Anthrax by m.khoury 1


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Anthrax by m.khoury 1

  1. 1. Anthrax MIlad khoury Spring 2011
  2. 2. ARTICLE <ul><li>“ New medical weapons to protect against Anthrax attacks” </li></ul><ul><li>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>
  3. 3. Outline <ul><li>I Introduction </li></ul><ul><li>II History of the disease </li></ul><ul><li>III Its use as a biological weapons </li></ul><ul><li>IV Bacillus anthracis </li></ul><ul><li>V the 3 routs of inection </li></ul><ul><li>VI Pathogenesis </li></ul><ul><li>VII The fight against anthrax </li></ul><ul><li>VIII Conclusion </li></ul>
  4. 4. Anthrax: basics <ul><li>From the Greek word anthracis for coal. </li></ul><ul><li>caused by the bacteria B.anthracis </li></ul><ul><li>Zoonotic disease in herbivores (e.g., sheep, goats, cattle) </li></ul><ul><li>Human infection typically acquired through contact with anthrax-infected animals or animal products . </li></ul><ul><li>Three forms </li></ul><ul><li>-Cutaneous </li></ul><ul><li>-Inhalational </li></ul><ul><li>-Gastrointestinal </li></ul>
  5. 5. history <ul><li>1500 B.C </li></ul><ul><li>Moses threatened the Egyptian pharaoh that the hand of the lord will fall on the livestock ,horses and birds and kill everything. </li></ul><ul><li>5 th century B.C </li></ul><ul><li>the Greek Doctor Hippocrates named the disease that caused black skin lesions as anthracis. </li></ul>
  6. 6. 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. </li></ul><ul><li>The disease was also called Wool Sorter’s disease and Rag Picker’s disease . </li></ul><ul><li>1876 - German bacteriologist Robert Koch confirmed bacterial origin of anthrax. </li></ul><ul><li>1881: Louis Pasteur developed the first vaccine </li></ul>
  7. 7. 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 . </li></ul><ul><li>1979 - In Soviet Union , aerosolized anthrax spores were released accidentally at a military facility, affecting 94 and killing 64 people. </li></ul><ul><li>1995 - Iraq produced 8,500 liters of concentrated anthrax as part of the biological weapon program under Saddam Hussein’s administration. </li></ul>
  8. 8. Anthrax cases 2001 <ul><li>22 cases </li></ul><ul><li>-11 cutaneous </li></ul><ul><li>-11 inhalational </li></ul><ul><li>5 deaths ( all inhalational ) </li></ul><ul><li>-case in Florida </li></ul><ul><li>-2 postal workers in Maryland </li></ul><ul><li>-hospital worker in NY city </li></ul><ul><li>Farm woman in Connecticut </li></ul>
  9. 9. Bacillus anthracis <ul><li>Gram positive rod </li></ul><ul><li>has a diameter of 1-1.5 µm and a length of 3-10 µm. </li></ul><ul><li>Facilitative anaerobe </li></ul><ul><li>Belogns to the B.cereus family </li></ul><ul><li>- Nonmotile </li></ul><ul><li>-glutamyl-polypeptide capsule </li></ul><ul><li>-soil dwelling </li></ul>
  10. 10. Bacillus anthracis <ul><li>1200 strains distributed worldwide </li></ul><ul><li>Forms spores </li></ul><ul><li>-infectious form </li></ul><ul><li>-1micrometer in size </li></ul><ul><li>Vegetative state </li></ul><ul><li>-non infectious </li></ul><ul><li>- fragile </li></ul>
  11. 11. The spore <ul><li>Sporulation conditions: </li></ul><ul><li>-starvation </li></ul><ul><li>- presence of oxygen </li></ul><ul><li>-changes in environmental conditions </li></ul><ul><li>- resistant to cold, heat,dryness and chemicals </li></ul><ul><li>-lethal dose of 2500 to 5500 spores </li></ul><ul><li>- spore viability increases in soil with organic content, alkaline PH, high calcium concentration ,high moisture </li></ul><ul><li>- </li></ul>
