Bacterial diseases 2011


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Bacterial diseases 2011

  1. 2. DISEASE Occurrence of Disease
  2. 4. Wild Animals Involved in MPXV Transmission (USA, 2003) Gambian Giant Rat (Crycetomys sp.) Prairie Dog (Cynomis sp.)
  3. 5. Ghana TX WI IL * IA 15/4 09/04 Entry and Distribution Route of Crycetomys sp . and Cynomys sp. Involved in MPXV Outbreak (USA, 2003) Source: MMWR 52 (23), CDC, 2003. 15/4
  4. 6. Index case in Marshfield, 26 May 2003: Disseminated lesions.
  5. 7. Distribution of MPXV Cases in the USA WI IL IN OH KS MO Number of cases = 87 WI = 38 IN = 24 IL = 19 OH = 4 KS = 1 MO = 1 Source: MMWR 52 (23), CDC, 2003.
  6. 9. Signs & Symptoms of Disease <ul><li>Fever </li></ul><ul><li>Fatigue </li></ul><ul><li>White Blood Cell Count </li></ul><ul><li>Pain </li></ul><ul><li>Muscle Aches </li></ul><ul><li>Blood Pressure </li></ul>
  7. 19. Protective Responses <ul><li>General protection – skin, stomach acid, mucous membranes, cilia, macrophages, enzymes. </li></ul>
  8. 24. Protective Responses <ul><li>Specific protection – immune response cells recognize one special organism at a time. </li></ul>
  9. 25. Specific Protection <ul><li>Cooperation of immune response cells </li></ul><ul><li>Immune response </li></ul><ul><li>recognition of antigen (invader) as foreign and different </li></ul><ul><li>introduction (presentation) to and activation of immune response cells </li></ul><ul><li>protective responses: antibodies, immune cells </li></ul><ul><li>Memory (booster) responses to provide future antibodies </li></ul>
  10. 27. Antigen Presentation
  11. 28. Vaccine Development <ul><li>Most vaccines do not make it to market </li></ul><ul><li>Some make it but do not reach original product goals </li></ul><ul><li>A few make it and perform as designed </li></ul>
  12. 29. Vaccine Development <ul><li>Is a large risk and investment. </li></ul>
  13. 30. Key Issues <ul><li>Target group </li></ul><ul><li>Immunogenicity </li></ul><ul><li>Efficacy </li></ul><ul><li>Safety </li></ul><ul><li>Cost </li></ul><ul><li>10 years to completion </li></ul>
  14. 31. Phases of Development <ul><li>Preclinicals – animals </li></ul><ul><li>Toxicity </li></ul><ul><li>Immunogenicity </li></ul><ul><li>Combination potential </li></ul><ul><li>Stability data </li></ul><ul><li>Potency </li></ul><ul><li>Protection (if model is available) </li></ul>
  15. 32. Phases of Development <ul><li>Investigational New Drug (IND) </li></ul><ul><li>Filing </li></ul><ul><li>*Phase I – weeks to months </li></ul><ul><li>10 to 40 human volunteers </li></ul><ul><li>Safety </li></ul><ul><li>Dose size and administration route </li></ul><ul><li>Mode of action of immune response </li></ul><ul><li>Characterization of vaccine </li></ul>
  16. 33. Phases of Development <ul><li>Phase II – months to several years </li></ul><ul><li>50 to 500 volunteers </li></ul><ul><li>Rates and severity of common adverse effects </li></ul><ul><li>Immune response to target group </li></ul><ul><li>Phase III – 2 – 5 years </li></ul><ul><li>several thousand to 20,000-50,000 volunteers </li></ul><ul><li>Placebo-controlled </li></ul><ul><li>Safety </li></ul><ul><li>Efficacy (if combo., correlates to protection) </li></ul><ul><li>BLA filing – 1-2 years </li></ul>
  17. 34. Post-Market Surveillance <ul><li>Monitoring after licensure </li></ul><ul><li>Safety </li></ul><ul><li>Efficacy </li></ul><ul><li>New indications </li></ul>
