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PRE TEST Diphtheria has been eradicated

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Presentation on theme: "PRE TEST Diphtheria has been eradicated"— Presentation transcript:

1 DIPHTHERIA The Past, Present & the Future Dr Cummings Henry Consultant Paediatrician DELSUTH

2 PRE TEST Diphtheria has been eradicated
The is a resurgence of diphtheria The mainstay of treatment is antibiotics Vaccination remain the most effective control measure.

3 Outline The Past The Present The future

4 Diphtheria, The Past: Introduction Epidemiology Aetio-pathogenesis
Immunology Clinical Presentation Complications Differentials Investigations Treatment Prognosis Prevention

5 Introduction An ancient disease described by Hippocrates in the 5th century BC Plagued Europe & the American colonies in the 18th century Diphtheria is an acute toxic infectious disease A localized infection of mucous membrane &/or skin May have systemic complications/manifestations

6 Epidemiology Reservoir - Exclusively in humans
- Skin infection and skin carriage constitute silent reservoir Mode of spread * primarily by airborne respiratory droplets * direct contact with; -respiratory secretions of infected individuals -exudates from infected skin lesions

7 Epidemiology contd. In the U.S
- Pre-vaccination era(1920s) > 115,000 cases and 10,000 deaths reported annually - Recently, < 5 cases are reported annually In Nigeria - 5,039 cases reported in 1989 - 3,995 cases in 2000 - 2,468 cases in 2001 cases in 2006 (7.8% of global report)


9 Epidemiology contd. Carriers are important in transmission constitute 3-5% of healthy individuals in endemic region Estimated mortality rates→5-10% (up to 20% in <5yrs, & > 40yrs)

10 Epidemiology contd. Sex
No significant difference in the incidence in males & females of similar immunization status Age - Commoner in 6month-12yrs (esp. in the pre-vaccination era)

11 Risk factors Incomplete or absent immunization Low herd immunity
Travel to endemic areas or regions with current epidemic Immunocompromised states e.g. HIV/AIDS Low socio-economic status Poor health care facilities Overcrowding

12 Aetio-pathogenesis Caused by toxigenic Corynebacterium diphtheriae
Types - Corynebacterium diphtheriae * mitis * intermedius * belfanti * gravis - Corynebacterium ulcerans- causes cutaneous disease

13 Characteristics Gram positive Club-shaped bacillus Aerobic Non-motile
Non-encapsulated About 2-4μm in length Assume L &/or V configuration to each other Form a Chinese lettering pattern

14 Corynebacterium diphtheria

15 Corynebacterium diphtheria
Gram stain Methylene blue stain

16 Virulence Depends on the ability to produce the diphtheria toxin-an exotoxin Toxigenicity depends on the presence of a lysogenic bacteriophage Non-toxigenic strain can become toxigenic by coming in contact with toxigenic strains

17 B-phage that carries the tox gene that encodes the diphtheria toxin

18 The Exotoxin A 62,000 dalton polypeptide
Composed of 2 joined major segments (A and B)

19 Actions of the Toxin Segment B bind receptors on susceptible cells and facilitate entrance of segment A Segment A mediates toxic actions: - inactivates RNA translocase - inhibits protein synthesis - causing tissue necrosis

20 Actions of The Toxin contd.
Formation of pseudomembrane * a dense necrotic coagulum of organism, epithelial cells, fibrin, leucocytes & RBCs * grayish-white or brown in colour

21 The Pseudomembrane Histological Gross

22 Other effects of the toxin
Paralysis of palate & hypopharynx Systemic absorption: - renal tubules necrosis - thrombocytopenia - cardiomyopathy - demyelination of nerves - paralysis of the diaphragm The toxin is converted to toxoid (for vaccination) when treated with formalin

23 Immunology Organisms invasion usually remain localized
The main immune response is to the exotoxin Immune response is antibody-mediated The antibody is of the IgG type – Antitoxin Immunity does not prevent colonization rather it protects against the effects of the toxin

24 Immunology Contd. Active antibodies production may be induced by:
- active disease - carrier state - vaccination with the toxoid Passive immunity –transplacentally transferred Immunity was previously thought to be life long

25 Assessment of immunity
The Schick test: - Intradermal injection of 0.1ml 1:50 dilution of toxin - positive result: inflammation appearing after 24-36hrs & persisting for ≥ 4days – no antitoxin – no immunity - negative result – has antitoxin - immune

26 Immunity assessment contd.
Assay of serum level of antitoxin - full protection: ≥0.1IU/mL - basic protection: ≥0.01- <0.1IU/mL - no protection : < 0.01IU/mL N.B: Epidemic outbreak is likely when > 90% of the population has < 0.01IU/mL of antitoxin