  12. 12. Spore anatomy <ul><li>Cr: core </li></ul><ul><li>Cx: cortex </li></ul><ul><li>Ct: coat </li></ul><ul><li>Is: interspace </li></ul><ul><li>Ex:exosporium </li></ul><ul><li>Thin-section electron micrograph </li></ul>
  13. 13. Spore anatomy <ul><li>The core: </li></ul><ul><li>-protects the spore from Uv radiation and stress </li></ul><ul><li>-forms the center part of the spore </li></ul><ul><li>- chromosomes form complexes with small acid soluble proteins abbreviated as SASP </li></ul><ul><li>-high levels of dipicolinic acid and ions </li></ul><ul><li>The Cortex </li></ul><ul><li>- important in providing resistance to the spore and keeping the core dry . </li></ul>
  14. 14. Spore anatomy <ul><li>The coat </li></ul><ul><li>- multilayer protein shell that prevents the entry of large degradative molecules and microbe predators into the spore’s core </li></ul><ul><li>- flexible ridges that unfold, allowing the core's volume to increase when water enters the spore during germination. </li></ul><ul><li>The exosporium </li></ul><ul><li>-forms the outermost structure of the spore that interacts with the environment </li></ul><ul><li>-This protein shell is composed of surface proteins </li></ul>
  15. 15. The anthrax cycle
  16. 16. Cutaneous anthrax <ul><li>Infection of the skin due to direct contact with B.anthracis </li></ul><ul><li>contact with animal hides or hair, bone products, and wool. </li></ul><ul><li>Stages </li></ul><ul><li>-primary lesion appears as papule similar to an insect bite </li></ul><ul><li>-papule enlarges,small vesicles form on its surface </li></ul><ul><li>-the vesicles fill up with neutrophils and bacilli. </li></ul><ul><li>-the vesicles undergoe necrosis and form painless alcer surrounded by an eschar </li></ul><ul><li>tr </li></ul>
  17. 17. Cutaneus anthrax <ul><li>Most common naturally occurring form </li></ul><ul><li>Case fatality after infection </li></ul><ul><li>-untreated 20 % </li></ul><ul><li>-with antimicrobial therapy 2% </li></ul><ul><li>Complications </li></ul><ul><li>infection can spread into blood stream and cause shock and death. </li></ul><ul><li>Treatment </li></ul><ul><li>doxycyclene antibiotic for 60 days </li></ul>
  18. 18. Cutaneus anthrax
  19. 19. Gastrointestinal anthrax <ul><li>Caused by the ingestion of meat contaminating Bacillus anthracis </li></ul><ul><li>Uncommon in the US </li></ul><ul><li>Case fatality rate:50-75% </li></ul><ul><li>2 different forms of GI anthrax </li></ul><ul><li>1) oral- pharyngeal </li></ul><ul><li>2) abdominal </li></ul>
  20. 20. Gastrointestinal anthrax <ul><li>Oral -pharyngeal form </li></ul><ul><li>results from the deposition and germination of spores in the upper GI tract </li></ul><ul><li>causes infection of lymph glands and lymph channels,edema,sepsis </li></ul><ul><li>Abdominal form </li></ul><ul><li>-develops from the disposition and germination of spores in the lower GI tract. </li></ul><ul><li>-causes gastroenteritis and symptoms such as vomiting and abdominal pain </li></ul>
  21. 21. Gastrointestinal anthrax <ul><li>Abdominal anthrax </li></ul><ul><li>oral-Pharyngeal anthrax </li></ul>
  22. 22. Inhalation anthrax <ul><li>The most lethal type of anthrax </li></ul><ul><li>Caused by the inhalation of anthrax spores. </li></ul><ul><li>Initial phase: </li></ul><ul><li>- nonspecific, flue like symptoms, fever and malaise </li></ul><ul><li>Second phase: </li></ul><ul><li>-respiratory distress </li></ul><ul><li>-dyspnea, cyonosis ,mediastinal widening and death </li></ul><ul><li>Case fatality :75-90% if untreated </li></ul>
  23. 23. Inhalation anthrax
