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Bordetella class notes

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Bordetella class notes

  1. 1. Bordetella, Francisella & Brucella
  2. 2. General Overview of Bordetella, Francisella & Brucella <ul><ul><ul><li>Extremely small </li></ul></ul></ul><ul><ul><ul><li>Aerobic nonfermenters </li></ul></ul></ul><ul><ul><ul><li>Gram-negative coccobacilli </li></ul></ul></ul><ul><ul><ul><li>True pathogens : isolation always associated with disease; i.e., always clinically significant </li></ul></ul></ul><ul><ul><ul><li>NOTE : Previously studied nonfermenters were all opportunistic pathogens </li></ul></ul></ul>
  3. 3. Human Disease & Associated Pathogens Brucellosis melintensis Brucella Brucellosis abortus Brucellosis suis Brucellosis canis Tularemia tularensis Francisella Disease Species Genus Bronchopulmonary disease bronchiseptica Pertussis (milder form) parapertussis Pertussis pertussis Bordetella
  4. 4. Bordetella pertussis
  5. 5. Bordetella pertussis Basics <ul><li>Aerobic, Gram negative coccobacillus </li></ul><ul><li>Alcaligenaceae Family </li></ul><ul><li>Specific to Humans </li></ul><ul><li>Colonizes the respiratory tract </li></ul><ul><ul><li>Whooping Cough (Pertussis) </li></ul></ul>http://microvet.arizona.edu/Courses/MIC420/lecture_notes/bordetella_pertussis/ gram_pertussis.html
  6. 6. <ul><li>Man is only natural host ; obligate parasites of man </li></ul><ul><li>Disease is highly communicable (highly infectious) </li></ul><ul><li>Person-to-person spread via inhalation of infectious aerosols </li></ul><ul><li>Incidence in U.S.A. significantly reduced with required DPT vaccine; Incidence increasing as some local school boards stop requirement </li></ul><ul><li>Children under one year at highest risk , but prevalence increasing in older children and adults </li></ul>Epidemiology of Bordetella pertussis Infection
  7. 7. Bordetella pertussis <ul><li>Gram-negative bacterium </li></ul><ul><li>Must attach to host cells to survive </li></ul><ul><li>Virulence factors damage host tissue </li></ul><ul><li>Contains LPS with unusual structure </li></ul>
  8. 8. Lipopolysaccharide <ul><li>Normal LPS contains three components: </li></ul><ul><ul><li>O-Antigen </li></ul></ul><ul><ul><li>Core Polysaccharide </li></ul></ul><ul><ul><li>Lipid A </li></ul></ul><ul><li>Pertussis LPS lacks a highly polymerized O-side chain </li></ul><ul><li>Contains unusual sugars </li></ul>
  9. 9. Incidence & Severity of Pertussis Cases in USA
  10. 10. Age Distribution & Severity of Pertussis Cases
  11. 11. Changes in Age Distribution for Pertussis Cases Blue = 1988 Orange = 1998
  12. 12. Clinical Progression of Pertussis Most infectious, but generally not yet diagnosed Inflammation of respiratory mucosal memb. , or death
  13. 13. <ul><li>Fimbriae not primarily involved in adherence; Exotoxin & hemagglutinin mediate attachment specifically to ciliated epithelium of bronchial tree </li></ul><ul><li>Cells multiply among cilia of epithelial cells and produce filamentous hemaglutinin and classic A-B exotoxin and other toxins leading to localized tissue damage and systemic toxicity </li></ul><ul><ul><li>Pertussis toxin, adenylate cyclase toxin, tracheal cytotoxin, dermonecrotic toxin, filamentous hemagglutinin, LPS (lipid A & lipid X) </li></ul></ul><ul><li>Classical A-B exotoxin has three distinct activities </li></ul><ul><ul><li>Histamine sensitizing factor </li></ul></ul><ul><ul><li>Lymphocytosis promoting factor </li></ul></ul><ul><ul><li>Islet activating protein </li></ul></ul>Virulence Factors Associated with Bordetella pertussis
  14. 14. Virulence Factors Associated with Bordetella pertussis
  15. 15. Adhesions <ul><li>Filamentous hemagglutinin </li></ul><ul><li>Pertactin </li></ul><ul><li>Fimbriae </li></ul>http://www.rivm.nl/infectieziektenbulletin/bul1306/kinkhoest.jpg http://www.my-pharm.ac.jp/~yishibas/research/Pertussis1.jpg
  16. 16. Toxins <ul><li>Pertussis Toxin </li></ul><ul><li>Adenylate Cyclase Toxin </li></ul><ul><li>Tracheal cytotoxin </li></ul><ul><li>Dermonecrotic toxin </li></ul><ul><li>Heat-labile toxin </li></ul>www.ibl.fr/u447/u447.htm
