MMI 133 Part four

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MMI 133 Part four
2013-03-25 14:41:51

Before fourth midterm
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  1. 2 divisions of the respiratory tract
    • Upper respiratory tract (URT): nose, pharynx, (throat), middle ear, eustacian (auditory) tubes, sinus, nasolacrimal ducts
    • Lower Respiratory tract (LRT): Larynx (voice box), trachea (windpipe), bronchial tubes, alveoli (compose lung tissue), pleura
  2. URT defenses
    • Nose hairs
    • Ciliated mucous membranes - nose, throat
    • Lymphoid tissues (tonsils, adenoids) at nose/throat junction; contains macrophages
    • BUT: tonsils and adenoids can be infected - spread through URT to ears
  3. Normal Flora of the Respiratory Tract
    • Potential pathogens
    • Microbial antagonism is important
    • alpha-Streptococci are dominant
    • Staphylococcus aureus
    • Staphylococcus epidermidis
    • Haemophilus influenzae
    • Neisseria sp.
  4. Normal Flora of the Respiratory Tract
    • Mostly sterile
    • Exception: trachea
    • "Ciliary escalator" is normally very efficient
  5. Paryngitis
    • Microbrial disease of the URT
    • Inflammation of mucous membranes of the throat (sore throat)
  6. Laryngitis
    • Microbrial disease of the URT
    • Inflammation of the larynx
    • -spread from URTI
    • -S. pyogenes, S. pneumonia, virus, combination
  7. Tonsillitis
    • Microbrial disease of the URT
    • Inflammation of tonsils
  8. Sinusitis
    • Microbrial disease of the URT
    • Inflammation of mucous membranes of sinus
    • -S. pneumonia, Haemophilus influenza (usually self-limiting)
  9. Epiglottitis
    • Microbrial disease of the URT
    • Inflammation of epiglottis (H. influenza)
    • -epiglottis - prevents ingested material from entering larynx
    • -most threatening -> death within a few hours
    • -usually opportunistic
  10. URT Microbial diseases
    • Pharyngitis
    • Laryngitis
    • Tonsillitis
    • Sinusitis
    • Epiglottitis
  11. URTI - Bacterial
    • Mucus membranes of URTI often point of entry for many respiratory or systemic infections
    • Common complication: otitis media (infection of middle ear)
    • -pathogens cause buildup of pus resulting in pressure against eardrum - painful inflammation
    • -very common in children <3 yrs old: nearly 50% of office visits to pediatricians
    • -S. pneumonia, H. influenza, Moraxella catarrhalis, S. pyogenes
  12. Streptococcal Pharyngitis (strep throat)
    • Group A beta-hemolytic streptococci (S. pyogenes)
    • Only ~5-10% of sore throats are caused by S. pyogenes - most are viral1!!
    • Virulence factors (M protein, streptokinase, hemolysin, leukocidin)
    • Transmission: respiratory secretions
    • Symptoms: Local inflammation, fever; + tonsillitis, lymph node enlargement, otitis media
    • Cannot be diagnosed visually, lab tests required: agglutination test (latex particles coated with anti-strep A antibodies, if present, particles will aggluntinate, clumps can be seen with naked eye) Quick, but false positives
    • Treatment: penicillin
  13. Scarlet Fever
    • S. pyogenes strain that produces erythrogenic toxin
    • -lysogenized strains only
    • -high fever, pinkish-red sandpaper type rash
    • -strawberry tongue (tongue becomes red and enlarged, skin often peels off as if sunburned)
    • Complications: glomerulonephritis, rheumatic fever
    • Transmission: inhalation of infected droplets
    • Treatment: Penicillin
    • Erythrogenic toxin is produced by strains of Streptococcus pyogenes that have been lysogenized
    • erythro=red; gen=producing
    • Function: damaged plasma membranes of cells in blood capillaries; results in vasodilation; vasodilation produces characteristic red rash
    • Toxin may also cause hypersensitivity reaction (allergy) resulting in rash
  14. Whooping Cough
    • 100 days cough
    • Bordetella pertussis (G negative aerobic coccobacilli)
    • Virulent strains are encapsulated
    • Extremely contagious; inhalation
    • Protective antibodies are produced
    • Produce exotoxins: penetrate tissues, immobilize cilia, kill cells, cause mucous accumulation in airway
  15. Whooping cough pathogenesis
    • Airborne transmission
    • Bacteria attach to ciliated cells of the trachea
    • Release exotoxins to cause disease:
    • -Tracheal cytotoxin: kills ciliated epithelial cells; stops ciliary escalator; impairs mucous clearance
    • -Pertussis toxin: A-B toxin; decreases phagocytic activity
    • -Secreted adenylate cyclase: taken up by phagocytes; inhibits bactericidal activity
  16. Symptoms of Whooping cough
