Diptheria an update

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Diptheria update

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  • You are going to be doctors in the field of stomatology. So you may be the first doctors to find the clinical cases in a possible outbreaks in the future. That means you all have to pay attention to this disease.
  • Diptheria an update

    1. 1. Diphtheria an update Dr.T.V.Rao MD Dr.T.V.Rao MD
    2. 2. Diphtheria • • • • Greek diphtheria (leather hide) Caused by Aerobic Gram +ve rods Corynebacterium diphtheria Exotoxin production only if infected by virus phage infected carrying toxin gene Dr.T.V.Rao MD 2
    3. 3. Corynebacterium • Gram + Non Acid fast, Non motile, • Irregularly stained with granules, • Club shaped swelling at one or both ends so the name • Important Pathogen Corynebacterium diphtheria, Diptheros meaning leather, Dr.T.V.Rao MD 3
    4. 4. What is Diphtheria • An infection of local tissue of URT with production of toxin which causes systemic effects on Heart and Peripheral tissues, Dr.T.V.Rao MD 4
    5. 5. Definition • Diphtheria is an acute, toxinmediated disease caused by toxigenic Corynebacterium diphtheria. • It’s a very contagious and potentially life-threatening bacterial disease. Dr.T.V.Rao MD 5
    6. 6. Definition • It’s a localized infectious disease, which usually attacks the throat and nose mucous membrane Dr.T.V.Rao MD 6
    7. 7. Etiology • C. diphtheriae is an aerobic grampositive bacillus. – Pleomorphic, club-end – Non-spore-forming – Non-acid-fast – Non-motile Dr.T.V.Rao MD 7
    8. 8. Etiology • The major virulence determinant is an exotoxin, diphtheria toxin. After binding to the host cells, the active subunit will interrupt the protein synthesis of the target host cell and results in cell death. • Toxoid made from diphtheria toxin can be used as vaccine. Dr.T.V.Rao MD 8
    9. 9. Etiology • There are three biotypes — gravis, Intermedius, and mitis. The most severe clinical type of this disease is associated with the gravis biotype, but any strain may produce toxin. Dr.T.V.Rao MD 9
    10. 10. Pathogenesis • Entry ------ the bacilli multiply locally in the throat and elaborate a powerful exotoxin ----produce local and systemic symptoms. Local lesions : • Exotoxin causes necrosis of the epithelial cells and liberates serous and fibrin us material which forms a grayish white pseudo membrane • The membrane bleeds on being dislodged • Surrounding tissue is inflamed and edematous Dr.T.V.Rao MD 10
    11. 11. Fauces ( throat ) Fauces : - two pillars of mucous membrane. Anterior : known as the palatoglossal arch and Posterior : the palatopharyngeal arch Dr.T.V.Rao MD Between these two arches is the palatine tonsil. 11
    12. 12. Typical Presentation of Bull Neck Dr.T.V.Rao MD 12
    13. 13. Local manifestation Depend on the site of lesion: Nasal diphtheria : • • • Faucial diphtheria : • Redness and Unilateral or bilateral swelling over serosanguineous ( blood and Fauces serous fluid ) discharge from the nose • Exudates on the Excoriation of upper lip tonsils coalesces to Toxemia is minimal form grayish white pseudo membrane • Regional lymph nodes are inflamed Dr.T.V.Rao MD • Sore throat and 13
    14. 14. Dr.T.V.Rao MD 14
    15. 15. Corynebacterium diphtheria • • • • • Slender rods Clubbing at both ends Pleomorphic Non capsulate / Acid fast Gram + Granules are composed of polymetapohosphate • Staining with Loffler's methylene blue show bluish purple metachromatic granules. with polar bodies, Dr.T.V.Rao MD 15
    16. 16. Dr.T.V.Rao MD 16
    17. 17. Staining methods • Grams method • • • • Albert's stain Neissers stain Ponders stain On staining seen as Pairs, Appear as v and L letters, resembling Chinese letter pattern or also called cuneiform arrangement. Dr.T.V.Rao MD 17
    18. 18. Cultural characters • • • • • • • Need enrichment Media Contain Blood, Serum or Egg 37 c ph 7.4 Aerobic/Facultative anaerobic. Commonly used medium Loffler serum slope, Tellurite Blood agar, Dr.T.V.Rao MD 18
    19. 19. Gram +ve Bacilli and Colonies Dr.T.V.Rao MD 19