  18. 37. 2005 - Rubella declared no longer endemic in the US
  19. 41. Types of Bacterial Vaccines <ul><li>Whole cell </li></ul><ul><li>Acellular </li></ul><ul><li>Toxoids </li></ul><ul><li>Polysaccharides </li></ul><ul><li>Conjugates </li></ul><ul><li>Combinations </li></ul>
  20. 42. Whole Cell Vaccines
  21. 43. Pertussis <ul><li>Whooping cough – is an acute infectious disease caused by Bordetella pertussis. </li></ul><ul><li>First isolated in 1906 </li></ul><ul><li>Prior to 1940’s over 200,000 cases per year </li></ul><ul><li>3,700 cases per year since 1980. </li></ul><ul><li>In unimmunized populations – 300,000 deaths per year </li></ul>
  22. 44. Bordetella pertussis <ul><li>Small aerobic gram negative rod </li></ul><ul><li>Fastidious and requires special media for isolation </li></ul>
  23. 45. Acellular Vaccines
  24. 46. Pathogenesis <ul><li>Pertussis antigens allow invasion of host defenses </li></ul><ul><li>Local tissue damage in respiratory tract </li></ul>
  25. 49. ADACEL (0.5ml) <ul><li>Contains </li></ul><ul><li>pertussis toxin (PT) 2.5 µg </li></ul><ul><li>filamentous hemagglutinin (FHA) </li></ul><ul><li>5 µg pertactin (PRN) </li></ul><ul><li>3 µg fimbriae types 2 and 3 (FIM)5 µg </li></ul>
  26. 51. Bacterial Toxins <ul><li>Toxins that lyse cells – hemolysins and leukocidins </li></ul><ul><li>Toxins that elevate cAMP </li></ul><ul><li>Toxins that block protein synthesis </li></ul><ul><li>Toxins that block nerve function </li></ul>
  27. 52. Vibrionaceae
  28. 53. Vibrio – isolated in 1884
  29. 55. Vibrionaceae <ul><li>Curved or straight bacilli </li></ul><ul><li>Aerobic or anaerobic growth </li></ul><ul><li>Oxidase positive, non spore formers </li></ul><ul><li>Primarily found in water </li></ul><ul><li>Produce GI disease </li></ul><ul><li>Vibrio, Aeromonas, & Plesiomonas </li></ul>
  30. 56. Vibrio <ul><li>Grow on alkaline media but not acidic media </li></ul><ul><li>Polar flagella </li></ul>
  31. 57. Physiology & Structure <ul><li>Broad temperature range: 18C to 37C </li></ul><ul><li>Gram - negative </li></ul>
  32. 59. Vibrio cholerae <ul><li>Six groups based on somatic O antigens </li></ul><ul><li>O1 group: 2 biotypes - el tor & cholerae </li></ul><ul><li>2 serological subgroups: ogawa, inaba </li></ul><ul><li>Strains with both ogawa & inaba = hikajima </li></ul>
  33. 63. Pathogenesis <ul><li>Toxin binds to specific receptors in the small intestine </li></ul><ul><li>Enters the mucosal cells </li></ul><ul><li>Effects a series of reactions that result in the rapid secretion of Na, K and bicarbonate into the intestinal lumen </li></ul>
  34. 64. Transmission
  35. 67. Pathogenesis <ul><li>1 liter of fluid loss per hour </li></ul><ul><li>Vibrio penetrates through the mucous covering the surface of the intestine and adheres to the mucosal cell layer </li></ul>
  36. 68. Virulence Factors – V. cholerae <ul><li>Cholera enterotoxin, cytotoxin, flagellum, adhesions, mucinase </li></ul>
  37. 69. Cholera Cot – Cholera Facies
  38. 70. Treatment <ul><li>Because death from cholera is a consequence of dehydration, the disease is treated using oral rehydration therapy (ORT), which consists of large volumes of water mixed with a blend of sugar and salts. </li></ul>