    • 3 stages:
    • Catarrhal stage (1-2 weeks)
    • -highly contagious
    • -similar to common cold
    • Paroxysmal stage (3rd week - 2 months)
    • -prolonged coughing fits (several times per day)
    • -mucous accumulation
    • -bouts of many coughs on a single expiration followed by "whopping" inspiration
    • -gasping for breath produces characterisitic "whoop"
    • -violent -> broken ribs
    • Convalescence state (2-3 months)
    • -coughing subsides, recovery
  17. Whooping cough diagnosis and treatment
    • Diagnosis: usually depends on clinical signs and symptoms
    • Treatment: erythromycin (only before paroxysmal stage); antibiotics may not result in rapid improvement, but they do make patient noninfectious
  18. Whooping Cough Prevention
    • Vaccine in available: very effective
    • Part of DTaP vaccine: aP=acellular pertussis
    • 2 types: killed whole bacteria - problems: higher levels of LPS than most vaccines (organism in Gram-negative)
    • -acellular: against various combinations of toxins; fewer adverse reactions, but efficacy is variable depending on strain present
    • Vaccination has lowered annual # of cases from 250,000 to ~ 7,000
    • Generally <10 deaths
  19. Diptheria
    • Cornyebacterium diphtheriae: gram-positive, non-endospore-forming rod
    • Diphtheria was leading infectious killer of children in the USA until 1935: now < 5 cases per year in US; vaccination started; DTaP vaccine: diphtheria, tetanus, pertusiss; diphtheria - toxoid vaccine; boosters are required (~10 years)
    • Population is largely immune - nonvirulent strains of C. dipthereriae are often found in normal flora
    • Virulent strains are lysogenized and produce an exotoxin (diphtheria toxin)
    • Bacteria does not invade tissues - the exotoxin diffuses out into tissue
    • Toxin - inhibits protein synthesis in hose cells
  20. Diptheria Toxin
    • A-B toxin
    • Toxin consists of 2 parts (A and B)
    • A = active (enzyme) component
    • B = binding component
    • B must bind to receptor on host cell to allow the A component to enter and reach its target
    • Diphtheria toxin: the A component inhibits protein synthesis - host cell dies
  21. Diphtheria Symptoms
    • Sore throat
    • Fever
    • Malaise
    • Swelling of neck (lymphadenopathy) "bull neck"
    • Formation of tough grayish membrane in throat: pseudomembrane; contains fibrin, dead tissue, bacterial cells, WBC; may block air passage; avoid scraping off pseudomembrane as this may lead to bleeding and release/spread of toxin
    • Toxin can kill all cells, so location of toxin determines the severe symptoms
    • Cardiac: arrhythmia, mycocarditis
    • Nervous: partial paralysis
    • Kidney: dysfuntion
    • When organs are involved the disease can be rapidly fatal
  22. Diphtheria Pseudomembrane
    • Diphtheria toxin:
    • Causes death of epithelial cells in the throat
    • RESULT: inflammation -> accumulation of phagocytes
    • Formation of tough grayish membrane in throat:
    • -pseudomembrane
    • -contains fibrin, dead tissue, bacterial cells, WBC, toxin
    • -may block air passage
    • -very hard to remove - grows out of tissue and bleeds if you try to dislodge it
    • -disruption may lead to bleeding and release/spread of toxin
  23. Diphtheria: Diagnosis and treatment
    • IMPORTANT to differentiate between nonvirulent strains commonly found in normal flora and virulent toxin-producing strains
    • Both may be found in same patient
    • All isolates must be tested for TOXIN PRODUCTION
    • Treatment (two parts)**
    • Antibiotics - penicillin, erythromycin: control bacterial growth, DO NOT neutralize toxin
    • Antitoxin: neutralize toxin (unbound only); antibiotic therapy should ALWAYS be used together with antitoxin
  24. Otitis Media
    • Infection of the middle ear (earache)
    • Common complication of respiratory infection
    • Can be caused by numerous pathogens: S. pneumonia (35%), H. influenza (20-30%) Moraxella catarrhalis (10-15%) S. pygoenes (8-10%) S. aureus (1-2%) viruses (3-5%)
    • Most frequent in early childhood: auditory canal is small, easily blocked by infection
  25. Otitis Media: treatment
    • Usually assume bacterial cause
    • Use broad spectrum antibiotics: amoxicillin
  26. Acute Epiglottitis
    • Most often in young children, usually due to Haemophilus influenza type b (Gram negative bacilli)
    • Not common - vaccine part of recommended course (Hib vaccine)
    • Bacteria spread from nasopharynx to epiglottis, causes severe inflammation and swelling
    • Life threatening - NEEDS INTUBATION!!!
    • Get help fast!
