory cells CELLMEDIATED IMMUNITY HUMORAL IMMUNITY Lymphokines: small molecules Produce immunoglobulins that affect immune system and killer cells TYPES OF ANTIBODIES: IgM the largest molecule, first on the scene (5% of the total) IgG Secondary response, lasting immunity, maternal antibodies (80% of total) IgA Secretory immunoglobulin, GI and respiratory tracts (10% of total) IgE Response to anaphylactic allergies IgD They serve as receptors for antigens on surface of B cell lymphocytes ANAMNESTIC (MEMORY) RESPONSE long term humoral immunity and long term cellmediated immunity (CMI) CLONAL SELECTION HYPOTHESIS The initial cadre of Bcells expanded by transposon mutations Antibodies, Immunity and Serology Activities neutralization of viruses or toxins, opsonization (coating of foreign particles), complement lysis COMPLEMENT (C') SYSTEM 11 Proteins function in a cascade fashion 1. Heat sensitive components: inhibit C' by 56C for 30 minutes (differentiates activity of C' from antibodies) 2. Activities: a) opsonization b) chemotaxis c) bacteriolysis d) immune adherence e) anaphylaxis 3. PATHWAYS OF COMPLEMENT ACTIVATION A. CLASSICAL Initiated by "antigenantibody" complex [IgM or IgG] antibody recognizes cells surface, C' binds to Fc portion of ab C1q then C1r C1s bind C4 is altered by C1 complex C4b attached to membrane C2 is cleaved by C1s C2a + C2b C4b activate C3 Immune Adherence Complex C3a + C3b C4b,2a,3b anaphylotoxin chemotaxin Activates C5 C5a + C5b Cell Membrane then C6C7C8C9 "Membrane Attack complex" Cell Lysis B. ALTERNATE PATHWAY May Be Activated By: endotoxin, zymosan, & capsular polysaccharide {No C1, C4 or C2 INVOLVEMENT} Initiating factor + Activator C3 Proactivator properdin activated C3 binds to cell surface {No ANTIBODY INVOLVED} splits C3 Then works the same as the "classical" pathway SEROLOGY: "AntigenAntibody Reactions" Not all react or are all reactions easy to observe. Some require secondary reactions to observe and some may need to be diluted. Haptens and blocking antibodies may cause problems. 1. Radioimmunoassay Used to measure concentration of low molecular weight antigens. [very highly sensitive] known amount of Ag* + unknown Ag + known Ab AgAb & Ag*Ab Measure the remaining soluble Ag* Precipitated Standard curve is used to extrapolate the amount of Ag in sample 3. Neutralization [against toxins and viruses] Specific antitoxin or antiviral antibodies are added to tissue culture or injected into a control animal to neutralize the virus or toxin. This requires that you have two injected animals, both with toxin, and one with antitoxin. If the one that received the antitoxin survives and the one that only received the toxin died, then you known which specific toxin was in the sample. 4. Precipitation This reaction involves a soluble antigen and a specific antibody that bind to form a lattice structure that precipitates, if the concentrations of Ab and Ag are just right. Gel diffusion is easier because you allow the Ab and Ag to diffuse through the gel to reach just the right concentration to precipitate. 5. Agglutination This reaction involves a particulate Ag and a specific antibody that clump together rapidly. [not concentration dependent] PASSIVE AGGLUTINATION Attach soluble Ag to carrier particles (latex spheres or killed bacteria), then they will agglutinate in the presence of specific Ab. IMMUNE DISORDERS Hypersensitvity a state of increased sensitivity to an antigen arising from previous exposure to that antigen. [may involve antibodies or T cells] Immediate vs. Delayed Type Hypersensitivity (DTH) Types I IV I III = Immediate Type IV = DTH 1. Type I = Anaphylactic Hypersensitivity cause vigorous contractions of the smooth muscles allergen (bee venom, pollen, penicillin, serum protein) ~ 1g sensitizing dose B cells produce IgE which is fixed to mast cells and basophils [containing granules with vasoactive substances] This may require more than one sensitizing dose! Event: allergen binds to IgE antibody on cell inhibits adenylate cyclase Release granular contents cell swells Reduction of cAMP Reactions Release: histamine, serotonin, bradykinin, SRSA (a) edema = skin swelling (fluid accumulation) (b) urticaria = burning itching rash (c) bronchial