  39. 71. <ul><li>Antibiotics. While antibiotics are not a necessary part of cholera treatment, some of these drugs may reduce both the amount and duration of cholera-related diarrhea. A single dose of doxycycline (Adoxa, Monodox) or azithromycin (Zithromax, Zmax) may be effective. </li></ul>
  40. 72. Toxin Producing Bacteria <ul><li>Tetanus – lockjaw ( risus sardonicus) </li></ul><ul><li>Diphtheria – upper respiratory & cardiac problems </li></ul>
  41. 73. Tetanus <ul><li>Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. </li></ul>
  42. 74. Clostridium tetani <ul><li>Spores found in soil, dust, animal feces; may persist for months to years </li></ul><ul><li>Multiple toxins produced with growth of bacteria </li></ul><ul><li>Tetanospasmin estimated lethal dose = 150ng </li></ul>
  43. 75. Clostridium tetani <ul><li>Grown in hamburger! </li></ul><ul><li>Peptone based medium. </li></ul>
  44. 79. Neonatal Tetanus <ul><li>Generalized tetanus in newborn infant </li></ul><ul><li>Infant born without protective passive immunity </li></ul><ul><li>High fatality rate without therapy </li></ul><ul><li>Estimated 500,000 deaths worldwide in 2004 </li></ul>
  45. 80. Tetanus cases reported worldwide 1990-2004. Ranging from strongly prevalent (dark red) to very few cases (in light yellow) (grey data).
  46. 81. Tetanus
  47. 82. Tetanus Complications <ul><li>Laryngospasm – spasms of vocal cords and respiratory muscles </li></ul><ul><li>Fractures – spine and long bones due to muscle spasms and seizures </li></ul>
  48. 86. <ul><li>Formalin-inactivated tetanus toxin </li></ul><ul><li>Schedule: 3 or 4 doses + booster, booster every 10 years </li></ul><ul><li>Efficacy: approximately 100% </li></ul><ul><li>Duration: approximately 10 years </li></ul>
  49. 87. <ul><li>Antibiotics help kill the bacteria. Penicillin G is the most commonly used antibiotic for tetanus infection. You might receive it orally or intravenously. </li></ul>
  50. 89. Diphtheria <ul><li>Diphtheria is an acute, toxin mediated disease caused by Corynebacterium diphtheriae. Diphthera – Greek for leather hide. </li></ul><ul><li>Antitoxin developed in 1891. </li></ul><ul><li>Toxoid developed in the 1920’s. </li></ul>
  51. 90. Diphtheria <ul><li>Cultures are grown in a modified Mueller and Miller medium. </li></ul><ul><li>Purified by serial ammonium sulfate fractionation and diafiltration. </li></ul>
  52. 91. C. diphtheriae <ul><li>Aerobic gram-positive bacilli </li></ul><ul><li>Toxin production occurs only when the bacillus is itself infected (lysogenized) by a specific virus carrying the genetic information for the toxin (tox gene). Only toxigenic strains can cause severe disease. </li></ul>
  53. 93. Diptheria
  54. 95. <ul><li>Treatment is with erythromycin orally or by injection (40 mg/kg/day; maximum, 2 gm/day) for 14 days, or procaine penicillin G daily, intramuscularly (300,000 U/day for those weighing 10 kg or less and 600,000 U/day for those weighing more than 10 kg) for 14 days. </li></ul>
  55. 96. <ul><li>The disease is usually not contagious 48 hours after antibiotics are instituted. Elimination of the organism should be documented by two consecutive negative cultures after therapy is completed. </li></ul>
  56. 97. Polysaccharides <ul><li>Bacteria with capsules </li></ul><ul><li>Haemophilus influenzae, type b </li></ul><ul><li>Neisseria meningitidis </li></ul><ul><li>Streptococcus pneumoniae </li></ul>
  57. 98. Capsules