  27. Acute Epiglottitis: what to watch for
    • Intensely painful throat, difficulty speaking or swallowing
    • Drooling
    • Soft inspiratory stridor (wheezing)
    • Rapidly increasing respiratory difficult over hours
    • Child sits immobile, upright with an open mouth in an attempt to optimise the airway
  28. URTI - Viral (The common cold)
    • >200 different viruses can cause a cold; immunity usually doesn't develop
    • 50% -> rhinoviruses: infective dose: 1 particle!
    • 15-20% -> coronaviruses
    • 10% -> several other identifiable viruses
    • The rest: no agent can be identified
  29. URTI - Viral symptoms
    • Sneezing, nasal secretion, congestion
    • Can spread to ear, LRT, sinus
    • Usually no fever
  30. URTI - Viral: transmission & treatment
    • Not clear - conflicting experimental results
    • Airborne? direct contact? fomites?
    • Treatment:
    • None
    • Non-prescription treatments: zinc lozenges, vitamin C (not reported to affect recovery time)
    • Cough suppressants, antihistamines (relieve symptoms, do no affect recovery time)
    • Expect recovery to take one week
  31. LRT
    • Infections of the lower respiratory tract tend to be more severe
    • Choice of antimicrobial therapy important and may be life-saving
  32. Croup
    • Common in children
    • Croup (swelling of the mucous membrane)
    • Larynx and trachea have non-expandable rings of cartilage and since children have narrow tubes, obstruction can occur
    • Typical symptom is seal-like barking cough (croup = "to cry hoarsely")
    • No antivirals, no vaccine
    • Parainfluenza virus common cause of croup in children
  33. Bronchiolitis
    • Disease restricted to children usually <2 years
    • Bronchioles of children are very small in diameter - if the cells lining them are inflamed and swollen the passage of air to and from alveoli is reduced
    • Necrosis of epithelial cells (spread on the lung and cause interstitial pneumonia)
    • 75% caused by RSV = Respiratory Synyctial Virus
  34. Tuberculosis (Mycobacterium tuberculosis)
    • Bacilli, classed as Gram positive but cannot be stained with Gram stain
    • Stained with Ziehl-Neelsen (acid fast)
    • Very resistant to drying and chemicals due to thick cell wall with high content of mycolic acids, etc (wax-like)
    • Capable of intracellular growth in macrophages, no toxin produced (survival may be due to mycolic acids)
    • Transmission: airborne
  35. Tuberculosis
    • 10% of the world's population infected
    • TB is responsible for 5-6% of all infection-related deaths worldwide
    • Cell-mediated immunity usually controls infection but is also responsible for the pathology of the disease
  36. 3 things that could happen if you're exposed to TB?
    • 1. Latent infection wher few TB organisms enter macrophages and remain latent there
    • 2. Primary tubercle forms but the immune system can stop replication
    • 3. Spread of active infection - this happens in immunocompromised individuals
  37. Primary tuberculosis infection
    • Often in lungs, and host walls off the infection in a "tubercle"
    • If infection is arrested at this point by the host defenses, the tubercle becomes calcified "Ghon complex" seen on x-ray
    • Disseminated infection occurs if the tubercle does not form, or forms but ruptures and the bacteria spread to the blood and lymph systems - disseminated infection called "military tuberculosis"
  38. Active TB infection
    • Miliary infection = disseminated through body
    • May be directly disseminated from a primary infection or may be a reactivation of a latent infection
    • Characterized by spread of tubercles in tissues
    • Symptoms: weight loss, fever, night sweats, chronic cough, coughing up blood, lethargia (earlier called consumption)
  39. TB infection versus TB disease (latent vs active)
    TB infection (latent)          TB disease (active) (in lungs)
    • MTB present                 MTB present
    • Tuberculin skin test positive    Tuberculin skin test positive
    • Chest X-ray normal      Chest X-ray usually reveals lesion
    • Sputum smears and cultures negative  Sputum smears and cultures positive
    • No symptoms      Symptoms: cough, fever, weight loss
    • Not infectious      Often infectious before treatment
    • Not defines as a case of TB   Defined as a case of TB
  40. Risk factors for clinical (active) TB
    • Presence of another infection, eg. HIV
    • Physiological and environmental stress; eg. malnutrition
    • Depressions of the immune system eg. elderly
  41. Diagnosis of TB: skin tests
    • Test for cell-mediated (acquired) immunity
    • Tuberculin Test used as screening test for disease in North America
