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Diphtheria Dr. Harivansh Chopra, MD, DCH Professor,

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1 Diphtheria Dr. Harivansh Chopra, MD, DCH Professor,
Department of Community Medicine, LLRM Medical College, Meerut.

2 Objectives To study the epidemiology of Diphtheria.
To study the complications of diphtheria, and their management. To study the treatment and prevention of Diphtheria. Dr.Harivansh Chopra

3 Diphtheria Acute infectious disease characterised by liberation of an exotoxin resulting in: Formation of greyish / yellowish membrane (“false membrane”) over tonsils, pharynx, or larynx, with well-defined edges. Dr.Harivansh Chopra

4 Diphtheria Congestion, Oedema, or Local Tissue Destruction.
Regional lymphadenopathy (Bullneck). Toxemia. Child with bullneck diphtheria Dr.Harivansh Chopra

5 Problem Statement – World
Rare disease in most developed countries owing to vaccination. Global burden in 2002: 185,000 DALYs. 5000 deaths. Dr.Harivansh Chopra

6 Problem Statement – India
Endemic, with declining trend. 99.06% Dr.Harivansh Chopra

7 Diphtheria – Major Types
Anterior Nasal. Faucial. Laryngeal. Dr.Harivansh Chopra

8 Diphtheria – Other Types
Conjunctival. Skin. Genital. Dr.Harivansh Chopra

9 Diphtheria – Agent Factor
.Corynebacterium diphtheriae. Gram positive, Non-motile. Dr.Harivansh Chopra

10 Diphtheria – Agent Factor
. Types – Gravis. Mitis. Dr.Harivansh Chopra

11 Diphtheria – Agent Factor
. Types – Intermedius. May be – Toxigenic. Non-toxigenic – bacteriophage can convert them into toxigenic. C. diptheriae intermedius Dr.Harivansh Chopra

12 Diphtheria – Host Factors
Source of infection – Cases. Carriers – 95 carriers for 5 cases: Types – Temporary & Chronic. May be nasal or throat. Incidence is 0.1 – 5.0%. Dr.Harivansh Chopra

13 Diphtheria – Infective Material
Nasopharyngeal secretions. Discharge from skin lesions. Fomites – Throat spatulas. Utensils. Toys. Pencils. Dr.Harivansh Chopra

14 Period of Infectivity 14 – 28 days unless treated.
Carriers may remain infective for much longer period. Dr.Harivansh Chopra

15 Diphtheria – Portal of entry
Respiratory Route Non-Respiratory Route Dr.Harivansh Chopra

16 Mode of Transmission Droplet infection. Droplet nuclei.
Through infected cutaneous lesions. Through – Milk. Foods. Fomites. Dr.Harivansh Chopra

17 Incubation Period 2 – 6 days. Dr.Harivansh Chopra

18 Diphtheria – Environmental Factors
Transmission favoured in winter season. Dr.Harivansh Chopra

19 Diphtheria – Clinical Features
Anterior Nasal: More common in Infants. Rhinorrhoea – Discharge may be: Watery. Serosanguinous. Purulent. Foul-smelling. Dr.Harivansh Chopra

20 Diphtheria – Clinical Features
Anterior Nasal: White membrane. Delayed systemic manifestations. Dr.Harivansh Chopra

21 Diphtheria – Clinical Features
Pharyngeal/Tonsillar : Symptoms: Sore throat. 50% have fever. Few have dysphagia, hoarseness, malaise, or headache. Dr.Harivansh Chopra

22 Diphtheria – Clinical Features
Pharyngeal/Tonsillar : Signs: Unilateral or bilateral tonsillar membrane formation, which extends to cover uvula, soft palate, posterior oropharynx, hypopharynx, and glottis. Dr.Harivansh Chopra

23 Diphtheria – Clinical Features
Pharyngeal/Tonsillar : Signs: Soft tissue oedema. Enlarged lymph nodes, resulting in bull-neck appearance. Effort to remove membrane results in haemorrhage. Dr.Harivansh Chopra

24 Diphtheria – Clinical Features
Laryngeal: Noisy breathing. Stridor. Hoarseness of voice. Dry cough. Fever. May lead to asphyxia. Dr.Harivansh Chopra

25 Diphtheria – Clinical Features
Cutaneous: Ulcers around mouth and nose. Ulcers: Defined border. Membranous base. Dr.Harivansh Chopra

26 Diphtheria – Clinical Features
Conjunctival: Affects palpebral conjunctiva. Presentation: Oedematous. Membrane formation. Dr.Harivansh Chopra

27 Diphtheria – Clinical Features
Aural: Otitis externa. Discharge: Persistant. Purulent. Foul-smelling. Dr.Harivansh Chopra