  58. 99. Polysaccharides <ul><li>Bacteria with capsules </li></ul><ul><li>Evade APCs – no T-cells activated </li></ul><ul><li>children & older adults make few or no antibodies, or short-lived antibodies </li></ul><ul><li>No memory cell production </li></ul><ul><li>Antibodies working with APCs are important for bacterial disease protection </li></ul>
  59. 100. Neisseria meningitidis <ul><li>Encapsulated </li></ul><ul><li>Gram-negative diplococci </li></ul><ul><li>Colonize nasopharynx </li></ul><ul><li>Cause meningitis </li></ul>
  60. 101. Neisseria meningitidis <ul><li>Bacterial Strains: A/B/C/Y/W-135 </li></ul>
  61. 102. Signs and Symptoms <ul><li>Stiff neck </li></ul><ul><li>Nausea </li></ul><ul><li>Vomiting </li></ul><ul><li>Discomfort around bright light </li></ul><ul><li>Confusion </li></ul><ul><li>Sleepiness </li></ul><ul><li>High fever </li></ul><ul><li>Seizures (as the disease progresses) </li></ul>
  62. 107. <ul><li>Commonly used meningitis treatments include cephalosporins, especially Claforan (cefotaxime) and Rocephin (ceftriaxone). Various penicillin-type antibiotics, aminoglycoside drugs such as gentamicin, and others, are also used </li></ul>
  63. 108. Menomune A/C/Y/W-135 <ul><li>Injected subcutaneously. </li></ul><ul><li>Do not inject ID, IM or IV </li></ul>
  64. 109. Conjugate Vaccines <ul><li>Capsule bonded to a protein. </li></ul><ul><li>Stimulate a more vigorous immune response. More antibody is produced along with memory. </li></ul>
  65. 110. Conjugate Vaccine <ul><li>Conjugate vaccines work much better in young children whose immune systems are immature. </li></ul>
  66. 112. Conjugate Vaccines <ul><li>Haemophilus influenzae type b infections – ActHIB </li></ul><ul><li>Streptococcus pneumoniae – Prevnar </li></ul><ul><li>Neisseria meningitidis - Menactra </li></ul>
  67. 113. Menactra <ul><li>This vaccine provides protection against bacterial strains A, C, W135, and Y but not against B </li></ul>
  68. 114. Menactra <ul><li>This is the new meningococcal conjugate vaccine from Sanofi-Pasteur licensed in January 2005. It is licensed for 2 to 55 year olds. </li></ul>
  69. 115. Haemophilus influenzae B
  70. 116. Act-HIB Haemophilus influenzae type b (Hib) Act-HIB ® (Haemophilus b conjugate vaccine, tetanus protein - conjugate) 01959034 5 x 0.5 mL
  71. 117. Haemophilus influenzae produces beta-lactamases, and it is also able to modify iHaemophilus influenzae produces beta-lactamases, and it is also able to modify its penicillin-binding proteins, so it has gained resistance to the penicillin family of antibiotics.
  72. 118. In severe cases, cefotaxime and ceftriaxone delivered directly into the bloodstream are the elected antibiotics, and, for the less severe cases, an association of ampicillin and sulbactam, cephalosporins of the second and thirdgeneration, or fluoroquinolones are preferred. (Fluoroquinolone-resistant Haemophilus influenzae has been observed.)
  73. 119. <ul><li>Macrolide antibiotics (e.g., clarithromycin) may be used in patients with a history of allergy to beta-lactam antibiotics. [ citation needed ] Macrolide resistance has also been observed </li></ul>
  74. 120. Combination Vaccines – should be <ul><li>stable for 18 to 24 months </li></ul><ul><li>Recommended at same age - age appropriate vaccine cocktail </li></ul><ul><li>Adverse effects equal to < separate vaccines </li></ul><ul><li>Immune response at protective levels </li></ul><ul><li>Benefit fewer injections </li></ul>