  17. 17. Pertussis Toxin <ul><li>Colonizing factor and endotoxin </li></ul><ul><li>Cell bound and extracellular </li></ul>gsbs.utmb.edu / microbook/ch031.htm www.med.sc.edu:85/ ghaffar/pertussis.jpg
  18. 18. Adenylate Cyclase Toxin <ul><li>Invasive toxin </li></ul><ul><li>Activated by host cell calmodulin </li></ul><ul><li>Impairment of immune effector cells </li></ul>Babu et al., 2001
  19. 19. Laboratory Culture, Prevention & Treatment of Bordetella <ul><li>Inactivated whole bacterial cells and toxoid are prepared in formalin for inclusion in DPT vaccine </li></ul><ul><li>Subunit (acellular) vaccine also available </li></ul><ul><li>Treatment with erythromycin, suction, oxygen </li></ul><ul><li>Treatment does not eliminate symptoms </li></ul><ul><li>Nonmotile </li></ul><ul><li>Fastidious and slow-growing </li></ul><ul><ul><li>Requires nicotinamide and charcoal, starch, blood, or albumin to absorb toxic substances </li></ul></ul><ul><ul><li>Requires prolonged growth </li></ul></ul><ul><ul><li>Isolated on modified Bordet-Gengou agar </li></ul></ul>
  20. 20. Differential Characteristics of Bordetella Species
  21. 21. Pertussis Laboratory Confirmation <ul><li>Isolation of Bordetella pertussis from a clinical specimen </li></ul><ul><li>Positive polymerase chain reaction assay (PCR) </li></ul><ul><li>Direct fluorescent antibody (DFA) testing should NOT be used (low sensitivity and variable specificity) </li></ul>
  22. 22. Bordetella pertussis Culture <ul><li>Cultures most often positive if the nasopharyngeal swab is obtained within the first week of cough onset </li></ul><ul><li>Beyond the first 3 weeks of illness the organism is recovered less often </li></ul><ul><li>Demonstration video of NP swab technique available on the broadcast updates and resources webpage </li></ul><ul><li>www.cdc.gov/vaccines/ed/surv07/surv07-resources.htm </li></ul>
  23. 23. PCR Testing <ul><li>Widely available </li></ul><ul><li>Rapid, sensitive, and specific </li></ul><ul><li>Some PCR assays have not been completely reliable </li></ul><ul><li>Cultures should continue to be performed even if PCR tests are used </li></ul>
  24. 24. Critical Data for Pertussis Case Investigation <ul><li>Demographic information </li></ul><ul><li>Clinical data </li></ul><ul><li>Complications </li></ul><ul><li>Vaccination history </li></ul><ul><ul><li>Date </li></ul></ul><ul><ul><li>Vaccine type </li></ul></ul><ul><ul><li>Manufacturer </li></ul></ul><ul><ul><li>Lot number </li></ul></ul>
  25. 25. Francisella tularensis
  26. 26. Francisella tularensis Infections
  27. 27. Francisella tularensis Infections (cont.)
  28. 28. Clinical Presentation of Tularemia NOTE: Also Gastrointestinal & Pneumonic forms of disease
  29. 29. <ul><li>Rabbits, ticks & muskrats are main reservoirs in US </li></ul><ul><li>Two biochemical varieties </li></ul><ul><ul><li>F. tularensis bv. tularensis (a.k.a., Jellison Type A ) </li></ul></ul><ul><ul><li>F. tularensis bv. palaearctica (a.k.a., Jellison Type A) </li></ul></ul><ul><li>Jellison Type A strains are the major biovar associated with severe disease in North America </li></ul><ul><ul><li>Most commonly, transmission by tick vectors from rabbit reservoirs or direct contact with rabbits </li></ul></ul>Epidemiology of F. tularensis Infection
  30. 30. Biochemical Variants (Biovar) of Francisella tularensis
  31. 31. <ul><li>Antiphagocytic capsule </li></ul><ul><ul><li>Thin lipid capsule present in pathogenic strains </li></ul></ul><ul><li>Facultative intracellular parasite that can survive in macrophages of the reticuloendothelial system </li></ul>Virulence Factors of Fransicella tularensis
  32. 32. <ul><li>Nonmotile </li></ul><ul><li>Fastidious and slow-growing </li></ul><ul><ul><li>Requires cysteine-supplemented specialized media wi </li></ul></ul><ul><ul><li>Requires prolonged growth </li></ul></ul><ul><li>Disease prevention: </li></ul><ul><ul><li>Avoidance of reservoirs and vectors </li></ul></ul><ul><ul><li>Protective clothing and gloves </li></ul></ul><ul><ul><li>Laboratory personnel should be made aware of potential for Fransicella in clinical specimens </li></ul></ul>Laboratory Culture, Prevention & Treatment of F. tularensis
  33. 33. Antibody Response to Francisella tularensis Infections
  34. 34. Brucella spp.