    20. 20. Culturing • Selective & differential medium • Corynebacterium are resistant to tellurite – Reduced to tellurium • Forms deposit in colonies – Colonies appear dark • Biotypes – gravis, Intermedius, mitis Dr.T.V.Rao MD 20
    21. 21. Growing on Culture Plates • Loffler serum slope Grows rapidly in 6 -8 hours, Small white opaque disks Turns to yellow Tellurite blood agar Modified Mac Leod Hoyles medium. Dr.T.V.Rao MD 21
    22. 22. Commonly used medium • Tellurite blood agar Contains tellurite 0.04 tellurite Inhibits other bacteria • Produce Grey/Black colonies. Dr.T.V.Rao MD 22
    23. 23. Classification of McLeod Classified in to 3 Types 1 Gravis 2 Intermedius 3.Mitis Gravis produce Most serious Hemorrhagic Paralytic complications - Epidemic Intermedius Hemorrhagic Mitis - obstructive complications, Endemic Geographic locations differ Testing for toxigenicity is more important, Dr.T.V.Rao MD 23
    24. 24. Biochemical Reactions • Acid Glucose,Galactose Maltose, Dextrin Do not produce acid with Lactose, Mannitol, sucrose. All fermentation reactions tested in Hiss serum sugars Urease test negative. Proteolytic Dr.T.V.Rao MD 24
    25. 25. Toxin • Pathogenicity associated with Toxin • Gravis/Intermedius 95-99% are toxigenic • Mitis 80 – 85% • Some abundant others poorly • Toxin production park William 8 • Toxin M W 62,000 0.0001 can kill guinea pig Dr.T.V.Rao MD 25
    26. 26. Diphtheria toxin: Part A • Active site • Enzyme • Blocks protein synthesis – ADP-ribosyl transferase – elongation factor 2 (EF2) • Specific for mammalian cells – Prokaryotes have different EF2 Dr.T.V.Rao MD 26
    27. 27. Diphtheria Toxin: Part B • Binding Site • Binds to cell receptor • Bound receptor internalized • Endosome – Hydrolyzed by protease – Disulfide broken – Part A released Dr.T.V.Rao MD 27
    28. 28. Activation of Diphtheria Toxin A A A B B B A B Dr.T.V.Rao MD 28
    29. 29. Toxin ( Contd ) • Toxin contain two components A 24,000 B 38,000 A produce toxigenicity by proteolytic effect B Produce binding Toxin + Formalin = Toxoid What is Toxoid – Antigenic, not toxigenic Tox + Corynephage Toxin production Dr.T.V.Rao MD 29
    30. 30. Toxin ( contd ) • Need iron 0.1 mg/liter. • Toxin inhibits protein synthesis • Fragment A catalyzes the transfer of ADP ribose from the Nicotinamide adenine dinucleotide ( NAD ) to the eukaryotic elongation factor 2 /(Fragment A inhibits polypeptide chain elongation in the presence of Nicotinamide adenine dinucleotide by inactivating elongation factor • Causes involvement with affinity. Myocarditis, Adrenals Nerve endings, Dr.T.V.Rao MD 30
    31. 31. Antigenic structure • • • • Gravis 13, Intermedius 4 Mitis 40 Bacteriophage typing 15 types Dr.T.V.Rao MD 31
    32. 32. Resistance • Can be killed at 580 c in 10 mt 1000 c in 1 mt Survive in Blankets, Floor dust, toys inanimate objects Dr.T.V.Rao MD 32
    33. 33. Pathogenicity • Bacteria Invade, Colonise,Proliferate • Bacteria are lysogenized by Beta phage • Produce toxin, • Kills epithelial and Neutrophils, • Produce Pharyngitis and cutaneous lesions. Dr.T.V.Rao MD 33
    34. 34. Pathogenicity • Incubation 3 – 4 days / one day • Faucal / Nasal /Laryngeal / Otic / Conjunctiva,/Genital / Vulvae Coetaneous Diphtheria is a toxemic condition. Malignant Sever toxemia ,Adenitis Bull neck Circulatory failure Septic Gangrene , pseudo membrane. Dr.T.V.Rao MD 34
    35. 35. Pathogenicity • Hemorrhagic Epistaxis , Purpura General Bleeding tendency Asphyxia , Acute circulatory failure, Paralysis Pneumonia, Septic shock, Otitis media. Toxemia, Necrotic changes Death in Guinea pigs Dr.T.V.Rao MD 35
    36. 36. Diphtheria • Nasopharyngeal diphtheria – Pharyngeal – Laryngeal • Cutaneous diphtheria • Systemic complications DIAGNOSIS MUST BE CLINICAL!!!! Dr.T.V.Rao MD 36
    37. 37. Clinical features • • • • • • • Malaise, Sore throat, Fever Adherent grey pseudo membrane Nasal ulcers, Obstruction of larynx and lower airways, Difficulty in swallowing Lead to Myocarditis, Peripheral neuritis, Paralysis of limbs, Dr.T.V.Rao MD 37