27 Clinical Presentation
Incubation: usually 2-4days with a range of 1-7days Classified into: - Respiratory Tract Diphtheria - Non-Respiratory Tract disease - Complicated disease

28 Respiratory tract diphtheria
Nasal Diphtheria - commoner in infants - little or no constitutional symptoms - serosanguineous nasal discharge - epistaxis

29 Nasal Diphtheria contd.
- purulent foul smelling discharge - shallow ulcers +/- pseudomembrane - unilateral or bilateral - may persist for several weeks - major source of transmission

30 Tonsilo-Pharyngeal Most common (90% of cases) Malaise
Fever – mild to moderate Sore throat – drooling, odynophagia +/- dysphagia Bull-neck appearance Pseudomembrane of variable extent

31 Bull-Neck appearance

32 Pseudomenbrane

33 Laryngeal Diphtheria Usually an extension of pharyngeal disease
Hoarseness of voice Cough Inspiratory stridor

34 Laryngeal Diphtheria contd.
Suprasternal, substernal & subcostal recessions Symptoms & signs of sudden airway obstruction Sudden death May require intubation/tracheotomy

35 Tracheo-bronchial diphtheria
Usually an extension from pharynx & larynx Diphtheria pneumonia – hemorrhagic Bronchiolar pseudomembrane Airway obstruction/sudden death

36 Diphtheria Pneumonia

37 Non-Respiratory disease

38 Cutaneous diphtheria

39 Cutaneous diphtheria superficial, non-healing ulcers
well defined margins pseudomembrane on floor of ulcer erythema & tenderness of surrounding skin important in transmission in the community

40 Cutaneous diphtheria contd.
Predisposing factors: - pre-existing dermatoses - laceration - burns - bites - impetigo

41 Other non-respiratory disease
Ear- otitis externa Eye – purulent and ulcerative conjunctivitis Genital tract – purulent and ulcerative vulvo-vaginitis Rarely septicaemia

42 Complications Toxic Cardiomyopathy
- commonly myocarditis, rarely endocarditis - usually occurs at the end of 2nd wk of illness - tachycardia out of proportion to fever - arrhythmias - symptoms & signs of CCF - occurs in 10-25% of patients - accounts for 50-60% of deaths

43 Toxic Cardiomyopathy contd.
ECG findings: - prolonged PR interval - ST segment elevation - 1st, 2nd, or 3rd degree heart block Echocardiogram: - dilated cardiomyopathy - hypertrophic cardiomyopathy - vegetations

44 Toxic Neuropathy Usually occurs at 3-4wks
Affects mainly motor functions Paralysis of soft palate &pharyngeal wall - nasal voice - difficulty in swallowing (esp. fluids)

45 Toxic Neuropathy contd.
Occulomotor N. & cillary paralysis - strabismus &/or blurred vision Peripheral neuritis – diminished DTR & paralysis - occasionally glove & stockings neuropathy ( like GBS) Paralysis of the diaphragm

46 Airway obstruction Commoner in laryngeal disease May be sudden
Usually due to dislodgement of Pseudomembrane May require intubation/tracheotomy & mechanical ventilation

47 Differentials Tonsillo-Pharyngitis Viral Croup Epiglottitis
Peritonsilar abscess Angioedema Myocarditis (other causes) Peripheral neuropathy 2o GBS

48 Laboratory Studies Methylene blue &/or gram staining
Culture using tellurite-Loeffler media Toxigenicity test: - Elek test - PCR

49 Laboratory studies contd.
FBC – moderate leucocytosis Urinalysis – transient proteinuria Serum assay of antibodies – immunity Serum assay of troponin 1 – myocarditis

50 Radiological studies Echocardiogram & ECG findings
Neck soft tissue X-ray – prevertebral soft tissue swelling:

51 Treatment Diphtheria Antitoxin - mainstay of treatment
- give at clinical diagnosis - can only neutralize free toxins - efficacy diminishes with delay - only available from CDC/WHO - preferably given IV - dosage depends on site involved & duration of illness

52 Dosage of Antitoxin (units)
Site and extent of lesion illness<72hrs illness >72hrs Nasal ,000-20, ,000-20,000 One tonsil , ,000-40,000 Both tonsils+/- Pharyngeal ,000-40, ,000-60,000 Laryngeal or Combined types ,000-80, ,000-80,000 Very extensive Disease ,000-80, , ,000 N.B. Test for sensitivity before administration and desensitized if necessary

