1. CORYNEFORM BACTERIA

2. Diphteroids  Pleomorphic gram-positive rods.  Club Shaped (Chinese Letter like, V forms)  Catalase +ve  Non sporing  Non acid fast

3. Diphteroids (Continued)  Commensals of the throat and skin of low pathogenicity.  Morphologically similar to the pathogenic C.diphtheriae.  Can be found as contaminants of blood cultures and CSF.  Can cause opportunestic infections in Immunosupressed patients.

4. Corynebacterium diphtheriae (diphtheria)  Local infection of the throat with grayish adherent exudate (Pseudomembrane) and generalized toxaemia due to production and dissemination of a highly potent toxin.

5. Etiology Corynebacterium diphtheriae 3 Types of Colony:  Mitis (Mild disease)  Intermedius (Intermediate dis.)  Gravis (severe)  Strains may be toxegenic or non-toxegenic.  Production of toxin is mediated by bacteriophage (β phage) infection of the bacterium.

6. Etiology Corynebacterium diphtheriae (Continued)  The demonstration of toxin production is essential to differentiate toxegenic from commensal corynebacteria.  Toxogenicity is demonstrated by the agar gel precipitation (Elek) test or by the polymerase chain reaction (PCR).

7. Clinical Manifestation Usually gradual onset of local infection.  Membranous nasopharyngitis  Obstructive laryngotrachitis  With low grade fever  Malaise  Fatigue  Sore throat

8. Grey tonsillar membrane in acute diphtheria

9. Clinical Manifestation (Continued) Clinically:  Nasal diph.thick nasal discharge (intoxication rare)  Pharyngial thick, adherent pseudomembrane (intoxication common)  (tonsillar) Odema, Heat + Tenderness of tissue of neck (Bull neck)  Laryngial extension of membrane (asphyxia) (asphyxia)

10. Clinical Manifestation (Continued) Less Commonly:  Cutanous  Vaginal  Conjunctival or otic

11. Clinical Manifestation (Continued) Life threating complication include:  Upper airway obstruction (extension of membrane)  Myocarditis (heart failure)  Neurologic Peripheral neuritis  Vocal cord paralysis  Ascending paralysis  Difficulty in swallowing  Visual disturbance

12. Epidemiology  Humans are the only reservoir.  Sources of Infections:  Discharges from nose, throat, eye and skin lesions of infected patients or carriers (direct contact)  Most common in low socioeconomic groups in crowded conditions.  Since 1990 – epidemics in Soviet Union, Russia with 50,000 cases – 1750 deaths.

13. Epidemiology (Continued)  Case fatality 3% - 23%  Children are susceptable after 3-6 months (highest incidence).  Latent skin infection immunity.  Communicability 2 weeks (untreated person) <4 days (treated patients) <4 days (treated patients)  Incubation Period is 2- 5 days.

14. Pathogenesis Powerful exotoxin ( blood stream):  Toxin local and systemic toxicity (toxin mediated disease)  Cause of mortality in clinical diphtheria.  Affinity for heart muscles, nerve endings and adreral glands.  Produced by β phage infected C.diphtheriae.

15. Pathogenesis (Continued)  Rapidly diffused from local lesion irreversibly bound to tissues.  ADP ribosylating toxin protein synthesis inhibition cell death necrosis and neutroxic effects.  Bacilli (local effect), no deep penetration to blood or underlying tissue.  Inflammatory exudate and necrosis of pharyngeal muscles respiratory obstruction.

16. Diagnosis Clinical diagnosis:  Lab should not delay management.  Specimen for culture  Nose From both  ThroatPatient and carrier  Lesions

17. Elek plate demonstrating toxin from Corynebacterium diphtheriae

18. Diagnosis (Continued) Direct stained smear unreliable (Commensals)  Special media (Potassium -tellurite) and enriched Loefflers slope (selective) grey black colonies.  Albert stain metachromatic granules.  Toxogenicity test (Elek test, PCR) is most important, guinea pig inoculation.  Elek test: agar gel precipitation.

19. Management Patient:  Fatality with delay (0 -20%) 1- Antitoxin   Equine antitoxin – neutralize the toxin   Start soon if clinically suspected. 2- Isolation of the patient (droplet precautions) 3- Antibiotics (no effect on toxin) to eradicate organism and prevent spread (a) Penicillin – oral (b) Erythromycin

20. Management (Continued) 3- Contacts (Close)   Investigated for signs of disease Carriage (nose, throat)   Chemoprophylaxis (erythromycin)   Immunization of susceptiable contacts (diph. toxoid)   Carriers isolated and treated.

21. Prevention and Control  Universal immunization with diph. toxoid the only effective control measure.  High immunization rate among children (3 doses of DPT + 2 boosters at 2 month age)  Regular booster (Td every 10 years).  Vaccine = formalin treated toxin – highly antigenic, not toxic.