Diphtheria Dr. Harivansh Chopra, MD, DCH Professor, Department of Community Medicine, LLRM Medical College, Meerut. harichop@gmail.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Incubation Period 2 – 6 days. Dr.Harivansh Chopra

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 – 120000 Must be used only after sensitivity test. Dr.Harivansh Chopra

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

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

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

Dr.Harivansh Chopra

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Management of Contacts – Treatment Non-immunised Contacts: 1000-2000 units of Diphtheria antitoxin. Actively immunised against diphtheria. Dr.Harivansh Chopra

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

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

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

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

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

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

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

DTP vaccine – Schedule 1st dose – 6th week. 2nd dose – 10th week. 3rd dose – 14th week. 1st booster – 18-24 months. 2nd booster – 4-5 years. Dr.Harivansh Chopra

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

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

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

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

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

boostrix

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

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

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

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.

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).

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.

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.

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

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

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

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

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

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

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

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

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

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

10. Antimicrobial therapy in diphtheria can be given by Erythromycin 40-50 mg/kg/day for 14 days Crystalline Penicillin 1-1.5 lac I.U./kg/day for 14 days Procaine Penicillin 25000 -50000 I.U./kg/day for 14 days Any of the above Ans. 4. Dr.Harivansh Chopra

Thank you Dr.Harivansh Chopra