  35. 35. Brucella Infections
  36. 36. Brucella Infections (cont.)
  37. 37. <ul><li>Animals are natural reservoir </li></ul><ul><ul><li>Cattle, goats, sheep, swine, bison, elk, dogs, foxes, coyotes </li></ul></ul><ul><li>500,000 human cases per year worldwide </li></ul><ul><li>Less than 100 annual cases in the U.S. due to successful control of the disease in livestock and the animal reservoir </li></ul><ul><li>Transmission via i) ingestion of contaminated milk or cheese, or ii) direct contact with infected animals or animal products </li></ul><ul><li>Because it can be transmitted to humans , brucellosis is one of the most regulated diseases of cattle in the U.S. </li></ul>Epidemiology of Brucellosis
  38. 38. Incidence of Brucellosis in USA
  39. 39. <ul><li>Brucella infect organs rich in erythritol (a sugar metabolized in preference to glucose) like breast, uterus, placenta and epididymis (tube that connects a pair of ducts that conduct spermatozoa during ejaculation) </li></ul><ul><li>Asymptomatic carriage, sterility or abortions </li></ul><ul><li>Transmitted between animals in aborted tissues </li></ul>Brucellosis in Animals
  40. 40. Human Brucellosis & Associated Species Severe
  41. 41. Brucellosis in Humans <ul><li>Reportable disease </li></ul><ul><li>Human brucellosis = Bang's disease , named for Bernhard Bang & Sir David Bruce who discovered Brucella </li></ul><ul><li>Facultative intracellular pathogens of mononuclear-phagocyte system (formerly reticuloendothelial system which is involved in immune defense against microbial infection and removal of worn-out blood cells) </li></ul><ul><ul><li>Bacteria are phagocytosed by macrophage or polymorphonuclear leukocyte </li></ul></ul><ul><ul><li>Survive intracellularly by inhibiting killing </li></ul></ul><ul><ul><li>Carried to spleen, liver, bone marrow, lymph nodes, kidneys </li></ul></ul><ul><li>Form granulomas (mass of granulation tissue produced in response to chronic infections, inflammation, or foreign bodies) and cause destructive tissue damage </li></ul>
  42. 42. <ul><li>Consumption of contaminated unpasteurized milk or direct contact with infected animal reservoir </li></ul><ul><ul><li>Disease associated with contact with infected cattle, cattle products, or dogs is a milder form </li></ul></ul><ul><ul><li>Disease associated with contact with goats and sheep is acute and severe with complications common </li></ul></ul><ul><ul><li>Disease associated with contact with swine is chronic & suppurative with destructive lesions and localization in cells of the reticuloendothelial system (RES) </li></ul></ul><ul><li>Occupational hazard of laboratory personnel, veterinarians, farm workers, and meat handlers at risk through direct contact or inhalation </li></ul><ul><li>Protective clothing for abattoir workers, avoidance of unpasteurized dairy products </li></ul><ul><li>Highest numbers of cases reported in CA and TX </li></ul>Brucellosis in Humans (cont.)
  43. 43. <ul><li>Acute disease often develops with initial nonspecific symptoms of malaise, chills, fatigue, weakness, myalgias (muscles), weight loss, arthralgias (joint), and nonproductive cough </li></ul><ul><li>Mild disease with rare suppurative complications </li></ul><ul><li>Chronic disease and recurrence are common because it can survive in phagocytic cells and multiply to high concentrations </li></ul><ul><li>May also take the form of destructive lesions </li></ul>Clinical Presentation of Human Brucellosis

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