muscles or GI muscles [contractions] [Antihistamines activate adenylate cyclase causing an increase in cAMP] Desensitization degranulate mast cells and/or induce production IgG blocking ab atopic allergies hay fever, asthma, food allergies Cause may be related to a breakdown in T cell (suppressor) control of IgE production 2. Type II Cytotoxic Hypersensitivity Ig reacts with cell surface antigens and damages or destroys that cell {Target cell} (complement may be activated and IgM may be involved) transfusion reactions incompatible blood types Erythroblastosis Fetalis (newborns) [RhoGam treatment] Immediately Autoimmune Disorders: Thrombocytopenia (poor blood clotting) Agranulocytosis (few granulocytes) Goodpasture's Syndrome (agab in kidneys activate C' cause blood & protein in urine) Myasthenia Gravis (damage to acetyl choline receptors, cancels nerve impulses) Graves Disease (over secretion of thyroxine, raise metabolic rate goiter) Hashimoto's Disease (under secretion of thyroxine) 3. Type III Immune Complex Hypersensitivity agab complexes accumulate in blood vessels or tissue surfaces, causing activation of C' C3a + C5a Degranulation Chemotaxis of PMNs Increase Vascular Permeability Cause tissue damage Serum Sickness hives; swollen face, neck and joints; kidney damage Systemic Lupus Erythematosis (SLE) antibodies are made against nucleoproteins of White Blood Cells agab complexes in skin and body organs C' activated butterfly Acute Glomeronephritis & Rheumatic Fever post group A streptococcal disease complications Rheumatoid Arthritis inflammation of the joints possibly Reye's Syndrome neuronal involvement IV. Type IV Cellular Hypersensitivity modulated by lymphokines released from Tcells causing a delayed reaction (24 72 hr) induration (hardening) and erythema (rash) a) infection allergy Tcells move to area express lymphokines that cause chemotaxis of PMN leading to phagocytosis. The Tcells stay in the area, and upon repeated exposure to the antigen cause heightened inflammation [tuberculosis, brucellosis, blastomycosis, histoplasmosis, candidiasis, smallpox, mumps and LGV] TB skin test b) contact allergy allergens in clothing, jewelry, insecticides, coins, cosmetics and furs. (also: formaldehyde, copper, dyes, bacterial enzymes, protein fibers) drying of the skin, erythema, scaling {poison ivy} 5. Immune Deficiency Diseases a) Bruton's agammaglobulinemia few plasma cells very low Ig and many infections with Staphylococci, Streptococci & Pneumococci {treated with artificially acquired passive immunity} b) DiGeorge's Syndrome T cell maturation is cancelled, highly susceptible to fungal, protozoal and some viral diseases. {treated by grafts of thymus tissue} c) ChediakHigashi Syndrome delayed PMN killing d) Job's Syndrome lazy leukocyte syndrome e) AIDS reversal of T4/T8 helper to suppressor ratio Transplantation Immunology 1870 first skin transplant autograft from another part of the same body isograft from an identical twin allograft same species (rejection rate tempered by relatedness) xenograft different species (seldom works) Rejection a) skin & tumor grafts T cells release lymphokines induce phagocytes which release lysosomal granules causing tissue necrosis [Type IV hypersensitivity] b) heart, kidney & other organs B cells make antibodies that travel to organs activate C' and undergo cytotoxic lysis cause O2 starvation [T cell interaction may supplement this] Type II Hypersensitivity c) Bone Marrow Transplant Graft vs. Host rejection Major Histocompatability Complex (HLA) chromosome #6 = 8 gene clusters with 50 alleles each gene {need tissue typing to match donor to recipient} [antimitotic drugs (e.g. cyclosporin A), steroids, Xirradiation] Tumor Immunology surface antigens a) oncofoetal antigen: alpha fetoprotein (AFP); carcino embryonic antigen (CEA) b) chemical carcinogens c) DNA viruses d) RNA viruses Tumors are kept in line by Killer Tcells and Natural Killer (NK) Tcells modulated by interferon {treatments BCG vaccination [stimulates]; IL2 [clones helper T cells]} AIRBORNE BACTERIAL DISEASES Respiratory Tract especially humans (isolation) 1. Tuberculosis 23 million deaths per year worldwide [650 700 per year in USA] crowded conditions, especially poverty spread