Lec 8 B DIPHTHERIA , PERTUSSIS - MPH.ppt

DIPHTHERIA, PERTUSSIS Dr Khalid Shafi  Bull-neck appearance of diphtheritic cervical lymphadenopathy Diphtheria (Corynebacterium diphtheriae) Diphtherais Greek word for leather  INTRODUCTION  An acute toxic infection caused by Corynebacterium...

DIPHTHERIA, PERTUSSIS Dr Khalid Shafi  Bull-neck appearance of diphtheritic cervical lymphadenopathy Diphtheria (Corynebacterium diphtheriae) Diphtherais Greek word for leather  INTRODUCTION  An acute toxic infection caused by Corynebacterium diphtheriae and rarely toxigenic strains of Corynebacterium ulcerans  aerobic, nonencapsulated, non–spore-forming, mostly nonmotile, pleomorphic, gram-positive bacilli  Differentiation of C. diphtheriae from C. ulcerans is based on urease activity, C. ulcerans is urease-positive  Four C. diphtheriae biotypes - mitis, intermedius, belfanti, gravis; differentiated by colonial morphology, hemolysis, and fermentation reactions  INTRODUCTION  Diphtheritic toxin production occurs only after acquisition of a lysogenic Corynebacteriophage by either C. diphtheriae or C. ulcerans, which encodes the diphtheritic toxin gene and confers diphtheria-producing potential on these strains  Toxin is lethal in human beings in an amount 130μg/kg BW  EPIDEMIOLOGY  Transmission: airborne respiratory droplets, direct contact with respiratory secretions of symptomatic individuals, or exudates from infected skin lesions  Asymptomatic respiratory tract carriage is important in transmission. Where diphtheria is endemic, 3-5% of healthy individuals can carry toxigenic organisms.  Skin infection and skin carriage are silent reservoirs and organisms can remain viable in dust or on fomites for up to 6 months  Transmission through contaminated milk and an infected food handler has been documented  EPIDEMIOLOGY  Children aged 1-5yrs are commonly infected  A herd immunity of 70% is required to prevent epidemics  Contaminated objects like thermometers, cups, spoons, toys and pencils can spread the disease  Overcrowding, poor sanitation and hygiene, illiteracy, urban migration and close contacts can lead to outbreak PATHOGENESIS  Local effect of diphtheritic toxin:  Paralysis of the palate and hypopharynx  Pneumonia  Systemic effects (Toxin absorption ):  kidney tubule necrosis  hypoglycemia  myocarditis and/or demyelination of nerves  Myocarditis:10-14 days  Demyelination of nerves: 3-7 weeks  CLINICAL MANIFESTATIONS  Influenced by the anatomic site of infection, the immune status of the host and the production and systemic distribution of toxin  Incubation period: 1-6 days  Classification (location):  nasal  pharyngeal  tonsillar  laryngeal or laryngotracheal  skin, eye or genitalia  CLINICAL MANIFESTATIONS  Nasal diphtheria: Infection of the anterior nares- more common among infants, causes serosanguineous, purulent, erosive rhinitis with membrane formation  Shallow ulceration of the external nares and upper lip is characteristic  Unilateral nasal discharge is quite pathognomic of nasal diphtheria  Accurate diagnosis of nasal diphtheria delayed-paucity of systemic signs and symptoms  Tonsillar and pharyngeal diphtheria: sore throat is the universal early symptom  Only half of patients have fever and fewer have dysphagia, hoarseness, malaise, or headache  Mild pharyngeal injection unilateral or bilateral tonsillar membrane formation extend to involve the uvula, soft palate, posterior oropharynx, hypopharynx, or glottic areas  Underlying soft tissue edema and enlarged lymph nodes: bull- neck appearance  Laryngeal diphtheria: At significant risk for suffocation because of local soft tissue edema and airway obstruction by the diphtheritic membrane  Classic cutaneous diphtheria is an indolent, nonprogressive infection characterized by a superficial, ecthymic, nonhealing ulcer with a gray-brown membrane Infection at Other Sites: ear (otitis externa), the eye (purulent and ulcerative conjunctivitis), the genital tract (purulent and ulcerative vulvovaginitis) and sporadic cases of pyogenic arthritis Diagnosis  Clinical features  Culture: from the nose and throat and any other mucocutaneous lesion. A portion of membrane should be removed and submitted for culture along with underlying exudate  Elek test: rapid diagnosis (16-24 hrs)  Enzyme immunossay  PCR for A or B portion of the toxic gene “tox”  Hypoglycemia, glycosuria, BUN, or abnormal ECG for liver, kidney and heart involvement Differential diagnosis: 1. Common cold 2. Sinusitis 3. Adenoiditis and foreign body in nose 4. Streptococcal pharyngitis 5. Infectious mononucleosis  COMPLICATIONS 1. Respiratory tract obstruction by pseudomembranes: bronchoscopy or intubation and mechanical ventilation 2. Toxic Cardiomyopathy: -in 10-25% of patients -responsible for 50-60% of deaths -the risk for significant complications correlates directly with the extent and severity of exudative local oropharyngeal disease as well as delay in administration of antitoxin -Tachycardia out of proportion to fever -prolonged PR interval and changes in the ST-T wave -Elevation of the serum aspartate aminotransferase concentration closely parallels the severity of myonecrosis 3. Toxic Neuropathy:  Acutely or 2-3 wk after: hypoesthesia and soft palate paralysis  Afterwards weakness of the posterior pharyngeal, laryngeal, and facial nerves : a nasal quality in the voice, difficulty in swallowing and risk for aspiration  Cranial neuropathies (5th wk): oculomotor and ciliary paralysis- strabismus, blurred vision, or difficulty with accommodation  Symmetric polyneuropathy (10 days to 3 mo): motor deficits with diminished deep tendon reflexes  Monitoring for paralysis of the diaphragm muscle Recovery from the neuritis is often slow but usually complete. Corticosteroids are not recommended.  TREATMENT 1. Antitoxin:  Mainstay of therapy  Neutralizes only free toxin, efficacy diminishes with elapsed time  Antitoxin is administered as a single empirical dose of 20,000- 120,000 U based on the degree of toxicity, site and size of the membrane, and duration of illness 2. Antimicrobial therapy  Halt toxin production, treat localized infection and prevent transmission of the organism to contacts  erythromycin (40-50 mg/kg/day 6 hrly [PO] or [IV]), aqueous crystalline penicillin G (100,000-150,000 U/kg/day 6 hrly IV or [IM]), or procaine penicillin (25,000-50,000 U/kg/day 12 hrly IM) for 14 days  Elimination of the organism should be documented by negative results of at least 2 successive cultures of specimens from the nose and throat (or skin) obtained 24 hr apart after completion of therapy  Prognosis: depends on the virulence of the organism (subspecies gravis), patient age, immunization status, site of infection and speed of administration of the antitoxin  The case fatality rate of almost 10% for respiratory tract diphtheria  At recovery, administration of diphtheria toxoid is indicated to complete the primary series or booster doses of immunization, because not all patients develop antibodies to diphtheritic toxin after infection  PREVENTION Asymptomatic Case Contacts:  Antimicrobial prophylaxis -erythromycin (40-50 mg/kg/day divided qid PO for 10 days) or a single injection of benzathine penicillin G (600,000U IM for patients 2 weeks with or without whoop and/or post-tussive vomiting is the hallmark feature of pertussis  Stage III (convalecence stage): period of gradual recovery even up to 6 months  COMPLICATIONS 1. Secondary pneumonia (1 in 5) and apneic spells (50%; neonates and infant