Anthrax by m.khoury

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Anthrax by m.khoury

  1. 1. Anthrax MIlad khoury Spring 2011
  2. 2. ARTICLE <ul><li>“New medical weapons to protect against Anthrax attacks”
  3. 3. Bouzianas et al. Current and Future Medical Approaches To Combat the Anthrax Threat. Journal of Medicinal Chemistry, 2010; 53 (11): 4305 DOI: 10.1021/jm901024b </li></ul>
  4. 4. Outline I Introduction II History of the disease III Its use as a biological weapons IV Bacillus anthracis V the 3 routs of inection VI Pathogenesis VII The fight against anthrax VIII Conclusion
  5. 5. Anthrax: basics <ul><li>From the Greek word anthracis for coal.
  6. 6. caused by the bacteria B.anthracis
  7. 7. Zoonotic disease in herbivores (e.g., sheep, goats, cattle)
  8. 8. Human infection typically acquired through contact with anthrax-infected animals or animal products .
  9. 9. Three forms </li></ul>-Cutaneous -Inhalational -Gastrointestinal
  10. 10. history <ul><li>1500 B.C
  11. 11. Moses threatened the Egyptian pharaoh that the hand of the lord will fall on the livestock ,horses and birds and kill everything.
  12. 12. 5 th century B.C
  13. 13. the Greek Doctor Hippocrates named the disease that caused black skin lesions as anthracis. </li></ul>
  14. 14. history <ul><li>Early 1800s - The first human cases of cutaneous anthrax in the US and UK were reported in men who contracted the disease after having been in contact with infected livestock.
  15. 15. The disease was also called Wool Sorter’s disease and Rag Picker’s disease .
  16. 16. 1876 - German bacteriologist Robert Koch confirmed bacterial origin of anthrax.
  17. 17. 1881: Louis Pasteur developed the first vaccine </li></ul>
  18. 18. Anthrax a biological weapon <ul><li>1915 - German agents injected horses, mules, and cattle with anthrax during WWI. This was the first recorded use of anthrax as a biological weapon .
  19. 19. 1979 - In Soviet Union , aerosolized anthrax spores were released accidentally at a military facility, affecting 94 and killing 64 people.
  20. 20. 1995 - Iraq produced 8,500 liters of concentrated anthrax as part of the biological weapon program under Saddam Hussein’s administration. </li></ul>
  21. 21. Anthrax cases 2001 <ul><li>22 cases
  22. 22. -11 cutaneous
  23. 23. -11 inhalational
  24. 24. 5 deaths ( all inhalational )
  25. 25. -case in Florida
  26. 26. -2 postal workers in Maryland
  27. 27. -hospital worker in NY city
  28. 28. Farm woman in Connecticut </li></ul>
  29. 29. Bacillus anthracis <ul><li>Gram positive rod
  30. 30. has a diameter of 1-1.5 µm and a length of 3-10 µm.
  31. 31. Facilitative anaerobe
  32. 32. Belogns to the B.cereus family
  33. 33. - Nonmotile
  34. 34. -glutamyl-polypeptide capsule
  35. 35. -soil dwelling </li></ul>
  36. 36. Bacillus anthracis <ul><li>1200 strains distributed worldwide
  37. 37. Forms spores
  38. 38. -infectious form
  39. 39. -1micrometer in size
  40. 40. Vegetative state
  41. 41. -non infectious
  42. 42. - fragile </li></ul>
  43. 43. The spore <ul><li>Sporulation conditions:
  44. 44. -starvation
  45. 45. - presence of oxygen
  46. 46. -changes in environmental conditions
  47. 47. - resistant to cold, heat,dryness and chemicals
  48. 48. -lethal dose of 2500 to 5500 spores
  49. 49. - spore viability increases in soil with organic content, alkaline PH, high calcium concentration ,high moisture
  50. 50. - </li></ul>
  51. 51. Spore anatomy <ul><li>Cr: core
  52. 52. Cx: cortex
  53. 53. Ct: coat
  54. 54. Is: interspace
  55. 55. Ex:exosporium
  56. 56. Thin-section electron micrograph </li></ul>
  57. 57. Spore anatomy <ul><li>The core:
  58. 58. -protects the spore from Uv radiation and stress
  59. 59. -forms the center part of the spore
  60. 60. - chromosomes form complexes with small acid soluble proteins abbreviated as SASP
  61. 61. -high levels of dipicolinic acid and ions
  62. 62. The Cortex
  63. 63. - important in providing resistance to the spore and keeping the core dry . </li></ul>
  64. 64. Spore anatomy <ul><li>The coat
  65. 65. - multilayer protein shell that prevents the entry of large degradative molecules and microbe predators into the spore’s core
  66. 66. - flexible ridges that unfold, allowing the core's volume to increase when water enters the spore during germination.