by droplets may require repeated exposure Mycobacterium tuberculosis lungs: chronic cough, high fever, thick sputum incubation period 2 to 10 weeks (up to 6 months) "tubercle" layers of cells: lymphocytes, giant cells, PMN with caseation necrosis of the center may calcify or cavitate and spread to organs (lethal) The bacterial cell surface contains waxy lipids and tuberculoprotein hard to stain, acidfast, and hard to kill by normal cells {requires "AngryActivated Macrophage"} TB test: Old tuberculin (OT) or Purified Protein Derivative (PPD) are injected intradermally {Mantoux test} look for erythema in 4872 hr (early detection has lowered the number of cases of TB in the USA by 50 to 60 thousand) Bacille Calmette Guerin (BCG) = vaccine {not generally used in USA) Treatment rifampin, isoniazide, streptomycin, ethambutol (prolonged and mixed) MAC disseminated infections in AIDS patients 2. Diphtheria Corynebacterium diphtheriae (gram positive, clubshaped rod) metachromatic granules seen inside the cell when stained with a special stain, grows in the throat and tonsillar regions produces toxin causes cell necrosis and accumulation of serum and leukocytes "Pseudomembrane" The exotoxin specifically ADPribosylates the Elongation Factor 2 (EF2) and stops protein synthesis by halting peptide elongation inside the intoxicated cells Lysogenic bacteriophage codes for the diphtheria toxin which causes a fatty degeneration of the heart leads to death may also cause nerve fiber damage paralysis Prevention: DTP Treatment: penicillins 3. Meningococcal Meningitis Gram negative diplococcus Neisseria meningitidis Droplets mucous membranes blood stream Spinal cord & brain Meningococcemia Inflammation Death (headache, stiff neck, rash) Isolate organism find an oxidase + Gram negative diplococcus Sensitive to: ampicillin, rifampin, sulfonamides {early treatment = stop nerve damage} Fragile microorganism human to human transmission Healthy nasopharyngeal carriers are common (this state will immunize them after two weeks of carriage) 4. Streptococcal Sore Throat (pharyngitis) Streptococcus pyogenes transmitted by droplets or direct contact cause inflammation of the throat (tonsils) Erythrogenic toxin (coded by lysogenic bacteriophage) causes a rash & fever only certain strains have this toxin and are capable of causing Scarlet Fever either may lead to Rheumatic Fever (immune disease) antibodies to streptococcal antigens attack heart valves may cause permanent damage hemolytic group A streptococcal sore throat should always be treated with antibiotics within 10 days! group A polysaccharide cell surface antigen "M" protein cell surface (anti"M" protein is protective, opsonin) hemolysins, streptokinase, streptodornase, hyaluronidase, leukocidin Diseases erysipelas, impetigo, glomerulonephritis, puerperal fever [hemolytic streptococci (normal flora) = endocarditis & subacute endocarditis] 5. Peumococcal pneumonia (bronchi and lungs) 80% of lobar & bronchial pneumonia due to Streptococcus pneumoniae Gram + diplococci, commonly carried by healthy individuals and acts as a secondary invader to: influenza, common cold, allergy, smoking (predisposing conditions) Symptoms: high fever, sharp chest pains, consolidation, "rusty sputum" usually susceptible to: penicillin and erythromycin 80 antigenic types of capsular polysaccharide (only 1012 capsule types are commonly isolated clinically) virulence factors: capsule, hyaluronidase, pneumolysin Vaccine: purified capsular polysaccharide (12 types) 2nd generation has 24 capsule types hemolytic streptococcus that is bile soluble (optochin sensitive) 6. Klebsiella pneumoniae Gram negative rod with a capsule (carried by 10% population) causes pneumonia and urinary tract infections (UTI) may cause permanent lung tissue damage; treat with cephalosporins 7. Whooping Cough Bordetella pertussis (Gram negative rod) ciliated epithelium of the trachea disrupted by the bacterium and its toxins children under 1 year highly susceptible, may be deadly, treatment should be early penicillin or erythromycin Vaccine DPT (merthiolatekilled, crude cell preparation) 1930s 200,000 cases USA 15,605 cases in 2010 8. Primary Atypical Pneumonia "Walking" Pneumonia Mycoplasma pneumoniae