    38. 38. Diphtheria Clinical Features Incubation period 2-5 days (range, 1-10 days) May involve any mucous membrane Classified based on site of infection anterior nasal pharyngeal and tonsillar laryngeal cutaneous ocular genital Dr.T.V.Rao MD 38
    39. 39. Diphtheria Clinical Features Incubation period 2-5 days (range, 1-10 days) May involve any mucous membrane Classified based on site of infection anterior nasal pharyngeal and tonsillar laryngeal cutaneous ocular genital Dr.T.V.Rao MD 39
    40. 40. Thick Membrane Dr.T.V.Rao MD 40
    41. 41. Dr.T.V.Rao MD 41
    42. 42. Pseudo membrane Dr.T.V.Rao MD 42
    43. 43. Skin Lesions Dr.T.V.Rao MD 43
    44. 44. Pathogenicity 1 Faucial Diphtheria very common, • Malignant or Hyper toxic toxemia Marked adenitis, circulatory failure, • Paralytic sequale 2 Septic ulceration cellulitis, gangrene Epistaxis Bleeding tendency, Dr.T.V.Rao MD 44
    45. 45. Complications • Asphyxia - causing mechanical obstruction. • May need tracheotomy • Circulatory failure. • Post Diphtheria paralysis Dr.T.V.Rao MD 45
    46. 46. Non toxigenic clinical manifestations • Bacteria can produce 1. Endocarditis, 2.Meingitis, 3 Cerebral abscess. 4 Osteoarthritis. Dr.T.V.Rao MD 46
    47. 47. Dr.T.V.Rao MD 47
    48. 48. Dr.T.V.Rao MD
    49. 49. Dr.T.V.Rao MD 49
    50. 50. Laboratory Diagnosis • Specific treatment is more important than Laboratory Diagnosis. 1 Isolation of Diphtheria bacilli. 2.Testing for toxigenicity, Dr.T.V.Rao MD 50
    51. 51. Collection of Specimens • Throat swabs • Smear examinations Gram s staining, Albert's, Ponders Immunoflorescent methods Cultures on Loeffers serum slope Tellurite Blood agar, Blood agar. Dr.T.V.Rao MD 51
    52. 52. Dr.T.V.Rao MD 52
    53. 53. Isolation of C.diptheria • Serum slope – Growth in 6 – 8 hours, • Stain with Neissers stain Albert's stain • Bacilli have metachromatic granules, • Tellurite Blood agar takes two days for manifestation of colonies, Dr.T.V.Rao MD 53
    54. 54. Virulence tests, • In Vivo and In Vitro • In Vivo in Animals • Subcutaneous tests Inject broth from culture into two Guinea pigs, 0.8 ml One animal given 500 units of antitoxin Other no Vaccine. Animal not given antitoxin will die Loss of Animals. Restricts its testing. Dr.T.V.Rao MD 54
    55. 55. Intracutaneous Method • One animal given 500 units before toxin • Other 50 units after Toxin • So the Animals can be saved Dr.T.V.Rao MD 55
    56. 56. In Vitro Testing • Elek s Gel precipitation testing • Filter paper impregnated with Diphtheria antitoxin 1000 Units / ml • Tested on the horse serum agar • Positive / Negative /Test strains tested for Immunodiffusion • Line of precipitation – test positive • Other methods testing in Tissue cultures. Dr.T.V.Rao MD 56
    57. 57. Toxigenicity Tests In Vitro Elek test In Vivo Animal inoculation rabbit skin testnecrosis guinea pig challenge testlethal low [Fe 2+] induces toxin Dr.T.V.Rao MD 57
    58. 58. Dr.T.V.Rao MD 58
    59. 59. Schick Test ( Out dated ) – Schick test: It is an intradermal test, the test is carried out by injecting intradermally into the skin of forearm 0.2 ml of diphtheria toxin, while into the opposite arm is injected as a control, the same amount of toxin which has been inactivated by heat. Dr.T.V.Rao MD 59
    60. 60. Interpretation • Negative reaction: If a person had immunity to diphtheria, no reaction will be observed on either arm. • Positive reaction: An area of in duration 10-15 mm in diameter generally appears within 24-36 hours reaching its maximum development by 4-7 days, the control arm shows no change. The person is susceptible to diphtheria. • False positive reaction: A red flush develops in both arms, the reaction fades very quickly, and disappears by 4th day. This is an allergic type of reaction found in certain individuals • Combined reaction: the control arm shows pseudo positive reaction and the test arm is true +ve reaction, Dr.T.V.Rao MD 60 susceptible and need vaccination
    61. 61. Schick Test • Injection of toxin I D • Produces redness/erythemati c in 2-4 days • No reaction – Protective immunity present. Dr.T.V.Rao MD 61