53 Testing for Sensitivity
Skin test: - Intradermal injection of 0.1mL of 1:10 dilution of antiserum in saline - read in 20mins - a wheal ≥ 1cm – positive – sensitive Conjunctiva test: - conjunctivitis & lacrimation – positive Caution! Ensure adrenalin is available

54 Desensitizing 0.1ml of a 1:20 dilution subcut. - wait 20mins 0.1ml of a 1:10 dilution subcut. - wait 20mins 0.1 ml undiluted subcut wait 20mins 0.3ml undiluted IM wait 20mins 0.5ml undiluted IM wait 20mins If no reaction has occurred the rest of the dose can be given IM

55 Antimicrobial therapy
Role: - halt toxin production - treat localized infection - prevent transmission Drugs/dosage - IV/IM penicillin * iv xtapen 100,000/kg/day in 6hrly dosing * im procaine pen. 25,000iu/kg/day, 12hrly - Oral erythromycin, 40mg/kg/day 6hrly

56 Antimicrobial contd. Other drugs that can be used: - Clindamycin
- Tetracycline Give for 10 – 14 days Elimination of organism should be confirmed by at least 2 successive negative culture obtained 24hrs apart.

57 Treatment contd. Isolation
- respiratory isolation for respiratory disease - contact isolation for cutaneous disease Bed rest Secure airway if necessary NG tube feeding – palatal/pharyngeal paralysis

58 Treatment contd. IV fluid administration if needed
Vaccinate – 10 series &/or boosters Disease notification Contact tracing

59 Contact tracing & Care The risk of developing the disease after household exposure to a case is ≈ 2% The risk of disease after exposure to a carrier is ≈ 0.3% Types of contacts: - asymptomatic case contact - carrier

60 Asymptomatic case contact
monitor for illness culture Antimicrobial prophylaxis Vaccinate primary schedule. booster dose

61 Carrier The reported rate of carriage in household contacts of case patients is 0-25% Antimicrobial prophylaxis x 7days Isolation Monitor Vaccination

62 Prognosis Depends on: Virulence of the organism. Gravis has the highest fatality followed by intermedius and the least is mitis. Age; higher mortality rates in individuals < 5yrs and those > 40yrs. Immunization status: worse in the unimmunized

63 Prognosis (contd.) Site of infection/involvement; mortality occur in:
< 1% of cutaneous disease ≈ 10% of uncomplicated respiratory disease 30 – 40% of bacteremic disease % of those with cardiac involvement. Speed of administration of antitoxin; worse with delay

64 Prevention Immunization is the mainstay of prevention Given as DPT
Immunization schedule (NPI) - DPT1 – 6wks - DPT2 – 10wks - DPT3 – 14wks

65 The Present

66 Emerging Issues Changing epidemiology
- recent re-emergence in some developed and developing countries - Shifting of the disease into the older population


68 Immunity wanes over time


70 Other Epidemiological issues
Questionable Notification from Nigeria Erratic values: - In 1996 reported cases - In ,, cases *DPT3 coverage in 1996 – 30%

71 Inconsistent figures In 2003 & 2004 – no case reported
* In 2003 Nigeria had the worst immunization coverage in the world DPT1 coverage – 43.2% DPT3 coverage – 24.8% Only 12.8% were fully immunized

72 Latest Immunization Coverage
Global: 79% estimated DPT3 coverage Current coverage in Nigeria: - DPT1 is ≈ 65% - DPT3 is ≈ 77% WHO proposed coverage is ≥ 90%



75 Changes In Immunization strategies
Effect of passive immunity on 10 series Commencing 1O series later e.g. - In the US DPT1 – 2mth DPT2 – 4mth DPT2 – 6mth

76 New Immunization Strategies contd.
Boosters: - Given at *18mths *5yrs *adolescence *every 10yrs thereafter


78 New Formulations of the Toxoid
Td - tetanus toxoid with lower dose of diphtheria toxoid - adult type *for adolescence & beyond - less side effects Tdap - tetanus toxoid + smaller dose diphtheria + acellular pertusis vaccine - may be used for pregnant women

79 Other Emerging Issues Antitoxin for Carriers:
* To give or not to give ? The need for vaccination of pregnant women

80 The Future

81 Recommendations Improve coverage of 10 schedule to 90% at least
4th & 5th DPT doses at 18mths & 5yrs respectively Improve disease Surveillance and notification

82 Recommendations contd.
Research to evaluate the need to - delay commencement of the primary series - give booster doses at adolescence & thereafter every 10yrs, using Td - give Td or Tdap to pregnant women

83 Conclusion The global goal is to eradicate diphtheria. This may only be achieved by not only making the right policies but also ensuring that these policies are completely and effectively implemented.


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