    • PPD (purified protein derivative) injected subcutaneously, and delayed hypersensitivity reaction measured by measuring the diameter of the induration (hardening of skin) and reddening of the area around the site
    • Mantoux test is a quantitative tuberculin test
  42. Laboratory Diagnosis for TB
    • Finding of acid-fast rods in sputum
    • Culture (takes up to 6 weeks for a negative result, positive cultures usually grow in 2-3 weeks)
    • QuantiferonGold test to check for activated T-lymphocytes: Blood samples from patient mixed with antigens, look for immune response
  43. TB vaccine
    • BCG: Bacillus Calmette-Guerin
    • Live culture of Mycobacterium bovis
    • In North America only given to children at high rick
    • In Europe and other countries, BCG was often given as a childhood vaccination
    • Effectivity of the vaccine is not very good: Reasonable in children that are high risk but almost 0% effectivity in adults
  44. TB treatment and antibiotic resistance
    • Multiple drug regimens used to prevent the development of drug resistance
    • Treatment6 mo - 1 yr because of slow growth of the bacterium
    • MDR (multi-drug resistant) - TB and XDR (extensively drug resistant) - TB is a growing problem
    • Patients not infection after ~2-3 weeks on drugs that are effective for treating the tuberculosis
  45. P
  46. Pneumonia ("The Old Man's Friend")
    • Typlical: classically caused by S. pneumoniae, responds to penicillin treatment
    • Atypical: caused by other organisms, penicillin resistant, includes virus, bacteria and fungi
    • Most common cause of infection related death
    • Causes of pneumonia in adults and children different:
    • Adults: mainly bacterial
    • Children: mainly viral
  47. Pneumococcal Pneumonia
    • Encapsulated Gram positive diplococcus - Streptococcus pneumonia (alpha hemolytic)
    • Most common cause of pneumonia, involved alveoli and bronchi
    • Symptoms: fever, rust coloured sputum (blood), breathing problems and chest pain
    • Often spreads to the blood (bacteremia)
    • Vaccines exist - polysaccharide/conjugate
  48. Viral Causes of Pneumonia
    • RSV (Respiratory Syncytial Virus), an enveloped RNA virus
    • Causes tissue damage by syncytia formation
    • Spread by direct contact
    • Infants and children < 5 yrs; children < 1 yr most at risk
    • Epidemics, late winter and early spring
    • Life-threatening pneumonia and bronchiolitis in infants
    • Symptoms: coughing and wheezing
    • Major risk factor to acquire RSV: prematurity
  49. Treatment/prevention of RSV
    • Treatment - no good antiviral, ribavirin sometimes tried
    • No vaccine but there is a monoclonal antibody which is effective...however, this is expensive and only given to a select few premature babies: Synagis
  50. Influenza
    • Three types: A, B and C
    • Influenza A, B C are enveloped viruses in the orthomyxoviridae family
    • "Segmented" RNA genomes
    • Influenza A + B have 8 RNA segments, C has 7
  51. Influenza A (proteins)
    • Neuraminidase (N) N1-N9
    • Hemagglutinin (H) H1-H16 (allows adhesion)
  52. Influenza A has subtypes
    • Only influenza A has subtypes, not B or C
    • Strains (subtypes) are named for the types of influenza, location of isolation, serial number year, and types of the H and N protiens
    • A/Port Chalmers/01/1973[H3N2]
    • A/USSR/90/1977[H1N1]
    • Official name for "swine flu" aka 2009 pandemic influenza:
    • A/California/07/2009[H1N1]
  53. Symptoms of Influenza A
    • Malaise
    • Fever
    • Headache
    • Myalgia
    • Cough
    • Sore throat
    • Most severe in smokers
  54. Incubation Period and Infectious Dose
    • Small infectious dose
    • Incubation 1-5 days
    • Virus viable on hard surfaces 24-48 hours
    • Droplet transmission? (airborne transmission unproven but suspected)
  55. Pandemic influenza is caused by "antigenic shift"
    • 3-4 pandemics/100 yrs
    • Significant mortality rates
    • Global spread of disease in 6-9 months
    • Usual start in China
  56. Epidemic influenza is cuased by "antigenic drift"
    • Annual occurrence in temperatre areas, winter-spring
    • 30,000 deaths/yr in the US with every epidemic
    • Nosocomial infection common, especially nursing homes
  57. Antigenic Shift vs antigenic drift
    • Antigenic shift                      Antigenic Drift
    • Due to reassortment (swapping) of RNA segments   Due to random mutation
    • Results in new H and/or N (new virus)   H and N accumulate mutations/changes
    • No immunity  Previous antibodies can still provide some protection
    • Causes pendemics or severe epidemics   Causes seasonal flu epidemics
  58. Summary - LRTIs
    • LRTIs tend to be more sever than URTI (choice of treatment very important!)
