DIPHTHERIA, PERTUSSIS & TETANUS

Dr Sarika Gupta, Asst. Professor

Diphtheria (Corynebacterium diphtheriae) Diphtherais Greek word for leather

Bull-neck appearance of diphtheritic cervical lymphadenopathy

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

Demonstration of diphtheritic toxin production or potential for toxin production by an isolate is necessary to confirm disease

The former is done in vitro using the agar immunoprecipitin technique (Elek test) or in vivo with the toxin neutralization test in guinea pigs, the latter by polymerase chain reaction testing for carriage of the toxin gene

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

Diphtheria is endemic in INDIA. 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. Congenital syphilis snuffle

3. Sinusitis

4. Adenoiditis and foreign body in nose

5. Streptococcal pharyngitis

6. 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 <30 kg, 1,200,000U IM for patients ≥30 kg)

Diphtheria toxoid vaccine-to immunized individuals who have not received a booster dose within 5 yr. Children who have not received their 4th dose should be vaccinated. Those who have received fewer than 3 doses of diphtheria toxoid or who have uncertain immunization status are immunized with an age-appropriate preparation on a primary schedule

Asymptomatic Carriers: Same+Repeat cultures are performed about 2 wk after completion of

therapy. if results are positive, an additional 10-day course of oral erythromycin should be given and follow-up cultures performed

VACCINE

Whooping cough: whooping sound made when gasping for air after a fit of coughing

Cough of 100 days

PERTUSSIS (WHOOPING COUGH)

INTRODUCTION

A highly contagious acute bacterial infection caused by the bacilli Bordetella pertussis

Currently worldwide prevalence is diminished due to active immunization

However it remains a public health problem among older children and adults

 It continues to be an important respiratory disease afflicting unvaccinated infants and previously vaccinated children and adults (waning immunity)

EPIDEMIOLOGY

Transmission: through the respiratory route in the form of droplet infection

Adolescents and adults are the reservoir. No animal or insect reservoir

A highly communicable disease. SAR 80% among households contacts

In the catarrhal stage and 2 weeks after the onset of cough

ETIOLOGY

Bordetella pertussis – aerobic gram-negative coccobacilli Produces toxins namely pertussis toxin, filamentous

hemagglutinin, hemolysin, adenylate cyclase toxin, dermonecrotic toxin and tracheal cytotoxin- responsible for clinical features (toxin mediated disease) and the immunity

PATHOGENESIS

CLINICAL MANIFESTATIONS

Incubation period: 7-10 days Infection lasts for 6 weeks – 10 weeks Stage I (catarrhal stage; 1-2 weeks): insidious onset of

coryza, sneezing, low grade fever and occasional cough Stage II (paroxysmal cough stage; 1-6 weeks): due to

difficulty in expelling the thick mucous form the tracheobronchial tree

At the end of paroxysm long inspiratory effort is followed by a whoop

In between episodes child look well. During episode of cough the child may become cyanosed, followed by vomiting, exhaustion and seizures

CLINICAL MANIFESTATIONS

Cough increase for next 2-3 weeks and decreases over next 10 weeks

Absence of whoop and/or post-tussive vomiting does not rule out clinical diagnosis of pertussis

paroxysmal cough>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<6 months of age)

2. Neurological complications: seizures (1 in 100) and encephalopathy (1 in 300) due to the toxin or hypoxia or cerebral hemorrhage

3. Otitis media, anorexia and dehydration, rib frcture, pneumothorax, subdural hematoma, hernia and rectal prolapse

Differential diagnosis:

1. B. parapertussis, adenovirus, mycoplasma pneumonia, and chlamydia trachomatis

2. Foreign body aspiration, endobronchial tuberculosis and a mass pressing on the airway

DIAGNOSIS

1. Suspected on the basis of history and clinical examination and is confirmed by culture, genomics or serology

2. Elevated WBC count with lymphocytosis. The absolute lymphocyte count of ≥20,000 is highly suggestive

3. Culture: gold standard specially in the catarrhal stage. A saline nasal swab or swab from the posterior pharynx is preferred and the swab should be taken using dacron or calcium alginate and has to be plated on to the selective medium

DIAGNOSIS

However culture are not recommended in clinical practice as the yield is poor because of previous vaccination, antibiotic use, diluted specimen and faulty collection and transportation of specimen.