28 Diphtheria – Diagnosis
Specimen: Nasal and throat swab, or any other muco-cutaneous lesion. Portion of membrane, and underlying exudate submitted. Laboratory notified to use selective media. Dr.Harivansh Chopra

29 Diagnosis Early diagnosis is important.
Diagnosis based on high suspicion in a child with: Sore throat. Dyspnea. Noisy breathing. Fever. Dr.Harivansh Chopra

30 Differential Diagnosis
Tonsillopharyngeal type: Acute streptococcal membranous tonsillitis. Viral membranous tonsillitis. Dr.Harivansh Chopra

31 Differential Diagnosis
Tonsillopharyngeal type: Herpes tonsillitis. Thrush. Infectious mononucleosis. Dr.Harivansh Chopra

32 Differential Diagnosis
Nasal type: Foreign body in the nose. Snuffle. Rhinorrhoea. Dr.Harivansh Chopra

33 Treatment Start treatment at earliest on clinical suspicion.
Don’t wait for the laboratory report. Dr.Harivansh Chopra

34 Treatment – Principles
Antitoxins – Neutralising circulating Toxins. Antibiotics – Eradicate Bacteria. Supportive Treatment. Manage Complications. Dr.Harivansh Chopra

35 Passive Immunisation – Immunoglobulins
ADS of horse origin. ADS of human origin. Dr.Harivansh Chopra

36 Dosage of antitoxin (equine)
Duration of disease 48 hours Lesions Throat Larynx Dose (I.U.) 20 000 – 40000 Must be used only after sensitivity test. Dr.Harivansh Chopra

37 Dosage of antitoxin (equine)
Duration of disease Over 48 hours Lesions Membrane in naso-pharynx Swelling in neck Extensive disease > 3 days Dose (I.U.) 40000 – 60000 80000 Must be used only after sensitivity test. Dr.Harivansh Chopra

38 Antitoxin Treatment – human
Dose: 0.6 ml/kg body weight Intramuscular (Available as 2ml vial with 300 mg Globulins). Advantage over ADS (horse origin): Hypersensitivity absent. Longer protection. Dr.Harivansh Chopra

39 Treatment Antibiotics: Dosage: No substitute to anti-toxin.
Stops production of more toxin. Dosage: Erythromycin: 40-50mg/kg/24 hrs. divided 6 hourly orally QID X 14 days. Dr.Harivansh Chopra

40 Treatment Dosage: Crystalline Penicillin G: 100,000 – 150,000 IU/kg/24 hrs in 4 – 6 divided doses I.V./I.M. X 14 days. OR Procaine Penicillin: 25,000 – 50,000 IU/kg/24 hrs in 2 divided doses IM X 14 days. Dr.Harivansh Chopra

41 Dr.Harivansh Chopra

42 Diphtheria Complication – Asphyxia
Obstruction of respiratory passage by membrane: Tachypnea. Stridor. Use of accessory muscles of respiration. Cyanosis. Dr.Harivansh Chopra

43 Treatment of Asphyxia Tracheostomy. Humidified air.
Dr.Harivansh Chopra

44 Diphtheria Complication – Myocarditis
In acute phase. Toxic cardiomyopathy occurs in approx 10-25% patients and is responsible for 50-60% of deaths. Usually in 2nd – 3rd week of illness. Dr.Harivansh Chopra

45 Treatment of Myocarditis
Bed rest, Avoid exertion. Restrict fluid and salt intake. Diuretics. May need sedation and oxygen. Digoxin in decompensated heart. Dr.Harivansh Chopra

46 Diphtheria Complication – Neurological involvement
Parallel the onset of primary infection. Multiphasic in onset: Time period Neurological involvement 2 – 3 weeks Palatal and pharyngeal paralysis 5th week Cranial neuropathies 10 days – 3 months Polyneuropathy Dr.Harivansh Chopra

47 Diphtheria Complication – Neurological involvement
Palatal and Pharyngeal paralysis: Swallowing difficulty. Nasal voice. Regurgitation through nose. Dr.Harivansh Chopra

48 Diphtheria Complication – Neurological involvement
Peripheral Neuropathy: Occurs 1 – 3 months after. Paraesthesia. Resolves completely. Dr.Harivansh Chopra

49 Treatment of Neurological complications
Nasogastric feeding. Treatment of general weakness. Dr.Harivansh Chopra

50 Case fatality rate With Treatment – <5% (Unchanged for the past 50 years). Without treatment – 10%. Dr.Harivansh Chopra

51 Prognosis Prognosis is associated with:
Virulence of organism: Gravis strain has poor prognosis. Age. Immunisation status. Site of infection. Dr.Harivansh Chopra