    • Croup (parainfluenza) and bronchiolitis (RSV) and LRTIs that affect children
    • TB - latent infection vs tubercle vs active infection
    • Pneumonia: Typical S. pneumoniae. Atypical viruses (RSV), other bacteria, fungi
    • Influenza:
    • -subtypes/nomenclature (ie. A/California/07/2009[H1N1]
    • -Know H and N
    • -Antigenic shift vs antigenic drift
  59. Bacterial Diseases of the Digestive System
    • 2nd most common illnesses in USA (1st respiratory)
    • Usually result from ingestion of microorganisms and/or toxins in food and water
    • Fecal-oral cycle of transmission can be broken by: proper disposal of sewage; disinfection of drinking water; proper food prep and storage
  60. Diseases of the Digestive System
    • Dental caries, periodontal disease
    • Staphylococcal Enterotoxicosis; Shigellosis; Salmonellosis, Typhoid Fever; Cholera; Vibrio Gastroenteritis; Escherichia coli Gasteroenteritis; Campylovacter Gastroenteritis; Helicobacter Peptic Ulcer Disease; Yersinia Gasteroenteritis; Clostridium perfringens Gastroenteritis; Bacillus cereus Gastroenteritis
    • Mumps; hepatitis A-E; Viral Gastroenteritis
    • Nematode infestations
  61. Human Digestive System
    • GI tract (alimentary canal): mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum, anus "body as a tube"
    • accessory structures: teeth, tongue, salivary glands, liver, pancreas, gallbladder
    • -lie outside of GI tract, produce secretions that enter GI tract (except for teeth/tongue)
  62. Trivia
    • In an average life span, 25 tons of food pass through the digestive tract
    • On average humans produce 0.5-2L of intestinal gas per day
    • Up to 40% of fecal mass is microbial cell material
    • 1 mL of saliva contains millions of bacteria
  63. Normal Flora of the Mouth
    • Age and dentation dependent
    • More organisms/mL saliva than in feces
    • Streptococcus sp dominant
    • Micrococcus sp
    • Neisseria sp
    • Candida sp
    • Anaerobic bacteria including: Fusobacterium sp, Peptostreptococcus sp, Actinomyces sp
    • Entamoeba gingivalis: Tichonmonas tenax
  64. Bacterial Diseases of the Mouth
    • Mouth = entrance to digestive system
    • Presence of teeth in mouth allows for different set of microorganisms than pharynx
    • Excellent environment for growth of many varied microorganisms: saliva contains nutrients that encourage bacterial growth
    • Antimicrobial mechanisms: saliva ALSO contains antimicrobial substances (eg. lysozyme); crevicular fluid: substance similar to serum that flows into gingival crevice and protects teeth via flushing action; phagocytic cell and immunoglobulin content
  65. Bad breath
    Caused by waste products of anaerobic oral bacteria: hydrogen sulfide, cadaverine, etc
  66. Dental Caries
    • Teeth: hard surface
    • Coated with a pellicle: thin film of protein from saliva; bacterial attachment
    • Plaque: accumulation of bacteria and their products
    • SUCROSE: very important. sucrose -> lactic acid -> break down enamel
    • Streptococcus mutans: Most important cariogenic species
  67. Stages of Periodontal Disease
    • Healthy gingivae, gingivitis, periodontal pockets, periodontitis
    • Inflammation and degeneration of structures that support the teeth
    • Gingivitis: bleeding gums during brushing
    • Periodontitis: progression from gingivitis: responsible for ~ 10% of tooth loss in older adults.
  68. Vincent's Disease
    • "Trench Mouth"
    • Also called acute necrotizing ulcerative gingivitis ANUG or Vincent's Angina
    • -Anaerobi Gram negative bacilli (eg. Prevotella intermedius)
    • -Anaerobic Gram negative spirochaetes (eg. Borrelia vincentii)
    • -Severe ulcerative disease, pain, breath extremely foul
    • Treated with antibiotics active against anaerobes, surgery
  69. Infections of the Stomach
    • Normally protected from infection by high acidity pH < 2
    • Helicobacter pylori
    • -Cause of peptic ulcer disease (gastric and duodenal ulcers)
    • -Known for > 100 yrs by pathologists but first cultured in 1982
    • -Spiral shaped Gram negative microaerophilic bacterium
    • -30-50% of worlds population has antibodies
    • -Associated with contaminated drinking water and wells
  70. Helicobacter pylori infection
    • Specialized bacterium: survives in acid conditions of the stomach
    • Stomach lined with a layer of mucus protecting the stomach lining from the acidity
    • H. pylori has flagella that allow it to move in the thick mucus
    • H. pylori produced large amounts of urease, urea is broken down to ammonia and the pH locally around the bacterium increases (so neutralizes gastric acid)
    • Ammonia can also cause irritation on stomach wall (gastritis), then bacteria can attach and cause further tissue irritation
    • Stomach ulcers are formed!