filterable, pleomorphic organism containing no cell wall {cholesterol is required} there is low fluid involvement, dry hacking cough, fever, fatigue sensitive to erythromycin and tetracyclines {not penicillin} 9. Meningitis Haemophilus influenzae (Gram negative rod) common secondary invader to influenza most common cause of meningitis in infants (ages 0.5 to 2 years) 10. Legionnaires' Disease Legionella pneumophila (Gram negative rod) summer flu, defective cooling towers, only type 1, sensitive to erythromycin 3,000 cases in 2010 in USA [Pontiac fever, much milder, more common] FOODBORNE AND WATERBORNE BACTERIAL DISEASES 1. Botulism Clostridium botulinum Gram +(sporeforming rod) exotoxin most potent known to mankind [1 oz. Kill 30 billion people] found in intestine of man, fish, cows, birds and horses; also present in manure, sewage, and organic fertilizers spores cling to vegetables and germinate & grow in anaerobic conditions toxin encoded by a bacteriophage only slight growth needed to produce the toxin botulism symptoms blurred vision, difficulty swallowing, slurred speech, respiratory distress mech. of action of toxin no acetylcholine released at the myoneural junction of the peripheral nervous system heat inactivates the toxin boiling a few minutes common contaminated foods sausage, salami, canned mushrooms, olives, canned salmon, mostly homecanned foods (about 84 cases this year in the USA, with 6 foodborne) Respiratory therapy, antitoxin Infant Botulism SIDS? infectionintoxication, (no honey under age 2yr.) [about 90 cases per year] 2. Staphylococcal food poisoning Staphylococcus aureus (Gram + coccus, clusters) only certain strains produce an exotoxin (mol. wt. = 35kD), heat stable short incubation 2 to 6 hours {projectile vomiting, cramps, diarrhea, nausea} foods creamed, mayonnaise, potato salads, pastries, custards reservoir humans, anterior nares, boils 3. perfringens food infectionintoxication Clostridium perfringens toxin produced during sporulation, usually in the intestines cause intestinal cramps, diarrhea usually found in proteinrich foods {beans, meats, gravies} 4. Typhoid Fever Salmonella typhi (gram rod) usually transmitted in contaminated water or food human carriers (may be chronic or transient) found in contaminated shellfish and sewage symptoms constipation, then bloody diarrhea, then fever & "Rose" spots on the abdomen (rash) isolate organisms from the urine, feces, blood, bone marrow Widal test serum agglutination test 26,000 cases/yr in USA in 1931 391 cases/yr in USA in the last five years Salmonellosis (hundreds of serotypes) food infection Salmonella enterica [about 40,000 cases per year] symptoms nausea, cramps, diarrhea, vomiting (gastroenteritis) 10 to 20 hr incubation period (no bloody stool) ice cream, potato salad, poultry products (especially eggs) Bacillary Dysentery Shigella (Gram rod) 13,166 cases in 2009 in USA, mostly S. sonnei dose small several hundred reservoir humans (transmitted by water, eggs, shellfish, dairy products) organisms produce toxin that attacks the colonic cells cause a watery diarrhea, with some blood (may cause dehydration, convulsion & death) many bowel movements, small volume Resistance Transfer Factors (RTF) plasmids carrying DNA coding for resistance to several antibiotics Cholera Vibrio cholerae (Gram rod) causes vomiting, cramps and diarrhea (dehydration) untreated mortality approaches 70% [Haiti 4722 cases: 303 deaths 10/28/10] a disease of the upper intestines, the bacteria attach to the jejunum and ileum, produce toxin and it causes loss of fluid and electrolytes 7 Pandemics in history Classical vs. El Tor biotype usually requires large inoculum to get past the acid in the stomach exotoxin A and B subunits (B binds and A intoxicates) {enterotoxin is bacteriophage encoded} A causes adenylate cyclase enzymes to produce high levels of cAMP, which inhibits uptake of Na+ ions and increases release of Cl ions, causing release of NaCl, NaHCO3 and water {leading to dehydration and acidosis} "Rice Water" stools diarrhea with mucus cells, and electolytes ( 25 L per day) Escherichia coli diarrhea usually less severe than cholera Enterotoxigenic E. coli (ETEC) traveler's diarrhea Enteropathogenic E. coli (EPEC) infantile diarrhea Enteroinvasive E. coli (EIEC) like shigellosis Enterohemorrhagic E. coli (EHEC) bloody diarrhea & hemolytic uremic syndrome (HUS) Enteroaggregative E. coli (EAEC) infantile & traveler's Brucellosis Brucella abortus, B. melitensis, & B. suis (small Gram rod) causes abortions in cattle & sheep {erythritol = tissue localization factor} symptoms in humans weakness, night sweats, backache, headache, fever occupational hazard inhaled, ingested, conjunctiva, abrasions facultative intracellular parasite inoculum = 10 to 100 organisms "zoonosis" treat with tetracyclines or erythromycin B. canis dogs, especially beagles in kennels Campylobacteriosis Campylobacter jejuni (Gram , curved rod) causes a bloody diarrhea, abdominal pain, occasional enteric fever from: chickens, cattle, turkeys, milk (unpasteurized) Vibrio parahaemolyticus (Gram curved rod) from eating contaminated shellfish marine vibrio that causes cramps, diarrhea and vomiting Yersinia enterocolitica (Gram rod) usually from contaminated water gastroenteritis, usually in children or immunosuppressed individuals SOILBORNE AND ARTHROPODBORNE BACTERIAL DISEASES 1. Anthrax Bacillus anthracis (Gram + sporeforming rod) zoonosis a disease of cattle and sheep, spread to humans spores in the soil cattle & sheep highly susceptible (fulminating septicemia in cattle and sheep) polyDglutamic acid capsule (virulence factor) "invasin" humans usually resistant {woolsorters' disease = lungs} gastrointestinal violent bloody diarrhea skin malignant pustule Exotoxins Lethal Factor (LF), Edema Factor (EF), and Protective Antigen (PA) any alone = no effect ; LF + PA = death; EF + PA = edema picked up in animal products leather and animal bristle brushes treatment penicillin, ciprofloxacin vaccine PA then capsulefree (attenuated B. anthracis) 2. Tetanus Clostridium tetani (Gram + sporeforming anaerobe) tetanus toxin (exotoxin) 2.5 ng human lethal dose {1 oz. kill 12 billion} coded for by 4070 mD plasmid, toxin labile to heat & light, strychninelike action on the central nervous system (CNS: suppresses synaptic inhibition) causes total spasms spores everywhere in the soil, air and water (especially horse manure) deep puncture wound anaerobic slight growth toxin synthesis about 27 cases per year in the USA the last five years 38% fatality rate this is reduced with symptomatic treatment: respiratory therapy, antitoxin, curare, barbiturates, antibiotics 3. Gas Gangrene Clostridium perfringens (Gram + spore forming anaerobic) also C. novyi & C. septicum (mixed contamination) require much traumatized, devascularized tissue in the wound to initiate myonecrosis grow fast, much gas, spreads through healthy tissue virulence factors lecithinase, hyaluronidase, hemolysin, collagenase treatment penicillin, debridement, amputation, hyperbaric oxygen 4. Listeriosis Listeria monocytogenes (Gram + motile rod) from soil, animals, and unpasteurized milk healthy carriers slaughterhouse workers, food processors Listeric meningitis stiff neck headache and coma uterine form abortions in humans some bacteria are very resistant to heat and/or cold 4. Bubonic Plague Yersinia pestis (Gram rod) The reservoir is the rat, the rat flea is the vector and humans are incidental hosts When fleas are infected it closes their esophagus and they think they are hungry and bite more goes to the blood lymph lymph nodes (swelling = buboes) may go to the lungs and cause "pneumonic" plague and be contagious spread by aerosol hemorrhages in the skin black death sylvatic plague desert rodents in the southwest USA 5. Tularemia Francisella tularensis (Gram rod) "rabbit fever" rodents in the USA cause craterlike ulcer & swollen lymph nodes hard to diagnose, treat with tetracycline or streptomycin concentrated in: Missouri, Arkansas, and Oklahoma 6. Leptospirosis Leptospira interrogans (Gram spirochete) transmitted in contaminated soil or water (urine of rodents) occupational hazard for: dock workers, mine workers, farmers, sewage plant workers, frequently transmitted to domestic animals first then to humans symptoms: fever, jaundice, blood in vomit, splenomegaly, skin hemorrhage penicillin much more effective if given early 7. Relapsing Fever Borrelia recurrentis (Gram