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Diptheria update

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Information about Diptheria update
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Published on February 17, 2014

Author: doctorrao

Source: authorstream.com

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Diphtheria an update : Diphtheria an update Dr.T.V.Rao MD Dr.T.V.Rao MD PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 5 Definition Diphtheria is an acute, toxin-mediated disease caused by toxigenic Corynebacterium diphtheria. It ’ s a very contagious and potentially life-threatening bacterial disease. Dr.T.V.Rao MD PowerPoint Presentation: 6 Definition It ’ s a localized infectious disease, which usually attacks the throat and nose mucous membrane Dr.T.V.Rao MD PowerPoint Presentation: 7 Etiology C. diphtheriae is an aerobic gram-positive bacillus. Pleomorphic, club-end Non-spore-forming Non-acid-fast Non-motile Dr.T.V.Rao MD PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Fauces ( throat ) Fauces : - two pillars of mucous membrane. Anterior : known as the palatoglossal arch and Posterior : the palatopharyngeal arch Between these two arches is the palatine tonsil . Dr.T.V.Rao MD 11 PowerPoint Presentation: Typical Presentation of Bull Neck Dr.T.V.Rao MD 12 PowerPoint Presentation: Local manifestation Depend on the site of lesion: Nasal diphtheria : Unilateral or bilateral serosanguineous ( blood and serous fluid ) discharge from the nose Excoriation of upper lip Toxemia is minimal Faucial diphtheria : Redness and swelling over Fauces Exudates on the tonsils coalesces to form grayish white pseudo membrane Regional lymph nodes are inflamed Sore throat and dysphagia Dr.T.V.Rao MD 13 PowerPoint Presentation: Dr.T.V.Rao MD 14 PowerPoint Presentation: 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 PowerPoint Presentation: Dr.T.V.Rao MD 16 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Gram +ve Bacilli and Colonies Dr.T.V.Rao MD 19 PowerPoint Presentation: 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 Culturing PowerPoint Presentation: 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 PowerPoint Presentation: Commonly used medium Tellurite blood agar Contains tellurite 0.04 tellurite Inhibits other bacteria Produce Grey/Black colonies. Dr.T.V.Rao MD 22 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Activation of Diphtheria Toxin A A B B A B A B Dr.T.V.Rao MD 28 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Antigenic structure Gravis 13, Intermedius 4 Mitis 40 Bacteriophage typing 15 types Dr.T.V.Rao MD 31 PowerPoint Presentation: Resistance Can be killed at 58 0 c in 10 mt 100 0 c in 1 mt Survive in Blankets, Floor dust, toys inanimate objects Dr.T.V.Rao MD 32 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Diphtheria Nasopharyngeal diphtheria Pharyngeal Laryngeal Cutaneous diphtheria Systemic complications DIAGNOSIS MUST BE CLINICAL!!!! Dr.T.V.Rao MD 36 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Thick Membrane Dr.T.V.Rao MD 40 PowerPoint Presentation: Dr.T.V.Rao MD 41 PowerPoint Presentation: Pseudo membrane Dr.T.V.Rao MD 42 PowerPoint Presentation: Skin Lesions Dr.T.V.Rao MD 43 PowerPoint Presentation: 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 PowerPoint Presentation: Complications Asphyxia - causing mechanical obstruction. May need tracheotomy Circulatory failure. Post Diphtheria paralysis Dr.T.V.Rao MD 45 PowerPoint Presentation: Non toxigenic clinical manifestations Bacteria can produce 1. Endocarditis, 2.Meingitis, 3 Cerebral abscess. 4 Osteoarthritis. Dr.T.V.Rao MD 46 PowerPoint Presentation: Dr.T.V.Rao MD 47 PowerPoint Presentation: Dr.T.V.Rao MD PowerPoint Presentation: Dr.T.V.Rao MD 49 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Dr.T.V.Rao MD 52 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Toxigenicity Tests In Vitro Elek test In Vivo Animal inoculation rabbit skin test-necrosis guinea pig challenge test- lethal low [Fe 2+] induces toxin Dr.T.V.Rao MD 57 PowerPoint Presentation: Dr.T.V.Rao MD 58 PowerPoint Presentation: Schick Tes t ( 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 PowerPoint Presentation: 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 4 th 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, susceptible and need vaccination Dr.T.V.Rao MD 60 PowerPoint Presentation: Schick Test Injection of toxin I D Produces redness/erythematic in 2-4 days No reaction – Protective immunity present. Dr.T.V.Rao MD 61 PowerPoint Presentation: Dr.T.V.Rao MD 62 PowerPoint Presentation: 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 PowerPoint Presentation: Prophylaxis Immunization Active – Passive Both passive and Active. Herd Immunity. Schick test Immunization with Antitoxin Dr.T.V.Rao MD 64 PowerPoint Presentation: 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 PowerPoint Presentation: 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 PowerPoint Presentation: 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 FOR ADOLESCENTS AND ADULTS: 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 VACCINATION IN ADOLESCENTS: 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 7- through 10-year-olds who are not fully immunized against pertussis. Dr.T.V.Rao MD Vaccination in Pregnant Women : 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 Some children should not get DTaP vaccine or should wait.: 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 PowerPoint Presentation: 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 PowerPoint Presentation: Diphtheria Epidemiology Reservoir Human carriers Usually asymptomatic Transmission Respiratory Skin and fomites rarely Temporal pattern Winter and spring Communicability Up to several weeks without antibiotics Dr.T.V.Rao MD 73 PowerPoint Presentation: Treating Contacts All contacts are advised to receive 500 mg Erythromycin 4 times a day. Dr.T.V.Rao MD 74 PowerPoint Presentation: Dr.T.V.Rao MD 75 PowerPoint Presentation: 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 PowerPoint Presentation: Diptheroids Resembles C.diptheria Commensals in throat, skin, C.hofmani C.xerosi Propioniebacterium P.acnes P.granulosum Dr.T.V.Rao MD 77 PowerPoint Presentation: 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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