  71. Helicobacter diagnosis
    • Urea breath test (c14 labelled urea)
    • Drink solution and breath other. If urease present, then carbon dioxide exhaled will be C14 marked
    • Serology, culture of biopsy specimens
  72. Infection of the Parotid Gland
    • "Mumps" RNA paramyxovirus
    • Parotid gland = salivary gland
    • Virus transmitted by droplet transmission
    • Most infectious 48 hours before symptoms begin
    • Viruses multiply in lymph glands in throat, then penetrate the parotid glands via the blood
  73. Mumps
    • Target: parotid (salivary) glands
    • -incubation 16-18 days
    • -transmission: resp. secretions
    • -entry: rep. tract
    • -most infective 48 hrs prior to onset of symptoms
    • Symptoms:
    • -inflammation and swelling of parotid glands
    • -fever, pain on swallowing
    • -swelling of testes (20-35% of males part puberty)
    • Complications:
    • -sterility, meningitis, ovarian inflammation, ancreatitis
    • MMR vaccine
    • 2nd attacks are rare
  74. Symptoms and Complications of Mumps
    • Symptoms: inflammation and swelling of the parotid glands, fever, pain on swallowing
    • Complications:
    • -encephalitis
    • -Orchitis (inflammation of testis)
    • -Oophoritis
    • -Sterility if unlucky
  75. Predominant flora of the intestine:
    • Gram negatives, both anaerobes and aerobes
    • Bacteroides* (dominate)
    • Fusobacterium
    • Enterobacteriaceae:
    • Proteus, Klebsiella, Enterobacter, Serratia Pseudomonas sp
    • Micrococci, Enterococcus
    • other Streptococcus sp.
    • Lactobacillus
    • Clostridium
    • Candida
  76. Bacterial Diseases of the LDS (lower digestive system)
    • Diarrhea -> important cause of infant mortality in developing countries. May be reduced by oral rehydration therapy
    • Dysentery: sever diarrhea with blood, often pus and/or mucus. eg. E. histolytica, Shigella dysenteriae
    • Gastroenteritis: inflammation of the stomach and the intestinal mucosa, no pus. eg. Vibrio cholerae, Cryptosporidium
    • Common symptoms: diarrhea, vomiting, abdominal cramps, nausea
  77. Main pathogenic mechanisms of lower alimentary tract pathogens
    • Attachment
    • Cell invasion
    • Loss of Microvilli
    • Toxin production: those that increase secretion of water and electrolytes; those that inhibit protein synthesis and cause cell death.
  78. Bacterial Diseases of the lower digestive system
    2 types:
    • Infection: pathogen enters GI tract and multiplies
    • -delay in appearance of GI disturbance (12hr - 2 weeks)
    • -fever
    • Intoxication: ingestion of preformed toxin
    • -sudden appearance of GI disturbance (1-48 hours)
    • -usually no fever
    • Symptoms (both types): abdominal cramps, nausea, vomiting, diarrhea
    • Treatment: fluid and electrolyte replacement
    • Often related to food ingestion (food poisoning)
  79. Intoxications
    • Staphylococcus aureus: 5-25% of cases, 2-4 hrs to start, vomiting main symptom, typically in meats, custards, salads
    • Bacillus cereus (vomiting toxin*), 1-2% of cases, 1-6 hrs to start, vomiting and diarrhea main symptoms, typically in rice, meat, vegetables
    • Clostridium botulinum 5-15% of cases, 12-72 hrs to start, Neuromuscular paralysis as main symptom, typically in improperly persevered vegetables, fish, meat
    • *Bacillus cereus can cause either an intoxication or an infection!
  80. Intoxication
    Staphylococcal Enterotoxicosis
    • From improperly stored or handled food
    • -toxin is heat stable (30 minute boil)
    • -toxin is superantigen (enterotoxin)
    • High risk: custards, cream pies, hams
    • Vomiting reflex triggered early (1-6 hrs) -> diarrhea, abdominal cramps, usually over in 24 hrs
  81. Staphylococcal Enterotoxicosis
    • Diagnosis: usually based on symptoms (short incubation time)
    • Bacteria can be cultured if food wasn't reheated
    • -grow well on 7.5% NaCl (selective isolation)
    • -produce hemolysins and caugulase
    • -form golden-yellow colonies
    • -no obvious spoilage when growing in food
    • Caused by Staphylococcus aurease
  82. Bacillus cereus
    Food associated disease can have two forms
    • 1. diarrhea from production of enterotoxin in gut (8-16 hr) (infection)
    • 2. vomiting due to ingestion of enterotoxin in food (1-6 hr)
    • Gram positive bacilli, aerobic, spore forming
    • B. cereus is usally considered harmless otherwise
    • Heating food may not kill spores, common in rice dises
    • Self limiting disease
  83. Lower digestion infections
    Most common causes
    • Salmonella
    • Shigella
    • Campylobacter
    • E. coli (ETEC, EIEC, EPEC, EHEC)
    • Clostridium perfringes
    • Bacillus cereus (both intoxication and infection)
    • Vibrio cholerae
    • E. histolytica, Giardia, Cryptosporidum
    • Rotavirus, norovirus
    • Hepatitis A
  84. Infections
    Organism, clinical syndrome, pathogenic mechanism
    • Salmonella, enteric types; dysentery, mucosal invasion
    • Salmonella typhi; enteric fever; dissemination to blood
    • Shigella; dysentery; mucosal invasion, cytotoxin
    • Campylobacter; dysentery; mucosal inflammation
    • E. coli EHEC; watery diarrhea; cytotoxin
    • C. difficile; dysentery; cyto and enterotoxin
    • C. perfiringens; Watery diarrhea; enterotoxin
    • B. cereus; Watery diarrhea; enterotoxin
    • Vibrio cholerae; watery diarrhea; enterotoxin
    • Rotavirus; watery diarrhea; mucosal destruction
    • Norovirus; watery diarrhea; mucosal destruction
    • Giardia; watery diarrhea; mucosal irritation
    • Entamoeba histolytica; dysentery; mucosal invasion
    • Cryptosporidium; watery diarrhea, ?