52 Prognosis Prognosis is associated with:
Speed of administration of toxin. Myocarditis, CHF. Poor respiratory monitoring. Phrenic nerve paralysis. Dr.Harivansh Chopra

53 Contact and Carrier Reported rates of carriage in household contacts of case patients are 0-25%. Risk of developing diphtheria after exposure: To case: approx. 2%. To carrier: approx. 0.3%. Dr.Harivansh Chopra

54 Management of contacts – Detection “Schick Test”
TEST ARM CONTROL ARM 0.2 ml of (1/50 MLD) of Schick Test Toxin ID. 0.2 ml of (1/50 MLD) of Schick Test Toxin ID inactivated by heat. Dr.Harivansh Chopra

55 Schick Test – Analysis of findings
Test Arm Control Arm Result No reaction Negative. Immunity to Diphtheria. 24-36 hrs. – Circumscribed red flush (10 – 50 mm). 4th-7th day – maximum size of rash. Thereafter – fades into brown patch, & desquamation. Positive. Susceptible to Diphtheria. Dr.Harivansh Chopra

56 Schick Test – Analysis of findings
Test Arm Control Arm Result Red flush of smaller size than positive reaction. Fades quickly by 4th day. Red flush exactly as test arm. Pseudo-positive. Allergic reaction. Positive reaction. Pseudo-positive reaction Combination reaction. Person susceptible but allergic. Dr.Harivansh Chopra

57 Management of Contacts – Treatment
Prophylactic Antibiotics – Given to all contacts, regardless of immunisation status. Erythromycin: 40-50mg/kg/24 hrs divided QID orally X 7 days (Max. 2gm/24 hrs). Benzathine Penicillin G: 600,000 U IM for <30kg, & 1,200,000 U IM for ≥30kg single dose. Dr.Harivansh Chopra

58 Management of Contacts – Treatment
Non-immunised Contacts: units of Diphtheria antitoxin. Actively immunised against diphtheria. Dr.Harivansh Chopra

59 Management of Contacts – Treatment
Immunised contacts: Booster dose, or Primary Immunisation within past 2 years. Booster dose, or Primary Immunisation more than 2 years ago. No action Required. Booster dose of dT. Dr.Harivansh Chopra

60 Management of Contacts – Surveillance
Medical surveillance of all contacts for 1 week after exposure. Bacteriological surveillance weekly for several weeks. Dr.Harivansh Chopra

61 Management of Carriers
Detection of carriers by nasal & throat swab examination. Age appropriate diphtheria toxoid given immediately if booster has not been given for past 1 year. Dr.Harivansh Chopra

62 Management of Carriers
Antibiotic Treatment: Erythromycin – 500mg QID X 7 days. Rifampicin – 600mg OD X 7 days. Bacteriological surveillance needed. Dr.Harivansh Chopra

63 Immunisation Does not prevent the occurrence of Carrier State.
Combined or mixed vaccines: DPT (Diphtheria-pertussis-tetanus). DT (Diphtheria-tetanus toxoid). dT (Diphtheria-tetanus, adult type). Dr.Harivansh Chopra

64 Immunisation Single vaccines: Antisera: FT (formal-toxoid).
APT (alum-precipitated toxoid). PTAP (purified toxoid aluminium phosphate). PTAH (purified toxoid aluminium hydroxide). TAF (toxoid-antitoxin floccules). Antisera: Diphtheria anti-toxin. Dr.Harivansh Chopra

65 DTP Vaccine Content (BE ltd.): Dose – 0.5 ml.
Diptheria toxoid ≥20Lf to ≤30Lf. Pertussis ≥4 IU. Tetanus toxoid ≥5Lf to ≤25Lf. Dose – 0.5 ml. Route – Deep intramuscular. Recommended site – Antero-lateral part of thigh. Dr.Harivansh Chopra

66 DTP vaccine – Schedule 1st dose – 6th week. 2nd dose – 10th week.
3rd dose – 14th week. 1st booster – months. 2nd booster – 4-5 years. Dr.Harivansh Chopra

67 DTP vaccine – Side-effects
Local swelling. Tenderness. Slight fever. Dr.Harivansh Chopra

68 DTP vaccine – Side-effects
Excessive somnolence. Protracted inconsolable crying. Neurological reactions: Convulsions. Encephalopathy. Dr.Harivansh Chopra

69 DTP vaccine – Contraindications
Acute febrile illness. Evolving or suspected neurological illness. Severe reaction to a prior dose of DPT. Dr.Harivansh Chopra

70 dT vaccine – Adult type Contains: Indications:
Diphtheria toxoid = 2lf. Tetanus toxoid. Indications: Non-immunised children > 7 years of age. Dr.Harivansh Chopra

71 dT vaccine – Adult type Dosage:
Two doses at an interval of 4 – 8 weeks. Booster: First, after 6 – 12 months. Second after 10 years. Dr.Harivansh Chopra

72 boostrix

73 Each 0.5mL dose contains: • ≥ 2 IU (2.5 Lf U) of diphtheria toxoid
• ≥ 20 IU (5 Lf U) of tetanus toxoid • 8 mcg of pertussis toxoid, 8 mcg of filamentous haemagglutinin and 2.5 mcg of pertactin

74 The inactive ingredients in the vaccine are:
Aluminium hydroxide, Aluminium phosphate, formaldehyde, phenoxyethanol, polysorbate 80, sodium chloride (salt), glycine and water.