    62. 62. Dr.T.V.Rao MD 62
    63. 63. Epidemiology • • • • • • Eradicated in developed nations, Children between 2 – 5 years. A symptomatic carriers Person to person contact. Carriers spread. Prolonged contact. Dr.T.V.Rao MD 63
    64. 64. Prophylaxis • • • • • • Immunization Active – Passive Both passive and Active. Herd Immunity. Schick test Immunization with Antitoxin Dr.T.V.Rao MD 64
    65. 65. Active Immunization. • • • • • • • • • Toxoid – Toxin treated with Formaldehyde Absorbed Toxoid Given by Intramuscular route Given in DTP –Triple Vaccine Primary Immunization Three Doses of DPT at least 4 weeks apart. Non vaccinated Three doses of Toxoid four weeks apart One dose after One Year. Dr.T.V.Rao MD 65
    66. 66. Prevention Vaccination: Immunisation with diphtheria toxoid, combined with tetanus and pertussis toxoid (DTP vaccine), should be given to all children at two, three and four months of age. Booster doses are given between the ages of 3 and 5 . The child is given a further booster vaccine before leaving school and is then considered to be protected for a further 10 years (16 – 18 years). Dr.T.V.Rao MD 66
    67. 67. Passive Immunization • • • • • Given in Acute infections Give Subcutaneously 500 – 1000 Units of Antitoxin Given as Horse Serum Combined in Acute Infections ( Both Active Immunization with Toxoid and Antitoxin. Dr.T.V.Rao MD 67
    68. 68. FOR ADOLESCENTS AND ADULTS Td is a tetanus-diphtheria vaccine given to adolescents and adults as a booster shot every ten years, or after an exposure to tetanus under some circumstances. Tdap is similar to Td but also containing protection against pertussis. Tdap should be given as a one-time booster in place of Td. Tdap is especially important for those in close contact with infants. Dr.T.V.Rao MD
    69. 69. VACCINATION IN ADOLESCENTS Adolescents 11 through 18 years of age (preferably at age 11-12 years) and adults 19 years of age and older should receive a single dose of Tdap. Tdap should also be given to 7through 10-year-olds who are not Dr.T.V.Rao against pertussis. fully immunized MD
    70. 70. Vaccination in Pregnant Women Pregnant women should receive a dose of Tdap during each pregnancy, preferably at 27 through 36 weeks to maximize that amount of protective antibodies passed to the baby, but the vaccine can be safely given at any time during pregnancy. Dr.T.V.Rao MD
    71. 71. Some children should not get DTaP vaccine or should wait. Children with minor illnesses, such as a cold, may be vaccinated. But children who are moderately or severely ill should usually wait until they recover before getting DTaP vaccine. Any child who had a life-threatening allergic reaction after a dose of DTaP should not get another dose. Any child who suffered a brain or nervous system disease within 7 days after a dose of DTaP should not get another dose. Dr.T.V.Rao MD
    72. 72. Treatment • • • • • • • • • Antibiotic not useful in Acute infections, Antitoxin a must. Anti toxin obtained from horse serum Mild 20,000 to 40,000 Moderate 40,000 to 60,000 Severe 80,000 to 1,00,000 Commonly used antibiotics, Penicillin parentally, Oral Erythromycin Dr.T.V.Rao MD 72
    73. 73. Diphtheria Epidemiology Reservoir Transmission Human carriers Usually asymptomatic Respiratory Skin and fomites rarely Temporal pattern Winter and spring Communicability Up to several weeks without antibiotics Dr.T.V.Rao MD 73
    74. 74. Treating Contacts • All contacts are advised to receive 500 mg Erythromycin 4 times a day. Dr.T.V.Rao MD 74
    75. 75. Dr.T.V.Rao MD 75
    76. 76. Other Corynebacterium • • • • • • C.ulcerans Like C.diptheria Gravis type gelatin liquefied Transmitted through cows Milk Erythromycin effective. Diphtheria antitoxin is protective. Dr.T.V.Rao MD 76
    77. 77. Diptheroids • • • • • • Resembles C.diptheria Commensals in throat, skin, C.hofmani C.xerosi Propioniebacterium P.acnes P.granulosum Dr.T.V.Rao MD 77
    78. 78. • Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 78

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