  85. Shigellosis (Bacillary Dysentery)
    • Infection (4 species of Shigella)
    • Incubation: 12 hr - 2 weeks
    • small infective dose - ID50 = 200 cells
    • Resistant to stomach acid
    • Shiga toxin - a cytotxin: up to 20 BM in one day, painful BM, blood, mucous in stools
    • Diagnosis: recovery of microbes from rectal swabs
    • Some immunity results from recovery: no effective vaccine yet
    • Oral rehydration
    • Antibiotic therapy in extreme cases (fluoroquinolone)
  86. Shigellosis Infection
    • Shigella get to epithelial cells lining intestinal tract
    • 1. Shigella enter an epithelial cell
    • 2. Shigella multiply inside the cell
    • 3. Shigella invade neighboring cells, thus avoiding immune defenses
    • 4. An abscess forms as epithelia cells are killed by the infection. The bacteria do not usually spread in the bloodstream
  87. Salmonellosis (Salmonella Gastroenteritis)
    • infection: many serotypes
    • Salmonella enterica is the group name, then each serotype has its own name (Salmonella enteritidis, Salmonella typhimurium, most common in developed countries)
    • Incubation: 12-36 hrs
    • Infective dose: ID50 = 1000 cells: need high dose because susceptible to gastric acid
    • Death from septicemia in infants and elderly
    • 1 billion salmonellae/g feces
    • diagnosis: culture
    • Antibiotics: usually not used (can prolong shedding); if needed: fluoroquinolones
    • Sources of Salmonella: Poultry, eggs, egg products, pet reptiles; Undercooked eggs (sunny side up, 4 minute eggs) are risky; hollandaise sauce, cookie batter, Caesar salad
  88. Salmonellosis Infection
    • Salmonella connect with epithelial cells lining intestinal tract
    • 1. Salmonella enter an epithelial cell
    • 2. Salmonella multiply within vesicle inside cell
    • 3. Salmonella cross epithelial cell membrane, or the cell lyses, and bacteria enter the blood and lympatic vessels
  89. Typhoid fever
    • Salmonella typhi: most virulent strain of salmonella:
    • -2 week incubation, symptoms last 2-3 weeks
    • -bacteria multiplies in phagocytic cells (not epithelium)
    • -bacteria can be isolated from blood, urine, feces
    • -perforation of intestinal wall can occur
    • -mortaliy: now -> 1-2%, once 10%
    • Spread only from human to human (fecal-oral)
    • -incidence decreasing with improved sanitation
    • -2 week incubation period
    • High fever, headache, diarrhea (2nd-3rd week)
    • Treatment: ALWAYS antibiotics
    • -cephalosporins or fluoroquinolines; vaccine available
    • Recovery = immunity
    • 1-3 % of recovered patients become chronic carriers
  90. Cholera
    • Vibrio cholerae (curved G- rod)
    • endemic in Asia, South America; rare in Western countries
    • "Spore-like" state during unfavorable conditions: infectious in both spore-like and normal form
    • Grow in small intestine and produce enterotoxin
    • Results in "rice water stools": sudden loss of fluids and electrolytes causes shock, collapse and often death (12-20L of fluid may be lost in 1 day); viscous blood, violent vomiting; usually no fever
    • Recover -> immunity against same strain only
    • Treatment: rehydration glucose + electrolytes (antibiotics to reduce numbers of bacteria AFTER rehydration)
    • Untreated: 50% mortality, treated <1%
  91. Other forms of Gastroenteritis
    • Campylobacter jejuni (G-curved)
    • -leading cause of foodbourne illness in US
    • -90% of retail chicken contaminated
    • -normally recover in ~1 week
    • Vibrio parahaemolyticus (curved G- rod)
    • -raw oysters and crustaceans: very common in Japan; pasteurization
    • -<24 hr incubation - short generation time (10')
    • -abdominal pain, "burning" in stomach, vomiting, watery stools (like cholera)
    • -recovery in a few days
    • Yersinia gastroenteritis (Y. enterocolitica) (G-): meat, milk, transfused blood; can grow at 4 C; severe pain, misdiagnosed as appendicitis
    • Clostridium perfringens gastroenteritis (G+, anaerobic): meat or meat stews contaminated during slaughter; endospores survive routine heating; multiply during RT holding or inadegquate refrigeration; symptoms relatively mild