4. PCR: most sensitive to diagnose; can be done even after antibiotic exposure. It should always be used in addition with cultures

5. Direct fluorescent antibody testing: low sensitivity and variable specifity

TREATMENT

1. Avoidance of irritants, smoke, noise and other cough promoting factors

2. Antibiotics: effective only if started early in the course of illness. Erythromycin (40-50 mg/kg/day 6 hrly orally for 2 weeks or Azithromycin 10 mg/kg for 5 days in children<6 months and for children>6 months 10 mg/kg on day 1, followed by 5mg/kg from day2-5 or Clarithromycin 15 mg/kg 12 hrly for 7 days

3. Supplemental oxygen, hydration, cough mixtures and bronchodilators (in individual cases)

PREVENTION

All household contacts should be given erythromycin for 2 weeks

Children <7 years of age not completed the four primary dose should complete the same at the earliest

Children <7 years of age completed primary vaccination but not received the booster in the last 3 years have to be given a single booster dose

VACCINE

Tetanus

LOCKJAW

INTRODUCTION

Tetanus is an acute, fatal, severe exotoxin mediated nervous system disorder characterized by muscle spasm

Caused by the toxin producing anaerobe, Clostridium tetani Tetanus is the only vaccine preventable disease that is

infectious but not contagious from person to person

EPIDEMIOLOGY

C. tetani is a part of the normal flora in human and animal intestines and is disseminated through excreta

In spore form they are hard and long lasting in soil and dust The contamination of wound, unhygienic and improper

handling of the umbilical cord in newborns, lack of hygienic habits and aseptic care during and after delivery are the main risk factors for infection

PATHOGENESIS

PREDISPOSING FACTORS

A penetrating injury – inoculation of C. tetani spores Coinfection with other bacteria Devitalized tissue A foreign body Localized ischemia Therefore tetanus develop in these clinical settings:

neonates, obstetric patients, postsurgical patients, patients with dental infection, diabetic patients with infected extremity ulcers, patients who inject illicit and/or contaminated drugs

CLINICAL MANIFESTATIONS

Incubation period: 1-8 days Generalized tetanus: Presenting feature is trismus Symptoms of autonomic overactivity such as irritability,

restlessness, sweating, tachycardia, cardiac arrhythmias, labile hypotension or hypertension and fever

Tonic contractions of skeletal muscles (stiff neck, opisthotonus, risus sardonicus, board like rigid abdomen) and intermittent intense muscular spasms with no impairment of consciousness

Painful spasms, triggered by loud noises or other sensory stimuli such as physical contact or light

CLINICAL MANIFESTATIONS

Period of apnea and/or upper airway obstruction due to contraction of thoracic muscles and/or glottal or pharyngeal muscle

Neonatal tetanus: Manifested by rigidity, spasms, trismus, inability to suck and

seizures

Diagnosis: mainly clinical

TREATMENT

Best in the ICU as child may need  early and aggressive airway management

The goals of treatment include

1. Halting toxin production Wound debridement Antimicrobial therapy: metronidazole or penicillin G for 7-

10 days

2. Neutralization of unbound toxin: HTIG-3,000-6,000 units i.m. Equine antitoxin 1,500-3,000 units i.m. or i.v.

TREATMENT

3. Control of muscle spasms Avoidance of sensory stimuli Sedatives: diazepam

4. Management of autonomic dysfunction: Magnesium sulfate, beta blockers, morphine sulfate

5. Airway management and other supportive measures Main treatment as bound tetanus toxin can not be displaced

from the nervous system Endotracheal intubation/tracheostomy, nutritional support,

physical therapy as soon as spasms have ceased

PREVENTION

Immunization and proper treatment of wounds and traumatic injuries

PROGNOSIS: The average mortality of tetanus is 45-55% Neonatal tetanus: 60-70% Most important factor influencing outcome is supportive care

PREVENTION

VACCINE: DPT vaccine: 3 primary doses starting at 6 weeks of age 1st booster at 16-18 months of age, 2nd booster at 5 years of

age At 10 years of age Tdap/Td followed by Td every 10 years Catch-up vaccination: Below 7 years: DPT at 0,1 and 6 months