  67. 67. The exosporium
  68. 68. -forms the outermost structure of the spore that interacts with the environment </li></ul>-This protein shell is composed of surface proteins
  69. 69. The anthrax cycle
  70. 70. Cutaneous anthrax <ul><li>Infection of the skin due to direct contact with B.anthracis
  71. 71. contact with animal hides or hair, bone products, and wool.
  72. 72. Stages
  73. 73. -primary lesion appears as papule similar to an insect bite
  74. 74. -papule enlarges,small vesicles form on its surface </li></ul>-the vesicles fill up with neutrophils and bacilli. -the vesicles undergoe necrosis and form painless alcer surrounded by an eschar tr
  75. 75. Cutaneus anthrax <ul><li>Most common naturally occurring form
  76. 76. Case fatality after infection
  77. 77. -untreated 20 %
  78. 78. -with antimicrobial therapy 2%
  79. 79. Complications
  80. 80. infection can spread into blood stream and cause shock and death.
  81. 81. Treatment
  82. 82. doxycyclene antibiotic for 60 days </li></ul>
  83. 83. Cutaneus anthrax
  84. 84. Gastrointestinal anthrax <ul><li>Caused by the ingestion of meat contaminating Bacillus anthracis
  85. 85. Uncommon in the US
  86. 86. Case fatality rate:50-75%
  87. 87. 2 different forms of GI anthrax
  88. 88. 1) oral- pharyngeal
  89. 89. 2) abdominal </li></ul>
  90. 90. Gastrointestinal anthrax <ul><li>Oral -pharyngeal form
  91. 91. results from the deposition and germination of spores in the upper GI tract
  92. 92. causes infection of lymph glands and lymph channels,edema,sepsis
  93. 93. Abdominal form
  94. 94. -develops from the disposition and germination of spores in the lower GI tract.
  95. 95. -causes gastroenteritis and symptoms such as vomiting and abdominal pain </li></ul>
  96. 96. Gastrointestinal anthrax <ul><li>Abdominal anthrax
  97. 97. oral-Pharyngeal anthrax </li></ul>
  98. 98. Inhalation anthrax <ul><li>The most lethal type of anthrax
  99. 99. Caused by the inhalation of anthrax spores.
  100. 100. Initial phase:
  101. 101. - nonspecific, flue like symptoms, fever and malaise
  102. 102. Second phase:
  103. 103. -respiratory distress
  104. 104. -dyspnea, cyonosis ,mediastinal widening and death
  105. 105. Case fatality :75-90% if untreated </li></ul>
  106. 106. Inhalation anthrax
  107. 107. Inhalation anthrax <ul><li>Diagnosis:
  108. 108. - Blood cultures
  109. 109. - Chest x-ray or CT scan of the chest
  110. 110. - Sputum cultures
  111. 111. Treatment: Inhalation anthrax is usually treated with intravenous (IV) ciprofloxacin plus another antibiotic sixty days
  112. 112. Complications: Hemorrhagic meningitis, shock and death </li></ul>
  113. 113. Pathogenesis <ul><li>The most studied strain of anthrax is the aimes strain
  114. 114. Consists of one chromosome and 2 plasmids (pX01 and pX02) that carry genes that encode the virulence factors.