  92. Viral Gastroenteritis
    • Infection seen in all parts of the world
    • In developing countries non-bacterial gastroenteritis is a major cause of death, especially in children
    • Not distinguishable clinically from other gastroenteritis
    • Viruses are specific to humans
    • Fecal-oral transmission
    • 90% of cases caused by rotavirus or Norwalk virus
  93. Rotavirus Gastroenteritis
    • RNA, reoviridae, non-enveloped
    • Most common cause of viral gastroenteritis in children
    • Same incidence in developed and underdeveloped nations
    • Disease of children, most < 2 years
    • Incubation 2-3 days
    • Often nosocomial
    • Symptoms: low-grade fever, diarrhea, vomiting (1 week duration)
    • New vaccines are available1 (eg. Rotorix, Rotateq)
  94. Norovirus (Norwalk Virus) - Gastroenteritis
    • RNA, non-enveloped
    • Causes major epidemics of viral gastroenteritis (2/3 of cases of food poisoning)
    • 2 day incubation period, pathogenesis similar to Rotavirus
    • Symptoms: nausea, abdominal cramps, diarrhea, vomiting for 1-3 days, sudden onset; self-limiting; NO PRODROME
  95. Parasitic Diseases of the GI
    • Protozoan Diseases (diarrhea)
    • -Giardia lamblia
    • -Cryptosporidiosis
    • -Entamoeba histolytica
    • Helminthic Diseases (no diarrhea)
    • -Tapeworm (cestode)
    • -Roundworm (nematode)
  96. Ascaris lumbricoides
    • eggs shed in feces
    • ingested
    • eggs hatch in upper intestine
    • bloodstream -> lungs
    • migrate to throat
    • larvae swallowed
    • develop to adults in intestine
    • migrations can cause "distress"
    • -teeth can penetrate tissue; infect abdominal cavity; exit via navel, nostrils, anus
    • treatment: mebendazole
  97. Infections of auxiliary organs
    • Inflammation of the liver
    • Hepatitis A, B, C, D, E (5 different viruses)
    • -different virus families!
    • CMV and EBV can also cause infectious hepatitis
  98. Hepatitis A virus (HAV)
    • Non-enveloped RNA virus (Picornaviridae family)
    • Virus is resistant to chlorine
    • Transmission: fecal-oral route, water and mollusks
    • Incubation period 2-4 weeks
    • Pathogenesis
    • -after infection the virus multiplies in intestinal epithelial cells, enters the blood stream (viremia) and infects liver, kidneys and spleen cells, causing damage
    • -virus exits by biliary tract to feces for excretion
    • Symptoms: Nausea, fever, anorexia, vomiting, jaundice: usually sudden onset
    • Clinical course: self-limiting; 50% of infections are subclinical: No chronic diease
    • Diagnosis: HAV IgM antibodies in serum
    • Immunity: lifelong, vaccine exists
  99. Hepatitis B virus (HBV)
    • Enveloped DNA virus (Hepadnavriridea family)
    • Transmission: bloodborne disease, STI
    • Can cause both acute and chronic disease:
    • -Acute: symptoms include liver inflammation, vomiting, jaundice...most people recover in a few weeks (~10% of adults become chronically infected, higher in children)
    • -Chronic: cirrhosis, hepatocellular carcinoma (liver cancer)
    • There is a vaccine available
    • U of A connection: one antiviral drug for HBV (lamivudine) developed by Drs . Robbins (Chemistry) and L. Tyrrell (MMI)
  100. Hepatitis C virus (HCV)
    • Enveloped RNA virus (Flaviviridae family)
    • Transmission: bloodborne disease
    • Like HBV can cause both acute and chronic disease:
    • -acute: mild and vague symptoms (malaise)... but 80% become chronically infected
    • -chronic: cirrhosis liver cancer
    • No vaccine available
    • New antivirals approved in 2011
    • U of A connetion: HCV was discovered by Dr. M. Houghton (now MMI) in 1989
  101. Hepatitis D virus
    • Enveloped RNA virus (no family yet)
    • Transmission: similar to HBV
    • Can only grow in the presence of HBV
    • Coexists with HBV to cause disease
  102. Hepatitis E virus
    • Non-enveloped RNA virus (Calicivirdae family)
    • Transmission: fecal-oral, like Hepatitis A
    • Endemic in areas with poor sanitation. e.g. India and SE Asia
    • No chronic disease
    • Risk for pregnant women, up to 20% mortality