spirochete) transmitted by ticks and lice (filth and poverty) symptoms: similar to leptospirosis, but symptoms cycle up to 10 times because of surface antigen capping (genetically altering surface ag) treat with tetracyclines 8. Lyme Disease Borrelia burgdorferi (Gram spirochete) transmitted by Ixodes scapularis (tick), reservoir white footed mouse and whitetailed deer humans are incidental hosts symptoms: rash (50%), arthritis (common), neurological signs (less common) early treatment more effective CONTACT AND ENDOGENOUS BACTERIAL DISEASES Gonorrhea Neisseria gonorrhoeae (Gram diplococcus) 300 thousand cases per year reported in the USA microbe fragile, nutr. fastidious, temp. sens., sens. to drying and heavy metals (mercury, bismuth, etc.) Pelvic Inflammatory Disease (PID) in females, also commonly asymptomatic males urethritis, epididymitis, sharp pain, possible sterility (also in females) conjunctivitis, pharyngitis, ophthalmia neonatorum (AgNO3 treatment of the eyes at birth) treatment penicillin: PPNG = spectinomycin or tetracycline diagnosis pussy penile discharge PMN with Gram diplococcus, oxidase +, catabolizes glucose not maltose Syphilis Treponema pallidum (Gram spirochete) obligate extracellular parasite (was much more deadly when it was a new disease) attacks mucous membranes 1. Primary stage Chancre "hard raised" and painless (infectious) loaded with spirochetes usually found on the genitals, lips, skin or pharynx; 21 day incubation {cases increasing in the last few years) heals < 1 mo. 2. Secondary Stage maculopapillary rash (containing spirochetes): the person may die or may recover may go to latent syphilis (high ab titer, no symp.) 3. Tertiary Stage gummas (and lesions of cardiovascular or nervous system) paralysis, heart failure, insanity darkfield micro exam., TPI or serum FTAABS, VDRL, Rapid Plasma Reagin, TP hemagglutinin test. treatment: penicillin for primary & secondary syphilis number of cases (now 1012,000 cases per year in USA) All stages over 30,000 cases (300400 cases congenital) Chancroid Haemophilus ducreyii (Gram rod) soft, painful lesion, swelling of inguinal lymph nodes Nongonococcal Urethritis (NGU) Chlamydia trachomatis (obligate intracellular parasite) most common type of STD in USA (650,000 cases per year) may cause sterility. Ureaplasma urealyticum (no cell wall, requires cholesterol & urea) similar to gonorrhea, abortions, sterility, prostatitis all treated with tetracyclines Leprosy Mycobacterium leprae (Gram + rod) treatment places Molokai & Carville Louisiana 10 million people affected around the world, long incubation period may be years treatment dapsone Immunity CMI (lepromin test) Yaws tropical disease (Africa, S.America, Asia) syphilis like organism Treponema pertenue bejel & pinta from the soil through abrasions an ulcerous lesion may spread to other areas may disappear, mostly in children treat with penicillin Actinomycosis Actinomyces israelii (Gram + anaerobic rod) lumpy jaw in cattle, cervicofacial lesion in humans swelling draining sinuses, may be in the thoracic or abdominal cavity an IUD may lead to infectious abortion or PID normal flora of the oral cavity; treat with penicillin Trench Mouth "stressinduced" synergistic disease Acute Necrotizing Ulcerative Gingivitis (ANUG) Leptotrichia buccalis & Treponema vincentii destruction of the gingiva & papilli (bad odor & bad taste in the mouth) also Eikenella corrodens & Treponema denticola treat with penicillin, hydrogen peroxide or use good oral hygiene Toxic Shock Syndrome (TSS) 1978 Staphylococcus aureus with specific toxin: SPE or SEF causes rash, fever, vomiting, watery diarrhea, desquamation of the palms of the hands and the soles of the feet shock death Rely tampons fibers caused strains to grow better and produce more toxin Urinary Tract Infections (UTI) frequently endogenous E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecalis cystitis (bladder infection) Bacteroides anaerobic abscesses abdomen, peritoneum, oral cavity ...
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This note was uploaded on 02/05/2012 for the course MIC 201 taught by Professor Lacroix during the Fall '08 term at Rhode Island.

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