75 Dosage and administration
A single intramuscular injection (0.5 mL). Suspension for injection in 0.5-mL single-dose vials or syringes.

76 Boostrix is the brand name for the Tdap vaccine, which is designed for teens and preteens aged 10 to 18 years old. Boostrix, which was approved for use in 2005 by the Food and Drug Administration (FDA), gives this age group protection against whooping cough (pertussis), tetanus and diphtheria.

77 It is at this age in particular that the protection received from vaccinations given in early childhood begins to wear off. The vaccine, which is currently made and marketed by GlaxoSmithKline, is recommended by the Society for Adolescent Medicine and the American Academy of Pediatrics (AAP).

78 BOOSTRIX is a vaccine indicated for active booster immunization against tetanus, diphtheria, and pertussis as a single dose. BOOSTRIX is approved for use in individuals 10 through 64 years of age.

79 contraindications Severe allergic reaction (e.g., anaphylaxis) to any component of BOOSTRIX. Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous pertussis antigen-containing vaccine.

80 Conclusions Diphtheria is a vaccine-preventable disease characterised by formation of a pseudo-membrane, tissue destruction, and lymph node enlargement. Early detection and treatment is essential to prevent life-threatening complications. Dr.Harivansh Chopra

81 Which of the following is not true for diphtheria
M.C.Q Which of the following is not true for diphtheria Diphtheria bacilli produces a powerful exotoxin The source of infection is either a case or a carrier Chronic carrier state may last up to 2 years Incubation period of diphtheria is 2-6 days Ans. 3. Dr.Harivansh Chopra

82 All of the following are true for diphtheria except
Immunization does not prevent carrier state. Unless treated, period of infectivity varies from 1-2 weeks from the onset of disease. Unapparent infections result in the development of immunity. 99% of children over the age of 5 years are immune to diphtheria usually. Ans. 2. Dr.Harivansh Chopra

83 It occurs in 10-25% patients of diphtheria
3. Which of the following is not true for toxic myocardiopathy of diphtheria It occurs in 10-25% patients of diphtheria It is responsible for 50-60% of deaths in diphtheria Elevation of serum Aspartate Aminotransferase concentration does not parallel the severity of myonecrosis All degree of heart blocks can occur in it Ans. 3. Dr.Harivansh Chopra

84 4. Cranial neuropathy in diphtheria occurs in 1st week of illness
3rd week of illness 5th week of illnees 6th week of illness Ans. 3. Dr.Harivansh Chopra

85 5. Which of the following is not true for diphtheria
Neurological complications are multiphasic in onset Cranial neuropathy lead to oculomotor & ciliary paralysis CSF findings can differentiate between polyneuropathy of diphtheria &GB syndrome Paralysis of diaphragm can occur Ans. 3. Dr.Harivansh Chopra

86 6. The prognosis of diphtheria depends on Virulence of the organism
Site of infection Speed of administration of antibiotic All of the above Ans. 4. Dr.Harivansh Chopra

87 7. Majority of deaths in diphtheria occur due to
Mechanical obstruction Myocarditis Both of the above None of the above Ans. 3. Dr.Harivansh Chopra

88 8. The dose of Antitoxin of human origin (Dipglobe) for the treatment of diphtheria
0.2 ml/kg 0.4 ml/kg 0.6 ml/kg 0.8 ml/kg Ans. 3. Dr.Harivansh Chopra

89 9. The management of asymptomatic case contact includes
Monitoring of individuals for 7 days Monitoring + culture of lesion Monitoring + culture + antimicrobial prophylaxis Monitoring + culture + antimicrobial prophylaxis + diphtheria toxoid vaccine irrespective of immunization status Ans. 3. Dr.Harivansh Chopra

90 10. Antimicrobial therapy in diphtheria can be given by
Erythromycin mg/kg/day for 14 days Crystalline Penicillin lac I.U./kg/day for 14 days Procaine Penicillin I.U./kg/day for 14 days Any of the above Ans. 4. Dr.Harivansh Chopra

91 Thank you Dr.Harivansh Chopra


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