  24. 24. Inhalation anthrax <ul><li>Diagnosis: </li></ul><ul><li>- Blood cultures </li></ul><ul><li>- Chest x-ray or CT scan of the chest </li></ul><ul><li>- Sputum cultures </li></ul><ul><li>Treatment: Inhalation anthrax is usually treated with intravenous (IV) ciprofloxacin plus another antibiotic sixty days </li></ul><ul><li>Complications: Hemorrhagic meningitis, shock and death </li></ul>
  25. 25. Pathogenesis <ul><li>The most studied strain of anthrax is the aimes strain </li></ul><ul><li>Consists of one chromosome and 2 plasmids (pX01 and pX02) that carry genes that encode the virulence factors. </li></ul><ul><li>Px01 </li></ul><ul><li>- protective antigen (PA) </li></ul><ul><li>Px02: </li></ul><ul><li>-edema factor (EF) </li></ul><ul><li>-Lethal factor (LF) </li></ul><ul><li>-poly-D-glutamic acid capsule </li></ul>
  26. 26. Pathogenesis <ul><li>Capsule: protects the bacteria in the vagitative state against phagocytosis. </li></ul><ul><li>PA: binds to the cell host's cell receptor and help AF And EF enter the cell by endocytosis. </li></ul><ul><li>EF: is an adenylate cyclase that affects all cells </li></ul><ul><li>1- converting ATP to cAMP </li></ul><ul><li>2- cAmp concentration increases </li></ul><ul><li>3-water imbalance occurs </li></ul><ul><li>4-edema </li></ul>
  27. 27. pathogenesis <ul><li>LF: metalloprotease that affects only macrophages </li></ul><ul><li>-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
  28. 28. Pathogenesis mechanism
  29. 29. The Fight against anthrax <ul><li>vaccines and antitoxins target the protective antigen PA </li></ul><ul><li>Vaccines: </li></ul><ul><li>-first-generation: </li></ul><ul><li>(+) contained a culture from an attenuated strain </li></ul><ul><li>(-) difficult to manufacture and has side effects </li></ul><ul><li>-second-generation </li></ul><ul><li>(+) contained nontoxic recombinant rPA molecule </li></ul><ul><li>(-) slow and expensive </li></ul>
  30. 30. New breakthrough <ul><li>Researchers at university of taxis medical branch </li></ul><ul><li>rapid immunization of large, at-risk populations after potential exposure to anthrax </li></ul><ul><li>- vaccine applied to mucosal surfaces to replace intramuscular vaccination </li></ul><ul><li>-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>
  31. 31. Results <ul><li>NE immunization was effective in inducing both serum anti-PA immunoglobulin IgA and IgG antibodies </li></ul><ul><li>high titers of lethal-toxin-neutralizing serum antibodies </li></ul><ul><li>sGuinea pigs nasally immunized with rPA-NE vaccine were protected against an intradermal challenge with 1,000 times the 50% lethal dose </li></ul><ul><li>a needle-free anthrax vaccine requiring fewer doses and having fewer side effects than the traditional vailable human vaccine </li></ul>
  32. 32. results
  33. 33. 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 </li></ul><ul><li>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. </li></ul><ul><li>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>
  34. 34. Reference <ul><li>Baillie, L. 2001. The development of new vaccines against anthrax. J. Appl. Microbiol. 9: 609–613 . </li></ul><ul><li>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. </li></ul><ul><li>Franz D. 2009. Preparedness for an anthrax attack. Molecular aspects of medicine 30:503-510. </li></ul><ul><li>Friedlander A. M. 1986. Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. Journal of Biological Chemistry 261:7123. </li></ul><ul><li>Shadonly S., T. Smith. 2008. Anthrax. Journal of the American Veterinary Medical Association 233:63-72. </li></ul>