Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Bacteria Pathogenicity Ability to Cause Infection Infectious Diseases • • • • Encounter-bug meets host (reservoir) Bug adheres to host Entry-bug enters host Multiplication- bug multiplies in host – Infectious Diseases • Damage to host – Virulence of bug or host response • Outcome- bug or host wins or • Coexist- chronic infection Reservoir • Exposure to microbe – Humans – Animals – Environment Virulence Factors • Enhance colonization & growth • # of cells required to establish infection • Measure of pathogenicity Adherence (Virulence Factor) • Attachment to host cells • Adhesins on pathogen (proteins) – Bind to complimentary surface receptor Adherence • Prevent infection • Influenza changes adhesions over time • Neisseria gonorrhoeae -variety of adhesions Portals of Entry • Mucous membranes – Respiratory – GI – Genitourinary • Conjunctiva Portals of Entry • Skin • Bugs have preferred portal • C. tetani spores in soil --- anaerobic wound Inoculum • Number of microbes-dose • Greater dose, more chance infection will occur • ID50 or LD50 expresses virulence – Infectious or lethal dose for 50% of population – LD50 used for toxins ID50 • ID50 for B.anthracis via skin is 10 to 50 endospores • Via which route is infection more likely? • Via which route is infection more lethal? Invasins • Adherence of microbe to surface • Activates factors that let microbe inpenetration • Microbes produce invasins (proteins) • Endocytosis Colonization • Requires multiplication • Compete with normal flora for space & nutrients Colonization • Overcome local host defenses – IgA (mucosal surfaces) • Avoid IgA – Rapid turnover of fimbriae/pili – Antigenic variation in type of pili – IgA proteases (enzymes) destroy IgA Multiplication • Need Fe to multiply – Most is bound in host – Have own iron-binding molecules that compete for Fe-siderophores •\ Avoid Phagocytosis • Avoid recognition & attachment • Capsule – Impairs phagocytosis DT negative charges – Produce antibodies to capsule –\ Avoiding Phagocytosis • Components of cell wall –virulence – Mycolic acids in M. tuberculosis Surviving Within Phagocyte • Escape from phagosome, vesicle, before fuses with lysosome • Prevent fusion with lysosome • Grow inside phagocyte protected from host Tuberculosis • • • • • Ancient disease 1/3 of world population infected 8 million develop active TB each year 2 million die each year AIDs increases activation of latent TB Tuberculosis • Dependent upon virulence of strain & host resistance • Produces cell mediated immunity which prevents active disease in many people • Multi drug resistance has developed S & S of Pulmonary TB • • • • • Chronic disease Progressive weight loss Night sweats Chronic cough Hemoptysis Mycobacterium tuberculosis • • • • Acid fast bacillus (AFB) Resistant to drying Aerobic, slow growth Airborne transmission Mycobacterium tuberculosis • Inhale airborne droplets • Ingested by alveolar macrophages • Multiply in macrophages even with ongoing immune response TB Response • Host immune response-delayed type hypersensitivity reaction • Tissue damage DT Inflammatory response TB Conversion • TST skin reaction is positive • Occurs within 24 – 48 hours after exposure to TB antigens • Purified protein derivative of bacillus • Cell mediated immunity • Sensitized T cells react with proteins QuantiferonGold • Blood test • Detects interferon gamma How to Confirm Diagnosis • Sputum cultures for AFB smear & culture • Chest xray Pathogenesis • LTBI (latent TB infection) – – – – Immune defenses contain organism Formation of tubercle TB converter No S&S of disease Active Disease • Low resistance – – – – Disease not controlled Cytokines damage lung Acute pulmonary infection Can spread & cause death TB Outcomes • Primary infection- positive skin test – 90% immune system controls infection via cellular immunity • TB germs isolated within tubercles( Activated macrophages) TB Outcomes • 10% progressive primary infection-not controlled – Illness or death if not treated – Cavities in lungs – Spread throughout body Secondary or Reactivation Infection • Reinfection-2nd exposure or • Bacteria escape immune systemreactivation • Activated macrophages release cytokines • Delayed hypersensitivity reaction Prevention of Transmission • • • • • Negative pressure rooms Respirator masks-fit tested Admit staff aware of symptoms of TB Yearly TST