  115. 115. Px01
  116. 116. - protective antigen (PA)
  117. 117. Px02:
  118. 118. -edema factor (EF)
  119. 119. -Lethal factor (LF)
  120. 120. -poly-D-glutamic acid capsule </li></ul>
  121. 121. Pathogenesis <ul><li>Capsule: protects the bacteria in the vagitative state against phagocytosis.
  122. 122. PA: binds to the cell host's cell receptor and help AF And EF enter the cell by endocytosis.
  123. 123. EF: is an adenylate cyclase that affects all cells
  124. 124. 1- converting ATP to cAMP
  125. 125. 2- cAmp concentration increases
  126. 126. 3-water imbalance occurs
  127. 127. 4-edema </li></ul>
  128. 128. pathogenesis <ul><li>LF: metalloprotease that affects only macrophages
  129. 129. -cleaves most activated protein kinase kinases MAPKKS and trigger an apoptotic pathway to lyses the cells </li></ul>LF+PA necrosis EF+PA edema EF+LF inactive EF+LF+PA edema+ necrosis
  130. 130. Pathogenesis mechanism
  131. 131. The Fight against anthrax <ul><li>vaccines and antitoxins target the protective antigen PA
  132. 132. Vaccines:
  133. 133. -first-generation:
  134. 134. (+) contained a culture from an attenuated strain
  135. 135. (-) difficult to manufacture and has side effects
  136. 136. -second-generation
  137. 137. (+) contained nontoxic recombinant rPA molecule
  138. 138. (-) slow and expensive </li></ul>
  139. 139. New breakthrough <ul><li>Researchers at university of taxis medical branch
  140. 140. rapid immunization of large, at-risk populations after potential exposure to anthrax
  141. 141. - vaccine applied to mucosal surfaces to replace intramuscular vaccination
  142. 142. - There study examined the use of soybean oil-and-water nanoemulsions (NEs) as a mucosal adjuvant for an rPA vaccine to replace the aluminum adjuvant of the traditional vaccines </li></ul>
  143. 143. Results <ul><li>NE immunization was effective in inducing both serum anti-PA immunoglobulin IgA and IgG antibodies
  144. 144. high titers of lethal-toxin-neutralizing serum antibodies
  145. 145. sGuinea pigs nasally immunized with rPA-NE vaccine were protected against an intradermal challenge with 1,000 times the 50% lethal dose
  146. 146. a needle-free anthrax vaccine requiring fewer doses and having fewer side effects than the traditional vailable human vaccine </li></ul>
  147. 147. results
  148. 148. Conclusion <ul><li>although the rate of natural anthrax infection has declined, this topic remains a controversial one because of its relation to bio terrorism
  149. 149. this breakthrough is an excellent starting point and scientists should introduce the vaccine to humans and test it's success rate. In the future, research must focus on finding an antitoxin that can effectively cure vaccinated and non vaccinated humans after infection or exposure to the spores.
  150. 150. the fight against anthrax and all other biological weapons should be taken more seriously in the future to prevent any surprising attack from taking place. </li></ul>
  151. 151. Reference Baillie, L. 2001. The development of new vaccines against anthrax. J. Appl. Microbiol. 9: 609–613 . Bailey-Smith, K., Todd, S.J., Southworth, T.W., Proctor, J., Moir, A., 2005. The ExsA protein of Bacillus cereus is required for assembly of coat and exosporium onto the spore surface. J. Bacteriol. 187, 3800–3806. Franz D. 2009. Preparedness for an anthrax attack. Molecular aspects of medicine 30:503-510. Friedlander A. M. 1986. Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. Journal of Biological Chemistry 261:7123. Shadonly S., T. Smith. 2008. Anthrax. Journal of the American Veterinary Medical Association 233:63-72.

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