of staff Conversions treated with 6-9 months of INH Treatment • INH for LTBI or TB conversion • TB disease-active TB – 4 drugs till drug sensitivities return – DOT • 9- 12 months of treatment – Slow growing – Impedes abx entering cell wall Resistant TB • MDR TB – Resistant to INH, & 1 other TB drug • XDR TB – Resistant to all 1st line drugs – Use 2nd line drugs for several years – Often leads to death • DT improper treatment BCG • Live culture of M. bovis – Attenuated strain – Used in other countries to protect children from miliary disease – Can cause positive reaction on TST Latent vs Active • Latent TB – Infected but no S&S – Not infectious • Active TB – S&S of disease – Infectious if pulmonary TB Leprosy • Hanson’s disease- discovered in 1873 • Seen in tropics and underserved countries • U.S.-150 new cases per year Leprosy • Infection of nervous system • Infects the peripheral nerves within skin • 2 forms of disease dependent upon immune response M. leprae • Tuberculoid form – Regions of skin, lost sensation surrounded by nodules – Lose pigmentation – Causes strong cell mediated response – Activated macrophages keep microbe under control Lepromatous Form • Weak immune response & microbe spreads • Skin & nerve cells infected • Shed large #s in nasal secretions and oozing sores-more infectious Invasion via Enzymes • Exoenzymes- excreted to outside • Coagulases-clot fibrinogen in blood Kinases • Breakdown fibrin – Produced by strep – Invades tissues & spreads – Used to isolate infections Enzymes • Hyaluronidases – hydrolyzes hyaluronic acid (polysaccharide) • IgA proteases – Destroys IgA antibodies in secretions Enzymes • Leukocidins – Kill neutrophils • Hemolysins-staph & strep – Dissolve RBCs – Able to obtain Fe Invasion via Toxins • Toxins – Poisonous substances damage tissues – Cause shock, fever, inhibit protein synthesis • Two types – Exotoxins – Endotoxins Exotoxins • • • • Produced inside cell Mostly proteins, kill in low concentrations Mainly gram positive Gene on plasmids or phages – Not bacterial genes Exotoxins • Destroy part of cell or inhibit metabolic processes – Specific for each exotoxin • Toxin responsible for S &S of disease Exotoxins • Antitoxins – Antibodies to toxin • Toxoid – Inactivated exotoxin – Use to induce immunity to toxins – Vaccines A-B Toxins • • • • • • 2 parts-polypeptides A-active or enzyme component B-binding component B binds toxin to host cell A-B toxin enters Components separate & A kills host – Disrupts protein synthesis Superantigens • Bacterial toxins provoke intense response • Stimulate nonspecifically T cells • T cells release cytokines – Fever, N & V, diarrhea – System wide effect with organ failure Naming of Exotoxins • • • • • Neurotoxins attack nerve cells Cardiotoxins-heart cells Hepatoxins-liver cells Leukotoxins-WBCs Enterotoxins-release of fluids-nausea, vomiting & diarrhea • Cytotoxins-variety of cells Endotoxin • Lipid A • Stimulates macrophages to release cytokines – High levels are toxic • Activate complement & immune defenses S&S • Chills, fever, weakness, aches • Later shock and death • Activate blood clotting – Clots obstruct capillaries – Death of tissues-DIC • Endotoxin shock sepsis Shock • • • • Loss of blood pressure Gram negatives-endotoxin shock Cytokine-tumor necrosis factor (TNF) Damages blood vessels -leaky Endotoxins • Do not promote antitoxins ( abs to Lipid A) • Antibodies produced to bug don’t affect toxin • Assay to detect minute amounts of endotoxins in drugs & body fluids Staphylococci • • • • Staph divided based upon coagulase S. aureus is coagulase positive S. epidermidis (CNS) Found on humans and animals S. aureus • Named for yellow pigmented colonies • Facultative anaerobe, catalase positive • Grows well in nares-colonization S. aureus • If infected, shed high numbers – Don’t work around food or patients • Survives well in environment-resists drying • Now resistant to most antibiotics • MRSA Epidemiology • Nasal carriers have 2-7 times greater risk of infection than non carriers • Screening of high risk pts Successful Pathogen • • • • Biofilm Capsule Exoenzymes Toxins Biofilm • Protective growth medium for microorganisms – WBCs, antibodies, antibiotics • • • • ET & trach tubes-PNA IV catheters-BSIs Implants- SSIs Facilitates transfer of resistant genes Capsule • Protection from phagocytes • Attachment • Prevents dehydration Enzymes • Proteases – Degrade fibrous protein in collagen • Hyaluronidase – Degrades cement between cells • Promote spread in tissues Enzymes • Lipases – Colonize hair follicles – Breaks down sebum • Leukocidins – Kill WBCs – Pus formation (pyogenic) Skin Infections • Pimples, boils, abscesses – Impetigo of newborn, blisters – Infection of insect bites, burns, scrapes etc. • Cellulitis – Spread of bug through skin and soft tissue • Wound infections-major cause • Use of antibiotics • Resistant MRSA Invasion via Toxins • Produce many exotoxins • Secreted to outside – Increase ability to invade tissue and cause damage • Exfoliatin toxin-scalded skin syndrome – Occurs in infants Toxic shock syndrome • Superantigen • Symptoms – High fever, hypotension, vomiting, rash & death • Female normal flora – Use of tampons abrade wall S. aureus Intoxication • Enterotoxin causes food poisoning – Restricted to GI tract • S&S – Vomiting, diarrhea, abdominal cramps • Prevention-hand hygiene & refrigerate food – Toxin not produced Treatment • • • • Use of antibiotics for infections only Over use/misuse Resulted in selection of MRSA in hospitals Isolate these patients CA-MRSA • MRSA in community • Patient lacks risk factors for HA-MRSA – – – – – Hospitalization Surgery Long term care Dialysis Indwelling catheters Outbreaks in Community • • • • • • Sports participants Daycare, elementary schools Inmates Military recruits Men having sex with men (MSM) Tattoo recipients CA-MRSA • Susceptible to more antibiotics • Gene for Panton-Valentine leukocidin (PVL) • Causes skin & soft tissue infections PVL Gene • May be associated with severe necrotizing infections • HA MRSA & S. aureus strains rarely carry this gene Preventing Transmission • • • • Exclude from work, school, sports, etc. Dispose of used bandages in trash Avoid sharing personal items Shower every day with Dial or antibacterial soap Clostridium botulinum • Gram positive rod • Soil and vegetation • Produces several exotoxins- neurotoxin Neurotoxin • Toxin causes flaccid paralysis of muscles • Prevents release of neurotransmitter, acetylcholine – Muscles can’t contract Botulism-Foodborne Disease • Disease caused by exposure to toxin – Microbe can’t compete with normal gut flora in adults • Infant botulism-don’t have protective gut flora – Associated with honey • Treatment-supportive care – Ventilator – Antitoxins-trivalent Toxin • 1 pt kills everyone in world • 1 oz kills everyone in US • Botox –type A Clostridium tetani • Gram positive, endospore forming rod • Found in soil contaminated with animal feces • Encounter- deep puncture wounds with dirt Neurotoxin • Released by lysis of bacteria • Binds to nerve cells that control contraction of skeletal muscles • Toxin blocks relaxing pathway so both muscles contract spasm • Jaw muscles first, can’t open mouth Lockjaw • Death from spasms of respiratory tract – Pneumonia & regurgitation of stomach contents • Prevention – DPT -toxoid, inactivated toxin – Anti toxin neutralizes toxin Clostridium difficile • Anaerobe • Endospore forming rod • Vegetative cells – Survive for at least 24 hr on inanimate surfaces Epidemiology • Present in soil and water • Found in gut of humans & animals • Hospitals are a major reservoir – 20-40% of pts become colonized • Recently, found in pork Range of Disease • Asymptomatic carriage ( outnumber those with disease) • Clostridium difficile infection (CDI) • Pseudomembranous colitis • Toxic megacolon • Sepsis • Death Pathogenesis of CDI • C. difficile ingested either as vegetative form or spores • Spores germinate in small intestine • Normal flora disrupted by antibiotic therapy, disease can occur • C. difficile releases toxins causing severe inflammation of colon New Issues • CDI rates are increasing • Epidemic strain found in US, Canada, & Europe • More severe disease – Higher mortality – Higher rates of colectomy Treatment • Stop the inciting antibiotics • 25% recover without further treatment • Flagyl is first line of therapy Treatment • Must monitor response to therapy • Vanco po for moderate to severe disease • Both antibiotics disrupt the normal flora – Susceptible to relapses or re-infection Transmission • • • • Fecal-oral route Contaminated hands of HCWs Contaminated hands of patients Contaminated environment Environment • Clean and disinfect surfaces in close proximity of the patient • Patient care equipment. • Use bleach for C. difficile • Privacy drapes